Role of exosomal circular RNAs as microRNA sponges and potential targeting for suppressing hepatocellular carcinoma growth and progression

In this editorial,we comment on the article by Lyu et al published in the recent issue of the World Journal of Gastroenterology(2023;2219-2840).Hepatocellular carcinoma(HCC)is a frequently encountered and highly aggressive primary liver cancer,which remains the third-commonest cause of cancer-related death despite the current therapeutic modalities.There is urgency in developing novel thera-peutic approaches,such as by manipulating extracellular vesicles,which con-stitute a highly heterogeneous nanoparticle population that contains various cargoes.These cargoes have a pivotal role in cell-to-cell communication and can modify the functional level of the recipient cells via their uptake by other recipient cells.Exosomal non-coding RNAs have particular evolving significance in HCC,such as circular RNAs,which have been found differentially expressed in normal hepatic and HCC tissues.The aberrations in their expression levels have a key role in the HCC development and progression and the overall prognosis.In this editorial,we will shed light on the emerging role of exosomal circular RNAs in HCC development and progression,focusing on the oncogenic or potentially tumor suppressive effect of mesenchymal stem cells-derived exosomal non-coding RNAs.

A Comparative Study on the Post-Buckling Behavior of Reinforced Thermoplastic Pipes(RTPs)Under External Pressure Considering Progressive Failure

The collapse pressure is a key parameter when RTPs are applied in harsh deep-water environments.To investigate the collapse of RTPs,numerical simulations and hydrostatic pressure tests are conducted.For the numerical simulations,the eigenvalue analysis and Riks analysis are combined,in which the Hashin failure criterion and fracture energy stiffness degradation model are used to simulate the progressive failure of composites,and the“infinite”boundary conditions are applied to eliminate the boundary effects.As for the hydrostatic pressure tests,RTP specimens were placed in a hydrostatic chamber after filled with water.It has been observed that the cross-section of the middle part collapses when it reaches the maximum pressure.The collapse pressure obtained from the numerical simulations agrees well with that in the experiment.Meanwhile,the applicability of NASA SP-8007 formula on the collapse pressure prediction was also discussed.It has a relatively greater difference because of the ignorance of the progressive failure of composites.For the parametric study,it is found that RTPs have much higher first-ply-failure pressure when the winding angles are between 50°and 70°.Besides,the effect of debonding and initial ovality,and the contribution of the liner and coating are also discussed.

Overview of the immunological mechanisms in hepatitis B virus reactivation:Implications for disease progression and management strategies

Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

Imbalance of Circulating Follicular Regulatory and Follicular Helper T Cell Subpopulations Is Associated with Disease Progression and Serum CYFRA 21-1 Levels in Patients with Non-small Cell Lung Cancer

Objective This study aimed to investigate the changes of follicular helper T(TFH)and follicular regulatory T(TFR)cell subpopulations in patients with non-small cell lung cancer(NSCLC)and their significance.Methods Peripheral blood was collected from 58 NSCLC patients at different stages and 38 healthy controls.Flow cytometry was used to detect TFH cell subpopulation based on programmed death 1(PD-1)and inducible co-stimulator(ICOS),and TFR cell subpopulation based on cluster determinant 45RA(CD45RA)and forkhead box protein P3(FoxP3).The levels of interleukin-10(IL-10),interleukin-17a(IL-17a),interleukin-21(IL-21),and transforming growth factor-β(TGF-β)in the plasma were measured,and changes in circulating B cell subsets and plasma IgG levels were also analyzed.The correlation between serum cytokeratin fragment antigen 21-1(CYFRA 21-1)levels and TFH,TFR,or B cell subpopulations was further explored.Results The TFR/TFH ratio increased significantly in NSCLC patients.The CD45RA^(+)FoxP3^(int) TFR subsets were increased,with their proportions increasing in stages Ⅱ to Ⅲ and decreasing in stage IV.PD-1^(+)ICOS+TFH cells showed a downward trend with increasing stages.Plasma IL-21 and TGF-β concentrations were increased in NSCLC patients compared with healthy controls.Plasmablasts,plasma IgG levels,and CD45RA^(+)FoxP3^(int) TFR cells showed similar trends.TFH numbers and plasmablasts were positively correlated with CYFRA 21-1 in stages Ⅰ-Ⅲ and negatively correlated with CYFRA 21-1 in stage IV.Conclusion Circulating TFH and TFR cell subpopulations and plasmablasts dynamically change in different stages of NSCLC,which is associated with serum CYFRA 21-1 levels and reflects disease progression.

