Omics-based biomarkers as useful tools in metabolic dysfunctionassociated steatotic liver disease clinical practice:How far are we?

Unmet needs exist in metabolic dysfunction-associated steatotic liver disease(MASLD)risk stratification.Our ability to identify patients with MASLD with advanced fibrosis and at higher risk for adverse outcomes is still limited.Incorporating novel biomarkers could represent a meaningful improvement to current risk predictors.With this aim,omics technologies have revolutionized the process of MASLD biomarker discovery over the past decades.While the research in this field is thriving,much of the publication has been haphazard,often using single-omics data and specimen sets of convenience,with many identified candidate biomarkers but lacking clinical validation and utility.If we incorporate these biomarkers to direct patients’management,it should be considered that the roadmap for translating a newly discovered omics-based signature to an actual,analytically valid test useful in MASLD clinical practice is rigorous and,therefore,not easily accomplished.This article presents an overview of this area’s current state,the conceivable opportunities and challenges of omics-based laboratory diagnostics,and a roadmap for improving MASLD biomarker research.

The first record of dermochelyid turtles in the Eocene of Tierra del Fuego:new insights on the evolution of the Weddellian faunas

The Antarctic Paleogene marine fossil record has been the key to reconstructing the evolution of the Weddellian Sea and final dismemberment of Southern Gondwana.In this context,Eocene marine vertebrates from Seymour(Marambio)Island have provided valuable information.We present the first Eocene record of marine reptiles from the southern Atlantic Coast of South America.This corresponds to several postcranial turtle remains represented by a proximal end of the right humerus,three caudal and one thoracic vertebrae,a fragment of the left pubis,and ten ossicles of the dorsal carapace,coming from the Leticia Formation(late-mid Eocene)at Cabo Tiburones,Tierra del Fuego,Argentina.These materials show severalfeatures such as the size and general morphology of the humerus and vertebrae,and the presence of relatively small,irregular,smooth,and unkeeled ossicles,which allow us to assign them to Dermochelyidae indet.Dermochelyids are a cosmopolitan group ofcryptodiran turtles,registered from the late Cretaceous up to the recent,with some physiological-biological peculiarities(e.g.,endothermy and an exclusive jellyfish-based diet)and characterized by the presence of an osseous carapace formed by ossicles.The new finding from the Leticia Formation is an addition to the scarce and extremely fragmentary record of Eocene dermochelyids from the southern seas like those from the La Meseta and Submeseta formations(Antarctica)and the Waihao and Burnside formations(New Zealand).This new information allows us to discuss the presence of these turtles in such high latitudes in the past and its implication in the evolution of the Weddellian fauna.

Long-term trends in the abundance and breeding performance in Adélie penguins:the Argentine Ecosystem Monitoring Program

In this work,we report long-term trends in the abundance and breeding performance of Adélie penguins(Pygoscelis adeliae)nesting in three Antarctic colonies(i.e.,at Martin Point,South Orkneys Islands;Stranger Point/Cabo Funes,South Shetland Islands;and Esperanza/Hope Bay in the Antarctic Peninsula)from 1995/96 to 2022/23.Using yearly count data of breeding groups selected,we observed a decline in the number of breeding pairs and chicks in crèche at all colonies studied.However,the magnitude of change was higher at Stranger Point than that in the remaining colonies.Moreover,the index of breeding success,which was calculated as the ratio of chicks in crèche to breeding pairs,exhibited no apparent trend throughout the study period.However,it displayed greater variability at Martin Point compared to the other two colonies under investigation.Although the number of chicks in crèche of Adélie penguins showed a declining pattern,the average breeding performance was similar to that reported in gentoo penguin colonies,specifically,those undergoing a population increase(even in sympatric colonies facing similar local conditions).Consequently,it is plausible to assume a reduction of the over-winter survival as a likely cause of the declining trend observed,at least in the Stranger Point and Esperanza colonies.However,we cannot rule out local effects during the breeding season affecting the Adélie population of Martin Point.

Review of the Cretaceous avian diversity of Antarctica:a changing scenario for the evolution of early Neornithine birds

The worldwide record of Cretaceous Neornithes and Neornithine-like birds is both controversial and poorly understood.However,in recent years,the Antarctic continent has yielded a substantial number of Maastrichtian avian specimens,contributing significantly to our understanding of the early evolution of this group.Simultaneously,the keen interest and collaborative efforts of various paleornithologists have resulted in a wealth of knowledge,which we have thoroughly reviewed,updated,and discussed in the context of recent discoveries.

