Development and validation of nomograms for predicting prognosis in patients with solitary HCC: A TRIPOD-Compliant study.

Objective: To develop and validate nomograms for predicting the OS and CSS of patients with Solitary Hepatocellular Carcinoma (HCC). Methods: Using the TRIPOD guidelines, this study identified 5206 patients in the Surveillance, Epidemiology, and End Results (SEER) 17 registry database. All patients were randomly divided in a ratio of 7:3 into a training cohort (n = 3646) and a validation cohort (n = 1560), and the Chinese independent cohort (n = 307) constituted the external validation group. The prognosis-related risk factors were selected using univariate Cox regression analysis, and the independent prognostic factors of OS and CSS were identified using the Lasso-Cox regression model. The nomograms for predicting the OS and CSS of the patients were constructed based on the identified prognostic factors. Their prediction ability was evaluated using the concordance index (C-index), receiver operating characteristic (ROC) curve, and calibration curve in both the training and validation cohorts. Results: We identified factors that predict OS and CSS and constructed two nomograms based on the data. The ROC analysis, C-index analysis, and calibration analysis indicated that the two nomograms performed well over the 1, 3, and 5-year OS and CSS periods in both the training and validation cohorts. Additionally, these results were confirmed in the external validation group. Decision curve analysis (DCA) demonstrated that the two nomograms were clinically valuable and superior to the TNM stage system. Conclusion: We established and validated nomograms to predict 1,3, and 5-year OS and CSS in solitary HCC patients, and our results may also be helpful for clinical decision-making.

B63: The Most Stable Bilayer Structure with Dual Aromaticity.

The emergence of a bilayer B48 cluster, which has been both theoretically predicted and experimentally observed, as well as the recent experimental synthesis of bilayer borophene sheets on Ag and Cu surfaces, has generated tremendous curiosity in the bilayer structures of boron clusters. However, the connection between bilayer boron cluster and bilayer borophene remains unknown. By combining a genetic algorithm and density functional theory calculations, a global search for the low-energy structures of the B63 cluster was conducted, revealing that the Cs bilayer structure with three interlayer B-B bonds is the most stable bilayer structure. This structure was further examined in terms of its structural stability, chemical bonding, and aromaticity. Interestingly, the interlayer bonds induce strong electronegativity and robust aromaticity. Furthermore, the dual aromaticity stems from diatropic currents originating from virtual translational transitions for both σ and π electrons. This unprecedent bilayer boron cluster is anticipated to enrich the concept of dual aromaticity and serve as a potential precursor for bilayer borophene.

Genistin: A Novel Estrogen Analogue Targeting ERß to Alleviate Thrombocytopenia.

Thrombocytopenia, a prevalent hematologic challenge, correlates directly with the mortality of numerous ailments. Current therapeutic avenues for thrombocytopenia are not without limitations. Here, we identify genistin, an estrogen analogue, as a promising candidate for thrombocytopenia intervention, discovered through AI-driven compound library screening. While estrogen's involvement in diverse biological processes is recognized, its role in thrombopoiesis remains underexplored. Our findings elucidate genistin's ability to enhance megakaryocyte differentiation, thereby augmenting platelet formation and production. In vivo assessments further underscore genistin's remedial potential against radiation-induced thrombocytopenia. Mechanistically, genistin's efficacy is attributed to its direct interaction with estrogen receptor ß (ERß), with subsequent activation of both ERK1/2 and the Akt signaling pathways membrane ERß. Collectively, our study positions genistin as a prospective therapeutic strategy for thrombocytopenia, shedding light on novel interplays between platelet production and ERß.

Activating SRC/MAPK signaling via 5-HT1A receptor contributes to the effect of vilazodone on improving thrombocytopenia.

