Dynamics and thermochemistry of the negatively charged clusters in a 2-hydroxyethylhydrazinium nitrate ionic liquid system.

The formation and fragmentation of negatively charged 2-hydroxyethylhydrazinium nitrate ([HOCH2CH2NH2NH2]+NO3-, HEHN) ionic liquid clusters were examined using a guided-ion beam tandem mass spectrometer furnished with collision-induced dissociation of selected ions with Xe atoms. Measurements included the compositions of cluster ions formed in the ionization source, and the dissociation products, cross sections, and 0 K threshold energies for individually selected cluster ions. To identify the structures of the main cluster ion series [(HEHN)n(HNO3)0-1NO3]- formed, molecular dynamics simulations were employed to create initial geometry guesses, followed by optimization at the ωB97XD/6-31+G(d,p) level of theory, from which global minimum structures were identified for reaction thermodynamics analyses. A comparison was made between the cluster formation and fragmentation in the negatively charged 2-hydroxyethylhydrazinium nitrate with those in the positive mode (reported by W. Zhou et al., Phys. Chem. Chem. Phys., 2023, 25, 17370). In both modes, the cluster ions were predominantly composed of m/z below 350; loss of a neutral 2-hydroxyethylhydrazinium nitrate ion pair represents the most important cluster fragmentation pathway, followed by intra-ion pair proton transfer-mediated 2-hydroxyethylhydrazine and HNO3 elimination; and all clusters started to dissociate at threshold energies less than 1.5 eV. The overwhelming similarities in the formation and fragmentation chemistry of positively vs. negatively charged 2-hydroxyethylhydrazinium nitrate clusters may be attributed to their inherent ionic nature and high electric conductivities.

Characteristics and Clinical Implications of Immunoglobulins Derived from Non B Cells in the Skin.

Skin is the most prominent tissue and organ, as well as the first line of defence, of the body. Because it is situated on the body's surface, it is constantly exposed to microbial, chemical, and physical factors such as mechanical stimulation. Therefore, skin has evolved substantial immune defences, regenerative ability, and anti-injury capacity. Epidermal cells produce antibacterial peptides that play a role in immune defence under physiological conditions. Additionally, IgG or IgA in the skin also participates in local anti-infective immunity. However, based on the classical theory of immunology, Ig can only be produced by B cells which should be derived from local B cells. This year, thanks to the discovery of Ig derived from non B cells (non B-Ig), Ig has also been found to be expressed in epidermal cells and contributes to immune defence. Epidermal cell-derived IgG and IgA have been demonstrated to have potential antibody activity by binding to pathogens. However, these epidermal cell-derived Igs show different microbial binding characteristics. For instance, IgG binds to Staphylococcus aureus and IgA binds to Staphylococcus epidermidis. Epidermal cells producing IgG and IgA may serve as an effective defense mechanism alongside B cells, providing a novel insight into skin immunity.

Efficient Aperture Fill Time Correction for Wideband Sparse Array Using Improved Variable Fractional Delay Filters.

To solve the problem of aperture fill time (AFT) for wideband sparse arrays, variable fractional delay (VFD) FIR filters are applied to eliminate linear coupling between spatial and time domains. However, the large dimensions of the filter coefficient matrix result in high system complexity. To alleviate the computational burden of solving VFD filter coefficients, a novel multi-regultion minimax (MRMM) model utilizing the sparse representation technique has been presented. The error function is constrained by the introduction of L2-norm and L1-norm regularizations within the minimax criterion. The L2-norm effectively resolves the problems of overfitting and non-unique solutions that arise in the sparse optimization of traditional minimax (MM) models. Meanwhile, the use of multiple L1-norms enables the optimal design of the smallest sub-filter number and order of the VFD filter. To solve the established nonconvex model, an improved sequential-alternating direction method of multipliers (S-ADMM) algorithm for filter coefficients is proposed, which utilizes sequential alternation to iteratively update multiple soft-thresholding problems. The experimental results show that the optimized VFD filter reduces system complexity significantly and corrects AFT effectively in a wideband sparse array.

Two novel SUCLA2 variants cause mitochondrial DNA depletion syndrome, type 5 in two siblings.

