Estradiol mediates greater germinal center responses to influenza vaccination in female than male mice.

Adult females of reproductive age develop greater antibody responses to inactivated influenza vaccines (IIV) than males. How sex, age, and sex steroid concentrations impact B cells and durability of IIV-induced immunity and protection over 4 months post-vaccination (mpv) was analyzed. Vaccinated adult females had greater germinal center B cell and plasmablast frequencies in lymphoid tissues, higher neutralizing antibody responses 1-4 mpv, and better protection against live H1N1 challenge than adult males. Aged mice, regardless of sex, had reduced B cell frequencies, less durable antibody responses, and inferior protection after challenge than adult mice, which correlated with diminished estradiol among aged females. To confirm that greater IIV-induced immunity was caused by sex hormones, four core genotype (FCG) mice were used, in which the testes-determining gene, Sry, was deleted from chromosome Y (ChrY) and transferred to Chr3 to separate gonadal sex (i.e., ovaries or testes) from sex chromosome complement (i.e., XX or XY complement). Vaccinated, gonadal female FCG mice (XXF and XYF) had greater numbers of B cells, higher antiviral antibody titers, and reduced pulmonary virus titers following live H1N1 challenge than gonadal FCG males (XYM and XXM). To establish that lower estradiol concentrations cause diminished immunity, adult and aged females received either a placebo or estradiol replacement therapy prior to IIV. Estradiol replacement significantly increased IIV-induced antibody responses and reduced morbidity after the H1N1 challenge among aged females. These data highlight that estradiol is a targetable mechanism mediating greater humoral immunity following vaccination among adult females.IMPORTANCEFemales of reproductive ages develop greater antibody responses to influenza vaccines than males. We hypothesized that female-biased immunity and protection against influenza were mediated by estradiol signaling in B cells. Using diverse mouse models ranging from advanced-age mice to transgenic mice that separate sex steroids from sex chromosome complement, those mice with greater concentrations of estradiol consistently had greater numbers of antibody-producing B cells in lymphoid tissue, higher antiviral antibody titers, and greater protection against live influenza virus challenge. Treatment of aged female mice with estradiol enhanced vaccine-induced immunity and protection against disease, suggesting that estradiol signaling in B cells is critical for improved vaccine outcomes in females.

Ultra-processed food consumption and increased risk of metabolic syndrome in Korean adults: A cross-sectional analysis of the KNHANES 2016-2020.

OBJECTIVE: This study aimed to investigate the association between ultra-processed food (UPF) intake and the risk for metabolic syndrome (MetS) in Korean adults. METHODS: The study consisted of 22 688 Korean adults ≥19 y of age from the Korea National Health and Nutrition Examination Survey (KNHANES) 2016-2020. The NOVA classification categorizes foods according to the nature, extent, and purpose of industrial processing. MetS was defined based on the National Cholesterol Education Program Adult Treatment Panel III criteria and a modified waist circumference cut-off for Korean adults. We estimated the usual percent total food intake from UPFs. We used multivariate logistic regression to assess the association between UPFs and risk for MetS, adjusted for age, sex, education level, income level, smoking status, alcohol drinking, physical activity, and total energy intake. We further analyzed the association of UPFs with each component of MetS. RESULTS: The median usual percent total food intake from UPFs was 22%, and the midpoint of intake ranged from 3% (quartile 1) to 48% (quartile 4). The group with the highest UPF consumption had a 19% higher risk for developing MetS than the lowest quartile of UPF consumption (odds ratio [OR],1.19; 95% confidence interval [CI], 1.06-1.33; Ptrend = 0.006). In analysis of the relationship between UPF intake and MetS components, a higher UPF was associated with an increased risk for hypertension (OR, 1.13; 95% CI, 1.01-1.26; Ptrend = 0.037) and abdominal obesity (OR, 1.19; 95% CI, 1.07-1.33; Ptrend = 0.001), but had no significant association with other components (hyperglycemia, hypertriacylglycerolmia, and low high-density lipoprotein cholesterol, all P > 0.05). CONCLUSION: Higher UPF contribution to total daily food intake is associated with an increased risk for MetS, particularly with a higher risk for hypertension and abdominal obesity.

