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1.
Neural Regen Res ; 20(3): 900-912, 2025 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38886961

RESUMO

JOURNAL/nrgr/04.03/01300535-202503000-00033/figure1/v/2024-06-17T092413Z/r/image-tiff The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures. However, the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies. Thus, we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina. In this study, we showed that postnatal retinal explants undergo normal development, and exhibit a consistent structure and timeline with retinas in vivo. Initially, we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells. We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin, respectively. Ki-67- and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis, and exhibited a high degree of similarity in abundance and distribution between groups. Additionally, we used Ceh-10 homeodomain-containing homolog, glutamate-ammonia ligase (glutamine synthetase), neuronal nuclei, and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells, Müller glia, mature neurons, and microglia, respectively. The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas. Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development. The findings confirm the accuracy and credibility of this model and support its use for long-term, systematic, and continuous observation.

2.
BMC Plant Biol ; 24(1): 746, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39098914

RESUMO

BACKGROUND: The male sterile lines are an important foundation for heterosis utilization in wheat (Triticum aestivum L.). Thereinto, pollen development is one of the indispensable processes of wheat reproductive development, and its fertility plays an important role in wheat heterosis utilization, and are usually influencing by genes. However, these key genes and their regulatory networks during pollen abortion are poorly understood in wheat. RESULTS: DEFECTIVE IN TAPETAL DEVELOPMENT AND FUNCTION 1 (TDF1) is a member of the R2R3-MYB family and has been shown to be essential for early tapetal layer development and pollen grain fertility in rice (Oryza sativa L.) and Arabidopsis thaliana. In order to clarify the function of TDF1 in wheat anthers development, we used OsTDF1 gene as a reference sequence and homologous cloned wheat TaTDF1 gene. TaTDF1 is localized in the nucleus. The average bolting time of Arabidopsis thaliana overexpressed strain (TaTDF1-OE) was 33 d, and its anther could be colored normally by Alexander staining solution, showing red. The dominant Mosaic suppression silence-line (TaTDF1-EAR) was blue-green in color, and the anthers were shrimpy and thin. The TaTDF1 interacting protein (TaMAP65) was confirmed using Yeast Two-Hybrid Assay (Y2H) and Bimolecular-Fluorescence Complementation (BiFC) experiments. The results showed that downregulated expression of TaTDF1 and TaMAP65 could cause anthers to be smaller and shrunken, leading to pollen abortion in TaTDF1 wheat plants induced by virus-induced gene-silencing technology. The expression pattern of TaTDF1 was influenced by TaMAP65. CONCLUSIONS: Thus, systematically revealing the regulatory mechanism of wheat TaTDF1 during anther and pollen grain development may provide new information on the molecular mechanism of pollen abortion in wheat.


Assuntos
Infertilidade das Plantas , Proteínas de Plantas , Pólen , Triticum , Triticum/genética , Triticum/fisiologia , Infertilidade das Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Pólen/genética , Pólen/crescimento & desenvolvimento , Arabidopsis/genética , Arabidopsis/fisiologia , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/genética , Flores/genética , Flores/crescimento & desenvolvimento , Flores/fisiologia , Genes de Plantas
3.
Biosens Bioelectron ; 263: 116636, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39116631

RESUMO

The clinical diagnosis of pathogen infectious diseases increasingly requires sensitive and rapid RNA detection technologies. The RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)/Cas13a system has shown immense potential in molecular diagnostics due to its trans-cleavage activity. However, most Cas13a-based detection methods require an amplicon transcription step, and the multi-step open-tube operations are prone to contamination, limiting their widespread application. Here, we propose an ultrasensitive (single-copy range, ∼aM) and rapid (within 40 min) isothermal one-pot RNA detection platform, termed SATCAS (Simultaneous Amplification and Testing platform based on Cas13a). This method effectively distinguishes viable bacteria (0%-100%) under constant total bacterial conditions, demonstrating its robustness and universality. SATCAS excels in identifying single nucleotide polymorphisms (SNPs), particularly detecting 0.5% drug-resistant mutations. We validated SATCAS by detecting infections in biological samples from 68 HBV, 23 EBV, and 48 SARS-CoV-2 patients, achieving 100% sensitivity, 92.86% specificity, and 97.06% accuracy in HBV infection testing. We anticipate that SATCAS has broad application potential in the early diagnosis, subtyping, drug resistance detection, and point-of-care monitoring of pathogen infectious diseases.