Wear dependent virtual flow rate sensor for progressing cavity pumps with deformable stator

This contribution presents a novel wear dependent virtual flow rate sensor for single stage single lobe progressing cavity pumps. We study the wear-induced material loss of the pump components and the impact of this material loss on the volumetric efficiency. The results are combined with an established backflow model to implement a backflow calculation procedure that is adaptive to wear. We use a laboratory test setup with a highly abrasive fluid and operate a pump from new to worn condition to validate our approach. The obtained measurement data show that the presented virtual sensor is capable of calculating the flow rate of a pump being subject to wear during its regular operation.

A multi-platform analysis of human gingival crevicular fluid reveals ferroptosis as a relevant regulated cell death mechanism during the clinical progression of periodontitis

Ferroptosis is implicated in the pathogenesis of numerous chronic-inflammatory diseases,yet its association with progressive periodontitis remains unexplored.To investigate the involvement and significance of ferroptosis in periodontitis progression,we assessed sixteen periodontitis-diagnosed patients.Disease progression was clinically monitored over twelve weeks via weekly clinical evaluations and gingival crevicular fluid(GCF)collection was performed for further analyses.Clinical metrics,proteomic data,in silico methods,and bioinformatics tools were combined to identify protein profiles linked to periodontitis progression and to explore their potential connection with ferroptosis.Subsequent western blot analyses validated key findings.Finally,a single-cell RNA sequencing(scRNA-seq)dataset(GSE164241)for gingival tissues was analyzed to elucidate cellular dynamics during periodontitis progression.Periodontitis progression was identified as occurring at a faster rate than traditionally thought.GCF samples from progressing and non-progressing periodontal sites showed quantitative and qualitatively distinct proteomic profiles.In addition,specific biological processes and molecular functions during progressive periodontitis were revealed and a set of hub proteins,including SNCA,CA1,HBB,SLC4A1,and ANK1 was strongly associated with the clinical progression status of periodontitis.Moreover,we found specific proteins-drivers or suppressors-associated with ferroptosis(SNCA,FTH1,HSPB1,CD44,and GCLC),revealing the co-occurrence of this specific type of regulated cell death during the clinical progression of periodontitis.Additionally,the integration of quantitative proteomic data with scRNA-seq analysis suggested the susceptibility of fibroblasts to ferroptosis.Our analyses reveal proteins and processes linked to ferroptosis for the first time in periodontal patients,which offer new insights into the molecular mechanisms of progressive periodontal disease.These findings may lead to novel diagnostic and therapeutic strategies.

Progress in the generation of spinal cord organoids over the past decade and future perspectives

Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo.As emerging bioengineering methods have led to the optimization of cell culture protocols,spinal cord organoids technology has made remarkable advancements in the past decade.Our literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal axes.Moreover,fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional assessment.These qualities make spinal cord organoids valuable tools for disease modeling,drug screening,and tissue regeneration.By utilizing this emergent technology,researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord diseases.However,at present,spinal cord organoid technology remains in its infancy and has not been widely applied in translational medicine.Establishment of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.

Pressure stimulated current in progressive failure process of combined coal-rock under uniaxial compression:Response and mechanism

Effective monitoring of the structural health of combined coal-rock under complex geological conditions by pressure stimulated currents(PSCs)has great potential for the understanding of dynamic disasters in underground engineering.To reveal the effect of this way,the uniaxial compression experiments with PSC monitoring were conducted on three types of coal-rock combination samples with different strength combinations.The mechanism explanation of PSCs are investigated by resistivity test,atomic force microscopy(AFM)and computed tomography(CT)methods,and a PSC flow model based on progressive failure process is proposed.The influence of strength combinations on PSCs in the progressive failure process are emphasized.The results show the PSC responses between rock part,coal part and the two components are different,which are affected by multi-scale fracture characteristics and electrical properties.As the rock strength decreases,the progressive failure process changes obviously with the influence range of interface constraint effect decreasing,resulting in the different responses of PSC strength and direction in different parts to fracture behaviors.The PSC flow model is initially validated by the relationship between the accumulated charges of different parts.The results are expected to provide a new reference and method for mining design and roadway quality assessment.

