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Cadmium (Cd) is highly toxic to most organisms, but some rare plant species can hyperaccumulate Cd in aboveground tissues without suffering from toxicity. The mechanism underlying Cd detoxification by hyperaccumulators is interesting but unclear. Here, the heavy metal ATPase 3 (SpHMA3) gene responsible for Cd detoxification was isolated from the Cd/zinc (Zn) hyperaccumulator Sedum plumbizincicola. RNA interference (RNAi)-mediated silencing and overexpression of SpHMA3 were induced to investigate its physiological functions in S. plumbizincicola and a nonhyperaccumulating ecotype of Sedum alfredii. Heterologous expression of SpHMA3 in Saccharomyces cerevisiae showed Cd-specific transport activity. SpHMA3 was highly expressed in the shoots and the protein was localized to the tonoplast. The SpHMA3-RNAi lines were hypersensitive to Cd but not to Zn, with the growth of shoots and young leaves being severely inhibited by Cd. Overexpressing SpHMA3 in the nonhyperaccumulating ecotype of S. alfredii greatly increased its tolerance to and accumulation of Cd, but not Zn. These results indicate that elevated expression of the tonoplast-localized SpHMA3 in the shoots plays an essential role in Cd detoxification, which contributes to the maintenance of the normal growth of young leaves of S. plumbizincicola in Cd-contaminated soils.

This study examined story retelling in individuals with aphasia who scored at or above the 93.8 cutoff on the Aphasia Quotient (AQ) of the Western Aphasia Battery-Revised (WAB-R). The performance of these participants deemed \"not aphasic by WAB\" (NABW) was compared with the performance of non-aphasic participants and individuals with anomic aphasia. Most participants were from a test development dataset for the Brief Assessment of Transactional Success in communication in aphasia (BATS), including four groups of 16 individuals: (1) a group who tested NABW; (2) a group with anomic aphasia matched on gender, age, education, and time post-onset; (3) a group with mild anomic aphasia who scored just below the NABW cutoff; and (4) a group of non-aphasic individuals matched on gender, age, and education with the NABW group. Groups were compared on main concepts of the BATS story retelling. Groups with aphasia were also compared on the main concepts of stories retold by non-aphasic conversation partners following co-construction of stories and on self-reported scores of the impact of aphasia on everyday communication. The results showed significant differences in the retelling of the story's main concepts between the non-aphasic control and conversation partner groups, with non-monotonic decreases in performance in comparisons of groups with and without aphasia: from non-aphasic to NABW to mildly anomic to anomic. Individuals deemed NABW (and their conversation partners) did not perform significantly better than individuals with mild anomic aphasia (and their conversation partners) on story retell main concepts. There were significant differences in the production of AphasiaBank discourse main concepts between the group with anomia and both the non-aphasic and NABW groups, but not between the non-aphasic and NABW or those with mild aphasia. Individuals with aphasia who scored \"non-aphasic\" on the WAB demonstrated impairments in story retelling that align with their self-report of diminished everyday communicative functioning. This finding adds to growing support for the addition of a new measure of functional communication to the core outcome set of measures utilized in aphasia research. We propose the BATS, a measure that is sensitive across the spectrum of aphasia severity, including cases of mild and subclinical aphasia.

A pair-instability supernova (PISN) prevents black hole (BH) formation from stellar collapse within the approximate mass range M ∈ [65, 130] M ⊙. However, such BHs may form hierarchically through merging ancestral BHs, whose properties determine those of the “child” one: mass, spin, and recoil velocity. Crucially, the child will leave its host environment if its birth recoil exceeds the corresponding escape velocity, preventing further mergers. We exploit relations between the final recoil and spin of quasi-circular BH mergers to obtain posterior probability distributions for the hypothetical ancestral masses, spins, and birth recoils of the component BHs of GW190521. To this, we present a Bayesian framework applicable to existing estimates for the components of BH merger observations. We consider both the quasi-circular (generically spinning) analysis performed by the LIGO–Virgo–KAGRA collaboration and the eccentric (aligned-spin) one performed by Romero-Shaw et al. We evaluate the probability p 2g that the GW190521 components inferred by these analyses formed from the merger of stellar-origin BHs and were retained by their environment. For the primary component, which populates the PISN gap, such scenario is strongly suppressed if GW190521 happened in a globular cluster with p 2g ∼ 10−3 unless it was quasi circular and its ancestors had aligned spins, uncharacteristic of hierarchical formation channels, or small spins, which yields p 2g ≃ 10−2. If GW190521 was eccentric, we obtain p 2g ≃ 0.1 for any host other than an active galactic nucleus, and zero for a globular cluster. If GW190521 was quasi circular, a nuclear star cluster origin is possible with p 2g ∈ (∼0.4, ∼0.8).

