The status of binocular visual functions among Taiwan high-tech industry engineers and its correlation with computer vision symptom.

To analyze the status of binocular visual functions, the relationship between binocular visual function and computer vision-related symptoms in the high-tech industry group. The study sample was comprised of 33 participants aged between 20 and 40 years of age. After completing basic information and the Computer Vision Symptom Scale (CVSS-17) questionnaire, the participants underwent a comprehensive examination of binocular visual function. All data were statistically analyzed with SPSS V26.0 software. The value of the binocular vision function of the Taiwan high-tech industry group was significantly different compared with the Scheiman and Morgan standard value. Study subjects were generally found to exhibit larger exophoric at distance, which in turn might lead to a lower ability to maintain binocular fusion to a single image, or recover from fusional disruption at distance. Subjects also experienced accommodation and convergence problems at near at the same time. Age, gender, and refractive errors had no significant impact on CVSS-17 scores, only the duration of computer usage showed a significant effect, particularly for internal symptom factor (ISF) dimensions. In addition, the interaction between the ISF and external symptom factor resulted in more severe visual symptoms. Long-term use of electronic devices may lead to an imbalance in binocular vision function, thereby increasing or exacerbating visual symptoms. If the use of electronic devices is an unchangeable trend, interventions in prescription, visual training or the visual design of electronic products become worthwhile topics for development.

Transcriptomic integrity of human oocytes used in ARTs: technical and intrinsic factor effects.

BACKGROUND: Millions of children have been born throughout the world thanks to ARTs, the harmlessness of which has not yet been fully demonstrated. For years, efforts to evaluate the specific effects of ART have focused on the embryo; however, it is the oocyte quality that mainly dictates first and foremost the developmental potential of the future embryo. Ovarian stimulation, cryopreservation, and IVM are sometimes necessary steps to obtain a mature oocyte, but they could alter the appropriate expression of the oocyte genome. Additionally, it is likely that female infertility, environmental factors, and lifestyle have a significant influence on oocyte transcriptomic quality, which may interfere with the outcome of an ART attempt. OBJECTIVE AND RATIONALE: The objective of this review is to identify transcriptomic changes in the human oocyte caused by interventions specific to ART but also intrinsic factors such as age, reproductive health issues, and lifestyle. We also provide recommendations for future good practices to be conducted when attempting ART. SEARCH METHODS: An in-depth literature search was performed on PubMed to identify studies assessing the human oocyte transcriptome following ART interventions, or in the context of maternal aging, suboptimal lifestyle, or reproductive health issues. OUTCOMES: ART success is susceptible to external factors, maternal aging, lifestyle factors (smoking, BMI), and infertility due to endometriosis or polycystic ovary syndrome. Indeed, all of these are likely to increase oxidative stress and alter mitochondrial processes in the foreground. Concerning ART techniques themselves, there is evidence that different ovarian stimulation regimens shape the oocyte transcriptome. The perturbation of processes related to the mitochondrion, oxidative phosphorylation, and metabolism is observed with IVM. Cryopreservation might dysregulate genes belonging to transcriptional regulation, ubiquitination, cell cycle, and oocyte growth pathways. For other ART laboratory factors such as temperature, oxygen tension, air pollution, and light, the evidence remains scarce. Focusing on genes involved in chromatin-based processes such as DNA methylation, heterochromatin modulation, histone modification, and chromatin remodeling complexes, but also genomic imprinting, we observed systematic dysregulation of such genes either after ART intervention or lifestyle exposure, as well as due to internal factors such as maternal aging and reproductive diseases. Alteration in the expression of such epigenetic regulators may be a common mechanism linked to adverse oocyte environments, explaining global transcriptomic modifications. WIDER IMPLICATIONS: Many IVF factors and additional external factors have the potential to impair oocyte transcriptomic integrity, which might not be innocuous for the developing embryo. Fortunately, it is likely that such dysregulations can be minimized by adapting ART protocols or reducing adverse exposure.

Intrinsic factors behind long COVID: III. Persistence of SARS-CoV-2 and its components.

