The Mechanism of Na+/K+ Selectivity in Mammalian Voltage-Gated Sodium Channels Based on Molecular Dynamics Simulation

AbstractVoltage-gated sodium (Nav) channels and their Na+/K+ selectivity are of great importance in the mammalian neuronal signaling. According to mutational analysis, the Na+/K+ selectivity in mammalian Nav channels is mainly determined by the Lys and Asp/Glu residues located at the constriction site within the selectivity filter. Despite successful molecular dynamics simulations conducted on the prokaryotic Nav channels, the lack of Lys at the constriction site of prokaryotic Nav channels limits how much can be learned about the Na+/K+ selectivity in mammalian Nav channels. In this work, we modeled the mammalian Nav channel by mutating the key residues at the constriction site in a prokaryotic Nav channel (NavRh) to its mammalian counterpart. By simulating the mutant structure, we found that the Na+ preference in mammalian Nav channels is collaboratively achieved by the deselection from Lys and the selection from Asp/Glu within the constriction site

Data mining on varieties, therapeutic uses and medicinal characteristics of Traditional Chinese Medicine preparations for treating hair loss

Purpose: To review the varieties, therapeutic uses, and medicinal characteristics of traditional Chinese medicine (TCM) preparations for treating hair loss, and to provide a reference for research and development of new drugs.Methods: For this review, literature from the last 50 years pertaining to the treatment of hair loss via TCM were collected mainly from China National Knowledge Infrastructure database and Wanfang Data Resource System database. Information on Chinese traditional patent medicines and ethnomedicines for treating hair loss was drawn from books.Results: A total of 322 preparations were identified, including 135 preparations made by medical institutions, 108 Chinese traditional patent medicines, 60 preparations produced by doctors themselves, and 19 ethnomedicines. The forms of dosage included  decoctions, pills, capsules, tablets, granules, tinctures, liniments, and powders. These preparations are traditionally used in the treatment of skin and subcutaneous tissue diseases. A total of 400 medicinal materials were used in preparations, including 339 from plants, 40 from animals, 14 from minerals. The most commonly used Chinese medicinal materials in order of frequency were Rehmannia glutinosa (Gaertn.) DC., Fallopia multiflora (Thunb.) Haraldson, Angelica sinensis (Oliv.) Diels, Ligustrum lucidum W.T. Aiton and Ligusticum chuanxiong Hort.Conclusion: TCM preparations for treating hair loss are abundant in variety. They are mainly decoctions, and primarily botanical medicinal materials. Most of the preparations are composed of Chinese medicinal materials for ‘toning the kidneys’ and ‘nourishing the liver’. They are used mainly in the treatment of seborrheic alopecia and alopecia areat

Worldwide productivity and research trend of publications concerning electroactive materials and spinal cord injury: A bibliometric study

Purpose: We investigated the current state and trends in the area during the previous 10 years using bibliometric approaches to evaluate the global scientific output of research on electroactive materials and spinal cord injury.Methods: Studies on spinal cord injury in electroactive materials that were published between 2012 and 2022 were located using the Web of science (WOS) datebase. The software programs bibliometrix R-package and CiteSpace were used to do quantitative analyses of annual publications, nation, author, institution, journal source, co-cited references, and keywords. The studies were categorized by the research’s main points using a qualitative analysis, and publications having more than 10 citations each year.Results: In the final analysis, 1,330 relevant papers or reviews were included. There is an increased tendency in both the average annual citation rate and the number of publications in the discipline. The United States and the University of Toronto are the countries and institutions that have contributed the most to this discipline, respectively. The majority of authors are from the China and United States. Zhang Y is the author with the most published articles and holds the top position in the cited author h-index species. The journal with the highest number of published articles is “Disability and rehabilitation”; the journal is divided into four main areas including physics, materials, chemistry, molecular, and biology. The keyword analysis revealed a shift in research hotspots from schwann cell, fracture, and urinary disorders to carbon-based materials, functional recovery, and surgery. Analysis of qualitative data revealed that the role and mechanism of injectable conductive hydrogels in spinal cord healing after damage is a hot topic of current study, with the mechanism primarily focusing on the inhibition of oxidative stress (Nrf2) and apoptosis (Casepase 3).Conclusion: Our bibliometric analysis indicates that research on electroactive materials for spinal cord injury remains an active field of study. Moreover, contemporary research is concentrated on carbon-based materials, functional rehabilitation, and surgery