Recent progress in Ni-rich layered oxides and related cathode materials for Li-ion cells

Undoubtedly,the enormous progress observed in recent years in the Ni-rich layered cathode materials has been crucial in terms of pushing boundaries of the Li-ion battery(LIB)technology.The achieved improvements in the energy density,cyclability,charging speed,reduced costs,as well as safety and stability,already contribute to the wider adoption of LIBs,which extends nowadays beyond mobile electronics,power tools,and electric vehicles,to the new range of applications,including grid storage solutions.With numerous published papers and broad reviews already available on the subject of Ni-rich oxides,this review focuses more on the most recent progress and new ideas presented in the literature references.The covered topics include doping and composition optimization,advanced coating,concentration gradient and single crystal materials,as well as innovations concerning new electrolytes and their modification,with the application of Ni-rich cathodes in solid-state batteries also discussed.Related cathode materials are briefly mentioned,with the high-entropy approach and zero-strain concept presented as well.A critical overview of the still unresolved issues is given,with perspectives on the further directions of studies and the expected gains provided.

Recent progress of gastroesophageal reflux after endoscopic myotomy

Per-oral endoscopic myotomy(POEM)is an innovative minimally invasive technique and has emerged as the preferred modality for treating achalasia and spastic esophageal disorders in numerous specialized centers worldwide.Gastroesophageal reflux(GER)is a common complication following POEM procedures.Recently,an article in the World Journal of Gastroenterology,providing a comprehensive update on post-POEM GER.In this article,the authors present novel insights and strategies that offer valuable implications for endoscopy.

The current role of dendritic cells in the progression and treatment of colorectal cancer

Colorectal cancer(CRC)is the third most common cancer and the second leading cause of cancer-related deaths worldwide.Dendritic cells(DCs)constitute a heterogeneous group of antigen-presenting cells that are important for initiating and regulating both innate and adaptive immune responses.As a crucial component of the immune system,DCs have a pivotal role in the pathogenesis and clinical treatment of CRC.DCs cross-present tumor-related antigens to activate T cells and trigger an antitumor immune response.However,the antitumor immune function of DCs is impaired and immune tolerance is promoted due to the presence of the tumor microenvironment.This review systematically elucidates the specific characteristics and functions of different DC subsets,as well as the role that DCs play in the immune response and tolerance within the CRC microenvironment.Moreover,how DCs contribute to the progression of CRC and potential therapies to enhance antitumor immunity on the basis of existing data are also discussed,which will provide new perspectives and approaches for immunotherapy in patients with CRC.

PAPS: Progressive Attention-Based Pan-sharpening

Pan-sharpening aims to seek high-resolution multispectral(HRMS) images from paired multispectral images of low resolution(LRMS) and panchromatic(PAN) images, the key to which is how to maximally integrate spatial and spectral information from PAN and LRMS images. Following the principle of gradual advance, this paper designs a novel network that contains two main logical functions, i.e., detail enhancement and progressive fusion, to solve the problem. More specifically, the detail enhancement module attempts to produce enhanced MS results with the same spatial sizes as corresponding PAN images, which are of higher quality than directly up-sampling LRMS images.Having a better MS base(enhanced MS) and its PAN, we progressively extract information from the PAN and enhanced MS images, expecting to capture pivotal and complementary information of the two modalities for the purpose of constructing the desired HRMS. Extensive experiments together with ablation studies on widely-used datasets are provided to verify the efficacy of our design, and demonstrate its superiority over other state-of-the-art methods both quantitatively and qualitatively. Our code has been released at https://github.com/JiaYN1/PAPS.

Glucocorticoids-based prodrug design:Current strategies and research progress

Attributing to their broad pharmacological effects encompassing anti-inflammation,antitoxin,and immunosuppression,glucocorticoids(GCs)are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus,nephritis,arthritis,ulcerative colitis,asthma,keratitis,macular edema,and leukemia.However,longterm use often causes undesirable side effects,including metabolic disorders-induced Cushing's syndrome(buffalo back,full moon face,hyperglycemia,etc.),osteoporosis,aggravated infection,psychosis,glaucoma,and cataract.These notorious side effects seriously compromise patients'quality of life,especially in patients with chronic diseases.Therefore,glucocorticoid-based advanced drug delivery systems for reducing adverse effects have received extensive attention.Among them,prodrugs have the advantages of low investment,low risk,and high success rate,making them a promising strategy.In this review,we propose the strategies for the design and summarize current research progress of glucocorticoid-based prodrugs in recent decades,including polymer-based prodrugs,dendrimer-based prodrugs,antibody-drug conjugates,peptide-drug conjugates,carbohydrate-based prodrugs,aliphatic acid-based prodrugs and so on.Besides,we also raise issues that need to be focused on during the development of glucocorticoid-based prodrugs.This review is expected to be helpful for the research and development of novel GCs and prodrugs.