Molecular mechanisms underlying SARS-CoV-2 hepatotropism and liver damage

In coronavirus disease 2019(COVID-19),severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)primarily targets the respiratory system,but evidence suggests extrapulmonary organ involvement,notably in the liver.Viral RNA has been detected in hepatic tissues,and in situ hybridization revealed virions in blood vessels and endothelial cells.Electron microscopy confirmed viral particles in hepatocytes,emphasizing the need for understanding hepatotropism and direct cytopathic effects in COVID-19-related liver injury.Various factors contribute to liver injury,including direct cytotoxicity,vascular changes,inflammatory responses,immune reactions from COVID-19 and vaccinations,and druginduced liver injury.Although a typical hepatitis presentation is not widely documented,elevated liver biochemical markers are common in hospitalized COVID-19 patients,primarily showing a hepatocellular pattern of elevation.Long-term studies suggest progressive cholestasis may affect 20%of patients with chronic liver disease post-SARS-CoV-2 infection.The molecular mechanisms underlying SARS-CoV-2 infection in the liver and the resulting liver damage are complex.This“Editorial”highlights the expression of the Angiotensin-converting enzyme-2 receptor in liver cells,the role of inflammatory responses,the impact of hypoxia,the involvement of the liver's vascular system,the infection of bile duct epithelial cells,the activation of hepatic stellate cells,and the contribution of monocyte-derived macrophages.It also mentions that pre-existing liver conditions can worsen the outcomes of COVID-19.Understanding the interaction of SARS-CoV-2 with the liver is still evolving,and further research is required.

Middle Eocene chondrichthyan fauna from Antarctic Peninsula housed in the Museo de La Plata,Argentina

In recent years,the taxonomy and systematics of the cartilaginous fish taxa from the Eocene La Meseta Formation of Seymour(Marambio)Island,Antarctica have been extensively discussed in a series of papers,resulting in a complete revision of the Antarctic Eocene ichthyofauna housed in the Vertebrate Paleontology collection of the Museo de La Plata,Argentina.This collection constitutes one of the largest and taxonomically most diverse in the world,with approximately 20000 specimens,which provides a solid database used for the analysis of qualitative and quantitative chondrichthyan taxonomic composition.The information provided herein might be useful to understand the sudden decline in chondrichthyan taxonomic diversity towards the top of La Meseta Formation as well as its potential relationship with environmental changes during the Eocene.

A new look at the first dinosaur discovered in Antarctica:reappraisal of Antarctopelta oliveroi(Ankylosauria:Parankylosauria)

The first dinosaur discovered in the Antarctic continent was the ankylosaur Antarctopelta oliveroi in the 1980s.Nevertheless,since then several hypotheses of phylogenetical relationships have been proposed because these have been depended on how the skeletal remains have been interpreted.The main obstacle for clarifying its phylogenetic position is that many portions of the skeleton remain unknown,in addition to the presence of unknown characters in typical ankylosaurs.Considered an ankylosaurid,nodosaurid,or even a chimaera,a recent proposal based on mostly complete material of a new ankylosaur from Chilean Patagonia provided support for a novel phylogenetic hypothesis:Antarctopelta and other southern ankylosaurs are an early branching clade,the Parankylosauria,whose origin probably dates to the Late Jurassic.In the light of this new view,a redescription of the available skeletal remains is provided together with a new reconstruction of the first Antarctic dinosaur known to the science community.

Perilipin 2 inhibits replication of hepatitis B virus deoxyribonucleic acid by regulating autophagy under high-fat conditions

Hepatitis B virus(HBV)infection poses a global health concern without a definitive cure;however,antiviral medications can effectively suppress viral replication.This study delves into the intricate interplay between lipid metabo-lism and HBV replication,implicating molecular mechanisms such as the stearoyl coenzyme A desaturase 1 autophagy pathway,SAC1-like phosphatidylinositol phosphatase,and galectin-9 mediated selective autophagy of viral core proteins in regulating HBV replication.Within lipid droplets,perilipin 2(PLIN2)emerges as a pivotal guardian,with its overexpression protecting against autophagy and downregulation stimulating triglyceride catabolism through the autophagy pathway.This editorial discusses the correlation between hepatic steatosis and HBV replication,emphasizing the role of PLIN2 in this process.The study underscores the multifaceted roles of lipid metabolism,autophagy,and perilipins in HBV replication,shedding light on potential therapeutic avenues.