Clinical Utility of Whole-Genome Analysis as One-for-All Test for Breast Cancer: A Case Series.

Introduction: Breast cancer exhibits vast genomic diversity, leading to varied clinical manifestations. Integrating molecular subtyping with in-depth genomic profiling is pivotal for informed treatment choices and prognostic insights. Whole-genome clinical analysis provides a holistic view of genome-wide variations, capturing structural changes and affirming tumor suppressor gene loss of heterozygosity. Case Presentation: Here we detail four unique breast cancer cases from Seoul St. Mary's Hospital, highlighting the actionable benefits and clinical value of whole-genome sequencing (WGS). As an all-in-one test, WGS demonstrates significant clinical utility in these cases, including: (1) detecting homologous recombination deficiency with underlying somatic causal variants (case 1), (2) distinguishing double primary cancer from metastasis (case 2), (3) uncovering microsatellite instability (case 3), and (4) identifying rare germline pathogenic variants in TP53 gene (case 4). Our observations underscore the enhanced clinical relevance of WGS-based testing beyond pinpointing a few driver mutations in conventional targeted panel sequencing platforms. Conclusion: With genomic advancements and decreasing sequencing costs, WGS stands out as a transformative tool in oncology, paving the way for personalized treatment plans rooted in individual genetic blueprints.

Genotypes of Echinococcus Species from Cattle in Tanzania.

Cystic echinococcosis is a zoonotic parasitic disease caused by Echinococcus species. Tanzania is one of the endemic countries with cystic echinococcosis. This study focussed on identifying genotypes of Echinococcus spp. in Tanzania. We collected 7 cysts from cattle in Mwanza municipal (n=4) and Loliondo district (n=3). The cysts from Mwanza were all E. ortleppi and fertile. In contrast, the cysts from Loliondo were all E. granulosus sensu stricto and sterile. Two from the 4 cysts were a new haplotype of E. ortleppi (G5). These results can improve the preventive and control programs for humans and livestock in Tanzania. To our knowledge, this study is considered the first to identify the genotype and haplotype of Echinococcus spp. in Tanzania.

Cerebral Cavernous Malformation 1 Determines YAP/TAZ Signaling-Dependent Metastatic Hallmarks of Prostate Cancer Cells.

Enhanced Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signaling is correlated with the extraprostatic extension of prostate cancer. However, the mechanism by which YAP/TAZ signaling becomes hyperactive and drives prostate cancer progression is currently unclear. In this study, we revealed that higher expression of CCM1, which is uniquely found in advanced prostate cancer, is inversely correlated with metastasis-free and overall survival in patients with prostate cancer. We also demonstrated that CCM1 induces the metastasis of multiple types of prostate cancer cells by regulating YAP/TAZ signaling. Mechanistically, CCM1, a gene mutated in cerebral cavernous malformation, suppresses DDX5, which regulates the suppression of YAP/TAZ signaling, indicating that CCM1 and DDX5 are novel upstream regulators of YAP/TAZ signaling. Our findings highlight the importance of CCM1-DDX5-YAP/TAZ signaling in the metastasis of prostate cancer cells.