Considerable research has been done in investigating SARS-CoV-2 infection, its characteristics, and host immune response. However, debate is still ongoing over the emergence of post-acute sequelae of SARS-CoV-2 infection (PASC). A multitude of long-lasting symptoms have been reported several weeks after the primary acute SARS-CoV-2 infection that resemble several other viral infections. Thousands of research articles have described various post-COVID-19 conditions. Yet, the evidence around these ongoing health problems, the reasons behind them, and their molecular underpinnings are scarce. These persistent symptoms are also known as long COVID-19. The persistence of SARS-CoV-2 and/or its components in host tissues can lead to long COVID. For example, the presence of viral nucleocapsid protein and RNA was detected in the skin, appendix, and breast tissues of some long COVID patients. The persistence of viral RNA was reported in multiple anatomic sites, including non-respiratory tissues such as the adrenal gland, ocular tissue, small intestine, lymph nodes, myocardium, and sciatic nerve. Distinctive viral spike sequence variants were also found in non-respiratory tissues. Interestingly, prolonged detection of viral subgenomic RNA was observed across all tissues, sometimes in multiple tissues of the same patient, which likely reflects recent but defective viral replication. Moreover, the persistence of SARS-CoV-2 RNA was noticed throughout the brain at autopsy, as late as 230 days following symptom onset among unvaccinated patients who died of severe infection. Here, we review the persistence of SARS-CoV-2 and its components as an intrinsic factor behind long COVID. We also highlight the immunological consequences of this viral persistence.

Modeling intrinsic factors of inclusive engagement in citizen science: Insights from the participants' survey analysis of CSI-COP.

Inclusive citizen science, an emerging field, has seen extensive research. Prior studies primarily concentrated on creating theoretical models and practical strategies for diversifying citizen science (CS) projects. These studies relied on ethical frameworks or post-project empirical observations. Few examined active participants' socio-demographic and behavioral data. Notably, none, to our knowledge, explored prospective citizen scientists' traits as intrinsic factors to enhance diversity and engagement in CS. This paper presents a new inclusive CS engagement model based on quantitative analysis of surveys administered to 540 participants of the dedicated free informal education MOOC (Massive Open Online Course) 'Your Right to Privacy Online' from eight countries in the EU funded project, CSI-COP (Citizen Scientists Investigating Cookies and App GDPR compliance). The surveys were filled out just after completing the training stage and before joining the project as active CSs. Out of the 540 participants who completed the surveys analyzed in this study, only 170 (32%) individuals actively participated as CSs in the project. Therefore, the study attempted to understand what characterizes these participants compared to those who decided to refrain from joining the project after the training stage. The study employed descriptive analysis and advanced statistical tests to explore the correlations among different research variables. The findings revealed several important relationships and predictors for becoming a citizen scientist based on the surveys analysis, such as age, gender, culture, education, Internet accessibility and apps usage, as well as the satisfaction with the MOOC, the mode of training and initial intentions for becoming a CS. These findings lead to the development of the empirical model for inclusive engagement in CS and enhance the understanding of the internal factors that influence individuals' intention and actual participation as CSs. The devised model offers valuable insights and key implications for future CS initiatives. It emphasizes the necessity of targeted recruitment strategies, focusing on underrepresented groups and overcoming accessibility barriers. Positive learning experiences, especially through MOOCs, are crucial; enhancing training programs and making educational materials accessible and culturally diverse can boost participant motivation. Acknowledging varying technological proficiency and providing necessary resources enhances active engagement. Addressing the intention-engagement gap is vital; understanding underlying factors and creating supportive environments can transform intentions into active involvement. Embracing cultural diversity through language-specific strategies ensures an inclusive environment for effective contributions.

A new Bayesian procedure for the estimation of the referees' decision thresholds and agreement. The case of professional handball refereeing.