Performance of next-generation sequencing for diagnosis of blood infections by Klebsiella pneumoniae

ObjectiveKlebsiella pneumoniae (Kp) bloodstream infections (BSI) can be a life-threatening opportunistic infection. We aimed to evaluate the diagnostic accuracy of metagenomic next-generation sequencing (mNGS) for Kp BSI.MethodsWe retrospectively analyzed 72 patients suspected with bloodstream infection and mNGS Kp positive in peripheral blood, who were hospitalized in our hospital from January 2022 to January 2023. Clinical data and laboratory parameters were collected. All patients had blood drawn and other samples for blood mNGS, blood cultures (BC) and other cultures (OC). The accuracy of mNGS results was analyzed according to infection site, clinical indicators, therapeutic effect and routine culture results. The detection of pathogenic microorganisms by blood mNGS and routine culture was compared.ResultsAmong 72 infection patients, 29 cases (40.28%) were BC positive, 43 cases (59.72%) were other culture (OC) positive, 16 cases (22.22%) were both BC and OC positive, 56 cases were positive for both mNGS and routine culture. Among the 56 double-positive cases, mNGS and conventional cultures were completely consistent in 27 cases, partially consistent in 15 cases, and completely inconsistent in 14 cases. Using the clinical diagnosis as the reference standard, There were 51 cases consistent with the results of mNGS with Kp BSI, the clinical consistency was 70.83% (51/72). The coincidence rate of mNGS and clinical diagnosis was higher than that of BC (54.17%, 39/72), indicating a statistically significant difference between the two methods (P<0.01).ConclusionsCurrent evidence indicates that mNGS exhibits excellent accuracy for the diagnosis of Kp BSI. Although it cannot replace blood culture detection technology, it can be used as a supplement to provide stronger diagnostic capabilities for BSI and optimize treatment

Association between behavioral patterns and depression symptoms: dyadic interaction between couples

BackgroundBehavioral patterns are sometimes associated with depression symptoms; however, few studies have considered the intra-couple effects. This study examined the effect of a spouses’ behavioral patterns on depression symptoms within themself and in their spouse.MethodsA total of 61,118 childbearing age participants (30,559 husband-wife dyads) were surveyed. The depression symptoms were assessed using the nine-item Patient Health Questionnaire (PHQ-9). The behavioral patterns were identified by the latent class analysis. The effects of behavioral patterns on the couple’s own depression symptoms (actor effect) and their partner’s depression symptoms (partner effect) were analyzed using the Actor-Partner Interdependence Model (APIM).ResultsThree behavioral patterns were identified: low-risk group, moderate-risk group, and high-risk group. The high risk of these behavior patterns would be associated with a higher score on the PHQ-9; for both husbands and wives, their behavioral patterns were positively associated with PHQ-9 scores (βhusband = 0.53, P < 0.01; βwife = 0.58, P < 0.01). Wives’ behavioral patterns were also positively associated with their husbands’ PHQ-9 scores (β = 0.14, P < 0.01), but husbands’ behavioral patterns were not associated with their wives’ PHQ-9 scores.ConclusionsWives’ depression symptoms were affected only by their own behavioral patterns, whereas husbands’ depression symptoms were influenced by both their own and their spouses’ behavioral patterns

YBX1 is required for maintaining myeloid leukemia cell survival by regulating BCL2 stability in an m6A-dependent manner