Assuntos
Técnicas Biossensoriais , Sistemas CRISPR-Cas , Técnicas de Amplificação de Ácido Nucleico , Polimorfismo de Nucleotídeo Único , SARS-CoV-2 , Humanos , Técnicas Biossensoriais/métodos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico/métodos , COVID-19/diagnóstico , COVID-19/virologia , RNA Viral/genética , Técnicas de Diagnóstico Molecular/métodos , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação
4.
BMC Psychol ; 12(1): 440, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138553

RESUMO

BACKGROUND: Social anxiety symptoms are common and harmful psychological illness in college students. Although some studies have illustrated that physical activity could reduce social anxiety symptoms, the specific mechanism is still unclear. Based on theoretical studies on resilience and sleep, this study constructed a serial mediation model to explore whether they mediate between physical activity and social anxiety symptoms among college students. METHODS: This study surveyed 9,530 college students from three colleges in China to explore the mediating effect of physical activity and sleep problems between physical activity and social anxiety symptoms. Participants were investigated with the International Physical Activity Questionnaire, Connor-Davidson Resilience Scale, Sleep-related problems, and the Social Interaction Anxiety Scale and the Social Phobia Scale. Correlations between variables were analysed using Pearson correlation analysis and mediation analyses were performed using SPSS PROCESS macro 3.3 software. RESULT: The study found that physical activity was negatively associated with social anxiety symptoms and sleep problems, but positively with psychological resilience. After controlling for sociodemographic variables, physical activity can not only indirectly alleviate social anxiety symptoms through the separate mediation of psychological resilience and sleep problems, but also through the serial mediation of psychological resilience and sleep problems. CONCLUSION: These results suggest that improving physical activity levels could reduce social anxiety scores by increasing psychological resilience and sleep quality. This is of great reference significance for the prevention and intervention of college students' mental health.


Assuntos
Ansiedade , Exercício Físico , Resiliência Psicológica , Transtornos do Sono-Vigília , Estudantes , Humanos , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Masculino , Feminino , China , Adulto Jovem , Universidades , Exercício Físico/psicologia , Ansiedade/psicologia , Ansiedade/epidemiologia , Transtornos do Sono-Vigília/psicologia , Adulto , Adolescente , Inquéritos e Questionários
5.
Front Vet Sci ; 11: 1442244, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39144081

RESUMO

Introduction: Fermented jujube powder (FJP) promotes a balance between the intestinal microflora and immune factors in animals. In this study, we aimed to investigate the effects of FJP on the production performance, nutrient digestion, rumen fermentation, and antioxidant properties of bulls. Methods: Forty Simmental bulls were randomly divided into four groups based on body weight and fed a basal diet with [5, 7.5, or 10% dry matter (DM)] or without FJP. The experimental period was 20 d for adaptation and 60 d for the feeding trial. Results: Dietary FJP supplementation did not affect DM intake (P > 0.05) but increased the average daily gain quadratically (P = 0.049) and decreased the feed conversion ratio linearly (P = 0.042). FJP quadratically enhanced DM and crude protein digestibility (P = 0.026 and P = 0.041, respectively) and linearly enhanced acid detergent fiber digestibility (P = 0.048). It also increased the total volatile fatty acid concentration quadratically (P = 0.037), acetate molar percentage, and acetate-to-propionate ratio linearly (P = 0.002 and 0.001), and reduced the ammonia nitrogen concentration linearly (P = 0.003). Additionally, xylanase and protease activities and Ruminococcus flavefaciens abundance increased linearly (P = 0.006, 0.018, and 0.009, respectively), and total bacteria, Ruminococcus albus, and Ruminobacter amylophilus abundance increased quadratically (P = 0.047, 0.011, and 0.021, respectively). FJP linearly increased serum total protein concentration and antioxidant capacity (P = 0.003 and 0.018, respectively) and decreased malonaldehyde content (P = 0.006). Discussion: FJP supplementation (7.5%) enhanced production performance, nutrient digestion, rumen fermentation, and serum antioxidant capacity in bulls. The improved nutrient digestion may be due to an increase in ruminal microorganisms and total volatile fatty acids from the FJP. High blood antioxidant levels indicate that FJP may preserve proteins, thereby boosting the production performance of bulls.