Thrombocytopenia caused by long-term radiotherapy and chemotherapy exists in cancer treatment. Previous research demonstrates that 5-Hydroxtrayptamine (5-HT) and its receptors induce the formation of megakaryocytes (MKs) and platelets. However, the relationships between 5-HT1A receptor (5-HTR1A) and MKs is unclear so far. We screened and investigated the mechanism of vilazodone as a 5-HTR1A partial agonist in promoting MK differentiation and evaluated its therapeutic effect in thrombocytopenia. We employed a drug screening model based on machine learning (ML) to screen the megakaryocytopoiesis activity of Vilazodone (VLZ). The effects of VLZ on megakaryocytopoiesis were verified in HEL and Meg-01 cells. Tg (itga2b: eGFP) zebrafish was performed to analyze the alterations in thrombopoiesis. Moreover, we established a thrombocytopenia mice model to investigate how VLZ administration accelerates platelet recovery and function. We carried out network pharmacology, Western blot, and immunofluorescence to demonstrate the potential targets and pathway of VLZ. VLZ has been predicted to have a potential biological action. Meanwhile, VLZ administration promotes MK differentiation and thrombopoiesis in cells and zebrafish models. Progressive experiments showed that VLZ has a potential therapeutic effect on radiation-induced thrombocytopenia in vivo. The network pharmacology and associated mechanism study indicated that SRC and MAPK signaling are both involved in the processes of megakaryopoiesis facilitated by VLZ. Furthermore, the expression of 5-HTR1A during megakaryocyte differentiation is closely related to the activation of SRC and MAPK. Our findings demonstrated that the expression of 5-HTR1A on MK, VLZ could bind to the 5-HTR1A receptor and further regulate the SRC/MAPK signaling pathway to facilitate megakaryocyte differentiation and platelet production, which provides new insights into the alternative therapeutic options for thrombocytopenia.

Immune Regulatory Networks and Therapy of γδ T Cells in Liver Cancer: Recent Trends and Advancements.

The roles of γδ T cells in liver cancer, especially in the potential function of immunotherapy due to their direct cytotoxic effects on tumor cells and secretion of important cytokines and chemokines, have aroused research interest. This review briefly describes the basic characteristics of γδ T cells, focusing on their diverse effects on liver cancer. In particular, different subtypes of γδ T cells have diverse or even opposite effects on liver cancer. We provide a detailed description of the immune regulatory network of γδ T cells in liver cancer from two aspects: immune components and nonimmune components. The interactions between various components in this immune regulatory network are dynamic and pluralistic, ultimately determining the biological effects of γδ T cells in liver cancer. We also integrate the current knowledge of γδ T-cell immunotherapy for liver cancer treatment, emphasizing the potential of these cells in liver cancer immunotherapy.

Characterization and mitigation of artifacts derived from NGS library preparation due to structure-specific sequences in the human genome.

BACKGROUND: Hybridization capture-based targeted next generation sequencing (NGS) is gaining importance in routine cancer clinical practice. DNA library preparation is a fundamental step to produce high-quality sequencing data. Numerous unexpected, low variant allele frequency calls were observed in libraries using sonication fragmentation and enzymatic fragmentation. In this study, we investigated the characteristics of the artifact reads induced by sonication and enzymatic fragmentation. We also developed a bioinformatic algorithm to filter these sequencing errors. RESULTS: We used pairwise comparisons of somatic single nucleotide variants (SNVs) and insertions and deletions (indels) of the same tumor DNA samples prepared using both ultrasonic and enzymatic fragmentation protocols. Our analysis revealed that the number of artifact variants was significantly greater in the samples generated using enzymatic fragmentation than using sonication. Most of the artifacts derived from the sonication-treated libraries were chimeric artifact reads containing both cis- and trans-inverted repeat sequences of the genomic DNA. In contrast, chimeric artifact reads of endonuclease-treated libraries contained palindromic sequences with mismatched bases. Based on these distinctive features, we proposed a mechanistic hypothesis model, PDSM (pairing of partial single strands derived from a similar molecule), by which these sequencing errors derive from ultrasonication and enzymatic fragmentation library preparation. We developed a bioinformatic algorithm to generate a custom mutation "blacklist" in the BED region to reduce errors in downstream analyses. CONCLUSIONS: We first proposed a mechanistic hypothesis model (PDSM) of sequencing errors caused by specific structures of inverted repeat sequences and palindromic sequences in the natural genome. This new hypothesis predicts the existence of chimeric reads that could not be explained by previous models, and provides a new direction for further improving NGS analysis accuracy. A bioinformatic algorithm, ArtifactsFinder, was developed and used to reduce the sequencing errors in libraries produced using sonication and enzymatic fragmentation.

Case Report: Kounis syndrome due to cryptopteran bite.