Mitochondrial DNA depletion syndrome (MDS), characterized by succinate-CoA ligase deficiency and loss of mitochondrial DNA (mtDNA), is caused by specific variants in nuclear genes responsible for mtDNA maintenance. SUCLA2-related mitochondrial DNA depletion syndrome, type 5 (MTDPS-5), presents as a rare, severe early progressive encephalomyopathy. This report investigates a new family exhibiting clinical manifestations of MTDPS-5 and elucidates the genetic basis of this disorder. In two affected siblings, a novel maternally inherited nonsense variant [c.1234C>T (p.Arg412*)] in the SUCLA2 gene and a unique paternally inherited indel variant (g.48569263-48571020del1758insATGA) were identified. Additionally, the siblings exhibited blood mtDNA content lower than 33% compared to age-matched controls. These findings underscore the importance of assessing SUCLA2 variants in patients with severe early progressive encephalomyopathy, even in the absence of methylmalonic aciduria or mtDNA loss, thereby broaden the mutational spectrum of this gene.

The density of the inner cell mass is a new indicator of the quality of a human blastocyst: a valid supplement to the Gardner scoring system.

STUDY QUESTION: Can the density of the inner cell mass (ICM) be a new indicator of the quality of the human blastocyst? SUMMARY ANSWER: The densification index (DI) developed in this study can quantify ICM density and provide positive guidance for ploidy, pregnancy, and live birth. WHAT IS KNOWN ALREADY: In evaluating the quality of ICM, reproductive care clinics still use size indicators without further evaluation. The main disadvantage of this current method is that the evaluation of blastocyst ICM is relatively rough and cannot meet the needs of clinical embryologists, especially when multiple blastocysts have the same ICM score, which makes them difficult to evaluate further. STUDY DESIGN, SIZE, DURATION: This observational study included data from 2272 blastocysts in 1991 frozen-thawed embryo transfer (FET) cycles between January 2018 to November 2021 and 1105 blastocysts in 430 preimplantation genetic testing cycles between January 2019 and February 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: FET, ICSI, blastocyst culture, trophectoderm biopsy, time-lapse (TL) monitoring, and next-generation sequencing were performed. After preliminary sample size selection, the 11 focal plane images captured by the TL system were normalized and the spatial frequency was used to construct the DI of the ICM. MAIN RESULTS AND THE ROLE OF CHANCE: This study successfully constructed a quantitative indicator DI that can reflect the degree of ICM density in terms of fusion and texture features. The higher the DI value, the better the density of the blastocyst ICM, and the higher the chances that the blastocyst was euploid (P < 0.001) and that pregnancy (P < 0.001) and live birth (P = 0.005) were reached. In blastocysts with ICM graded B and blastocysts graded 4BB, DI was also positively associated with ploidy, pregnancy, and live birth (P < 0.05). ROC analysis showed that combining the Gardner scoring system with DI can more effectively predict pregnancy and live births, when compared to using the Gardner scoring system alone. LIMITATIONS, REASONS FOR CAUTION: Accurate calculation of the DI value places high demands on image quality, requiring manual selection of the clearest focal plane and exposure control. Images with the ICM not completely within the field of view cannot be used. The association between the density of ICM and chromosomal mosaicism was not evaluated. The associations between the density of ICM and different assisted reproductive technologies and different culture conditions in embryo laboratories were also not evaluated. Prospective studies are needed to further investigate the impact of ICM density on clinical outcomes. WIDER IMPLICATIONS OF THE FINDINGS: ICM density assessment is a new direction in blastocyst assessment. This study explores new ways of assessing blastocyst ICM density and develops quantitative indicators and a corresponding qualitative evaluation scheme for ICM density. The DI of the blastocyst ICM developed in this study is easy to calculate and requires only TL equipment and image processing, providing positive guidance for clinical outcomes. The qualitative evaluation scheme of ICM density can assist embryologists without TL equipment to manually evaluate ICM density. ICM density is a simple indicator that can be used in practice and is a good complement to the blastocyst scoring systems currently used in most centers. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Key Research & Development Program of China (2021YFC2700603). The authors report no financial or commercial conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Psychometric validation of the Chinese versions of EQ-5D-Y-3L and the experimental EQ-TIPS in children and adolescents with COVID-19.