In double refereeing, agreement between referees is fundamental for the achievement of a flawless and smooth refereeing activity. Nonetheless, the agreeement can be affected by several external and internal factors, with a negative impact on the consistency of the refereeing and the fluidity of the game. The referee's Decision Threshold (DT) is the limit above which the evidence of a foul results in the call of an infraction by the referee. It represents the individual refereeing style, and it is one of the factors that can contribute to low agreement between the referees. We present an application of a new Bayesian procedure to estimate referee's DT in a typical refereeing task. To this end, 56 italian professional handball (FIGH) referees were asked to evaluate 96 potential foul plays, belonging to four different infraction types: 7-m throw, passive play, offensive foul, disciplinary sanctions. The proposed method provides information about: (i) referee's individual DT; (ii) the agreement between pairs of referees (i.e., one-to-one); (iii) the agreement between each referee and all the other referees (i.e., one-to-total); (iv) the agreement between each referee and a reference referee (i.e., one-to-expert); (v) the proportion of agreement between the referees and a reference referee for each potential foul play. Sport federations would profit by this procedure in different ways: by using the information about the DT to train referees, by detecting referees with a low agreement with their colleagues or with the reference referee, by focusing training on specific plays to improve the arbitration class internal consistency.

Update on Serum Biomarkers in Autoimmune Atrophic Gastritis.

BACKGROUND: Autoimmune atrophic gastritis (AAG) is a persistent, corpus-restricted immune-mediated destruction of the gastric corpus oxyntic mucosa with reduced gastric acid and intrinsic factor secretion, leading to iron deficiency and pernicious anemia as a consequence of iron and cobalamin malabsorption. Positivity toward parietal cell (PCA) and intrinsic factor (IFA) autoantibodies is very common. AAG may remain asymptomatic for many years, thus making its diagnosis complex and often delayed. Due to the increased risk of gastric neoplasms, a timely diagnosis of AAG is clinically important. CONTENT: The gold standard for AAG diagnosis is histopathological assessment of gastric biopsies obtained during gastroscopy, but noninvasive, preendoscopic serological screening may be useful in some clinical scenarios. Serum biomarkers for AAG may be divided into 2 groups: gastric autoimmunity-related biomarkers, such as PCA and IFA, and gastric corpus atrophy/reduced gastric acid secretion-related biomarkers, such as serum gastrin and pepsinogens. The present review focuses on the clinical significance and pitfalls of serum biomarkers related to gastric autoimmunity and gastric corpus atrophy, including some discussion of analytical methods. SUMMARY: Serum assays for PCA, IFA, gastrin, and pepsinogen I show good diagnostic accuracy for noninvasive diagnostic work-up of AAG. Diagnostic performance may increase by combining >1 of these tests, overcoming the problem of seronegative AAG. However, appropriately designed, comparative studies with well-characterized patient cohorts are needed to better define the reliability of these biomarkers in the diagnosis of patients with AAG. Currently, positive serum tests should always be followed by the state-of-art diagnostic test, that is, histopathological assessment of gastric biopsies obtained during gastroscopy to definitively confirm or rule out AAG and eventually neoplastic complications.

Natural Killer Cell Activation by Ubiquitin-specific Protease 6 Mediates Tumor Suppression in Ewing Sarcoma.

Ewing sarcoma is a rare and deadly pediatric bone cancer for which survival rates and treatment options have stagnated for decades. Ewing sarcoma has not benefited from immunotherapy due to poor understanding of how its immune landscape is regulated. We recently reported that ubiquitin-specific protease 6 (USP6) functions as a tumor suppressor in Ewing sarcoma, and identified it as the first cell-intrinsic factor to modulate the Ewing sarcoma immune tumor microenvironment (TME). USP6 induces intratumoral infiltration and activation of multiple innate immune lineages in xenografted nude mice. Here we report that natural killer (NK) cells are essential for its tumor-inhibitory functions, as NK cell depletion reverses USP6-mediated suppression of Ewing sarcoma xenograft growth. USP6 expression in Ewing sarcoma cells directly stimulates NK cell activation and degranulation in vitro, and functions by increasing surface levels of multiple NK cell-activating ligands. USP6 also induces surface upregulation of the receptor for the apoptosis-inducing ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), providing an additional route for enhanced sensitivity to NK cell killing. Furthermore, USP6-expressing Ewing sarcoma and NK cells participate in a paracrine immunostimulatory feedforward loop, wherein IFNγ secreted by activated NK cells feeds back on USP6/Ewing sarcoma cells to induce synergistic expression of chemokines CXCL9 and CXCL10. Remarkably, expression of USP6 in subcutaneous Ewing sarcoma xenografts induces systemic activation and maturation of NK cells, and induces an abscopal response in which growth of distal tumors is inhibited, coincident with increased infiltration and activation of NK cells. This work reveals how USP6 reprograms the Ewing sarcoma TME to enhance antitumor immunity, and may be exploited for future therapeutic benefit. Significance: This study provides novel insights into the immunomodulatory functions of USP6, the only cancer cell-intrinsic factor demonstrated to regulate the immune TME in Ewing sarcoma. We demonstrate that USP6-mediated suppression of Ewing sarcoma tumorigenesis is dependent on NK cells. USP6 directly activates NK cell cytolytic function, inducing both intratumoral and systemic activation of NK cells in an Ewing sarcoma xenograft model.

