Deregulation of interferon-gamma receptor 1 expression and its implications for lung adenocarcinoma progression

Interferon-gamma(IFN-γ)plays a dual role in cancer;it is both a pro-and an antitumorigenic cytokine,depending on the type of cancer.The deregulation of the IFN-γcanonic pathway is associated with several disorders,including vulner-ability to viral infections,inflammation,and cancer progression.In particular,the interplay between lung adenocarcinoma(LUAD)and viral infections appears to exist in association with the deregulation of IFN-γsignaling.In this mini-review,we investigated the status of the IFN-γsignaling pathway and the expression level of its components in LUAD.Interestingly,a reduction in IFNGR1 expression seems to be associated with LUAD progression,affecting defenses against viruses such as severe acute respiratory syndrome coronavirus 2.In addition,alterations in the expression of IFNGR1 may inhibit the antiproliferative action of IFN-γsignaling in LUAD.

In vitro polymerization of the dopamine-borate melanin precursor:A proof-of-concept regarding^(10)boron neutron-capture therapy for melanoma

The^(10)boron neutron-capture therapy(BNCT)is an emerging antitumoral method that shows increasing biomedical interest.BNCT is based on the selective accumulation of the^(10)boron isotope within the tumor,which is then irradiated with low-energy thermal neutrons,generating nuclear fission that produces 7lithium,4helium,andγrays.Simple catechol-borate esters have been rather overlooked as precursors of melanin biosynthesis,and therefore,a proof-of-concept approach for using dopamine-borate(DABO)as a suitable boron-containing candidate for potential BNCT is presented here.DABO can spontaneously oxidize and autopolymerize in vitro,giving a soluble,eumelaninlike brown-black poly-DABO product.Melanotic melanoma cell cultures treated with 1 mM DABO for 24 and 48 h were viable and showed no signs of damage or cell death.The stability and possible trans-esterification of DABO is shortly discussed.Chemical calculations and quantitative structure-activity relationships(QSAR)analysis of DABO and the BNCT agent BPA indicated that they should be cell permeant and accumulate within lysosomes and melanosomes.Molecular modeling allows visualization of both the DABO precursor and the structure of a borate derivative of the proposed catechol-porphycene model for eumelanin,showing interesting features from molecular orbital calculations.The main difference between DABO and other agents,such as BPA,is that it is not a boronic acid nor a boron cluster.This simple catechol-borate ester(protected from oxidation and blackening)could be administrated to living cells and organisms,in which biosynthesis of boron-melanin in melanoma melanocytes can lead to improved BNCT.

Giant Spinal Schwannomas. Presentation of Two Cases with Interdisciplinary Surgical Resection

Purpose: To report two quite rare cases of giant schwannomas of the cervical and thoracic spine. Surgical resection is usually the treatment of choice for these neoplasms. Methods: The first patient is a 48-year-old male that came to our department, complaining about weakness and paresthesia of both lower extremities and upper left extremity, and a considerably big dorsal palpable lump. MRI and CT scan were used to diagnose giant cervical schwannoma. Because of the intensity of symptoms, he was subjected to surgery. Multidisciplinary resection involving neurosurgical and oncosurgicalteamn was performed for intravertebral and extravertebral approaches. The second patient is a 55-year-old female that came to the hospital complaining about incapacitating pain and dysesthesia involving T6, T7, and T8 dermatomes, with no other deficits. MRI and CT scan were used to diagnose giant thoracic schwannoma. Because of the intensity of the pain, surgery was decided as the treatment of choice. Video assisted thoracoscopic surgery was performed and total resection was achieved, with improvement of the symptoms. Results: Both patients showed complete remission of the symptoms, with no major deficits after surgery. Conclusion: Although infrequent, giant spinal schwannomas may be the cause of visible lumps in the back with radicular symptoms. When asymptomatic, conservative treatment could be viable, but when they present symptoms, surgery offers good results.