OBJECTIVES: Respiratory infectious diseases like COVID-19 profoundly impacts the health of children and adolescents, but validated instruments to measure their impacts on health-related quality of life (HRQoL) are lacking. The EQ-5D-Y-3L, widely used for youth HRQoL, now features a Chinese value set. The experimental EQ-TIPS addresses HRQoL assessment for toddlers and infants. This study tested the psychometric properties of both instruments in paediatric COVID-19 patients, and compared the performance of self-complete and proxy EQ-5D-Y-3L. METHODS: This longitudinal study recruited 861 COVID-19 patients aged 0-18 years and their parental caregivers, with 311 dyads completing the follow-up. Digital administration included the EQ-TIPS, the EQ-5D-Y-3L, and Overall Health Assessment (OHA). Controls comprised 231 healthy children. Analysis encompassed known-group validity, child-parent agreement, and responsiveness to change in disease severity and OHA. RESULTS: COVID-19 children exhibited lower HRQoL than non-infected peers. The EQ-TIPS and the EQ-5D-Y-3L distinguished groups by disease presence, severity and symptoms, showing moderate to good known-group validity (ESs: 0.45-1.39 for EQ-TIPS, 0.44-1.91 for self-complete EQ-5D-Y-3L, and 0.32-1.67 for proxy EQ-5D-Y-3L). Child-parent agreement was moderate to good for EQ-5D-Y-3L (ICC: 0.653-0.823; Gwet's AC1: 0.470-0.738), and responsiveness was good for both EQ-TIPS Level Sum Score (LSS) (ESs: 1.21-1.39) and EQ-5D-Y-3L index scores (ESs: 1.00-1.16). CONCLUSIONS: This study demonstrates the reliability, validity, and responsiveness of the experimental EQ-TIPS and the EQ-5D-Y-3L in paediatric COVID-19 patients. It is the first evidence of the EQ-TIPS' responsiveness, supporting its use in assessing the impact of COVID-19 on paediatric HRQoL.

Landscape of clinical drug development of ADCs used for the pharmacotherapy of cancers: an overview of clinical trial registry data from 2002 to 2022.

BACKGROUND: To provide reference for clinical development of ADCs in the industry, we analyzed the landscape and characteristics of clinical trials about antibody-drug conjugates (ADCs). METHOD: Clinical trials to study ADCs used for the pharmacotherapy of cancers initiated by the sponsor were searched in the Cite line Pharma Intelligence (Trialtrove database), and the landscape and characteristics of these clinical trials were analyzed from multiple perspectives, such as the number, phases, status, indications, and targets of the clinical trials. RESULT: As of December 31, 2022, a total of 431 clinical trials have been initiated to study ADCs used for the pharmacotherapy of cancers, and the number of the last 10 years was 5.5 times as large as the first 11 years. These clinical trials involved 47 indications, including breast cancer, lymphoma (lymphoma, non-Hodgkin's and lymphoma, Hodgkin's), unspecified solid tumor, bladder cancer and lung cancer (lung, non-small cell cancer and lung, small cell cancer). As for each of these five indications, 50 + clinical trials have been carried out, accounting for as high as 48.50% (454/936). ADCs involve 38 targets, which are relatively concentrated. Among them, ERBB2 (HER2) and TNFRSF8 (CD30) involve in 100 + registered clinical trials, and TNFRSF17 (BCMA), NECTIN4 and CD19 in 10 + trials. The clinical trials for these five targets account for 79.02% (354/448) of the total number. Up to 93.97% (405/431) of these clinical trials explored the correlation between biomarkers and efficacy. Up to 45.91% (292/636) of Lots (lines of treatment) applied in the clinical trials were the second line. Until December 31, 2022, 54.52% (235/431) of the clinical trials have been completed or terminated. CONCLUSION: ADCs are a hotspot of research and development in oncology clinical trials, but the indications, targets, phases, and Lot that have been registered are seemingly relatively concentrated at present. This study provides a comprehensive analysis which can assist researchers/developer quickly grasp relevant knowledge to assess a product and also providing new clues and ideas for future research.

Limited transmission of carbapenem-resistant Klebsiella pneumoniae between animals and humans: a study in Qingdao.

