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.

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.

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.

Micromechanical testing and property upscaling of planetary rocks:A critical review

Knowledge of the mechanical behavior of planetary rocks is indispensable for space explorations.The scarcity of pristine samples and the irregular shapes of planetary meteorites make it difficult to obtain representative samples for conventional macroscale rock mechanics experiments(macro-RMEs).This critical review discusses recent advances in microscale RMEs(micro-RMEs)techniques and the upscaling methods for extracting mechanical parameters.Methods of mineralogical and microstructural analyses,along with non-destructive mechanical techniques,have provided new opportunities for studying planetary rocks with unprecedented precision and capabilities.First,we summarize several mainstream methods for obtaining the mineralogy and microstructure of planetary rocks.Then,nondestructive micromechanical testing methods,nanoindentation and atomic force microscopy(AFM),are detailed reviewed,illustrating the principles,advantages,influencing factors,and available testing results from literature.Subsequently,several feasible upscaling methods that bridge the micro-measurements of meteorite pieces to the strength of the intact body are introduced.Finally,the potential applications of planetary rock mechanics research to guiding the design and execution of space missions are environed,ranging from sample return missions and planetary defense to extraterrestrial construction.These discussions are expected to broaden the understanding of the microscale mechanical properties of planetary rocks and their significant role in deep space exploration.

Research Progress and Prospects of Total Factor Productivity in the Construction Industry

The high-quality development of the construction industry fundamentally stems from the significant improvement of total factor productivity.Therefore,it is of crucial significance for promoting the development of the construction industry to a higher level by scientifically and accurately measuring the total factor productivity of the construction industry and deeply analyzing the influencing factors behind it.Based on a comprehensive consideration of research methods and influencing factors,this paper systematically reviews the existing relevant literature on total factor productivity in the construction industry,aiming to reveal the current research development trend in this field and point out potential problems.This effort aims to provide a solid theoretical foundation and valuable reference for further in-depth research,and jointly promote the continuous progress and development of total factor productivity research in the construction industry.

Novel Accelerating Life Test Method and Its Application by Combining Constan Stress and Progressive Stress

Constant stress accelerated life tests(ALTs) can be applied to obtain a high estimation accuracy of reliability measure?ments, but these are time?consuming tests. Progressive stress ALTs can yield failures more quickly but cannot guaran tee the estimation accuracy of reliability measurements. In this paper, a progressive?constant combination stress ALT is proposed to combine the merits of both tests. The optimal plan, in which the design variables are the initial pro?gressive stress level, the progressive stress ramp rate, the sample allocation proportion of the progressive stress and the constant stress level, is determined using the principle of minimizing the asymptotic variance of the maximum likelihood estimator of the natural log reliable life for the connectors. A comparison between the optimal PCCSALT plan and the CSALT plan with the same sample size and estimation accuracy shows that the test time is reduced by 13.59% by applying the PCCSALT.

Progress on the ultrasonic testing and laser thermography techniques for NDT of tokamak plasma-facing components

During manufacturing and operation, different kinds of defects, e.g., delamination or surface cracks, may be generated in the plasma-facing components (PFCs) of a Tokamak device. To ensure the safety of the PFCs, various kinds of nondestructive testing (NDT) techniques are needed for different defect and failure mode. This paper gives a review of the recently developed ultrasonic testing (UT) and laser thermography methods for inspection of the delamination and surface cracks in PFCs. For monoblock W/Cu PFCs of divertor, the bonding quality at both W-Cu and Cu- CuCrZr interfaces was qualified by using UT with a focus probe during manufacturing. A noncontact, coupling-free and flexible ultrasonic scanning testing system with use of an electromagnetic acoustic transducer and a robotic inspection manipulator was introduced then for the in-vessel inspection of delamination defect in first wall (FW). A laser infrared thermography testing method is highlighted for the on-line inspection of delamination defect in FW through the vacuum vessel window of the Tokamak reactor. Finally, a new laser spot thermography method using laser spot array source was described for the online inspection of the surface cracks in FW.

Development of multi-functional anchorage support dynamic-static coupling performance test system and its application

In underground engineering with complex conditions,the bolt(cable)anchorage support system is in an environment where static and dynamic stresses coexist,under the action of geological conditions such as high stresses and strong disturbances and construction conditions such as the application of high prestress.It is essential to study the support components performance under dynamic-static coupling conditions.Based on this,a multi-functional anchorage support dynamic-static coupling performance test system(MAC system)is developed,which can achieve 7 types of testing functions,including single component performance,anchored net performance,anchored rock performance and so on.The bolt and cable mechanical tests are conducted by MAC system under different prestress levels.The results showed that compared to the non-prestress condition,the impact resistance performance of prestressed bolts(cables)is significantly reduced.In the prestress range of 50–160 k N,the maximum reduction rate of impact energy resisted by different types of bolts is 53.9%–61.5%compared to non-prestress condition.In the prestress range of 150–300 k N,the impact energy resisted by high-strength cable is reduced by76.8%–84.6%compared to non-prestress condition.The MAC system achieves dynamic-static coupling performance test,which provide an effective means for the design of anchorage support system.

Inflow and outflow permeability tests in a very soft clay under low stresses

In situ inflow and outflow permeability tests with the BAT probe at SarapuíII soft clay test site are presented.A description of the BAT permeability test is provided,discussing its advantages and shortcomings,especially in the case of very soft clays under low stresses.Pore pressures were monitored during probe installation and were found to be slightly lower than piezocone u2 pore pressures,consistent with the position of the filter.The role of filter tip saturation was investigated after the usual saturation procedure provided an unsatisfactory pore pressure response during probe installation.Results show that the vacuum saturation procedure provides adequate response during installation and increases the reliability of the coefficient of permeability determination in early measurements.Both inflow and outflow tests yielded similar results,indicating that careful execution of the test can lead to good test repeatability regardless of the loading condition.Various sequences of alternated inflow and outflow tests have yielded similar results,indicating that soil reconsolidation and filter clogging were negligible in the tests performed.Data are presented concerning the relationship between index parameters and the in situ coefficient of permeability for SarapuíII clay,which plot outside the range of existing databases.