Microglia depletion as a therapeutic strategy:friend or foe in multiple sclerosis models?

M ultiple sclerosis is a chro nic central nervous system demyelinating disease whose onset and progression are driven by a combination of immune dysregulation,genetic predisposition,and environmental fa ctors.The activation of microglia and astrocytes is a key player in multiple sclerosis immunopathology,playing specific roles associated with anatomical location and phase of the disease and controlling demyelination and neurodegeneration.Even though reactive mic roglia can damage tissue and heighten deleterious effects and neurodegeneration,activated microglia also perform neuroprotective functions such as debris phagocytosis and growth fa ctor secretion.Astrocytes can be activated into pro-inflammato ry phenotype A1 through a mechanism mediated by activated neuroinflammatory microglia,which could also mediate neurodegeneration.This A1 phenotype inhibits oligodendrocyte prolife ration and differe ntiation and is toxic to both oligodendrocytes and neurons.Howeve r,astroglial activation into phenotype A2 may also take place in response to neurodegeneration and as a protective mechanism.A variety of animal models mimicking specific multiple sclerosis features and the associated pathophysiological processes have helped establish the cascades of events that lead to the initiation,progression,and resolution of the disease.The colonystimulating facto r-1 receptor is expressed by myeloid lineage cells such as peripheral monocytes and macrophages and central nervous system microglia.Importantly,as microglia development and survival critically rely on colony-stimulating factor-1 receptor signaling,colony-stimulating factor-1 receptor inhibition can almost completely eliminate microglia from the brain.In this context,the present review discusses the impact of microglial depletion through colo ny-stimulating factor-1 receptor inhibition on demyelination,neurodegeneration,astroglial activation,and behavior in different multiple sclerosis models,highlighting the diversity of microglial effects on the progression of demyelinating diseases and the strengths and weaknesses of microglial modulation in therapy design.

How the interplay among the tumor microenvironment and the gut microbiota influences the stemness of colorectal cancer cells

Colorectal cancer(CRC)remains the third most prevalent cancer disease and involves a multi-step process in which intestinal cells acquire malignant characteristics.It is well established that the appearance of distal metastasis in CRC patients is the cause of a poor prognosis and treatment failure.Nevertheless,in the last decades,CRC aggressiveness and progression have been attributed to a specific cell population called CRC stem cells(CCSC)with features like tumor initiation capacity,self-renewal capacity,and acquired multidrug resistance.Emerging data highlight the concept of this cell subtype as a plastic entity that has a dynamic status and can be originated from different types of cells through genetic and epigenetic changes.These alterations are modulated by complex and dynamic crosstalk with environmental factors by paracrine signaling.It is known that in the tumor niche,different cell types,structures,and biomolecules coexist and interact with cancer cells favoring cancer growth and development.Together,these components constitute the tumor microenvironment(TME).Most recently,researchers have also deepened the influence of the complex variety of microorganisms that inhabit the intestinal mucosa,collectively known as gut microbiota,on CRC.Both TME and microorganisms participate in inflammatory processes that can drive the initiation and evolution of CRC.Since in the last decade,crucial advances have been made concerning to the synergistic interaction among the TME and gut microorganisms that condition the identity of CCSC,the data exposed in this review could provide valuable insights into the biology of CRC and the development of new targeted therapies.

Senescent mesenchymal stem/stromal cells in pre-metastatic bone marrow of untreated advanced breast cancer patients