Background: Kounis syndrome is an acute coronary syndrome (ACS) caused by allergic reactions, including coronary artery spasm (type I) caused by allergies without coronary predisposing factors, pre-existing coronary atherosclerosis, and coronary artery disease. Anaphylaxis leads to plaque rupture or erosion leading to acute myocardial infarction (type II) and acute coronary stent thrombosis (type III). Here we share a case of Kounis syndrome type I caused by an allergy caused by a Cryptopteran bite. Case presentation: A 47-year-old woman was admitted to the hospital due to an insect bite for 2 days and chest distress for more than 3 h. Outside the hospital, electrocardiogram(ECG) showed sinus rhythm, ST-segment elevation in leads V1-V3, high-sensitivity troponin 2.54 ng/ml(0-0.5 ng/ml). One hour later, the ECG of the patient showed that the ST segment elevation of lead V1-V4 was 0.10-0.20 mV. Emergency coronary angiography showed coronary spasm and moderate lumen stenosis in the middle segment of left anterior descending artery (LAD). After treatment, the patient's symptoms were relieved, and the ST segment of lead V1-V4 of electrocardiogram returned to normal. Conclusion: Kunis syndrome is a life-threatening condition that can also cause myocardial ischemic injury in patients with or without coronary artery disease. Timely identification and anti-allergic treatment can achieve a good prognosis.

Reprogramming Exosomes to Escape from Immune Surveillance for Mitochondrial Protection in Hepatic Ischemia-Reperfusion Injury.

Background: Therapeutic interventions such as synthetic drugs and microRNA (miR) modulators have created opportunities for mitigating hepatic ischemia/reperfusion injury (HIRI) by alleviating mitochondrial dysfunction. However, delivering multi-therapeutic ingredients with low toxicity to hepatocytes still lags behind its development. Methods: In this study, we endowed exosomes with delivery function to concentrate on hepatocytes for multidimensionally halting mitochondria dysfunction during HIRI. Concretely, exosomes were reprogrammed with a transmembrane protein CD47, which acted as a "camouflage cloak" to mimic the "don't eat me" mechanism to escape from immune surveillance. Besides, HuR was engineered bridging to the membrane by fusing with CD47 and located in the cytoplasm for miR loading. Results: This strategy successfully delivered dual payloads to hepatocytes and efficiently protected mitochondria by inhibiting the opening of mitochondrial permeability transition pore (mPTP) and upregulating mitochondrial transcription factor A (TFAM), respectively. Conclusions: The reprogramming of exosomes with CD47 and HuR for targeted delivery of CsA and miR inhibitors represents a promising therapeutic strategy for addressing HIRI. This approach shows potential for safe and effective clinical applications in the treatment of HIRI.

Interleukins in Platelet Biology: Unraveling the Complex Regulatory Network.

Interleukins, a diverse family of cytokines produced by various cells, play crucial roles in immune responses, immunoregulation, and a wide range of physiological and pathological processes. In the context of megakaryopoiesis, thrombopoiesis, and platelet function, interleukins have emerged as key regulators, exerting significant influence on the development, maturation, and activity of megakaryocytes (MKs) and platelets. While the therapeutic potential of interleukins in platelet-related diseases has been recognized for decades, their clinical application has been hindered by limitations in basic research and challenges in drug development. Recent advancements in understanding the molecular mechanisms of interleukins and their interactions with MKs and platelets, coupled with breakthroughs in cytokine engineering, have revitalized the field of interleukin-based therapeutics. These breakthroughs have paved the way for the development of more effective and specific interleukin-based therapies for the treatment of platelet disorders. This review provides a comprehensive overview of the effects of interleukins on megakaryopoiesis, thrombopoiesis, and platelet function. It highlights the potential clinical applications of interleukins in regulating megakaryopoiesis and platelet function and discusses the latest bioengineering technologies that could improve the pharmacokinetic properties of interleukins. By synthesizing the current knowledge in this field, this review aims to provide valuable insights for future research into the clinical application of interleukins in platelet-related diseases.

The immune response of hepatocellular carcinoma after locoregional and systemic therapies: The available combination option for immunotherapy.