ABSTRACTDespite no carbapenem use in food animals, carbapenem-resistant Klebsiella pneumoniae (CRKP) perseveres within food animals, rising significant concerns regarding public health risks originating from these non-clinical reservoirs. To investigate the potential link between CRKP in food animals and its infections in humans, we conducted a cross-sectional study encompassing human clinical, meat products, and farm animals, in Qingdao city, Shandong province, China. We observed a relatively higher presence of CRKP among hospital inpatients (7.3%) compared to that in the meat products (2.7%) and farm animals (pig, 4.6%; chicken, 0.63%). Multilocus sequence typing and core-genome phylogenetic analyses confirm there is no evidence of farm animals and meat products in the clinical acquisition of K. pneumoniae isolates and carbapenem-resistant genes. However, potential transmission of K. pneumoniae of ST659 and IncX3 plasmid harbouring blaNDM-5 gene from pigs to pork and farm workers was observed. Our findings suggest a limited role of farm animals and meat products in the human clinical acquisition of K. pneumoniae, and the transmission of K. pneumoniae is more common within settings, than between them.

A Study on Hydrogen Bonding and Energy Variation during Bubble Nucleation in Water on a Grooved Substrate by Molecular Dynamics Simulation.

In this paper, the bubble nucleation process of water was studied by molecular dynamics (MD) simulation. The nucleation mechanism of water on a grooved substrate was revealed from the perspective of hydrogen bond and energy change, and the effect of system pressure on nucleation was studied. The results show that the process of bubble nucleation of water molecules is essentially a process in which the thermal motion of water molecules gradually intensifies and the hydrogen bond continues to break with the increase in kinetic energy. As the hydrogen bond breaks, the kinetic energy of the water molecules is continuously converted to intermolecular potential energy. By analyzing the composition of the hydrogen bond energy, it is found that the electrostatic energy is much greater than the van der Waals energy, so the water nucleation process mainly overcomes the electrostatic force between molecules. With the gradual increase of pressure, although the kinetic energy distribution of molecules does not change significantly, it will cause the potential energy of water molecules to decrease significantly and then lead to the increase of the energy barrier that needs to be crossed for nucleation. Meanwhile, the rise of the nucleation barrier may result in the absence of obvious initial vapor nuclei inside the liquid so that the number of hydrogen bonds cannot be rapidly reduced, which is not conducive to boiling nucleation. The results of this study provide important implications for further understanding of the nucleate boiling process of water.

Impacts of Evidence-based Nursing on Quality of Life and Anxiety in Patients with Liver Injury.

Background: Plasma exchange is the most commonly applied method for treating severe hepatitis. As a kind of invasive treatment, plasma exchange may have various complications during treatment. Therefore, effective nursing should be implemented during plasma exchange treatment to prevent the incidence of complications. Objective: To compare the effects of traditional nursing methods versus evidence-based nursing practices on the quality of life and anxiety of patients with liver injury. Design: This was a retrospective study. Patient data were obtained from patient records. Setting: This study was carried out in the Department of Gastroenterology, Second Hospital of Hebei Medical University. Participants: One hundred and twenty severe hepatitis patients with 89 cases of early hepatic failure and 31 cases of middle hepatic failure admitted to our department from January 2020 to December 2022 were chosen, followed by randomly separating into a control group and an observation group. Interventions: The control group adopted nursing, while the observation group received evidence-based nursing including psychological nursing, nursing during treatment and post-treatment nursing. Primary Outcome Measures: (1) liver function (2) emotional state assessed by Self-rating Anxiety Scale (SAS) along with Self-rating Depression Scale (SDS) (3) coagulation function, (4) quality of life assessed by Short-Form 36 (SF-36) scale (5) nursing satisfaction, and (6) incidence of complications. Results: In contrast to the control group, the occurrence of complications in the observation group was significantly lower (P < .05). At 1-month review, the quality of life score in the observation group was higher in contrast to the control group (P < .05). In contrast to the control group, the nursing satisfaction of patients in the observation group was better (P < .05), alanine aminotransferase and total bilirubin levels in the observation group were lower, while albumin levels were higher (P < .05), the anxiety and depression scores of the observation group were lessened (P < .05), and the required time of coagulation function indexes in the observation group was shorter (P < .05). Conclusion: The application of evidence-based nursing to artificial liver therapy in patients with liver failure can effectively promote the liver function and coagulation index of patients, help to relieve negative emotions, and promote the quality of life of patients. This study may provide clinical reference for the nursing of artificial liver therapy in patients with liver failure.