5-Bromo-2'-deoxyuridine labeling:historical perspectives,factors infiuencing the detection,toxicity,and its implications in the neurogenesis

The halopyrimidine 5-bromo-2′-deoxyuridine(BrdU)is an exogenous marker of DNA synthesis.Since the introduction of monoclonal antibodies against BrdU,an increasing number of methodologies have been used for the immunodetection of this synthesized bromine-tagged base analogue into replicating DNA.BrdU labeling is widely used for identifying neuron precursors and following their fate during the embryonic,perinatal,and adult neurogenesis in a variety of vertebrate species including birds,reptiles,and mammals.Due to BrdU toxicity,its incorporation into replicating DNA presents adverse consequences on the generation,survival,and settled patterns of cells.This may lead to false results and misinterpretation in the identification of proliferative neuroblasts.In this review,I will indicate the detrimental effects of this nucleoside during the development of the central nervous system,as well as the reliability of BrdU labeling to detect proliferating neuroblasts.Moreover,it will show factors influencing BrdU immunodetection and the contribution of this nucleoside to the study of prenatal,perinatal,and adult neurogenesis.Human adult neurogenesis will also be discussed.It is my hope that this review serves as a reference for those researchers who focused on detecting cells that are in the synthetic phase of the cell cycle.

Impacts of PI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

Astrocytes are the most abundant type of glial cell in the central nervous system.Upon injury and inflammation,astrocytes become reactive and undergo morphological and functional changes.Depending on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,respectively.However,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and injuries.Transcriptomic analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their reactivity.Astrocytes actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune response.The phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo results.In astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory responses.Here,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their activation.We highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the PI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/PI3K/AKT/connexin 43,and Notch/PI3K/AKT pathways.While targeting the inactivation of the PI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial outcomes.This dual function of the PI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function modulation.The review emphasizes the importance of employing astrocyte-exclusive models to understand their functions accurately and these models are essential for clarifying astrocyte behavior.The findings should then be validated using in vivo models to ensure real-life relevance.The review also highlights the significance of PI3K/AKT pathway modulation in preventing central nervous system damage,although further studies are required to fully comprehend its role due to varying factors such as different cell types,astrocyte responses to inflammation,and disease contexts.Specific strategies are clearly necessary to address these variables effectively.

The relationship between DNA fragmentation and the intensity of morphologically abnormal human spermatozoa

Objective:To determine the relationship between teratozoospermia and sperm DNA fragmentation(SDF)in the human ejaculate.Methods:This retrospective study included 100 normozoospermic men as a control cohort(abnormal forms>14%),210 patients with a high level of abnormal forms(≤4%)and 65 patients presenting with a moderate level of abnormal forms(>4%to≤14%)based on the World Health Organization definitions.Sperm morphology was assessed using bright field microscopy.Sperm DNA fragmentation was assessed using the sperm chromatin dispersion assay.Non-parametric analyses were conducted to examine the relationship between abnormal sperm morphology and sperm DNA fragmentation;receiver operating characteristic(ROC)analyses were conducted to assess sensitivity and specificity of this relationship.Results:A correlation analysis revealed that the higher the proportion of abnormal spermatozoa in the ejaculate,the higher the level of SDF(Spearman's Rho=-0.230;P<0.001).Significant differences in the proportion of SDF were found when all cohorts were compared(P<0.001);these significant differences were also retained when the different cohorts were compared pairwise.ROC analysis showed a moderate but significant predictive value for SDF to differentiate patients with different levels of teratozoospemia.Conclusions:Although analysis of a more continuous range of values for teratozoospermia would help further clarify any causal relationship with SDF,there is clearly a synergistic or coincident affiliation between these variables that needs to be acknowledged by the clinician when interpreting the spermiogram.