Hepatocellular carcinoma (HCC) is associated with a highly heterogeneous immune environment that produces an immune response to various locoregional treatments (LRTs), which in turn affects the effectiveness of immunotherapy. Although LRTs still dominate HCC therapies, 50-60% of patients will ultimately be treated with systemic therapies and might receive those treatments for the rest of their life. TACE, SIRT, and thermal ablation can dramatically increase the immunosuppressive state of HCC, a condition that can be addressed by combination with immunotherapy to restore the activity of lymphocytes and the secretion of cellular immune factors. Immune treatment with locoregional and systemic treatments has dramatically changed the management of HCC. In this review, we examine the research on the changes in the immune microenvironment after locoregional or systemic treatment. We also summarize the regulation of various immune cells and immune factors in the tumor microenvironment and discuss the different infiltration degrees of immune cells and factors on the prognosis of HCC to better compare the efficacy between different treatment methods from the perspective of the tumor microenvironment. This information can be used to help develop treatment options for the upcoming new era of HCC treatment in the future.

Novel synergistically effects of palladium-iron bimetal and manganese carbonate carrier for catalytic oxidation of formaldehyde at room temperature.

The elimination of formaldehyde at room temperature holds immense potential for various applications, and the incorporation of a catalyst rich in surface hydroxyl groups and oxygen significantly enhances its catalytic activity towards formaldehyde oxidation. By employing a coprecipitation method, we successfully achieved a palladium domain confined within the manganese carbonate lattice and doped with iron. This synergistic effect between highly dispersed palladium and iron greatly amplifies the concentration of surface hydroxyl groups and oxygen on the catalyst, thereby enabling complete oxidation of formaldehyde at ambient conditions. The proposed method facilitates the formation of domain-limited palladium within the MnCO3 lattice, thereby enhancing the dispersion of palladium and facilitating its partial incorporation into the MnCO3 lattice. Consequently, this approach promotes increased exposure of active sites and enhances the catalyst's capacity for oxygen activation. The co-doping of iron effectively splits the doping sites of palladium to further enhance its dispersion, while simultaneously modifying the electronic modification of the catalyst to alter formaldehyde's adsorption strength on it. Manganese carbonate exhibits superior adsorption capability for activated surface hydroxyl groups due to the presence of carbonate. In situ infrared testing revealed that dioxymethylene and formate are primary products resulting from catalytic oxidation of formaldehyde, with catalyst surface oxygen and hydroxyl groups playing a crucial role in intermediate product decomposition and oxidation. This study provides novel insights for designing palladium-based catalysts.

Circularly Polarized Phosphorescence of Benzils Achieved by Chiral Supramolecular Polymerization.

In current approaches for circularly polarized phosphorescent materials, the crystallization of chiral phosphors suffers from poor processability, while integrating them into an amorphous polymer matrix results in unsatisfactory chiroptical signals due to the absence of chirality communication. Here, we have developed an innovative strategy through chiral supramolecular polymerization of benzil phosphors facilitated by intermolecular hydrogen bonds. The inherent film-forming capabilities of non-covalent supramolecular polymers obviate the need for an external polymer matrix. The pronounced helical asymmetry of benzil phosphors resulting from chiral supramolecular polymerization leads to enhanced circularly polarized phosphorescence compared to their non-hydrogen-bonded counterparts. The circularly polarized phosphorescent signals can be further modulated by varying the location of stereogenic centers or introducing halogen bonding to benzils. Incorporation of platinum(II) phosphor into the benzil supramolecular polymers induces both chirality and triplet-to-triplet energy transfer, leading to a change in circularly polarized phosphorescent color from yellow to red. In summary, chiral supramolecular polymerization of phosphors represents a novel and effective approach to circularly polarized phosphorescent materials.

[Analysis of Vegetation Change and Influencing Factors in Southwest Alpine Canyon Area].