Novel targets and therapies of metformin in dementia: old drug, new insights.

Dementia is a devastating disorder characterized by progressive and persistent cognitive decline, imposing a heavy public health burden on the individual and society. Despite numerous efforts by researchers in the field of dementia, pharmacological treatments are limited to relieving symptoms and fail to prevent disease progression. Therefore, studies exploring novel therapeutics or repurposing classical drugs indicated for other diseases are urgently needed. Metformin, a first-line antihyperglycemic drug used to treat type 2 diabetes, has been shown to be beneficial in neurodegenerative diseases including dementia. This review discusses and evaluates the neuroprotective role of metformin in dementia, from the perspective of basic and clinical studies. Mechanistically, metformin has been shown to improve insulin resistance, reduce neuronal apoptosis, and decrease oxidative stress and neuroinflammation in the brain. Collectively, the current data presented here support the future potential of metformin as a potential therapeutic strategy for dementia. This study also inspires a new field for future translational studies and clinical research to discover novel therapeutic targets for dementia.

Paroxetine alleviates dendritic cell and T lymphocyte activation via GRK2-mediated PI3K-AKT signaling in rheumatoid arthritis.

BACKGROUND: G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In the present work, we explored how paroxetine, a GRK2 inhibitor, modulates the differentiation and activation of immune cells in rheumatoid arthritis (RA). METHODS: The blood samples of healthy individuals and RA patients were collected between July 2021 and March 2022 from the First Affiliated Hospital of Anhui Medical University. C57BL/6 mice were used to induce the collagen-induced arthritis (CIA) model. Flow cytometry analysis was used to characterize the differentiation and function of dendritic cells (DCs)/T cells. Co-immunoprecipitation was used to explore the specific molecular mechanism. RESULTS: In patients with RA, high expression of GRK2 in peripheral blood lymphocytes, accompanied by the increases of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR). In animal model, a decrease in regulatory T cells (Tregs), an increase in the cluster of differentiation 8 positive (CD8+) T cells, and maturation of DCs were observed. Paroxetine, when used in vitro and in CIA mice, restrained the maturation of DCs and the differentiation of CD8+ T cells, and induced the proportion of Tregs. Paroxetine inhibited the secretion of pro-inflammatory cytokines, the expression of C-C motif chemokine receptor 7 in DCs and T cells. Simultaneously, paroxetine upregulated the expression of programmed death ligand 1, and anti-inflammatory cytokines. Additionally, paroxetine inhibited the PI3K-AKT-mTOR metabolic pathway in both DCs and T cells. This was associated with a reduction in mitochondrial membrane potential and changes in the utilization of glucose and lipids, particularly in DCs. Paroxetine reversed PI3K-AKT pathway activation induced by 740 Y-P (a PI3K agonist) through inhibiting the interaction between GRK2 and PI3K in DCs and T cells. CONCLUSION: Paroxetine exerts an immunosuppressive effect by targeting GRK2, which subsequently inhibits the metabolism-related PI3K-AKT-mTOR pathway of DCs and T cell in RA.

The In Vitro Promoting Angiogenesis Roles of Exosomes Derived from the Protoscoleces of Echinococcus multilocularis.

Alveolar echinococcosis (AE) is a persistent parasite condition that causes the formation of tumor-like growths. It is a challenge to treat the disease. These growths need neovascularization to get their oxygen and nutrients, and the disease is prolonged and severe. Considerable research has been conducted on exosomes and their interactions with Echinococcus multilocularis in the context of immunological evasion by the host. However, the extent of their involvement in angiogenesis needs to be conducted. The primary objective of this investigation was to preliminarily explore the effect of exosomes produced from E. multilocularis protoscoleces (PSC-exo) on angiogenesis, to elucidate the mechanism of their roles in the regulation of the downstream pathway of VEGFA activation, and to provide ideas for the development of novel treatments for AE. The study evaluated the impact of PSC-exo increases proliferation, migration, invasion, and tube formation of HUVECs at concentrations of up to 50 µg/ml. In addition, the study sought to validate the findings in vivo. This effect involved increased VEGFA expression at gene and protein levels and AKT/mTOR pathway activation. PSC-exo are crucial in promoting angiogenesis through VEGFA upregulation and AKT/mTOR signaling. This research contributes to our knowledge of neovascularization in AE.