Hydrogeochemical and isotopic assessment of the origin of NO_(3)^(−)and N-NH_(3)contents in the aquifer located in a closed lacustrine volcano-sedimentary basin in the metropolitan area of Mexico City

To explain the presence and spatial distribution of NO_(3)^(−)and N-NH_(3)in the Aquifer of the Metropolitan Area of Mexico City(AMAMC),a hydrogeochemical and isotopic analysis using^(13)C DIC(as well as the stable isotopes^(18)O and^(2)H)in groundwater was conducted.This aquifer is located in an old closed lacustrine volcano-sedimentary basin;some wells hosted in the semi-confined zone contain high N-NH_(3)concentrations,while others present NO_(3)^(−)contents in the recharge zones(hosted in an oxidizing environment).In this study,a change in the isotopic signature(primarily in^(18)O and^(2)H)was observed from the recharge zones to the basin center in some of the wells with high NO_(3)^(−)concentrations,this behavior can be attributed to evaporation during the incorporation of recently infiltrated water.In addition,the results for^(13)C(along with ^(2) H)in wells with the highest N-NH_(3)concentrations exhibited an atypically broad range of values.Results indicated the occurrence of hydrogeochemical and/or biochemical processes in the aquifer(in an oxidizing or reducing environment),such as organic degradation,bacterial decomposition(primarily in the ancient Lake Texcoco and which acts as a natural sink for carbon,nitrogen,sulfur,and phosphorus),besides rock weathering and dissolution,which may be responsible for a very marked isotopic modification of the^(13)C(and,to a lesser extent,2 H).Methanotrophic bacterial activity and methanogenic activity may be related to N-NH_(3)removal processes by oxidation and residual water incorporation respectively,whereas the increase in the NO_(3)^(−)content in some wells is due to the recent contribution of poor-quality water due to contamination.

Is it possible to anchor a tooth with photobiomodulation?

During orthodontic treatment,we can achieve differential movements by using photobiomodulation(PBM)as an adjuvant before applying force.We can expect a greater bone density that initially resists movement while applying PBM to the other teeth to achieve an accelerating effect.The proposed protocol is to use an 810 nm laser at 0.1W power,applying between 4 and 6J per tooth for 22 s on the vestibular and lingual root surfaces,following the axial axis of the tooth.The energy density depends on the tip selected in the instrument.Normal bone remodeling cannot be avoided by applying high doses of PBM.PBM should be applied before orthodontic force to reduce tooth movement.In addition,PBM can be used during force application to teeth that require acceleration to achieve differential movement in orthodontic treatments.The protocol is the same in both scenarios.

Coffee Leaf Rust(Hemileia vastatrix)Disease in Coffee Plants and Perspectives by the Disease Control

Coffee Leaf Rust(CLR)is caused by Hemileia vastatrix in Coffea spp.It is one of the most dangerous phytopathogens for coffee plantations in terms of coffee productivity and coffee cup quality.In this review,we resume the problem of CLR in Mexico and the pathogenesis of H.vastatrix.The review abord plant-pathogen interactions which lead a compatible or incompatible interactions and result in CLR disease or resistance,respectively.The review abord Coffea spp.defense response pathways involved in H.vastatrix pathogenicity.Additionally,current measures to control H.vastatrix proliferation and germination were aborded focused on phytosanitary actions,and biological and chemical control.Finally,new trendlines to reduce the impact of CLR as nanoparticles and nanotechnology were analyzed.

Morphometry and Mineral Content in the Seeds and Soil of Two Species of Argemone L.(Papaveraceae)in the Central Part of the Chihuahuan Desert