The southwest alpine canyon area is a typical ecologically fragile area. Understanding the characteristics of vegetation change here and its influencing factors can provide a theoretical basis for formulating countermeasures for ecological environment construction in the southwest alpine canyon area and has practical significance for realizing the harmonious and unified development of the regional economy, environment, and ecology. Based on the data set of NDVI, socio-economic factors, and natural factors from 2000 to 2019, the spatial and temporal variation and stability characteristics of NDVI in the southwest alpine canyon area were analyzed by using the methods of unary linear regression, Hurst index, geographic detector model, and coefficient of variation, and the influencing factors of the spatial differentiation of NDVI were also discussed. The results showed that:① in terms of spatial distribution, the vegetation was high in the southeast and low in the northwest. The area covered by medium and high vegetation accounted for 71.71%, and the vegetation cover was at a relatively high level. From the perspective of time, the area of vegetation showing an improvement trend accounted for 85.90%, and the recovery effect was obvious, and the future vegetation change trend will continue to be improved. ② Elevation, vegetation type, and soil type were the main factors affecting the spatial differentiation of NDVI, and the q value was no less than 0.40. Temperature and rainfall were secondary factors, with q values of 0.274 and 0.225, respectively. The dual-factor interaction enhanced the single factor influence, which was manifested as the dual-factor enhancement and nonlinear enhancement relationship. The highest q value was 0.714 for the combination of altitude ∩ vegetation, followed by 0.688 for the combination of altitude ∩ soil. ③ The overall stability of NDVI during the study period was good, and the proportion of the regional area with low fluctuating changes and slightly low fluctuating changes was 89.95%. The area with moderate fluctuation accounted for 10.05%, concentrated in the relatively fragile ecological environment with factors such as high altitude, low temperature, little rainfall, barren soil, and sparse vegetation. Vegetation change is the result of a combination of multiple factors, so it is necessary to adapt to local conditions and adopt different strategies to restore the ecological environment of the southwest alpine canyon area.

Glaucoma Characteristics and Influencing Factors during the COVID-19 Pandemic in the Huizhou Region.

Objective: Glaucoma in individuals who tested positive for the coronavirus disease 2019 (COVID-19) during the pandemic outbreak has not been comprehensively studied. Therefore, this study aimed to analyze the characteristics and risk factors of glaucoma during the COVID-19 pandemic in Huizhou. Methods: Retrospective data from outpatients with glaucoma at the Huizhou Hospital Affiliated with Guangzhou Medical University and Longmen County People's Hospital were collected during two periods: the COVID-19 pandemic period (Phase A: December 1, 2022, to January 19, 2023) and the prevention and control period (Phase B: December 1, 2021, to January 19, 2022). The demographic characteristics of the outpatients during both phases were compared. The characteristics of glaucoma in patients with COVID-19 during Phase A were examined. Multivariate logistic regression analysis was used to identify factors influencing the development of acute angle-closure glaucoma (AACG) in Phase A patients. Results: The proportion of patients with glaucoma was significantly higher during Phase A than during Phase B at both hospitals. No statistically significant differences were observed between patients with glaucoma during Phases A and B for age, sex, and region. A high COVID-19-positive rate was associated with old age, females, AACG, newly diagnosed glaucoma, and binocular involvement during phase A. Females testing positive for COVID-19, glaucoma that started after testing positive for COVID-19, and a history of medication use were associated with a higher proportion of AACG in phase A. Multivariable logistic regression analysis identified testing positive for COVID-19 as an independent potential risk factor for developing AACG. Conclusion: In summary, during the COVID-19 pandemic in Huizhou, patients with COVID-19 were primarily affected by AACG, especially females, older individuals, and those with binocular involvement. Testing positive for COVID-19 increases the risk of developing AACG.

Global genomic diversity and conservation of SARS-CoV-2 since the COVID-19 outbreak.

IMPORTANCE: Our results indicate that most severe acute respiratory syndrome coronavirus 2 genomes sampled from patients had a mutation rate ≤1.07 ‰ and genome-tail proteins (including S protein) were the main sources of genetic polymorphism. The analysis of the virus-host interaction network of genome-tail proteins showed that they shared some antiviral signaling pathways, especially the intracellular protein transport pathway.

Molecular phylogeny and taxonomy of the genus Vernaya (Mammalia: Rodentia: Muridae) with the description of two new species.

The climbing mouse is a rare, small mammal listed as an endangered species on the China species red list. Molecular phylogenetic analyses and the evolutionary history of the genus remain unexplored because of the extreme difficulty in capturing individuals and their narrow distribution. Here, we collected 44 specimens, sequenced one mitochondrial and eight nuclear genes, and integrated morphological approaches to estimate phylogenetic relationships, delimit species boundaries, and explore evolutionary history. Molecular analyses and morphological results supported the validity of these four species. Here, we describe two new species, Vernaya meiguites sp. nov. and Vernaya nushanensis sp. nov., and recognize Vernaya foramena, previously considered a subspecies of Vernaya fulva, as a valid species. The estimated divergence time suggests that the climbing mouse began to diversify during the Pliocene (3.36 Ma).

MB-DECTNet: a model-based unrolling network for accurate 3D dual-energy CT reconstruction from clinically acquired helical scans.