Pregnancy alters interleukin-1 beta expression and antiviral antibody responses during severe acute respiratory syndrome coronavirus 2 infection.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2, the disease-causing pathogen of the coronavirus disease 2019 pandemic, has resulted in morbidity and mortality worldwide. Pregnant women are more susceptible to severe coronavirus disease 2019 and are at higher risk of preterm birth than uninfected pregnant women. Despite this evidence, the immunologic effects of severe acute respiratory syndrome coronavirus 2 infection during pregnancy remain understudied. OBJECTIVE: This study aimed to assess the impact of severe acute respiratory syndrome coronavirus 2 infection during pregnancy on inflammatory and humoral responses in maternal and fetal samples and compare antibody responses to severe acute respiratory syndrome coronavirus 2 among pregnant and nonpregnant women. STUDY DESIGN: Immune responses to severe acute respiratory syndrome coronavirus 2 were analyzed using samples from pregnant (n=33) and nonpregnant (n=17) women who tested either positive (pregnant, 22; nonpregnant, 17) or negative for severe acute respiratory syndrome coronavirus 2 (pregnant, 11) at Johns Hopkins Hospital. We measured proinflammatory and placental cytokine messenger RNAs, neonatal Fc receptor expression, and tetanus antibody transfer in maternal and cord blood samples. In addition, we evaluated antispike immunoglobulin G, antispike receptor-binding domain immunoglobulin G, and neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 in serum or plasma collected from nonpregnant women, pregnant women, and cord blood. RESULTS: Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection expressed more interleukin-1 beta, but not interleukin 6, in blood samples collected within 14 days vs >14 days after performing severe acute respiratory syndrome coronavirus 2 test. Pregnant women with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection also had reduced antispike receptor-binding domain immunoglobulin G titers and were less likely to have detectable neutralizing antibody than nonpregnant women. Although severe acute respiratory syndrome coronavirus 2 infection did not disrupt neonatal Fc receptor expression in the placenta, maternal transfer of severe acute respiratory syndrome coronavirus 2 neutralizing antibody was inhibited by infection during pregnancy. CONCLUSION: Severe acute respiratory syndrome coronavirus 2 infection during pregnancy was characterized by placental inflammation and reduced antiviral antibody responses, which may impact the efficacy of coronavirus disease 2019 treatment in pregnancy. In addition, the long-term implications of placental inflammation for neonatal health require greater consideration.

B cells from young and old mice switch isotypes with equal frequencies after ex vivo stimulation.

To determine whether old B cells have the same capacity to switch isotypes as young cells, we purified splenic follicular, marginal zone, and age-associated B cell subsets from C57BL/6 mice. Cells were stimulated in culture with interleukin 4 and either lipopolysaccharide or anti-CD40, and switching to IgG1 was measured by flow cytometry of surface immunoglobulin. The results show that switching was robust in follicular and marginal zone B cells from old mice and was comparable to their young counterparts. However, age-associated B cells from old mice switched poorly relative to the other subsets. Expression of activation-induced deaminase, which initiates switching, was quantified by qPCR of mRNA, and it was equal between young and old follicular B cells. Thus, in this ex vivo system, the follicular and marginal zone cells from young and old mice behaved similarly, showing that the molecular machinery to perform switching is intact in old B cells.

A Clonorchiasis Case of a Leopard Cat, Prionailurus bengalensis euptilurus, Diagnosed by Ultrasonography and Egg Detection in Republic of Korea.

A clonorchiasis case in a captive leopard cat, Prionailurus bengalensis euptilurus, was confirmed by ultrasonographic findings and egg morphologies found in the bile juice sample in the Korea. The leopard cat was introduced from the wild habitat of Gyeongsangnam-do, to Cheongju Zoo in Cheongju-si, Chungcheongbuk-do, Korea in August 2014. Physical examinations were basically performed for quarantine and check-up health. The cat was comparatively good in health except anorexia. The cyst-like bile duct dilation and the increased echogenicity of gall bladder wall and hepatic parenchyma were observed by ultrasonography. Ultrasound-guided needle biopsy was conducted for collecting bile juice and the specimens were observed under light microscope. The numerous small trematode eggs were detected in the bile juice sample of the light microscopy. The eggs were 25-33 (28±3) µm by 18-22 (20±1) µm in size and showed typical characteristics of Clonorchis sinensis egg, i.e., a dominantly developed operculum, shoulder rim and dust-like wrinkles in surface. To treat the liver fluke infection, 20 mg/kg of praziquantel was orally administered only once to the case. Follow-up studies including fecal examinations were conducted during 2 years after treatment. But no more eggs were detected from the case. In the present study, we described the first clonorchiasis case of leopard cat, which was confirmed by ultrasonographic findings and egg morphologies from the bile juice sample in Korea.

Tracing Oncogene Rearrangements in the Mutational History of Lung Adenocarcinoma.