Inadequate public transportation was recognized as a barrier to social participation, especially for older adults in rural communities and with mobility issues. Older adults will not benefit from opportunities to engage with their community and maintain social networks if they are unable to access them. The purpose of this scoping review was to make recommendations for further research and to summarize areas for improvement identified in the literature that will aid in the development of public transportation initiatives that can better address social isolation for older adults (≥ 55 years of age). Nineteen articles met the inclusion criteria, identifying themes of access to rural public transportation, issues with public transportation, and mobility. In practice, older adults need to prepare for driving cessation and mobility transitions; sound policy requires input to tailor transportation initiatives to an aging population, and future research should explore older adults’ transportation needs and potential solutions in urban and rural communities.

According to the PRISMA criteria, a systematic review has been conducted to investigate the clinical relevance between patients with severe congenital neutropenia (SCN) and cyclic congenital neutropenia (CyN) induced by ELANE mutations. We have searched PubMed, EMBASE, Web of Science, Scopus, Cochrane, CNKI, Wanfang Medicine, and VIP for ELANE mutation related literature published from 1997 to 2022. Using Microsoft Excel collect and organize data, SPSS 25, GraphPad Prism 8.0.1, and Omap analyze and plot statistical. Compare the gender, age, geography, mutation sites, infection characteristics, treatment, and other factors of SCN and CyN patients induced by ELANE mutations, with a focus on exploring the relationship between genotype and clinical characteristics, genotype and prognosis. This study has included a total of 467 patients with SCN and 90 patients with CyN. The onset age of SCN and CyN are both less than 1 year old, and the onset and diagnosis age of SCN are both younger than CyN. The mutation of ELANE gene is mainly missense mutation, and hot spot mutations include S126L, P139L, G214R, c.597+1G>A. The high-frequency mutations with severe outcomes are A57V, L121H, L121P, c.597+1G>A, c.597+1G>T, S126L, C151Y, C151S, G214R, C223X. Respiratory tract, skin and mucosa are the most common infection sites, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli are the most common. Patients with refractory G-CSF are more likely to develop severe outcomes. The commonly used pre-treatment schemes for transplantation are Bu-Cy-ATG and Flu-Bu-ATG. The prognosis of transplantation is mostly good, but the risk of GVHD is high. https://www.crd.york.ac.uk/PROSPERO/. PROSPERO, identifier CRD42023434656.

In the present study, we have tested the hypothesis that fusion between an altered cell and a mesenchymal stem cell produces a hybrid cell with enhanced characteristics associated with metastatic cancer cells, and we have developed a flexible model for investigating the mechanisms of metastasis. Human HepG2 cells with low metastatic potential were induced to fuse with rat bone marrow mesenchymal stem cells, and the progeny were compared with the parental cells for possession of enhanced in vitro and in vivo characteristics of malignant cells. Compared to the parental cells, the fused cells exhibited enhanced expression of E-cadherin, vimentin, Twist, Snail, matrix metalloproteinase 2 and 9 activities, aneuploidy and enhanced in vitro invasion and migration. In an in vivo xenograft assay, the fused cells generated increased numbers of metastatic liver and lung lesions. This model system is a flexible tool for investigation of the mechanisms of stem cell fusion in carcinogenesis and metastasis and for the discovery of new therapeutic targets to inhibit metastasis.

Deep metabolomic, proteomic and immunologic phenotyping of patients suffering from an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have matched a wide diversity of clinical symptoms with potential biomarkers for coronavirus disease 2019 (COVID-19). Several studies have described the role of small as well as complex molecules such as metabolites, cytokines, chemokines and lipoproteins during infection and in recovered patients. In fact, after an acute SARS-CoV-2 viral infection almost 10-20% of patients experience persistent symptoms post 12 weeks of recovery defined as long-term COVID-19 syndrome (LTCS) or long post-acute COVID-19 syndrome (PACS). Emerging evidence revealed that a dysregulated immune system and persisting inflammation could be one of the key drivers of LTCS. However, how these biomolecules altogether govern pathophysiology is largely underexplored. Thus, a clear understanding of how these parameters within an integrated fashion could predict the disease course would help to stratify LTCS patients from acute COVID-19 or recovered patients. This could even allow to elucidation of a potential mechanistic role of these biomolecules during the disease course. This study comprised subjects with acute COVID-19 (n=7; longitudinal), LTCS (n=33), Recov (n=12), and no history of positive testing (n=73). H-NMR-based metabolomics with IVDr standard operating procedures verified and phenotyped all blood samples by quantifying 38 metabolites and 112 lipoprotein properties. Univariate and multivariate statistics identified NMR-based and cytokine changes. Here, we report on an integrated analysis of serum/plasma by NMR spectroscopy and flow cytometry-based cytokines/chemokines quantification in LTCS patients. We identified that in LTCS patients lactate and pyruvate were significantly different from either healthy controls (HC) or acute COVID-19 patients. Subsequently, correlation analysis in LTCS group only among cytokines and amino acids revealed that histidine and glutamine were uniquely attributed mainly with pro-inflammatory cytokines. Of note, triglycerides and several lipoproteins (apolipoproteins Apo-A1 and A2) in LTCS patients demonstrate COVID-19-like alterations compared with HC. Interestingly, LTCS and acute COVID-19 samples were distinguished mostly by their phenylalanine, 3-hydroxybutyrate (3-HB) and glucose concentrations, illustrating an imbalanced energy metabolism. Most of the cytokines and chemokines were present at low levels in LTCS patients compared with HC except for IL-18 chemokine, which tended to be higher in LTCS patients. The identification of these persisting plasma metabolites, lipoprotein and inflammation alterations will help to better stratify LTCS patients from other diseases and could help to predict ongoing severity of LTCS patients.