Objective.Over the past several decades, dual-energy CT (DECT) imaging has seen significant advancements due to its ability to distinguish between materials. DECT statistical iterative reconstruction (SIR) has exhibited potential for noise reduction and enhanced accuracy. However, its slow convergence and substantial computational demands render the elapsed time for 3D DECT SIR often clinically unacceptable. The objective of this study is to accelerate 3D DECT SIR while maintaining subpercentage or near-subpercentage accuracy.Approach.We incorporate DECT SIR into a deep-learning model-based unrolling network for 3D DECT reconstruction (MB-DECTNet), which can be trained end-to-end. This deep learning-based approach is designed to learn shortcuts between initial conditions and the stationary points of iterative algorithms while preserving the unbiased estimation property of model-based algorithms. MB-DECTNet comprises multiple stacked update blocks, each containing a data consistency layer (DC) and a spatial mixer layer, with the DC layer functioning as a one-step update from any traditional iterative algorithm.Main results.The quantitative results indicate that our proposed MB-DECTNet surpasses both the traditional image-domain technique (MB-DECTNet reduces average bias by a factor of 10) and a pure deep learning method (MB-DECTNet reduces average bias by a factor of 8.8), offering the potential for accurate attenuation coefficient estimation, akin to traditional statistical algorithms, but with considerably reduced computational costs. This approach achieves 0.13% bias and 1.92% mean absolute error and reconstructs a full image of a head in less than 12 min. Additionally, we show that the MB-DECTNet output can serve as an initializer for DECT SIR, leading to further improvements in results.Significance.This study presents a model-based deep unrolling network for accurate 3D DECT reconstruction, achieving subpercentage error in estimating virtual monoenergetic images for a full head at 60 and 150 keV in 30 min, representing a 40-fold speedup compared to traditional approaches. These findings have significant implications for accelerating DECT SIR and making it more clinically feasible.

BCL11B and the NuRD complex cooperatively guard T-cell fate and inhibit OPA1-mediated mitochondrial fusion in T cells.

The nucleosome remodeling and histone deacetylase (NuRD) complex physically associates with BCL11B to regulate murine T-cell development. However, the function of NuRD complex in mature T cells remains unclear. Here, we characterize the fate and metabolism of human T cells in which key subunits of the NuRD complex or BCL11B are ablated. BCL11B and the NuRD complex bind to each other and repress natural killer (NK)-cell fate in T cells. In addition, T cells upregulate the NK cell-associated receptors and transcription factors, lyse NK-cell targets, and are reprogrammed into NK-like cells (ITNKs) upon deletion of MTA2, MBD2, CHD4, or BCL11B. ITNKs increase OPA1 expression and exhibit characteristically elongated mitochondria with augmented oxidative phosphorylation (OXPHOS) activity. OPA1-mediated elevated OXPHOS enhances cellular acetyl-CoA levels, thereby promoting the reprogramming efficiency and antitumor effects of ITNKs via regulating H3K27 acetylation at specific targets. In conclusion, our findings demonstrate that the NuRD complex and BCL11B cooperatively maintain T-cell fate directly by repressing NK cell-associated transcription and indirectly through a metabolic-epigenetic axis, providing strategies to improve the reprogramming efficiency and antitumor effects of ITNKs.

Healthy aging, early screening, and interventions for frailty in the elderly.

With the intensification of population aging worldwide, the health problems of the elderly have become a particular concern. Functional disability is a prominent problem in the aging of this population, resulting in the decreased quality of life of senile people. Risk factors for functional disability in the elderly include geriatric syndromes and the associated diseases such as frailty. The influence of frailty on the health of the elderly has been a hot topic in recent years. As a dynamic and reversible geriatric syndrome, it has become one of the important public health problems emerging around the world. Frailty lies between self-reliance and the need for care and is reversible. Reasonable preventive interventions can restore the elderly to an independent life. If no interventions are implemented, the elderly will face a dilemma. There is no gold standard for frailty screening around the world. In order to alleviate frailty in the elderly, many countries have conducted early screening for frailty, mainly focusing on nutrition, physical activity, and social participation, in order to detect and prevent frailty earlier and to reduce the incidence of frailty. This topic provides an overview of the current status of frailty, early screening for frailty, and the interventions for frailty in most countries of the world.