Cathepsin B Is Not an Intrinsic Factor Related to Asparaginase Resistance of the Acute Lymphoblastic Leukemia REH Cell Line.

L-Asparaginase (ASNase) is a biopharmaceutical used as an essential drug in the treatment of acute lymphoblastic leukemia (ALL). Yet, some cases of ALL are naturally resistant to ASNase treatment, which results in poor prognosis. The REH ALL cell line, used as a model for studying the most common subtype of ALL, is considered resistant to treatment with ASNase. Cathepsin B (CTSB) is one of the proteases involved in the regulation of in vivo ASNase serum half-life and it has also been associated with the progression and resistance to treatment of several solid tumors. Previous works have shown that, in vitro, ASNase is degraded when incubated with REH cell lysate, which is prevented by a specific CTSB inhibitor, suggesting a function of this protease in the ASNase resistance of REH cells. In this work, we utilized a combination of CRISPR/Cas9 gene targeting and enzymatic measurements to investigate the relevance of CTSB on ASNase treatment resistance in the ALL model cell line. We found that deletion of CTSB in REH ALL cells did not confer ASNase treatment sensitivity, thus suggesting that intrinsic expression of CTSB is not a mechanism that drives the resistant nature of these ALL cells to enzymes used as the first-line treatment against leukemia.

Construction enterprises' green financing efficiency and its influencing factors including internal and external: Based on four-stage DEA model.

Under the background of carbon neutrality, green development is the theme of today's times. The construction industry is an important part of the green development plan, and it is of great significance to study its green financing efficiency. Based on this, this paper uses the four-stage DEA model to explore the green financing efficiency of listed construction companies from 2019 to 2020. The conclusion shows that: firstly, the green financing efficiency of listed construction companies is low, and the demand for green financing has not been met. It is necessary to strengthen the support of green finance to meet the needs of its expansion. Secondly, the efficiency of green financing is significantly and complexly affected by external influencing factors. It is necessary to dialectically treat external influencing factors such as local industry development support, financial development level, and the number of patent authorizations. Thirdly, among the internal influencing factors, the proportion of independent directors has a significant positive impact on the green financing efficiency of listed construction companies, and the proportion of R&D investment has a significant negative impact. Listed construction companies need to increase the proportion of independent directors and control the proportion of R&D investment.

Development and validation of a novel nomogram to predict the impact of the polymorphism of the ICAM-1 gene on the prognosis of ischemic cardiomyopathy.