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.

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.

Adjustments for Kurtosis and Continuity on the Prentice Test

The test of Prentice [1] is a non-parametric statistical test for the two-way analysis of variance using ranks. The null distribution of this test typically is approximated using the Chi-square distribution. However, the exact null distribution deviates from the Chi-square approximation in certain cases commonly found in applications of the test, motivating adjustments to the distribution. This manuscript presents adjustments to this null distribution correcting for continuity, multivariate skewness, and multivariate kurtosis. The effects of alternative scoring methods as non-polynomial functions of rank sums are also presented as a broader application of the approximation.

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.

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.

Two stages power generation test of the hot dry rock exploration and production demonstration project in the Gonghe Basin,northeastern Qinghai-Tibet plateau,China

The Hot Dry Rock(HDR)is considered as a clean and renewable energy,poised to significantly contribute to the global energy decarbonization agenda.Many HDR projects worldwide have accumulated valuable experience in efficient drilling and completion,reservoir construction,and fracture simulation.In 2019,China Geological Survey(CGS)initiated a demonstration project of HDR exploration and production in the Gonghe Basin,aiming to overcome the setbacks faced by HDR projects.Over the ensuing four years,the Gonghe HDR project achieved the first power generation in 2021,followed by the second power generation test in 2022.After establishing the primary well group in the initial phase,two directional wells and one branch well were drilled.Noteworthy progress was made in successfully constructing the targeted reservoir,realizing inter-well connectivity,power generation and grid connection,implementing of the real-time micro-seismic monitoring.A closed-loop technical validation of the HDR exploration and production was completed.However,many technical challenges remain in the process of HDR industrialization,such as reservoir fracture network characterization,efficient drilling and completion,multiple fracturing treatment,continuous injection and production,as well as mitigation of induced seismicity and numerical simulation technology.

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.

The Pathogenesis and Treatment Progress of Androgenic Alopecia

Androgenic alopecia, also known as seborrheic alopecia, is the most common hair loss disorder in dermatology clinics, mainly characterized by hair follicle miniaturization and progressive hair loss. The etiology and pathogenesis of androgenic alopecia are not clear, but may be related to heredity and androgen metabolism. Currently, minoxidil and finasteride are the only two drugs approved by the U.S. Food and Drug Administration (FDA) for AGA treatment, other treatments include oral minoxidil, hair transplantation, low energy laser therapy (LLLT), platelet-rich plasma (PRP), Chinese medicine microneedles, and combination therapy. With the development of medicine and science, we have ushered in the era of biologics and targeted therapy. In recent years, a variety of signaling pathways for androgenic alopecia have been found, which may provide a basis for targeted therapy for androgenic alopecia.

Multiplex Rapid Test with Acceptable Diagnosis Performance as a Solution to Increase Diagnosis of Hepatitis B and C Viruses in Pregnant Women in an Area of High Prevalence of Both Hepatitis Viruses Associated with HIV

Background and Objective: HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) are very widespread in the world, however, less than 20% of the people affected are diagnosed and treated. This study aimed to determine the prevalence of HIV, HCV and HBV co-infections in pregnant women at Bangui Community University Hospital and the cost of screening. Methods: A cross-sectional study involving consenting pregnant women who came for antenatal care was performed. HIV, HCV antibodies and HBV antigens were detected using Exacto Triplex? HIV/HCV/HBsAg rapid test, cross-validated by ELISA tests. Sociodemographic and professional data, the modes of transmission and prevention of HIV and both hepatitis viruses were collected in a standard sheet and analyzed using the Epi-Info software version 7. Results: Pregnant women aged 15 to 24 were the most affected (45.3%);high school girls (46.0%), and pregnant women living in cohabitation (65.3%) were the most represented. Twenty-five (16.7%) worked in the formal sector, 12.7% were unemployed housewives and the remainder in the informal sector. The prevalence of HIV, HBV, and HCV viruses was 11.8%, 21.9% and 22.2%, respectively. The prevalence of co-infections was 8.6% for HIV-HBV, 10.2% for HIV-HCV, 14.7% for HBV-HCV and 6.5% for HIV-HBV-HCV. All positive results and 10% of negative results by the rapid test were confirmed by ELISA tests. The serology of the three viruses costs 39,000 FCFA (60 Euros) by ELISA compared to 10,000 FCFA (15.00 Euros) with Exacto Triplex? HIV/HCV/AgHBs (BioSynex, Strasbourg, France). Conclusion: The low level of education and awareness of hepatitis are barriers to development and indicate the importance of improving the literacy rate of women in the Central African Republic (CAR). Likewise, the high prevalence of the three viruses shows the need for the urgent establishment of a national program to combat viral hepatitis in the CAR.

Fuzzing:Progress,Challenges,and Perspectives

As one of the most effective techniques for finding software vulnerabilities,fuzzing has become a hot topic in software security.It feeds potentially syntactically or semantically malformed test data to a target program to mine vulnerabilities and crash the system.In recent years,considerable efforts have been dedicated by researchers and practitioners towards improving fuzzing,so there aremore and more methods and forms,whichmake it difficult to have a comprehensive understanding of the technique.This paper conducts a thorough survey of fuzzing,focusing on its general process,classification,common application scenarios,and some state-of-the-art techniques that have been introduced to improve its performance.Finally,this paper puts forward key research challenges and proposes possible future research directions that may provide new insights for researchers.