RNA-binding proteins (RBPs) are critical regulators of transcription and translation that are often dysregulated in cancer. Although RBPs are increasingly recognized as being important for normal hematopoiesis and for hematologic malignancies as oncogenes or tumor suppressors, RBPs that are essential for the maintenance and survival of leukemia remain elusive. Here we show that YBX1 is specifically required for maintaining myeloid leukemia cell survival in an N6-methyladenosine (m6A)-dependent manner. We found that expression of YBX1 is significantly upregulated in myeloid leukemia cells, and deletion of YBX1 dramatically induces apoptosis and promotes differentiation coupled with reduced proliferation and impaired leukemic capacity of primary human and mouse acute myeloid leukemia cells in vitro and in vivo. Loss of YBX1 has no obvious effect on normal hematopoiesis. Mechanistically, YBX1 interacts with insulin-like growth factor 2 messenger RNA (mRNA)-binding proteins (IGF2BPs) and stabilizes m6A-tagged RNA. Moreover, YBX1 deficiency dysregulates the expression of apoptosis-related genes and promotes mRNA decay of MYC and BCL2 in an m6A-dependent manner, which contributes to the defective survival that results from deletion of YBX1. Thus, our findings have uncovered a selective and critical role of YBX1 in maintaining myeloid leukemia survival, which might provide a rationale for the therapeutic targeting of YBX1 in myeloid leukemia

Development and Validation of a Predictive Model Based on LASSO Regression: Predicting the Risk of Early Recurrence of Atrial Fibrillation after Radiofrequency Catheter Ablation

Background: Although recurrence rates after radiofrequency catheter ablation (RFCA) in patients with atrial fibrillation (AF) remain high, there are a limited number of novel, high-quality mathematical predictive models that can be used to assess early recurrence after RFCA in patients with AF. Purpose: To identify the preoperative serum biomarkers and clinical characteristics associated with post-RFCA early recurrence of AF and develop a novel risk model based on least absolute shrinkage and selection operator (LASSO) regression to select important variables for predicting the risk of early recurrence of AF after RFCA. Methods: This study collected a dataset of 136 atrial fibrillation patients who underwent RFCA for the first time at Peking University Shenzhen Hospital from May 2016 to July 2022. The dataset included clinical characteristics, laboratory results, medication treatments, and other relevant parameters. LASSO regression was performed on 100 cycles of data. Variables present in at least one of the 100 cycles were selected to determine factors associated with the early recurrence of AF. Then, multivariable logistic regression analysis was applied to build a prediction model introducing the predictors selected from the LASSO regression analysis. A nomogram model for early post-RFCA recurrence in AF patients was developed based on visual analysis of the selected variables. Internal validation was conducted using the bootstrap method with 100 resamples. The model’s discriminatory ability was determined by calculating the area under the curve (AUC), and calibration analysis and decision curve analysis (DCA) were performed on the model. Results: In a 3-month follow-up of AF patients (n = 136) who underwent RFCA, there were 47 recurrences of and 89 non-recurrences of AF after RFCA. P, PLR, RDW, LDL, and CRI-II were associated with early recurrence of AF after RFCA in patients with AF (p < 0.05). We developed a predictive model using LASSO regression, incorporating four robust factors (PLR, RDW, LDL, CRI-II). The AUC of this prediction model was 0.7248 (95% CI 0.6342–0.8155), and the AUC of the internal validation using the bootstrap method was 0.8403 (95% CI 0.7684–0.9122). The model demonstrated a strong predictive capability, along with favorable calibration and clinical applicability. The Hosmer–Lemeshow test indicated that there was good consistency between the predicted and observed values. Additionally, DCA highlighted the model’s advantages in terms of its clinical application. Conclusions: We have developed and validated a risk prediction model for the early recurrence of AF after RFCA, demonstrating strong clinical applicability and diagnostic performance. This model plays a crucial role in guiding physicians in preoperative assessment and clinical decision-making. This novel approach also provides physicians with personalized management recommendations