The current study investigated the association between polymorphisms of the ICAM-1 gene and prognosis of Ischemic cardiomyopathy (ICM), and developed a prognostic nomogram for ICM on the basis of ICAM-1 gene variants. The current study included totally 252 patients with ICM. In addition, PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) was used to genotype SNPs in the ICAM-1 gene in the patients. Later, the nomogram model was built by combining clinical data and ICAM-1 gene variants. This study used the least absolute shrinkage and selection operator (LASSO) regression model to optimize feature selection into an ICM prognostic model. Furthermore, multivariate Cox-regression was applied to build the prognostic model, which included clinical and gene features chosen by the LASSO regression model. Following that, the receiver operating characteristic (ROC) curve, C-index, calibration plot analyses and decision curve analysis (DCA) were carried out to evaluate the discrimination ability, consistency, and clinical utility of the prognostic model, and the bootstrap method was adopted for internal validation. predicting factors rs112872667, treating by PCI or CABG, ventricular arrhythmia, left ventricular end-diastolic diameter (LVDD), use of ß-blockers, systolic blood pressure (SBP), heart rate (HR), and serum sodium were incorporated into the prognostic nomogram. The constructed nomogram performed well in discrimination ability, as observed by the time-dependent C-index. Furthermore, as shown by calibration curves, our nomogram's predicted probabilities were highly consistent with measured values. With threshold probabilities, DCA suggested that our nomogram could be useful in the clinic. mutation of rs112872667 have critical predictive value on the prognosis of ICM, ICM patients with the mutant genotype (CT or TT) have higher survival probability than those with the wild genotype (CC). Mutation of rs112872667 in ICAM-1 gene have critical predictive value on the prognosis of ICM, ICM patients with the mutant genotype (CT or TT) have higher survival probability than those with the wild genotype (CC).

The association of hepcidin, reticulocyte hemoglobin equivalent and anemia-related indicators on anemia in chronic kidney disease.

Hepcidin is an essential regulator of iron homeostasis in chronic kidney disease (CKD) anemia, reticulocyte hemoglobin equivalent (RET-He) can be used to evaluate the availability of iron for erythropoiesis. Previous research has found that hepcidin indirectly regulates RET-He. This study aimed to investigate the association of hepcidin, RET-He and anemia-related indicators on anemia in chronic kidney disease. A total of 230 individuals were recruited, including 40 CKD3-4 patients, 70 CKD5 patients without renal replacement therapy, 50 peritoneal dialysis patients, and 70 hemodialysis patients. The serum levels of hemoglobin (Hb), reticulocyte, RET-He, serum iron, serum creatinine, serum ferritin, total iron binding capacity, hepcidin-25, high sensitivity C-reactive protein, transferrin, erythropoietin, intrinsic factor antibody, soluble transferrin receptor and interleukins-6 (IL-6) were measured. Hepcidin-25 was positively associated with IL-6, and negatively with total iron binding capacity, intrinsic factor antibody, and transferrin. Reticulocyte Hb equivalent was associated positively with Hb, serum ferritin, serum iron, transferrin saturation, and negatively with serum creatinine, reticulocyte, IL-6, STfR. Hepcidin-25 was not associated with RET-He, while IL-6 was independently associated with hepcidin-25 and RET-He, suggesting that hepcidin has no effffect on the iron dynamics of reticulocytes in CKD, may be related to IL-6, indicate a likelihood of a threshold for stimulation of hepcidin-25 expression by IL-6 in order to indirectly regulates RET-He.

Primary Neurologic Symptoms: Have You Considered Pernicious Anemia?

BACKGROUND: Vitamin B12, or cobalamin, is a nutrient that is vital for metabolic function. Absorption of ingested B12 is dependent on intrinsic factor, which is secreted by parietal cells within the stomach. Pernicious anemia is caused by an intrinsic factor deficiency or autoantibodies against intrinsic factor. The presence of parietal cell antibodies can destroy parietal cells, which can also lead to a deficiency in intrinsic factor. Both lead to megaloblastic anemia caused by vitamin B12 deficiency. The typical presentation of pernicious anemia includes fatigue, pale appearance, tingling sensation, depression, alterations to vision and smell, urinary incontinence, psychotic episodes, and weakness. The most effective treatment for pernicious anemia is intramuscular B12. CASE REPORT: A 27-year-old woman with a history of vitiligo presented to the emergency department (ED) with bilateral lower extremity weakness, clumsiness, numbness, and tingling. Physical examination revealed ataxia, no sensation below her umbilicus, decreased strength, and hyperreflexia in both lower extremities. Complete blood count in the ED revealed low hemoglobin and hematocrit and elevated mean corpuscular volume, concerning for pernicious anemia. Further laboratory testing upon inpatient admission revealed a low vitamin B12 level and parietal cell antibodies in the blood. The patient's pernicious anemia was treated with intramuscular vitamin B12 injections, which led to near complete resolution of her symptoms. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Early suspicion and detection of pernicious anemia in the ED can prevent serious and permanent hematologic and neurologic damage and the development of other autoimmune disorders.