A review on decoding the roles of YAP/TAZ signaling pathway in cardiovascular diseases: Bridging molecular mechanisms to therapeutic insights.

Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) serve as transcriptional co-activators that dynamically shuttle between the cytoplasm and nucleus, resulting in either the suppression or enhancement of their downstream gene expression. Recent emerging evidence demonstrates that YAP/TAZ is strongly implicated in the pathophysiological processes that contribute to cardiovascular diseases (CVDs). In the cardiovascular system, YAP/TAZ is involved in the orchestration of a range of biological processes such as oxidative stress, inflammation, proliferation, and autophagy. Furthermore, YAP/TAZ has been revealed to be closely associated with the initiation and development of various cardiovascular diseases, including atherosclerosis, pulmonary hypertension, myocardial fibrosis, cardiac hypertrophy, and cardiomyopathy. In this review, we delve into recent studies surrounding YAP and TAZ, along with delineating their roles in contributing to the pathogenesis of CVDs with a link to various physiological processes in the cardiovascular system. Additionally, we highlight the current potential drugs targeting YAP/TAZ for CVDs therapy and discuss their challenges for translational application. Overall, this review may offer novel insights for understanding and treating cardiovascular disorders.

[A new cucurbitane glycoside from Picrorhiza scrophulariiflora].

Chemical constituents from the ethanol extract of Picrorhiza scrophulariiflora were isolated and purified by column chromatography. Their structures were identified by HR-MS, 1D and 2D-NMR, and their cytotoxicity was assessed by CCK-8 assay. Four compounds were isolated and identified as follows: 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosterol-5,25-diene-22-one(1), 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,24-diene-22-one(2), 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5-ene-22-one(3) and 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,23-(E)-diene-22-one(4). Compound 1 represents a new cucurbitane glycoside. The half inhibitory concentrations of the 4 compounds exceeded 100 µmol·L~(-1) against four tumor cell lines, indicating no significant cytotoxicity.

Extracellular polymeric substances altered ferrihydrite (trans)formation and induced arsenic mobilization.

The behavior of As is closely related to trans(formation) of ferrihydrite, which often coprecipitates with extracellular polymeric substances (EPS), forming EPS-mineral aggregates in natural environments. While the effect of EPS on ferrihydrite properity, mineralogy reductive transformation, and associated As fate in sulfate-reducing bacteria (SRB)-rich environments remains unclear. In this research, ferrihydrite-EPS aggregates were synthesized and batch experiments combined with spectroscopic, microscopic, and geochemical analyses were conducted to address these knowledge gaps. Results indicated that EPS blocked micropores in ferrihydrite, and altered mineral surface area and susceptibility. Although EPS enhanced Fe(III) reduction, it retarded ferrihydrite transformation to magnetite by inhibiting Fe atom exchange in systems with low SO42-. As a result, 16% of the ferrihydrite was converted into magnetite in the Fh-0.3 treatment, and no ferrihydrite transformation occurred in the Fh-EPS-0.3 treatment. In systems with high SO42-, however, EPS promoted mackinawite formation and increased As mobilization into the solution. Additionally, the coprecipitated EPS facilitated As(V) reduction to more mobilized As(III) and decreased conversion of As into the residual phase, enhancing the potential risk of As contamination. These findings advance our understanding on biogeochemistry of elements Fe, S, and As and are helpful for accurate prediction of As behavior.

Molecular characteristics of Echinococcus multilocularis FABP1 and its regulatory functions on murine macrophages.

Fatty acid binding proteins (FABPs) have emerged as attractive vaccination candidates for several platyhelminth species. To explore the physiological functions of Echinococcus multilocularis (E. multilocularis) FABP, the molecular characteristics of EmFABP1 were analyzed by online software, and the regulatory roles of rEmFABP1 protein in murine macrophages were further investigated. The emfabp1 gene encodes 133 amino acids with the characteristic ß-barrel shape of the cytoplasmic FABP family. Natural EmFABP1 protein is predominantly expressed in protoscoleces tegument and germinal layer cells and is also detected in cyst fluid and exosomes of E. multilocularis. rEmFABP1 protein demonstrated a notable suppression of phagocytic activity and nitric oxide production in murine macrophages. Additionally, the protein was observed to promote apoptosis and regulate cytokine expression in macrophages. These findings suggested that E. multilocularis FABP1 is critical in modifying macrophage physiological processes and that this protein may have immunomodulatory roles during infection.