Breast cancer is the predominant form of carcinoma among women worldwide,with 70%of advanced patients developing bone metastases,with a high mortality rate.In this sense,the bone marrow(BM)mesenchymal stem/stromal cells(MSCs)are critical for BM/bone homeostasis,and failures in their functionality,transform the BM into a premetastatic niche(PMN).We previously found that BM-MSCs from advanced breast cancer patients(BCPs,infiltrative ductal carcinoma,stage III-B)have an abnormal profile.This work aims to study some of the metabolic and molecular mechanisms underlying MSCs shift from a normal to an abnormal profile in this group of patients.A comparative analysis was undertaken,which included self-renewal capacity,morphology,proliferation capacity,cell cycle,reactive oxygen species(ROS)levels,and senescence-associatedβ‑galactosidase(SA‑β‑gal)staining of BMderived MSCs isolated from 14 BCPs and 9 healthy volunteers(HVs).Additionally,the expression and activity of the telomerase subunit TERT,as well as telomere length,were measured.Expression levels of pluripotency,osteogenic,and osteoclastogenic genes(OCT-4,SOX-2,M-CAM,RUNX-2,BMP-2,CCL-2,M-CSF,and IL-6)were also determined.The results showed that MSCs from BCPs had reduced,self-renewal and proliferation capacity.These cells also exhibited inhibited cell cycle progression and phenotypic changes,such as an enlarged and flattened appearance.Additionally,there was an increase in ROS and senescence levels and a decrease in the functional capacity of TERT to preserve telomere length.We also found an increase in pro-inflammatory/pro-osteoclastogenic gene expression and a decrease in pluripotency gene expression.We conclude that these changes could be responsible for the abnormal functional profile that MSCs show in this group of patients.

Editorial:Metabolomics in chronic hepatitis C:Decoding fibrosis grading and underlying pathways

In the management of the growing population of hepatitis C virus-infected patients,a significant clinical challenge exists in determining the most effective methods for assessing liver impairment.The prognosis and treatment of chronic hepatitis C depend,in part,on the evaluation of histological activity,specifically cell necrosis and inflammation,and the extent of liver fibrosis.These parameters are traditionally obtained through a liver biopsy.However,liver biopsy presents both invasiveness and potential sampling errors,primarily due to inadequate biopsy size.To circumvent these issues,several non-invasive markers have been proposed as alternatives for diagnosing liver damage.Different imaging techniques and blood parameters as single markers or combined with clinical information are included.This Editorial discusses the identification of a set of six distinctive lipid metabolites in every fibrosis grade that appear to show a pronounced propensity to create clusters among patients who share the same fibrosis grade,thereby demonstrating enhanced efficacy in distinguishing between the different grades.

Identification of tree groups used by secondary cavity-nesting birds to simplify forest management in subtropical forests

In tropical and subtropical forest ecosystems,cavities formed by decay processes are a key but scarce resource for birds that nest and roost in them,which makes them a highly sensitive group to logging.The piedmont forest of northwestern Argentina is a complex ecosystem with 113 tree and 120 bird species.It has high logging pressure on the few,well-conserved forest remnants,complicating the delineation of sustainable management guidelines for each tree or bird species in a short time.Our objective was to reduce the complexity of subtropical forests by grouping tree species according to the characteristics used by secondary cavity-nesting birds(i.e.non excavators).In the piedmont forest,50 plots of 0.25 ha were sampled to record cavity trees and cavity characteristics.These were then used in a cluster analysis to form tree groups.Additionally,cavities were searched to identify the bird species using the decay-formed cavities.A total of 187 cavity trees,comprising 23 tree species,were recorded,and these formed four tree groups or clusters.We recorded 86 cavities that were used by secondary cavitynesting bird species.The four tree groups were unequally used by secondary cavity nesters.The tree group that included valuable timber species(Myroxylon peruiferum,Anadenanthera colubrina and Calycophyllum multiflorum)and had the greatest cavity availability represented 71%of total cavity use.Another tree group with valuable timber species(Cedrela balansae and Amburana cearensis),measured>73 cm DBH and>21 m tall,had cavity entrances>0.10 cm2,and contributed 14%of all cavity use by birds.A third group had no highly economically valuable tree species,and included the snag category(i.e.standing dead trees)as well as a 15%of cavity use.The fourth tree group had a DBH<0.40 cm,only one highly economically valuable tree species(Cordia trichotoma),and supported no cavity use.The clustering of subtropical trees can reduce the complexity of these forests,hence easing their management by focusing on those groups with tree species showing similar characteristics and providing suitable nesting sites for secondary cavity-nesting birds.