6.
STAR Protoc ; 5(3): 103265, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39146188

RESUMO

Preparation of perovskite solar cells (PSCs) with long-lasting passivation effectiveness is challenging. Here, we present a protocol for fabricating efficient and stable passivated perovskite solar cells. We describe steps for preparing the electron transporting layer (ETL) via chemical bath deposition and perovskite film. We then detail procedures for passivating the surface defects with excess terpyridine ligands and stability characterization. This protocol features a passivator-terpyridine whose passivation effect is independent of concentration, which greatly improves the durability of the passivation. For complete details on the use and execution of this protocol, please refer to Wang et al.1.

7.
Curr Biol ; 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39146937

RESUMO

The Yellow River Delta played a vital role in the development of the Neolithic civilization of China. However, the population history of this region from the Neolithic transitions to the present remains poorly understood due to the lack of ancient human genomes. This especially holds for key Neolithic transitions and tumultuous turnovers of dynastic history. Here, we report genome-wide data from 69 individuals dating to 5,410-1,345 years before present (BP) at 0.008 to 2.49× coverages, along with 325 present-day individuals collected from 16 cities across Shandong. During the Middle to Late Dawenkou period, we observed a significant influx of ancestry from Neolithic Yellow River farmers in central China and some southern Chinese ancestry that mixed with local hunter-gatherers in Shandong. The genetic heritage of the Shandong Longshan people was found to be most closely linked to the Dawenkou culture. During the Shang to Zhou Dynasties, there was evidence of genetic admixture of local Longshan populations with migrants from the Central Plain. After the Qin to Han Dynasties, the genetic composition of the region began to resemble that of modern Shandong populations. Our genetic findings suggest that the middle Yellow River Basin farmers played a role in shaping the genetic affinity of neighboring populations in northern China during the Middle to Late Neolithic period. Additionally, our findings indicate that the genetic diversity in the Shandong region during the Zhou Dynasty may be linked with their complex ethnicities.

8.
Biosystems ; : 105282, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39147308

RESUMO

A simple theoretical model (or a demonstrative example) was developed to illustrate how the evolution of cooperation can be affected by the density-dependent survival competition, in which we assume that the fertility of an individual depends only on the pairwise interaction between him and other individuals based on Prisoner's Dilemma game, while its viability is only related to the density-dependent survival competitiveness. Our results show that not only cooperation could be evolutionarily stable if the advantage of cooperators in viability can compensate for the cost they pay for their fertility, but also the long-term stable coexistence of cooperation and defection is possible if none of cooperation and defection is evolutionarily stable. Moreover, for the stochastic evolutionary dynamics in a finite population, our analysis shows that the increase (or decrease) of the survival competitiveness of cooperators (or defectors) should be conductive to the evolutionary emergence of cooperation.

9.
Front Plant Sci ; 15: 1392934, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39139727

RESUMO

Introduction: Rhizosphere effects (REs) have recently been identified as important regulators of root and microbial nutrient acquisition and are positively involved in nutrient cycling of belowground carbon (C), nitrogen (N), and phosphorus (P). Nutrient conditions of the fine roots and soil N are likely to influence REs. Still, it is unclear how REs of soil nutrients themselves variably impact the supply of nutrients to plants in terms of the responses to soil N due to succession. Methods: In this study, we applied both fine roots and extracellular enzymes for vector analysis and stoichiometry of N:P to explore the metabolic limitations of roots and rhizospheric soil microbes and their relationships with REs across five levels of soil N (0, 5, 10, 15, and 20 kg N m-2 year-1) along successional age classes of 42, 55, and 65 years in a Pinus tabuliformis forest. Results: Overall, the metabolism of root and rhizospheric soil microbes was mediated by soil N. N limitation of roots initially decreased before increasing, whereas that of microbes demonstrated opposite trends to the N levels owing to competition for inorganic N between them by REs of NO3 --N. However, N limitations of both roots and microbes were alleviated in young stands and increased with succession after the application of N. In addition, root N limitations were manipulated by REs of three different soil N-related indicators, i.e., total N, NH4 +-N, and NO3 --N. Rhizospheric soil microbial N limitation was almost unaffected by REs due to their strong homeostasis but was an important driver in the regulation of root N limitation. Discussion: Our results indicated that successional age was the most critical driver that directly and indirectly affected root N metabolism. However, the level of N application had a slight effect on root N limitation. Microbial N limitation and variations in the REs of N indicators regulated root N limitation in the rhizosphere. As a result, roots utilized REs to sequester N to alleviate N limitations. These findings contribute to novel mechanistic perspectives on the sustainability of N nutrition by regulating N cycling in a system of plant-soil-microbes in the rhizosphere to adapt to global N deposition or the heterogeneous distribution of bioavailable soil N with succession.