The genus Argemone L.(Papaveraceae)is found widely distributed in Mexico’s Chihuahuan Desert(CD).Some species of this genus are of phytochemical or ethnobotanical interest.They are inedible plants considered as scrubs.To date they have not been broadly studied;thus,their ecology is,to our knowledge,unknown.The present work was centered around carrying out a morphometric analysis and the determination of minerals in the soil and seeds of the wild populations of Argemone at sites belonging to two ecoregions of the CD in Mexico.In April 2021 and April 2022,seeds of Argemone spp.,and soil samples were collected at 10 sites of the CD.The seeds were selected under a randomized design,and weight,length,diameter,thickness,buoyancy,and mineral content were determined.The soil samples were obtained under the Mexican regulation NOM-021-RECNAT-2000,and determinations of mineral content,electrical conductivity,apparent density,and soluble anions were performed.The information obtained was grouped by variable,species,and place of precedence.The statistical tests consisted of an ANOVA,Tukey means tests considering p≤0.05,and a Principal Components Analysis.Argemone pleiacantha exhibited differences in terms of weight(F=54.79,p=0.001),length(F=90.83,p=0.001),thickness(F=104.89,p=0.001),and diameter(F=155.82,p=0.001),and the differences in Argemone mexicana were in weight(F=46.71,p=0.001),thickness(F=187.49,p=0.001),length(F=191.56,p=0.001),and diameter(F=215.83,p=0.001).The evaluated seeds reached their maximal imbibition velocity at 24 h of evaluation.The content of the micro-and macro-nutrients analyzed in the seeds and soil suggest a tight relation with the morphometric characteristics of the seeds.

Hypothalamic circuits and aging:keeping the circadian clock updated

Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and mental illness,have shown a significant increase,negatively impacting overall quality of life.Studies on aged animal models have unveiled a progressive discoordination at multiple regulatory levels,including transcriptional,translational,and post-translational processes,resulting from cellular stress and circadian derangements.The circadian clock emerges as a key regulator,sustaining physiological homeostasis and promoting healthy aging through timely molecular coordination of pivotal cellular processes,such as stem-cell function,cellular stress responses,and inter-tissue communication,which become disrupted during aging.Given the crucial role of hypothalamic circuits in regulating organismal physiology,metabolic control,sleep homeostasis,and circadian rhythms,and their dependence on these processes,strategies aimed at enhancing hypothalamic and circadian function,including pharmacological and non-pharmacological approaches,offer systemic benefits for healthy aging.Intranasal brain-directed drug administration represents a promising avenue for effectively targeting specific brain regions,like the hypothalamus,while reducing side effects associated with systemic drug delivery,thereby presenting new therapeutic possibilities for diverse age-related conditions.

Long-term effects of gestational diabetes mellitus on the pancreas of female mouse offspring

BACKGROUND Prolonged fetal exposure to hyperglycemia may increase the risk of developing abnormal glucose metabolism and type-2 diabetes during childhood,adolescence,and adulthood;however,the mechanisms by which gestational diabetes mellitus(GDM)predisposes offspring to metabolic disorders remain unknown.AIM To quantify the nerve axons,macrophages,and vasculature in the pancreas from adult offspring born from mouse dams with GDM.METHODS GDM was induced by i.p.administration of streptozotocin(STZ)in ICR mouse dams.At 12 wk old,fasting blood glucose levels were determined in offspring.At 15 wk old,female offspring born from dams with and without GDM were sacrificed and pancreata were processed for immunohistochemistry.We quantified the density of sensory[calcitonin gene-related peptide(CGRP)]and tyrosine hydroxylase(TH)axons,blood vessels(endomucin),and macro-phages(CD68)in the splenic pancreas using confocal microscopy.RESULTS Offspring mice born from STZ-treated dams had similar body weight and blood glucose values compared to offspring born from vehicle-treated dams.However,the density of CGRP+and TH+axons,endomucin+blood vessels,and CD68+macrophages in the exocrine pancreas was significantly greater in offspring from mothers with GDM vs control offspring.Likewise,the microvasculature in the islets was significantly greater,but not the number of macrophages within the islets of offspring born from dams with GDM compared to control mice.CONCLUSION GDM induces neuronal,vascular,and inflammatory changes in the pancreas of adult progeny,which may partially explain the higher propensity for offspring of mothers with GDM to develop metabolic diseases.

Unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neuropathology and behavioral deficits in parkinsonian rats withα-synucleinopathy

Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate the rNurr1-V5 effect,supporting its potential clinical use in the treatment of Parkinson’s disease.