Development of a Method for Identification and Quantification of Sulfadiazine and Pyrimethamine in Serum of Congenital Toxoplasmosis Pediatric Patients

Infection with Toxoplasma gondii, is one of the most widespread zoonoses in the world. Congenital Toxoplasmosis (CT) is particularly risky due to its fetal complications. Sulfadiazine (SDZ) and Pyrimethamine (PYR) are usually used for CT treatment in Argentina, to prevent morbidity. Due to the lack of commercial pediatric formulations, these must be prepared in the hospital pharmacy. This is the first report of serum concentrations measures in pediatric CT therapy for this combination of drugs. A bioanalytical method was developed for identification and simultaneous quantification of SDZ and PYR by High Performance Liquid Chromatography (HPLC) with UV detection. The validated method was applied to residual serum samples obtained from 6 pediatric patients undergoing treatment with SDZ 42.20 a 93.70 mg/kg/day and PYR 0.77 a 2.70 mg/kg/day. Sample pretreatment consisted on a deproteinization step followed by centrifugation and then injection of supernatant. Limit of Detection (LOD) and Quantification (LOQ) were (0.17 ± 0.02 and 0.13 ± 0.02) μg/mL and (0.46 ± 0.01 and 0.36 ± 0.01) μg/mL for SDZ and PYR respectively, with an appropriate linear range. Concentrations range found were ( - 162.04 ± 0.02) μg/mL for SDZ and ( - 7.30 ± 0.03) μg/mL for PYR. We developed and validated in real pediatric samples, an acute, precise and low-cost method for quantification of SDZ and PYR using a non-sophisticate chromatographic equipment, suitable for hospital therapeutic monitoring for public health system.

MicroRNAs contribute to ATP-binding cassette transporter-and autophagy-mediated chemoresistance in hepatocellular carcinoma

Hepatocellular carcinoma(HCC) has an elevated mortality rate, largely because of high recurrence and metastasis. Additionally, the main obstacle during treatment of HCC is that patients usually develop resistance to chemotherapy.Cancer drug resistance involves many different mechanisms, including alterations in drug metabolism and processing, impairment of the apoptotic machine, activation of cell survival signaling, decreased drug sensitivity and autophagy, among others. Nowadays, miRNAs are emerging as master regulators of normal physiology-and tumor-related gene expression. In HCC,aberrant expression of many miRNAs leads to chemoresistance. Herein, we particularly analyzed miRNA impact on HCC resistance to drug therapy. Certain miRNAs target ABC(ATP-binding cassette) transporter genes. As most of these miRNAs are downregulated in HCC, transporter levels increase and intracellular drug accumulation decrease, turning cells less sensitive to death. Others miRNAs target autophagy-related gene expression, inhibiting autophagy and acting as tumor suppressors. Nevertheless, due to its downregulation in HCC, these miRNAs do not inhibit autophagy or tumor growth and, resistance is favored.Concluding, modulation of ABC transporter and/or autophagy-related gene expression or function by miRNAs could be determinant for HCC cell survival under chemotherapeutic drug treatment. Undoubtedly, more insights on the biological processes, signaling pathways and/or molecular mechanisms regulated by miRNAs are needed. Anyway, miRNA-based therapy together with conventional chemotherapeutic drugs has a great future in cancer therapy.

Enhancing survival, engraftment, and osteogenic potential of mesenchymal stem cells

Mesenchymal stem cells(MSCs)are promising candidates for bone regeneration therapies due to their plasticity and easiness of sourcing.MSC-based treatments are generally considered a safe procedure,however,the long-term results obtained up to now are far from satisfactory.The main causes of these therapeutic limitations are inefficient homing,engraftment,and osteogenic differentiation.Many studies have proposed modifications to improve MSC engraftment and osteogenic differentiation of the transplanted cells.Several strategies are aimed to improve cell resistance to the hostile microenvironment found in the recipient tissue and increase cell survival after transplantation.These strategies could range from a simple modification of the culture conditions,known as cell-preconditioning,to the genetic modification of the cells to avoid cellular senescence.Many efforts have also been done in order to enhance the osteogenic potential of the transplanted cells and induce bone formation,mainly by the use of bioactive or biomimetic scaffolds,although alternative approaches will also be discussed.This review aims to summarize several of the most recent approaches,providing an up-to-date view of the main developments in MSCbased regenerative techniques.

Pendulum systems for harvesting vibration energy from railroad tracks and sleepers during the passage of a high-speed train: A feasibility evaluation

We evaluate the feasibility of recovering energy from the vibrations of track and sleepers,during passage of a high-speed train,by means of a pendulum harvester.A simple mathematical model of the parametric pendulum is employed to obtain numerical predictions,while measured data of vibration tests during the passage of a Thalys high-speed train are considered as input forcing.Since a sustained rotation is the most energetic motion of a pendulum,the possibility of achieving such state is evaluated,taking into account the influence of initial conditions,damping and other factors.Numerical simulations show that rotating pendulum harvesters with sufficiently low viscous damping could be able to generate a usable average power on the order of 5–6 W per unit.Considering a modular arrangement of devices,such energy is enough to feed variety of rail-side equipment,as wireless sensors or warning light systems.However,a suitable choice of initial conditions could be a difficult task,leading to the need of a control action.