Is cognitive behavioral therapy for insomnia more cost-effective? New-perspective on economic evaluations: a systematic review and meta-analysis.

STUDY OBJECTIVES: To investigate the cost-effectiveness of cognitive behavioral therapy for insomnia (CBTI), with an additional focus on digital CBTI (dCBTI) in adults with insomnia. METHODS: We searched eight electronic databases for economic evaluations of CBTI: PubMed, Scopus, Web of Science, psycINFO, Cochrane, Library, CINAHL, ProQuest, and National Health Service Economic Evaluation Database. Meta-analyses were performed to investigate the effects and costs between CBTI and control groups (no treatment, other treatments included hygiene education and treatment as usual). Subgroup analyses for dCBTI were conducted. RESULTS: Twelve randomized controlled trial studies between 2004 and 2023 were included in our systematic review and meta-analyses. The incremental cost-utility ratios and incremental cost-effectiveness ratios showed that the CBTI and dCBTI groups were more cost-effective than controls, from healthcare perspective and societal perspective, respectively. Compared to controls, CBTI demonstrated significantly better efficacy within 12 months. Healthcare costs were significantly higher in the CBTI groups compared to the controls within 6 months but there was no difference at 12 months. Additionally, dCBTI was associated with significantly lower presenteeism costs compared to controls at 6 months. CONCLUSIONS: Our findings suggest that CBTI is more cost-effective than other treatments or no treatment for adults with insomnia. It may bring more economic benefits in the long term, especially in long-lasting efficacy and cost reduction. In addition, dCBTI is one of the cost-effective options for insomnia. PROSPERO REGISTRATION NUMBER: CRD42 022 383 440. URL: www.crd.york.ac.uk/PROSPERO. NAME FOR PROSPERO REGISTRATION: Cost-effectiveness of cognitive behavioral therapy for insomnia (CBTI): a systematic review with meta-analysis.

Monitoring Hepatocellular Carcinoma Using Tumor Content in Circulating Cell-Free DNA.

PURPOSE: The objective of the study was to evaluate the use of tumor content in circulating cell-free DNA (ccfDNA) for monitoring hepatocellular carcinoma (HCC) throughout its natural history. EXPERIMENTAL DESIGN: We included 67 patients with hepatitis B virus-related HCC, of whom 17 had paired pre- and posttreatment samples, and 90 controls. Additionally, in a prospective cohort with hepatitis B virus surface antigen-positive participants recruited in 2012 and followed up biannually with blood sample collections until 2019, we included 270 repeated samples before diagnosis from 63 participants who later developed HCC (pre-HCC samples). Shallow whole-genome sequencing and the ichorCNA method were used to analyze genome-wide copy number and tumor content in ccfDNA. RESULTS: High tumor content was associated with advanced tumor stage (P < 0.001) and poor survival after HCC diagnosis [HR = 12.35; 95% confidence interval (CI) = 1.413-107.9; P = 0.023]. Tumor content turned negative after surgery (P = 0.027), whereas it remained positive after transarterial chemoembolization treatment (P = 0.578). In non-HCC samples, the mean tumor content (±SD) was 0.011 (±0.007) and had a specificity of 97.8% (95% CI = 92.2%-99.7%). In pre-HCC samples, the tumor content increased from 0.014 at 4 years before diagnosis to 0.026 at 1 year before diagnosis. The sensitivity of tumor content in detecting HCC increased from 22.7% (95% CI = 11.5%-37.8%) within 1 year before diagnosis to 30.4% (95% CI = 13.2%-52.9%) at the Barcelona Clinic Liver Cancer (BCLC) stage 0/A, 81.8% (95% CI = 59.7%-94.8%) at stage B, and 95.5% (95% CI = 77.2%-99.9%) at stage C. CONCLUSIONS: The tumor content in ccfDNA is correlated with tumor burden and may help in monitoring HCC 1 yearearlier than clinical diagnosis and in predicting patient prognosis.