Green tea extracts and tea catechins have been shown to prevent or alleviate diabetes. The present study tests the hypothesis that green tea leaves in powder form (GTP), which also contain fiber and other water non-extractable materials, are more effective than the corresponding green tea extracts (GTE) in impeding the development of diabetes in db/db mice. Female db/db mice were treated with a diet containing 1% of GTE, 2% of GTE, 2% of GTP (with the same catechin content as 1% GTE) or 1% GTP. The 1% GTE group had lower food intake, water consumption, body weight and fasting blood glucose levels than the control group, while 2% GTP did not have any significant effect. Dietary 1% GTE also preserved β-cell insulin secretion. However, 1% GTP increased food intake, water consumption and blood glucose levels. Microbiome analysis with 16S rRNA gene V4 sequencing showed that the gut microbiota was modified by GTE and GTP, and a few bacterial guilds were associated with blood glucose levels. In the Random Forest regression model, the leading predictor of metabolic outcome was food consumption, followed by changes in some bacterial guilds. The results illustrate the importance of food consumption and gut microbiota in affecting the progression of diabetes.

The enrichment of viable cells is an essential step to obtain effective products for cell therapy. While procedures exist to characterize the viability of cells, most methods to exclude nonviable cells require the use of density gradient centrifugation or antibody-based cell sorting with molecular labels of cell viability. We report a label-free microfluidic technique to separate live and dead cells that exploits differences in cellular stiffness. The device uses a channel with repeated ridges that are diagonal with respect to the direction of cell flow. Stiff nonviable cells directed through the channel are compressed and translated orthogonally to the channel length, while soft live cells follow hydrodynamic flow. As a proof of concept, Jurkat cells are enriched to high purity of viable cells by a factor of 185-fold. Cell stiffness was validated as a sorting parameter as nonviable cells were substantially stiffer than live cells. To highlight the utility for hematopoietic stem cell transplantation, frozen samples of cord blood were thawed and the purity of viable nucleated cells was increased from 65% to over 94% with a recovery of 73% of the viable cells. Thus, the microfluidic stiffness sorting can simply and efficiently obtain highly pure populations of viable cells.

Background and Objectives: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by multisystem involvement, including renal cysts, hepatic cysts, intracranial aneurysms, and aortic root dilatation and dissection. Though exceedingly rare, cervical artery dissections (CeAD) have been reported in association with ADPKD. The aim of this retrospective observational study is to investigate clinical features in patients with ADPKD that increase the probability of an associated CeAD diagnosis. Materials and Methods: The National Inpatient Sample from 2016 to 2020 was utilized to compare clinical features for patients with an ICD-10 code diagnosis of ADPKD, CeAD, and both ADPKD and CeAD. The Cochran–Armitage test and Chi-square test were utilized to assess clinical features or trends in ADPKD patients associated with a concurrent CeAD diagnosis. Results: Between 2016 and 2020, there were 224,065 people with ADPKD, 86,135 with CeAD and 155 with both (0.05%). The total cohort had a mean age of 56.74 years, with 47.26% female participants (p = 0.70), and was predominantly white (66.15%, p < 0.001). In patients with ADPKD, comorbid acute ischemic stroke (p < 0.001), transient ischemic attack (p < 0.001), aortic dissection (p < 0.001), coronary artery dissection (p < 0.001), subarachnoid hemorrhage (p < 0.001), coagulation defects (p = 0.002), and hypertension (p < 0.001) are risk factors associated with an increased probability of concomitant CeAD. Conclusions: CeAD in ADPKD patients is rare. In ADPKD patients, acute ischemic stroke, transient ischemic attack, aortic dissection, coronary artery dissection, subarachnoid hemorrhage, coagulation defects, and hypertension are risk factors of concomitant CeAD. Recognizing these factors can aid in the decision to screen for concomitant CeAD in patients with ADPKD.