Motives for physical activity participation among lebanese adults aged 18 to 50 years: a cross-sectional study / Motivos para participação de atividade física em libanes adultos de 18 a 50 anos: um estudo transversal

ABSTRACT Background: Sports participation motivations can be intrinsic, extrinsic, or even amotivational. Few studies on adult participation in PA have been found in the Lebanese context. This study aims to: a) investigate significant differences in sports participation motivation across gender, age, occupation, and time of practice, and b) investigate sports participation motives that discriminated the best between those variables. Material and methods: The Arabic version of the Sport Motivation Scale was collected electronically from 531 volunteers practicing regular PA for the last six months. Gender, occupation, marital status, and time of practice were all analyzed using Mann-Whitney U test and the Kruskal Wallis Test with 0.05 as level of significance. Results: Internal motivation subscales (particularly the intention to accomplish) were the most influential motives for both genders. A significant difference across gender was reported in the extrinsic motivation and amotivation subscales. Furthermore, age, occupation, marital status, and time of practice show significant differences in motivation factors either dependent or regardless of gender distribution (p<0.05). Conclusion: no significant differences in the intrinsic motivation for sports participation between genders. Other factors, on the other hand, had a substantial impact. Research contribution: these findings are intended to contribute to a better understanding of differences in motivation for participating in PA and to aid in its promotion among Lebanese adults

RESUMO Contexto: As motivações para a participação desportiva podem ser intrínsecas, extrínsecas ou mesmo amotivacionais. Poucos estudos sobre a participação de adultos em AF foram encontrados no contexto libanês. Este estudo tem como objetivos: a) investigar diferenças significativas na motivação para a prática desportiva em função do género, idade, profissão e tempo de prática, e b) investigar os motivos da prática desportiva que melhor discriminaram entre essas variáveis. Material e métodos: A versão árabe da Sport Motivation Scale foi coletada eletronicamente de 531 voluntários praticantes regulares de AF nos últimos seis meses. Gênero, ocupação, estado civil e tempo de atuação foram analisados por meio do teste U de Mann-Whitney e do teste de Kruskal Wallis com nível de significância de 0,05. Resultados: As subescalas de motivação interna (particularmente a intenção de realizar) foram os motivos mais influentes para ambos os sexos. Uma diferença significativa entre os gêneros foi relatada nas subescalas de motivação extrínseca e amotivação. Além disso, idade, ocupação, estado civil e tempo de prática mostram diferenças significativas nos fatores de motivação dependentes ou independentes da distribuição por gênero (p<0,05). Conclusão: não houve diferenças significativas na motivação intrínseca para a prática desportiva entre os sexos. Outros fatores, por outro lado, tiveram um impacto substancial. Contribuição da pesquisa: esses achados pretendem contribuir para uma melhor compreensão das diferenças na motivação para participar da AF e auxiliar na sua promoção entre adultos libaneses.

In Vivo Anticoagulant and Antithrombic Activity of Depolymerized Glycosaminoglycan from Apostichopus japonicus and Dynamic Effect-Exposure Relationship in Rat Plasma.

Glycosaminoglycan from Apostichopus japonicus (AHG) and its depolymerized fragments (DAHGs) are anticoagulant fucosylated chondroitin sulfate. The aim of this study was to further evaluate the anticoagulant and antithrombic activity of AHG and DAHGs, as well as reveal the dynamic relationship between exposure and effect in vivo. The results demonstrated that AHG100 (Mw~100 kDa), DAHG50 (Mw~50 kDa), and DAHG10 (Mw~10 kDa) exhibited potent anticoagulant activity by inhibiting intrinsic factor Xase complex (FXase) as well as antithrombin-dependent factor IIa (FIIa) and factor Xa (FXa). These glycosaminoglycans markedly prevented thrombosis formation and thrombin-induced platelet aggregation in a dose- and molecular weight-dependent manner in vitro and in vivo. The further bleeding time measurement indicated that DAHG10 exhibited obviously lower hemorrhage risks than native AHG100. Following oral administration, DAHG10 could be absorbed into blood, further dose-dependently prolonging activated partial thromboplastin time (APTT) and thrombin time (TT) as well as inhibiting FXa and FIIa partially through FXase. Anticoagulant activity was positively associated with plasma concentration following oral administration of DAHG10. Our study proposed a new point of view to understand the correlation between effects and exposure of fucosylated chondroitin sulfate as an effective and safe oral antithrombotic agent.