Global Dynamic Responses and Progressive Failure of Submerged Floating Tunnel Under Cable Breakage Conditions

The Submerged Floating Tunnel(SFT)relies on a tensioned mooring system for precise positioning.The sudden breakage of a single cable can trigger an immediate alteration in the constraint conditions of the tube,inducing a transient heave response within the structure along with a transient increase in cable tension experienced by adjacent cables.In more severe cases,this may even lead to a progressive failure culminating in the global destruction of the SFT.This study used ANSYS/AQWA to establish a numerical model of the entire length SFT for the hydrodynamic response analysis,and conducted a coupled calculation of the dynamic responses of the SFT-mooring line model based on Orca Flex to study the global dynamic responses of the SFT at the moment of cable breakage and the redistribution of cable internal forces.The most unfavorable position for SFT cable breakage was identified,the influence mechanism of cable breakage at different positions on the global dynamic response was revealed,and the progressive chain failure pattern caused by localized cable breakage are also clarified.

A progressive framework for rotary motion deblurring

The rotary motion deblurring is an inevitable procedure when the imaging seeker is mounted in the rotating missiles.Traditional rotary motion deblurring methods suffer from ringing artifacts and noise,especially for large blur extents.To solve the above problems,we propose a progressive rotary motion deblurring framework consisting of a coarse deblurring stage and a refinement stage.In the first stage,we design an adaptive blur extents factor(BE factor)to balance noise suppression and details reconstruction.And a novel deconvolution model is proposed based on BE factor.In the second stage,a triplescale deformable module CNN(TDM-CNN)is designed to reduce the ringing artifacts,which can exploit the 2D information of an image and adaptively adjust spatial sampling locations.To establish a standard evaluation benchmark,a real-world rotary motion blur dataset is proposed and released,which includes rotary blurred images and corresponding ground truth images with different blur angles.Experimental results demonstrate that the proposed method outperforms the state-of-the-art models on synthetic and real-world rotary motion blur datasets.The code and dataset are available at https://github.com/JinhuiQin/RotaryDeblurring.

PRSS50-mediated inhibition of MKP3/ERK signaling is crucial for meiotic progression and sperm quality

Serine protease 50(PRSS50/TSP50)is highly expressed in spermatocytes.Our study investigated its role in testicular development and spermatogenesis.Initially,PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes.To further explore this,we generated PRSS50 knockout(Prss50^(−/−))mice(Mus musculus),which exhibited abnormal spermatid nuclear compression and reduced male fertility.Furthermore,dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50^(−/−)mice,accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells.Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2(ERK1/2)and elevated levels of MAP kinase phosphatase 3(MKP3),a specific ERK antagonist,potentially accounting for testicular dysplasia in adolescent Prss50−/−mice.Taken together,these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis,with the MKP3/ERK signaling pathway playing a significant role in this process.

Computational Analysis of Novel Extended Lindley Progressively Censored Data

A novel extended Lindley lifetime model that exhibits unimodal or decreasing density shapes as well as increasing,bathtub or unimodal-then-bathtub failure rates, named the Marshall-Olkin-Lindley (MOL) model is studied.In this research, using a progressive Type-II censored, various inferences of the MOL model parameters oflife are introduced. Utilizing the maximum likelihood method as a classical approach, the estimators of themodel parameters and various reliability measures are investigated. Against both symmetric and asymmetric lossfunctions, the Bayesian estimates are obtained using the Markov Chain Monte Carlo (MCMC) technique with theassumption of independent gamma priors. From the Fisher information data and the simulatedMarkovian chains,the approximate asymptotic interval and the highest posterior density interval, respectively, of each unknownparameter are calculated. Via an extensive simulated study, the usefulness of the various suggested strategies isassessedwith respect to some evaluationmetrics such as mean squared errors, mean relative absolute biases, averageconfidence lengths, and coverage percentages. Comparing the Bayesian estimations based on the asymmetric lossfunction to the traditional technique or the symmetric loss function-based Bayesian estimations, the analysisdemonstrates that asymmetric loss function-based Bayesian estimations are preferred. Finally, two data sets,representing vinyl chloride and repairable mechanical equipment items, have been investigated to support theapproaches proposed and show the superiority of the proposed model compared to the other fourteen lifetimemodels.