10.
ACS Macro Lett ; : 1127-1132, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39141897

RESUMO

Polyelectrolyte (PE) brushes are widely used in biomaterials and nanotechnology to regulate the surface properties and interactions. Here, we apply the electrostatic correlation augmented self-consistent field theory to investigate the interactions between opposing PE brushes in a mixture of 1:1 and 3:1 salt solutions. Our theory predicts a hysteretic feature of the normal stress induced by strong ion correlations. In the presence of trivalent ions, the force profile is discontinuous: repulsive in the compression branch and adhesive in the separation branch. The molecular origin of the hysteretic force is the coexistence of two collapsed modes: two separated condensed layers on each surface in the compression and a single bundled condensed layer in the separation. With the systematic inclusion of ion correlations, our theory captures well the hysteretic force, adhesive separation, "jump-in" and "jump-out" features, and the "specific ion effect", all in good agreement with the reported experimental results.

11.
Chemosphere ; 364: 143101, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39151575

RESUMO

Short-term ambient fine particulate matter (PM2.5) exposure has been related to an increased risk of myocardial infarction (MI) death, but which PM2.5 constituents are associated with MI death and to what extent remain unclear. We aimed to explore the associations of short-term exposure to PM2.5 constituents with MI death and evaluate excess mortality. We conducted a time-stratified case-crossover study on 237,492 MI decedents in Jiangsu province, China during 2015-2021. Utilizing a validated PM2.5 constituents grid dataset at 1 km spatial resolution, we estimated black carbon (BC), organic carbon (OC), sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), and chloride (Cl-) exposure by extracting daily concentrations grounding on the home address of each subject. We employed conditional logistic regression models to evaluate the exposure-response relationship between PM2.5 constituents and MI death. Overall, per interquartile range (IQR) increase of BC (lag 06-day; IQR: 1.75 µg/m3) and SO42- (lag 04-day; IQR: 5.06 µg/m3) exposures were significantly associated with a 3.91% and 2.94% increase in odds of MI death, respectively, and no significant departure from linearity was identified in the exposure-response curves for BC and SO42-. If BC and SO42- exposures were reduced to theoretical minimal risk exposure concentration (0.89 µg/m3 and 1.51 µg/m3), an estimate of 4.55% and 4.80% MI deaths would be avoided, respectively. We did not find robust associations of OC, NO3-, NH4+, and Cl- exposures with MI death. Individuals aged ≥80 years were more vulnerable to PM2.5 constituent exposures in MI death (p for difference <0.05). In conclusion, short-term exposure to PM2.5-bound BC and SO42- was significantly associated with increased odds of MI death and resulted in extensive excess mortality, notably in older adults. Our findings emphasized the necessity of reducing toxic PM2.5 constituent exposures to prevent deaths from MI and warranted further studies on the relative contribution of specific constituents.

