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Single-cell investigation regarding COVID-19, sepsis, as well as Aids an infection shows hyperinflammatory and also immunosuppressive signatures in monocytes.
PURPOSE To evaluate the clinical characteristics and evolution of lamellar macular hole (LMH) in high myopia and the parameters associated with structural worsening, defined as the development of foveal detachment or full-thickness macular hole. METHODS Patients with high myopia and LMH were retrospectively recruited. The clinical characteristics and various parameters of optical coherence tomography were identified at baseline and during follow-up visits. Cox regression analysis was used to evaluate the hazard ratios for foveal detachment and full-thickness macular hole. RESULTS Among 112 eyes (98 patients), 64.3% were female; the mean axial length of all eyes was 29.6 ± 1.9 mm. The 'LMH without retinoschisis' group accounted for 39.3% of the eyes. Forty-two percent developed structural worsening within a median follow-up of 67 months. Multivariable regression on all cases showed elevated tissue inside the LMH (P = 0.003) protected against structural worsening while V-shaped LMH (P = 0.006) predicted it. In the "LMH with retinoschisis group", ellipsoid zone disruption (P = 0.035), and V-shaped LMH (P = 0.014) predicted structural worsening, while elevated tissue inside the LMH (P = 0.028) protected against it. In the "LMH without retinoschisis group", no associated factor was identified. CONCLUSIONS LMHs in high myopia are unstable, especially those with V-shaped LMH. Elevated tissue inside LMHs have a protective effect against further structural worsening.Toxoplasma gondii is an obligate intracellular parasite which is capable of establishing life-long chronic infection in any mammalian host. During the intracellular life cycle, the parasite secretes an array of proteins into the parasitophorous vacuole (PV) where it resides. Specialized organelles called the dense granules secrete GRA proteins that are known to participate in nutrient acquisition, immune evasion, and host cell-cycle manipulation. Although many GRAs have been discovered which are expressed during the acute infection mediated by tachyzoites, little is known about those that participate in the chronic infection mediated by the bradyzoite form of the parasite. In this study, we sought to uncover novel bradyzoite-upregulated GRA proteins using proximity biotinylation, which we previously used to examine the secreted proteome of the tachyzoites. Using a fusion of the bradyzoite upregulated protein MAG1 to BirA* as bait and a strain with improved switch efficiency, we identified a number of novel GRA proteins which are expressed in bradyzoites. After using the CRISPR/Cas9 system to characterize these proteins by gene knockout, we focused on one of these GRAs (GRA55) and found it was important for the establishment or maintenance of cysts in the mouse brain. These findings highlight new components of the GRA proteome of the tissue-cyst life stage of T. gondii and identify potential targets that are important for maintenance of parasite persistence in vivo.Heart failure with a preserved ejection fraction (HFpEF) is associated with multiple comorbidities, such as old age, hypertension, type 2 diabetes and obesity and is more prevalent in females. AZD5363 Although the male obese ZSF1 rat has been proposed as a suitable model to study the development of diastolic dysfunction and early HFpEF, studies in female animals have not been performed yet. Therefore, we aimed to characterize the cardiac phenotype in female obese ZSF1 rats and their lean counterparts. Additionally, we aimed to investigate whether differences exist in disease progression in obese male and female ZSF1 rats. Therefore, male and female ZSF1 rats, lean as well as obese (N = 6-9/subgroup), were used. Every two weeks, from 12 to 26 weeks of age, systolic blood pressure and echocardiographic measurements were performed, and venous blood was sampled. Female obese ZSF1 rats, as compared to female lean ZSF1 rats, developed diastolic dysfunction with cardiac hypertrophy and fibrosis in the presence of severe dyslipidemia, increased plasma growth differentiation factor 15 and mild hypertension, and preservation of systolic function. Although obese female ZSF1 rats did not develop hyperglycemia, their diastolic dysfunction was as severe as in the obese males. Taken together, the results from the present study suggest that the female obese ZSF1 rat is a relevant animal model for HFpEF with multiple comorbidities, suitable for investigating novel therapeutic interventions.The eastern Tibetan Plateau (TP) is a climatically sensitive area affected by the Indian Summer Monsoon (ISM). A new pollen record from a lacustrine sediment in Mao County shows that the study area was covered mainly by shrubs and herbs during the last deglaciation, indicating open and sparse forest grasslands. Hydrophilous herbs were mainly dominated by Cyperaceae, Poaceae, Myriophyllum, Polygonum and Typha, and they gradually increased from 18.7 to 16.8 ka, suggesting a transition to a more humid climate. This corresponds to climate cooling over the same period. From 16.8 to 14.6 ka, hydrophilous herbs continued to increase, coincident with a general ameliorating trend indicated by δ18O records from East Asia. Between 14.6 and 14.0 ka, the mean content of hydrophilous herbs reached peak in the sequence, corresponding to relatively high δ18O values during this period. From ~14.0 to 12.9 ka, the abundance of hydrophilous herbs decreased significantly. Over the same period, the Greenland ice core shows a decrease in δ18O and low-latitude cave stalagmites in China record an increase in δ18O. This implies that longitudinal temperature gradients increased and drove the southward retreat of the ISM, which in turn drove a continuous decrease in the abundance of hydrophilous herbs in the study area. From 12.9 to 11.6 ka, the mean content of hydrophilous herbs decreased to the lowest (8.3%) in the whole sequence, indicating a cold and dry climate in the study area. A positive shift in δ18O records during 11.6-10.6 ka was matched by a significant increase in the abundance of hydrophilous herbs in the study area, indicating a warm and humid climate trending. Hence, the ISM has had a significant impact on the climate of the eastern TP since the onset of deglaciation around ~16.8 ka.
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