The impact of platelets on pulmonary microcirculation throughout COVID-19 and its persistent activating factors.

Patients with COVID-19 often have hypoxemia, impaired lung function, and abnormal imaging manifestations in acute and convalescent stages. Alveolar inflammation, pulmonary vasculitis, and thromboembolism synergistically damage the blood-air barrier, resulting in increased pulmonary permeability and gas exchange disorders. The incidence of low platelet counts correlates with disease severity. Platelets are also involved in the impairment of pulmonary microcirculation leading to abnormal lung function at different phases of COVID-19. Activated platelets lose the ability to protect the integrity of blood vessel walls, increasing the permeability of pulmonary microvasculature. High levels of platelet activation markers are observed in both mild and severe cases, short and long term. Therefore, the risk of thrombotic events may always be present. Vascular endothelial injury, immune cells, inflammatory mediators, and hypoxia participate in the high reactivity and aggregation of platelets in various ways. Microvesicles, phosphatidylserine (PS), platelets, and coagulation factors are closely related. The release of various cell-derived microvesicles can be detected in COVID-19 patients. In addition to providing a phospholipid surface for the synthesis of intrinsic factor Xase complex and prothrombinase complex, exposed PS also promotes the decryption of tissue factor (TF) which then promotes coagulant activity by complexing with factor VIIa to activate factor X. The treatment of COVID-19 hypercoagulability and thrombosis still focuses on early intervention. Antiplatelet therapy plays a role in relieving the disease, inhibiting the formation of the hypercoagulable state, reducing thrombotic events and mortality, and improving sequelae. PS can be another potential target for the inhibition of hypercoagulable states.

Sexual Dimorphism of the Gut Microbiota in the Chinese Alligator and Its Convergence in the Wild Environment.

The gut microbiota forms a complex microecosystem in vertebrates and is affected by various factors. As a key intrinsic factor, sex has a persistent impact on the formation and development of gut microbiota. Few studies have analyzed sexual dimorphism of gut microbiota, particularly in wild animals. We used 16S rRNA gene sequencing to analyze the gut microbiota of juvenile and adult Chinese alligators, and untargeted metabolomics to study serum metabolomes of adult alligators. We observed significant sexual differences in the community diversity in juvenile, but not adult, alligators. In terms of taxonomic composition, the phylum Fusobacteriota and genus Cetobacterium were highly abundant in adult alligators, similar to those present in carnivorous fishes, whereas the gut microbiota composition in juvenile alligators resembled that in terrestrial reptiles, indicating that adults are affected by their wild aquatic environment and lack sex dimorphism in gut microbiota. The correlation analysis revealed that the gut microbiota of adults was also affected by cyanobacteria in the external environment, and this effect was sex-biased and mediated by sex hormones. Overall, this study reveals sexual differences in the gut microbiota of crocodilians and their convergence in the external environment, while also providing insights into host-microbiota interactions in wildlife.

Development of a Sensitive ELISA for Gastric Intrinsic Factor and Detection of Intrinsic Factor Immunoreactivity in Human Serum.

Gastric Intrinsic Factor (IF) is produced by the parietal cells of the stomach and secreted into the gastrointestinal tract where it ensures the active absorption of vitamin B12. We hypothesized that a small amount of IF ends up in the circulation and can be measured in serum. The aim of this study was to develop an assay for measuring human IF and to demonstrate its presence in serum. We designed a sensitive ELISA for measurement of human IF using a commercial monoclonal antibody and an in-house polyclonal antibody as capture and detecting antibody, respectively. Imprecision, accuracy, and linearity of the assay were examined. We established a reference interval based on serum samples from 240 healthy donors, and explored the daily IF fluctuations in 20 healthy subjects. Employing a prototype IF ELISA and size exclusion chromatography experiments, we demonstrated the presence of IF in human serum. In its final design, the IF ELISA has a measurement range of 0.2 to 50 pmol/L. The intra-assay and total imprecision were 7.9% and 15%, respectively. The 95% reference interval (18-65 years) was 1.7-11.6 pmol/L. No diurnal fluctuation or notable sex differences were observed. Our results suggest that the assay is capable of detecting and quantifying human IF in the circulation and may prove useful in the characterization of patients with impaired IF production.