12.
BMC Pregnancy Childbirth ; 24(1): 544, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39152393

RESUMO

OBJECTIVE: Pregnancy care can improve maternal pregnancy outcomes. Cluster nursing, an evidence-based, patient-centered model, enhances pregnancy care, can provide patients with high-quality nursing services, has been widely used in clinical practice in recent years. However, most previous studies evaluated cluster nursing program only for a single clinical scenario. In this study, we developed and implemented a antenatal cluster care program for various prenatal issues faced by puerpera to analyze its application effect. METHODS: This is a historical before and after control study. 89 expectant mothers who had their prenatal information files registered in the outpatient department of a grade III, level A hospital from June 2020 to September 2021 were finally enrolled in observation group, and received prenatal cluster management. Another set of 89 expectant mothers from January 2019 to December 2019 were included in the control group and received traditional routine prenatal management. The effect of cluster nursing management on maternal delivery and postpartum rehabilitation was evaluated and compared between the two groups. RESULTS: Compared with the control group, the observation group had a significantly higher natural delivery rate, better neonatal prognosis, higher rates of exclusive breastfeeding, lower incidence of postpartum complications, shorter postpartum hospital stay, better postpartum health status, and higher satisfaction with nursing services. Compared with before intervention, the SAS and SDS scores of the observation group showed significant improvement after intervention. CONCLUSION: Antenatal cluster care is beneficial to improve maternal and neonatal outcomes, and can have positive effects on natural pregnancy and breastfeeding, while improving the multimedia health education ability of medical care and emphasizing the importance of social support.


Assuntos
Cuidado Pré-Natal , Humanos , Feminino , Gravidez , Adulto , Cuidado Pré-Natal/métodos , Período Pós-Parto , Parto Obstétrico/métodos , Aleitamento Materno , Resultado da Gravidez
13.
J Lipid Res ; : 100623, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39154732

RESUMO

Natriuretic peptide receptor-C (NPR-C) is highly expressed in adipose tissues, and regulates obesity related diseases, however the detailed mechanism remains unknown. In this research, we aimed to explore the potential role of NPR-C in cold exposure and high-fat/high-sugar (HF/HS) diet induced metabolic changes, especially in regulating white adipose tissue (WAT) mitochondrial function. Our findings showed that NPR-C expression, especially in epididymal WAT (eWAT), was reduced after cold exposure. Global Npr3 (gene encoding NPR-C protein) deficiency led to reduced body weight, increased WAT browning, thermogenesis, and enhanced expression of genes related to mitochondrial biogenesis. RNA-sequencing of eWAT showed that Npr3 deficiency enhanced expression of mitochondrial respiratory chain complex genes and promoted mitochondrial oxidative phosphorylation in response to cold exposure. In addition, Npr3 KO mice were able to resist obesity induced by HF/HS diet. Npr3 knockdown in stromal vascular fraction (SVF)-induced white adipocytes promoted the expression of proliferator-activated receptor gamma coactivator 1α (PGC1α), uncoupling protein 1 (UCP1) and mitochondrial respiratory chain complexes. Mechanistically, NPR-C inhibited cGMP and calcium signaling in an NPR-B-dependent manner but suppressed cAMP signaling in an NPR-B-independent manner. Moreover, Npr3 knockdown induced browning via AKT and p38 pathway activation, which were attenuated by Npr2 knockdown. Importantly, treatment with the NPR-C specific antagonist, AP-811, decreased WAT mass and increased PGC-1α, UCP1 and mitochondrial complex expression. These findings demonstrate that NPR-C deficiency enhances metabolic health by boosting energy expenditure in WAT, emphasizing the potential of NPR-C inhibition for treating obesity and related metabolic disorders.

14.
Res Synth Methods ; 2024 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-39155538

RESUMO

Increasing integrity concerns in medical research have prompted the development of tools to detect untrustworthy studies. Existing tools primarily assess published aggregate data (AD), though scrutiny of individual participant data (IPD) is often required to detect trustworthiness issues. Thus, we developed the IPD Integrity Tool for detecting integrity issues in randomised trials with IPD available. This manuscript describes the development of this tool. We conducted a literature review to collate and map existing integrity items. These were discussed with an expert advisory group; agreed items were included in a standardised tool and automated where possible. We piloted this tool in two IPD meta-analyses (including 116 trials) and conducted preliminary validation checks on 13 datasets with and without known integrity issues. We identified 120 integrity items: 54 could be conducted using AD, 48 required IPD, and 18 were possible with AD, but more comprehensive with IPD. An initial reduced tool was developed through consensus involving 13 advisors, featuring 11 AD items across four domains, and 12 IPD items across eight domains. The tool was iteratively refined throughout piloting and validation. All studies with known integrity issues were accurately identified during validation. The final tool includes seven AD domains with 13 items and eight IPD domains with 18 items. The quality of evidence informing healthcare relies on trustworthy data. We describe the development of a tool to enable researchers, editors, and others to detect integrity issues using IPD. Detailed instructions for its application are published as a complementary manuscript in this issue.