Mutational processes giving rise to lung adenocarcinomas (LADCs) in non-smokers remain elusive. We analyzed 138 LADC whole genomes, including 83 cases with minimal contribution of smoking-associated mutational signature. Genomic rearrangements were not correlated with smoking-associated mutations and frequently served as driver events of smoking-signature-low LADCs. Complex genomic rearrangements, including chromothripsis and chromoplexy, generated 74% of known fusion oncogenes, including EML4-ALK, CD74-ROS1, and KIF5B-RET. Unlike other collateral rearrangements, these fusion-oncogene-associated rearrangements were frequently copy-number-balanced, representing a genomic signature of early oncogenesis. Analysis of mutation timing revealed that fusions and point mutations of canonical oncogenes were often acquired in the early decades of life. During a long latency, cancer-related genes were disrupted or amplified by complex rearrangements. The genomic landscape was different between subgroups-EGFR-mutant LADCs had frequent whole-genome duplications with p53 mutations, whereas fusion-oncogene-driven LADCs had frequent SETD2 mutations. Our study highlights LADC oncogenesis driven by endogenous mutational processes.

Protective role of endogenous plasmalogens against hepatic steatosis and steatohepatitis in mice.

Free cholesterol (FC) accumulation in the liver is an important pathogenic mechanism of nonalcoholic steatohepatitis (NASH). Plasmalogens, key structural components of the cell membrane, act as endogenous antioxidants and are primarily synthesized in the liver. However, the role of hepatic plasmalogens in metabolic liver disease is unclear. In this study, we found that hepatic levels of docosahexaenoic acid (DHA)-containing plasmalogens, expression of glyceronephosphate O-acyltransferase (Gnpat; the rate-limiting enzyme in plasmalogen biosynthesis), and expression of Pparα were lower in mice with NASH caused by accumulation of FC in the liver. Cyclodextrin-induced depletion of FC transactivated Δ-6 desaturase by increasing sterol regulatory element-binding protein 2 expression in cultured hepatocytes. DHA, the major product of Δ-6 desaturase activation, activated GNPAT, thereby explaining the association between high hepatic FC and decreased Gnpat expression. Gnpat small interfering RNA treatment significantly decreased peroxisome proliferator-activated receptor α (Pparα) expression in cultured hepatocytes. In addition to GNPAT, DHA activated PPARα and increased expression of Pparα and its target genes, suggesting that DHA in the DHA-containing plasmalogens contributed to activation of PPARα. Accordingly, administration of the plasmalogen precursor, alkyl glycerol (AG), prevented hepatic steatosis and NASH through a PPARα-dependent increase in fatty acid oxidation. Gnpat+/- mice were more susceptible to hepatic lipid accumulation and less responsive to the preventive effect of fluvastatin on NASH development, suggesting that endogenous plasmalogens prevent hepatic steatosis and NASH. CONCLUSION: Increased hepatic FC in animals with NASH decreased plasmalogens, thereby sensitizing animals to hepatocyte injury and NASH. Our findings uncover a novel link between hepatic FC and plasmalogen homeostasis through GNPAT regulation. Further study of AG or other agents that increase hepatic plasmalogen levels may identify novel therapeutic strategies against NASH. (Hepatology 2017;66:416-431).

Development of microsatellite markers for Viscum coloratum (Santalaceae) and their application to wild populations.

PREMISE OF THE STUDY: Microsatellite primers were developed for Viscum coloratum (Santalaceae), a semiparasitic medicinal plant that is known for its anticancer properties. Due to excessive human harvesting and loss of suitable habitat of its populations, it has become a potentially threatened species requiring immediate conservation efforts. METHODS AND RESULTS: Based on transcriptome data for V. coloratum, 124 primer pairs were randomly selected for initial validation, of which 19 yielded polymorphic microsatellite loci, with two to six alleles per locus. The usefulness of these markers was assessed for 60 individuals representing three populations of V. coloratum. Observed and expected heterozygosity values ranged from 0.033 to 0.833 and 0.032 to 0.672, respectively. Cross-species amplification for 19 loci in the related species V. album was conducted. CONCLUSIONS: The 19 newly developed loci are expected to be useful for studying the population genetics and ecological conservation of V. coloratum.

A Case of Chaunocephalosis by Chaunocephalus ferox (Digenea: Echinostomatidae) in an Oriental White Stork, Ciconia boyciana, in Korea.