Research progress on natural products against hepatocellular carcinoma

Hepatocellular carcinoma(HCC)remains a prevalent and challenging malignancy globally,characterized by its numerous causal factors and generally unfavorable prognosis.In the relentless pursuit of effective treatment modalities,natural products have emerged as a promising and relatively non-toxic alternative,garnering significant interest.The integration of natural products with contemporary medical research has yielded encouraging therapeutic outcomes in the management of HCC.This review offers a comprehensive overview of the causal factors underlying HCC,and the diverse treatment options available,and highlights the advancements made by natural products in anti-HCC research.Particularly,we provide an outline of the various types of natural products,their corresponding nomenclature,target molecules,and mechanisms of action that exhibit anti-HCC activities.Natural products are anticipated to play a pivotal role in future comprehensive treatment plans for liver cancer,potentially offering patients improved survival rates and an enhanced quality of life.

Bayesian and Non-Bayesian Analysis for the Sine Generalized Linear Exponential Model under Progressively Censored Data

This article introduces a novel variant of the generalized linear exponential(GLE)distribution,known as the sine generalized linear exponential(SGLE)distribution.The SGLE distribution utilizes the sine transformation to enhance its capabilities.The updated distribution is very adaptable and may be efficiently used in the modeling of survival data and dependability issues.The suggested model incorporates a hazard rate function(HRF)that may display a rising,J-shaped,or bathtub form,depending on its unique characteristics.This model includes many well-known lifespan distributions as separate sub-models.The suggested model is accompanied with a range of statistical features.The model parameters are examined using the techniques of maximum likelihood and Bayesian estimation using progressively censored data.In order to evaluate the effectiveness of these techniques,we provide a set of simulated data for testing purposes.The relevance of the newly presented model is shown via two real-world dataset applications,highlighting its superiority over other respected similar models.

Deep learning model based on PET/CT and combination with Cox proportional hazard model for predicting progression of lung invasive adenocarcinoma after surgery

Objective To observe the efficacy of deep learning(DL)model based on PET/CT and its combination with Cox proportional hazard model for predicting progressive disease(PD)of lung invasive adenocarcinoma within 5 years after surgery.Methods The clinical,PET/CT and 5-year follow-up data of 250 patients with lung invasive adenocarcinoma were retrospectively analyzed.According to PD or not,the patients were divided into the PD group(n=71)and non-PD group(n=179).The basic data and PET/CT findings were compared between groups,among which the quantitative variables being significant different between groups were transformed to categorical variables using receiver operating characteristic(ROC)curve and corresponding cut-off value.Multivariant Cox proportional hazard model was used to select independent predicting factors of PD of lung invasive adenocarcinoma within 5 years after surgery.The patients were divided into training,validation and test sets at the ratio of 6∶2∶2,and PET/CT data in training set and validation set were used to train model and tuning parameters to build the PET/CT DL model,and the combination model was built in serial connection of DL model and the predictive factors.In test set,the efficacy of each model for predicting PD of lung invasive adenocarcinoma within 5 years after surgery was assessed and compared using the area under the curve(AUC).Results Patients'gender and smoking status,as well as the long diameter,SUV max and SUV mean of lesions measured on PET images,the long diameter,short diameter and type of lesions showed on CT were statistically different between groups(all P<0.05).Smoking(HR=1.787[1.053,3.031],P=0.031)and lesion SUV max>4.15(HR=5.249[1.062,25.945],P=0.042)were both predictors of PD of lung invasive adenocarcinoma within 5 years after surgery.In test set,the AUC of PET/CT DL model for predicting PD was 0.847,of the combination model was 0.890,of the latter was higher than of the former(P=0.036).Conclusion DL model based on PET/CT had high efficacy for predicting PD of lung invasive adenocarcinoma within 5 years after surgery.Combining with Cox proportional hazard model could further improve its predicting efficacy.