15.
Talanta ; 280: 126691, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39151316

RESUMO

Staphylococcus aureus (S. aureus) is the most common pathogen in human purulent infections, which can cause local purulent infections, as well as pneumonia, pseudomembranous enteritis, pericarditis, and even systemic infections. The conventional methods including bacteria colony counting, polymerase chain reaction and enzyme-linked immunosorbent assay can't fully meet the requirement of highly sensitive detection of S. aureus due to their own disadvantages. Therefore, it's an urgent need to develop new platform to detect S. aureus in the early infection stage. In this study, a new surface-enhanced Raman scattering (SERS)-based nanoplatform based on dual-recognition of aptamer (Apt) and vancomycin (Van) was developed for the highly sensitive detection of S. aureus. The SERS nanoplatform consisted of two functional parts: aptamer-conjugated Fe3O4 magnetic nanoparticles (Fe3O4-Apt MNPs) for bacteria enrichment and vancomycin modified-Au nanoparticles (Van-Au NPs) as the SERS probes for S. aureus quantitative detection. Upon the target bacteria enrichment, the SERS signals of the supernatant after magnetic separation could be obtained and analyzed under different concentrations of S. aureus. The limit of detection of the proposed assay was found to be 3.27 CFU/mL. We believe that the proposed SERS-based nanoplatform has great potential as a powerful tool in the early detection of specific bacteria.

16.
ACS Nano ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39151414

RESUMO

mRNA vaccines have been revolutionizing disease prevention and treatment. However, their further application is hindered by inflammatory side effects, primarily caused by delivery systems such as lipid nanoparticles (LNPs). In response to this issue, we prepared cationic lipids (mLPs) derived from mildronate, a small-molecule drug, and subsequently developed the LNP (mLNP-69) comprising a low dose of mLP. Compared with the LNP (sLNP) based on SM-102, a commercially available ionizable lipid, mLNP-69 ensures effective mRNA delivery while significantly reducing local inflammation. In preclinical prophylactic and therapeutic B16-OVA melanoma models, mLNP-69 demonstrated successful mRNA cancer vaccine delivery in vivo, effectively preventing tumor occurrence or impeding tumor progression. The results suggest that the cationic lipids derived from mildronate, which exhibit efficient delivery capabilities and minimal inflammatory side effects, hold great promise for clinical application.

17.
Neurosci Lett ; 839: 137935, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39151574

RESUMO

OBJECTIVE: Bipolar disorder (BD) is a debilitating neuropsychiatric disorder, which is associated with genetic variation through "vast but mixed" Genome-Wide Association Studies (GWAS). Transcriptome-Wide Association Study (TWAS) is more effective in explaining genetic factors that influence complex diseases and can help identifying risk genes more reliably. So, this study aims to identify potential BD risk genes in pedigrees with TWAS. METHODS: We conducted a TWAS analysis with expression quantitative trait loci (eQTL) analysis on extended BD pedigrees, and the BD genome-wide association study (GWAS) summary data acquired from the Psychiatric Genomics Consortium (PGC). Furthermore, the BD-associated genes identified by TWAS were validated by mRNA expression profiles from the Gene Expression Omnibus (GEO) Datasets (GSE23848 and GSE46416). Functional enrichment and annotation analysis were implemented by RStudio (version 4.2.0). RESULTS: TWAS identified 362 genes with P value < 0.05, and 18 genes remain significant after Bonferroni correction, such as SEMA3G (PTWAS=1.07 × 10-11), ALOX5AP (PTWAS=3.12 × 10-8), and PLEC (PTWAS=1.27 × 10-7). Further 6 overlapped genes were detected in integrative analysis, such as UQCRB (PTWAS=0.0020, PmRNA=0.0000), TMPRSS9 (PTWAS=0.0405, PmRNA=0.0032), and SNX10 (PTWAS=0.0104, PmRNA=0.0015). Using genes identified by TWAS, Gene Ontology (GO) enrichment analysis identified 40 significant GO terms, such as mitochondrial ATP synthesis coupled electron transport, mitochondrial respiratory, aerobic electron transport chain, oxidative phosphorylation, mitochondrial membrane proteins, and ubiquinone activity. The Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway enrichment analysis identified significant 15 pathways for BD, such as Oxidative phosphorylation, endocannabinoids signaling, neurodegeneration, and reactive oxide species. CONCLUSIONS: We found a set of BD-associated genes and pathways, validating the important role of neurodevelopmental abnormalities, inflammatory responses, and mitochondrial dysfunction in the pathology of BD, offering novel information for comprehending the genetic basis of BD.