Woody plant taxonomic,functional,and phylogenetic diversity decrease along elevational gradients in Andean tropical montane forests:Environmental filtering and arrival of temperate taxa

Mountains are paramount for exploring biodiversity patterns due to the mosaic of topographies and climates encompassed over short distances.Biodiversity research has traditionally focused on taxonomic diversity when investigating changes along elevational gradients,but other facets should be considered.For first time,we simultaneously assessed elevational trends in taxonomic,functional,and phylogenetic diversity of woody plants in Andean tropical montane forests and explored their underlying ecological and evolutionary causes.This investigation covered four transects(traversing ca.2200 m a.s.l.)encompassing 114 plots of 0.1 ha across a broad latitudinal range(ca.10).Using Hill numbers to quantify abundance-based diversity among 37,869 individuals we observed a consistent decrease in taxonomic,functional,and phylogenetic diversity as elevation increased,although the decrease was less pronounced for higher Hill orders.The exception was a slight increase in phylogenetic diversity when dominant species were over-weighted.The decrease in taxonomic and functional diversity might be attributed to an environmental filtering process towards highlands,where the increasingly harsher conditions exclude species and functional strategies.Besides,the differences in steepness decrease between Hill orders suggest that rare species disproportionately contribute to functional diversity.For phylogenetic diversity the shifting elevational trend between Hill orders indicates a greater than previously considered influence in central Andean highlands of tropical lowlands originated species with strong niche conservatism relative to distantly related temperate lineages.This could be explained by a decreasing presence and abundance of temperate,extratropical taxa towards the central Andes relative to northern or southern Andes,where they are more prevalent.Copyright©2024 Kunming Institute of Botany,Chinese Academy of Sciences.

Implementation of a New Solution for the Preservation of Anatomical Specimens Made of Non-Toxic Substances

The preservation of anatomical pieces in Veterinary Anatomy is essential since it is not possible to dissect all domestic species. Most techniques use reagents with high levels of toxicity such as formaldehyde. The objective of this work was to develop a new preservation technique that uses reagents with zero toxicity and that allows obtaining preserved pieces suitable for anatomical studies. The alcohol propylene glycol technique was developed, the method of which uses a fixation step with alcohol, sodium chloride, commercial vinegar and subsequently the impregnation of the preservation solution made from propylene glycol and commercial vinegar, which are non-toxic. As a result of this work, adequately preserved sheep hearts were obtained that preserved their morphology with slight changes in size and weight, which did not affect their external and internal anatomical structure. Its coloration was not substantially affected, remaining a little lighter. The pieces obtained showed flexibility which allowed dissections to be carried out. The time to develop the technique was 20 days. A comparative study was carried out with the phenolated glycerin technique that uses toxic reagents (formaldehyde and phenol) and the pieces obtained with the alcohol propylene glycol technique were of better quality, observing that the pieces with phenolated glycerin tend to darken and are more rigid. And the time to develop the technique is 24 days. In conclusion, a preservation technique for anatomical pieces was developed that allowed the preservation of the organs under study, which allow their use for anatomical studies, and which have been preserved without changes until the time of this publication (8 months) and there are pieces preserved with this technique for 2 years.

The impact of maternal immune activation on the morphology and electrophysiological properties of postnatally-born neurons in the offspring

Pregnancy comes with a combination of physical changes and physiological immunosuppression that increases the susceptibility of women to pathogens and in turn,rises the prevalence of infectious diseases.

Chitosan Nanoparticles as Biostimulant in Lettuce (Lactuca sativa L.) Plants

Biodegradable nanoparticles such as chitosan nanoparticles (CSNPs) are used in sustainable agriculture since theyavoid damage to the environment;CSNPs have positive effects such as the accumulation of bioactive compoundsand increased productivity in plants. This study aimed to investigate the impact of applying CSNPs on lettuce,specifically focusing on enzymatic activity, bioactive compounds, and yield. The trial was conducted using a completelyrandomized design, incorporating CSNPs: 0, 0.05, 0.1, 0.2, 0.4, and 0.8 mg mL−1. The doses of 0.4 mg mL−1improve yields up to 24.6% increases and 0.1 mg mL−1 of CSNPs increases total phenols by 31.2% and antioxidantcapacity by 34.6%. In addition, when low concentrations of CSNPs (0.05 and 0.1 mg L−1) were applied, anincrease in catalase was determined. The CSNPs represent a good alternative to be used as a biostimulant in sustainableagriculture because they improve the yield and quality of lettuce by increasing the bioactive compounds.