Changes in leaflet shape and seeds per pod modify crop growth parameters, canopy light environment, and yield components in soybean

Seed number(SN)is the component most strongly associated with yield in soybean.SN depends on pod number(PN)and seeds per pod(SPP).Whereas SPP is a relatively stable component,PN is strongly influenced by environmental and management factors.However,the environmental cues involved in PN regulation are not completely understood.The influence of increasing SPP on other yield components is controversial.Field trials were conducted in two growing seasons using two pairs of lanceolate(L)and ovate(O)nearisogenic lines,sown at low(LD)and high(HD)plant densities to evaluate the effect of leaflet shape on crop growth parameters,canopy red/far-red(R/FR)ratio,their relationships with pod initiation,PN,and yield;and the effect of increasing SPP on PN,SN,and yield.L canopies showed a higher number of pods initiated(PI)than O canopies owing to the increase of PI on branches.No association between PI and crop growth rate during the pod set period was found.PI was negatively associated with leaf area index(LAI)and light interception.In contrast,a positive association between PI and canopy R/FR ratio was found.This latter association was sustained irrespective of whether the LAI was below or above its critical value,providing experimental evidence that R/FR ratio is positively associated with pod initiation in soybean canopies.An increase in SPP produced a direct and steady increase in SN regardless of PN and plant density.A yield increase was observed for the L-LD treatment,which combined the increased SPP of L lines with the highest PN of L-LD canopies.These results have implications for crop management and breeding strategies aimed at increasing the yield potential of soybean.

The fossil record of Antarctic land mammals:commented review and hypotheses for future research

The fossil record of terrestrial mammals in Antarctica is temporally and geographically constrained to the Eocene outcrops of La Meseta and Submeseta formations in Seymour(Marambio)Island in West Antarctica.The faunal assemblage indicates a clear South American imprint since all the groups have a close phylogenetic relationship with Cretaceous and Paleogene mammals from Patagonia.Despite the presence of several mammalian taxonomic groups:Dryolestida,Gondwanatheria,Eutheria and Metatheria,the presence of other major mammalian taxa should be expected and will probably be confirmed by new findings.Placental mammals with an inferred body mass between 10 to 400 kg in size,are represented by xenarthrans,and two groups of the so called South American native ungulates:Astrapotheria and Litopterna.The Metatheria are the smaller(less than 1 kg)and most abundant components of the fauna.Marsupials are represented by derorhynchid ameridelphians,several microbiotherian australidelphians(both microbiotheriids and woodburnodontids),and?glasbiid prepidolopod and polydolopid polydolopimorphians.Plus,there are remains of several mammalian teeth of indeterminate phylogenetic affinities.The present knowledge of the Southern Hemisphere mammalian evolution and paleogeographic change through time,indicates that Antarctica played a major role for land mammals,at least since the Jurassic.The actual representation of Paleogene terrestrial mammals in Antarctica is most probably biased,as all the evidence indicates that australosphenidan mammals should be present in this continent since the Jurassic.

Insights into induction of the immune response by the hepatitis B vaccine

After more than four decades of hepatitis B virus(HBV)vaccine implementation,its safety and efficacy in preventing HBV infection have been proven and several milestones have been achieved.Most countries have included HBV immunization schedules in their health policies and progress has been made regarding universalization of the first HBV vaccine dose at birth.All of these actions have significantly contributed to reducing both the incidence of HBV infection and its related complications.However,there are still many drawbacks to overcome.The main concerns are the deficient coverage rate of the dose at birth and the large adult population that has not been reached timely by universal immunization.Additionally,the current most widely used second-generation vaccines do not induce protective immunity in 5%to 10%of the population,particularly in people over 40-years-old,obese(body mass index>25 kg/m2),heavy smokers,and patients undergoing dialysis or infection with human immunodeficiency virus.Recently developed and approved novel vaccine formulations using more potent adjuvants or multiple antigens have shown better performance,particularly in difficult settings.These advances re-launch the expectations of achieving the World Health Organization’s objective of completing hepatitis control by 2030.