Age-dependent virulence of human pathogens.

Host age is often evoked as an intrinsic factor aggravating the outcome of host-pathogen interactions. However, the shape of the relationship between age and infection-induced mortality might differ among pathogens, with specific clinical and ecological traits making some pathogens more likely to exert higher mortality in older hosts. Here, we used a large dataset on age-specific case fatality rate (CFR) of 28 human infectious diseases to investigate i) whether age is consistently associated to increased CFR, ii) whether pathogen characteristics might explain higher CFR in older adults. We found that, for most of the infectious diseases considered here, CFR slightly decreased during the first years of life and then steeply increased in older adults. Pathogens inducing diseases with long-lasting symptoms had the steepest increase of age-dependent CFR. Similarly, bacterial diseases and emerging viruses were associated with increasing mortality risk in the oldest age classes. On the contrary, we did not find evidence suggesting that systemic infections have steeper slopes between CFR and age; similarly, the relationship between age and CFR did not differ according to the pathogen transmission mode. Overall, our analysis shows that age is a key trait affecting infection-induced mortality rate in humans, and that the extent of the aggravating effect on older adults depends on some key traits, such as the duration of illness.

Local Immunoglobulin E in nasal polyps: Role and modulation.

In the airway, IgE is traditionally regarded as a key mediator in allergic diseases, such as AR and allergic asthma. However, growing evidence demonstrates the importance of local IgE in airway inflammatory diseases, irrespective of the presence of allergy. In this review, we discuss the most recent evidence for IgE in chronic rhinosinusitis with nasal polyps(CRSwNP), including the local IgE's characteristics, the modulation of its synthesis, and its function. The levels of local IgE are significantly elevated in polyps independently of IgE serum levels and atopic status. Local IgE, which is correlated with type 2 inflammation, is polyclonal and functional. IgE is produced by active B cells and is dependent on the class switch recombination(CSR). In NPs, this process is triggered by not only allergens but also microbial colonization, especially the superantigen- Staphylococcus aureus. The production of local IgE is modulated by lymphocytes(such as Tfh, ILC2s, iTreg), cytokines(such as IL-4, IL-13, IFN-γ, TGF-ß, IL-2, IL-21), transcription factors, and B cell-intrinsic factor. Due to the central role of IgE in NPs, it is regarded as an ideal target for therapy and has been proved to be clinically successful. Based on this knowledge, we believe that exploring the trigger and regulatory factors for the activation of local B cells and CSR to IgE will provide more valuable information for us to recognize the pathological mechanisms of local IgE and offer the possible option for new therapeutic targets of nasal polyps.

Novel intrinsic factor Yun maintains female germline stem cell fate through Thickveins.

Germline stem cells (GSCs) are critical for the reproduction of an organism. The self-renewal and differentiation of GSCs must be tightly controlled to avoid uncontrolled stem cell proliferation or premature stem cell differentiation. However, how the self-renewal and differentiation of GSCs are properly controlled is not fully understood. Here, we find that the novel intrinsic factor Yun is required for female GSC maintenance in Drosophila. GSCs undergo precocious differentiation due to de-repression of differentiation factor Bam by defective BMP/Dpp signaling in the absence of yun. Mechanistically, Yun associates with and stabilizes Thickveins (Tkv), the type I receptor of Dpp/BMP signaling. Finally, ectopic expression of a constitutively active Tkv (TkvQD) completely suppresses GSC loss caused by yun depletion. Collectively, these data demonstrate that Yun functions through Tkv to maintain GSC fate. Our results provide new insight into the regulatory mechanisms of how stem cell maintenance is properly controlled.