Freeze-thaw cycles and associated geomorphology in a post-glacial environment:current glacial,paraglacial,periglacial and proglacial scenarios at Pico de Orizaba volcano,Mexico

The glacial history of Pico de Orizaba indicates that during the Last Glacial Maximum,its icecap covered up to~3000 m asl;due to the air temperature increasing,its main glacier has retreated to 5050 m asl.The retraction of the glacier has left behind an intense climatic instability that causes a high frequency of freeze-thaw cycles of great intensity;the resulting geomorphological processes are represented by the fragmentation of the bedrock that occupies the upper parts of the mountain.There is a notable lack of studies regarding the fragmentation and erosion occurring in tropical high mountains,and the associated geomorphological risks;for this reason,as a first stage of future continuous research,this study analyzes the freezing and thawing cycles that occur above 4000 m asl,through continuous monitoring of surface ground temperature.The results allow us to identify and characterize four zones:glacial,paraglacial,periglacial and proglacial.It was found that the paraglacial zone presents an intense drop of temperature,of up to~9℃ in only sixty minutes.The rock fatigue and intense freeze-thaw cycles that occur in this area are responsible for the high rate of rock disintegration and represent the main factor of the constant slope dynamics that occur at the site.This activity decreases,both in frequency and intensity,according to the distance to the glacier,which is where the temperature presents a certain degree of stability,until reaching the proglacial zone,where cycles are almost non-existent,and therefore there is no gelifraction activity.The geomorphological processes have resulted in significant alterations to the mountain slopes,which can have severe consequences in terms of risk and water.

Histopathological impact of SARS-CoV-2 on the liver:Cellular damage and long-term complications

Coronavirus disease 2019(COVID-19),caused by the highly pathogenic severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),primarily impacts the respiratory tract and can lead to severe outcomes such as acute respiratory distress syndrome,multiple organ failure,and death.Despite extensive studies on the pathogenicity of SARS-CoV-2,its impact on the hepatobiliary system remains unclear.While liver injury is commonly indicated by reduced albumin and elevated bilirubin and transaminase levels,the exact source of this damage is not fully understood.Proposed mechanisms for injury include direct cytotoxicity,collateral damage from inflammation,drug-induced liver injury,and ischemia/hypoxia.However,evidence often relies on blood tests with liver enzyme abnormalities.In this comprehensive review,we focused solely on the different histopathological manifestations of liver injury in COVID-19 patients,drawing from liver biopsies,complete autopsies,and in vitro liver analyses.We present evidence of the direct impact of SARS-CoV-2 on the liver,substantiated by in vitro observations of viral entry mechanisms and the actual presence of viral particles in liver samples resulting in a variety of cellular changes,including mitochondrial swelling,endoplasmic reticulum dilatation,and hepatocyte apoptosis.Additional ly,we describe the diverse liver pathology observed during COVID-19 infection,encompassing necrosis,steatosis,cholestasis,and lobular inflammation.We also discuss the emergence of long-term complications,notably COVID-19-related secondary sclerosing cholangitis.Recognizing the histopathological liver changes occurring during COVID-19 infection is pivotal for improving patient recovery and guiding decision-making.

THE SUMERIAN TERM u_(8)/ud_(5)/ab_(2)/eme_(3)/_(6)sila_(4)/maš_(2)/amar du_(3)(-a)

The aim of the present article is twofold:firstly,to prove that the expression animal+young du_(3)(-a),which is basically documented in texts from the 3rd millennium BC,refers to a dam that has just given birth,and secondly,to show the information concerning female animals and their newborns available in the texts.