We intended to describe a case of chaunocephalosis and morphological characteristics of its causative agent, Chaunocephalus ferox, recovered from an oriental white stork, Ciconia boyciana, in the Republic of Korea. An oriental white stork was referred to the Wildlife Center of Chungbuk in Korea in February 2014 for severe depression with cachexia and it died the next day. At necropsy, the stomach was severely expanded and 7 thick-walled nodules were observed in the upper part of the intestine. Although the stomach was filled with full of foreign materials, the intestine was almost empty. The nodules were globular and total 9 flukes were recovered. They were 8,030-8,091 µm in length and 3,318-3,333 µm in maximum width. Because the flukes had bulbous forebody with short narrow subcylindrical hindbody, 27 collar spines, and vitelline follicles not reaching to the posterior end, the specimens were identified as being C. ferox. The cyst formation induced thickening of the intestinal wall with narrowing of the lumen that could have contributed to the gastric impaction to the death of the host. This is the first described case of chaunocephalosis and its causative agent C. ferox found from an oriental white stork in Korea.

First ultrastructural data on the human tapeworm Taenia asiatica eggs by scanning and transmission electron microscopy (SEM, TEM).

Humans are definitive hosts of three species of the Taenia genus, namely Taenia solium, Taenia saginata and Taenia asiatica. The relative novelty of the latter explains the lack of knowledge concerning certain relevant aspects related to this parasite, such as its definite geographical distribution and whether its eggs can infect humans or not. So far, only the eggs of T. solium are known to be infective for humans, producing cysticercosis. Although eggs contain the infective stage, the oncosphere, there is a lack of research on the ultrastructure of eggs of human taeniids. We show, for the first time, the ultrastructure of eggs of T. asiatica by means of SEM and TEM analyses. We detected all the envelopes, namely the egg shell, vitelline layer, outer embryophoric membrane, embryophore, granular layer, basal membrane, oncospheral membrane and oncospheral tegument. Hooks surrounded by myofibrils and glycogen-like particles, the two types of secretory granules of the penetration glands, as well as several nuclei and mitochondria were also revealed in the oncospheres. In addition to the already known structures in eggs from other Taenia species, the presence of two types of small vesicles is described herein, possibly corresponding to exosomes and ectosomes because of their shape and size, which could participate in the host/parasite intercellular communication.

Facile surface modification of anion-exchange membranes for improvement of diffusion dialysis performance.

In this study, a facile membrane modification method by spin-coating of pyrrole (Py) monomers dissolved in a volatile solvent followed by an interfacial polymerization is proposed. The surface of a commercial anion-exchange membrane (i.e., Neosepta-AFX, Astom Corp., Japan) was successfully modified with polypyrrole (Ppy) to improve the acid recovery performance in diffusion dialysis (DD). The result of DD experiments revealed that both the acid and metal ion transports are significantly influenced by the surface modification. The metal crossover through the membranes was largely reduced while mostly maintaining the acid permeability by introducing a thin Ppy layer with excellent repelling property to cations on the membrane surface. As a result, the anion-exchange membrane modified with the optimum content of Py monomer (5 vol.%) exhibited excellent acid dialysis coefficient (KAcid) and selectivity (KAcid/KMetal) which is approximately twice as high as that of the pristine membrane.

Echinostoma macrorchis in Lao PDR: metacercariae in Cipangopaludina snails and adults from experimentally infected animals.

The echinostome metacercariae encysted in Cipangopaludina sp. snails that were purchased from a market in Vientiane Municipality, Lao PDR, were identified as Echinostoma macrorchis (Digenea: Echinostomatidae) through recovery of adult flukes after experimental infection to rats and a cat. The metacercariae were round, 113-128 (121)×113-125 (120) µm, having a thick cyst wall, a head collar armed with collar spines, and excretory granules. The adult flukes recovered from the rats and cat at day 14 and 30 post-infection, respectively, were elongated, ventrally curved, and 3.9-6.3×0.7-1.1 mm in size. The head collar was distinct, bearing 43-45 collar spines with 5 angle spines on each side. Two testes were large (as the name implies), tandem, and slightly constricted at the middle, with irregular margins. Eggs were operculated, ovoid to elliptical, and 88-95×56-60 µm. In scanning electron microscopy, the head collar was prominent, with 43-45 collar spines. Scale-like tegumental spines were densely distributed on the ventral surface between the oral and ventral suckers. Sensory papillae were distributed mainly on the tegument around the 2 suckers. It is confirmed that E. macrorchis is distributed in Lao PDR using Cipangopaludina sp. snails as the second intermediate host.