18.
Bioinformatics ; 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39153205

RESUMO

SUMMARY: Recent methodology advances in computational signal deconvolution have enabled bulk transcriptome data analysis at a finer cell-type level. Through deconvolution, identifying cell-type-specific differentially expressed (csDE) genes is drawing increasing attention in clinical applications. However, researchers still face a number of difficulties in adopting csDE detection methods in practice, especially in their experimental design. Here we present cypress, the first experimental design and statistical power analysis tool in csDE identification. This tool can reliably model purified cell-type-specific (CTS) profiles, cell-type compositions, biological and technical variations, offering a high-fidelity simulator for bulk RNA-seq convolution and deconvolution. cypress conducts simulation and evaluates the impact of multiple influencing factors, by various biostatistical metrics, to help researchers optimize experimental design and conduct power analysis. AVAILABILITY AND IMPLEMENTATION: cypress is an open-source R/Bioconductor package at https://bioconductor.org/packages/cypress/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

19.
Pain Manag Nurs ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39153959

RESUMO

PURPOSE: Pain is one of the most common and harmful symptoms experienced by individuals with acute herpetic neuralgia (AHN). In this population, studies to determine the causes that affect patients taking medications compliance are rare. This study aimed to construct a predictive model for medication compliance of patients with AHN and to verify its performance. DESIGN AND METHODS: In this prospective study of 398 patients with AHN who were discharged from a tertiary hospital with medications from July 2020 to October 2022, we used logistic regression analysis to explore the predictive factors of medication compliance of patients with AHN and to construct a nomogram. The area under the curve was used to evaluate the predictive effect of the model. RESULTS: A predictive model of drug compliance of patients with AHN was constructed based on the following four factors: disease duration, pain severity before treatment, medication beliefs, and comorbidity of chronic diseases. The area under the curve of the model was 0.766 (95% confidence interval [0.713, 0.819]), with a maximum Youden's index of 0.431, sensitivity of 0.776, and specificity of 0.655. A linear calibration curve was found with a slope close to 1. CONCLUSIONS: The prediction model constructed in this study had good predictive performance and provided a reference for early clinical screening of independent factors that affected the medication compliance of patients with AHN.

20.
Proc Natl Acad Sci U S A ; 121(34): e2410504121, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39150782

RESUMO

Clean production of hydrogen peroxide (H2O2) with water, oxygen, and renewable energy is considered an important green synthesis route, offering a valuable substitute for the traditional anthraquinone method. Currently, renewable energy-driven production of H2O2 mostly relies on soluble additives, such as electrolytes and sacrificial agents, inevitably compromising the purity and sustainability of H2O2. Herein, we develop a solution plasma catalysis technique that eliminates the need for soluble additives, enabling eco-friendly production of concentrated H2O2 directly from water and O2. Screening over 40 catalysts demonstrates the superior catalytic performance of carbon nitride interacting with discharge plasma in water. High-throughput density functional theory calculations for 68 models, along with machine learning using 29 descriptors, identify cyano carbon nitride (CCN) as the most efficient catalyst. Solution plasma catalysis with the CCN achieves concentrated H2O2 of 20 mmol L-1, two orders of magnitude higher than photocatalysis by the same catalyst. Plasma diagnostics, isotope labeling, and COMSOL simulations collectively validate that the interplay of solution plasma and the CCN accounts for the significantly increased production of singlet oxygen and H2O2 thereafter. Our findings offer an efficient and sustainable pathway for H2O2 production, promising wide-ranging applications across the chemical industry, public health, and environmental remediation.

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