miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells.

JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-05-14T021156Z/r/image-tiff Our previous study found that rat bone marrow-derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

Silk-based intelligent fibers and textiles: structures, properties, and applications.

Multifunctional fibers represent a cornerstone of human civilization, playing a pivotal role in numerous aspects of societal development. Natural biomaterials, in contrast to synthetic alternatives, offer environmental sustainability, biocompatibility, and biodegradability. Among these biomaterials, natural silk is favored in biomedical applications and smart fiber technology due to its accessibility, superior mechanical properties, diverse functional groups, controllable structure, and exceptional biocompatibility. This review delves into the intricate structure and properties of natural silk fibers and their extensive applications in biomedicine and smart fiber technology. It highlights the critical significance of silk fibers in the development of multifunctional materials, emphasizing their mechanical strength, biocompatibility, and biodegradability. A detailed analysis of the hierarchical structure of silk fibers elucidates how these structural features contribute to their unique properties. The review also encompasses the biomedical applications of silk fibers, including surgical sutures, tissue engineering, and drug delivery systems, along with recent advancements in smart fiber applications such as sensing, optical technologies, and energy storage. The enhancement of functional properties of silk fibers through chemical or physical modifications is discussed, suggesting broader high-end applications. Additionally, the review addresses current challenges and future directions in the application of silk fibers in biomedicine and smart fiber technologies, underscoring silk's potential in driving contemporary technological innovations. The versatility and sustainability of silk fibers position them as pivotal elements in contemporary materials science and technology, fostering the development of next-generation smart materials.

Stimuli-responsive polymer-based nanosystems for cardiovascular disease theranostics.

Stimulus-responsive polymers have found widespread use in biomedicine due to their ability to alter their own structure in response to various stimuli, including internal factors such as pH, reactive oxygen species (ROS), and enzymes, as well as external factors like light. In the context of atherosclerotic cardiovascular diseases (CVDs), stimulus-response polymers have been extensively employed for the preparation of smart nanocarriers that can deliver therapeutic and diagnostic drugs specifically to inflammatory lesions. Compared with traditional drug delivery systems, stimulus-responsive nanosystems offer higher sensitivity, greater versatility, wider applicability, and enhanced biosafety. Recent research has made significant contributions towards designing stimulus-responsive polymer nanosystems for CVDs diagnosis and treatment. This review summarizes recent advances in this field by classifying stimulus-responsive polymer nanocarriers according to different responsiveness types and describing numerous stimuli relevant to these materials. Additionally, we discuss various applications of stimulus-responsive polymer nanomaterials in CVDs theranostics. We hope that this review will provide valuable insights into optimizing the design of stimulus-response polymers for accelerating their clinical application in diagnosing and treating CVDs.

Clypeasterol, a novel aromatic ergosterol skeleton from the mushroom Entoloma clypeatum.

Chemical investigation of the wild mushroom Entoloma clypeatum led to the isolation of one new A-nor B-aromatic C28 steroid (1), along with eight known compounds (2-9) from this mushroom. As far as we know, compound 1 represents an unprecedented type of natural product. The structure of the new compound was elucidated based on extensive spectroscopic data analysis of HR-ESI-MS, 1D, and 2D NMR, while the relative configuration was confirmed by NOESY correlations. In addition, the anti-inflammatory activity of compound 1 was evaluated against LPS induced NO production in RAW 264.7 macrophages. Compound 1 exhibited a moderate anti-inflammatory activity with an IC50 value of 24.56 ± 1.72 µM.

Auxetic Biomedical Metamaterials for Orthopedic Surgery Applications: A Comprehensive Review.

Poisson's ratio in auxetic materials shifts from typically positive to negative, causing lateral expansion during axial tension. This scale-independent characteristic, originating from tailored architectures, exhibits specific physical properties, including energy adsorption, shear resistance, and fracture resistance. These metamaterials demonstrate exotic mechanical properties with potential applications in several engineering fields, but biomedical applications seem to be one of the most relevant, with an increasing number of articles published in recent years, which present opportunities ranging from cellular repair to organ reconstruction with outstanding mechanical performance, mechanical conduction, and biological activity compared with traditional biomedical metamaterials. Therefore, focusing on understanding the potential of these structures and promoting theoretical and experimental investigations into the benefits of their unique mechanical properties is necessary for achieving high-performance biomedical applications. Considering the demand for advanced biomaterial implants in surgical technology and the profound advancement of additive manufacturing technology that are particularly relevant to fabricating complex and customizable auxetic mechanical metamaterials, this review focuses on the fundamental geometric configuration and unique physical properties of negative Poisson's ratio materials, then categorizes and summarizes auxetic material applications across some surgical departments, revealing efficacy in joint surgery, spinal surgery, trauma surgery, and sports medicine contexts. Additionally, it emphasizes the substantial potential of auxetic materials as innovative biomedical solutions in orthopedics and demonstrates the significant potential for comprehensive surgical application in the future.

Chlorogenic acid alleviates renal fibrosis by reducing lipid accumulation in diabetic kidney disease through suppressing the Notch1 and Stat3 signaling pathway.

AIMS: Abnormal renal lipid metabolism causes renal lipid deposition, which leads to the development of renal fibrosis in diabetic kidney disease (DKD). The aim of this study was to investigate the effect and mechanism of chlorogenic acid (CA) on reducing renal lipid accumulation and improving DKD renal fibrosis. METHODS: This study evaluated the effects of CA on renal fibrosis, lipid deposition and lipid metabolism by constructing in vitro and in vivo models of DKD, and detected the improvement of Notch1 and Stat3 signaling pathways. Molecular docking was used to predict the binding between CA and the extracellular domain NRR1 of Notch1 protein. RESULTS: In vitro studies have shown that CA decreased the expression of Fibronectin, α-smooth muscle actin (α-SMA), p-smad3/smad3, alleviated lipid deposition, promoted the expression of carnitine palmitoyl transferase 1 A (CPT1A), and inhibited the expression of cholesterol regulatory element binding protein 1c (SREBP1c). The expression of Notch1, Cleaved Notch1, Hes1, and p-stat3/stat3 were inhibited. These results suggested that CA might reduce intercellular lipid deposition in human kidney cells (HK2) by inhibiting Notch1 and stat3 signaling pathways, thereby improving fibrosis. Further, in vivo studies demonstrated that CA improved renal fibrosis and renal lipid deposition in DKD mice by inhibiting Notch1 and stat3 signaling pathways. Finally, molecular docking experiments showed that the binding energy of CA and NRR1 was -6.6 kcal/mol, which preliminarily predicted the possible action of CA on Notch1 extracellular domain NRR1. CONCLUSION: CA reduces renal lipid accumulation and improves DKD renal fibrosis by inhibiting Notch1 and stat3 signaling pathways.

Research Progress on the Association between Schizophrenia and Toxoplasma gondii Infection.

Toxoplasma gondii( T. gondii or Tg), is an obligatory intracellular parasite with humans as its intermediate hosts. In recent years, significant correlations between T. gondii infection and schizophrenia have been reported, including the possible mediating mechanisms. Currently, mechanisms and hypotheses focus on central neurotransmitters, immunity, neuroinflammation, and epigenetics; however, the exact underlying mechanisms remain unclear. In this article, we review the studies related to T. gondii infection and schizophrenia, particularly the latest research progress. Research on dopamine (DA) and other neurotransmitters, the blood-brain barrier, inflammatory factors, disease heterogeneity, and other confounders is also discussed. In addition, we also summarized the results of some new epidemiological investigations.

Development of a diagnostic nomogram for alpha-fetoprotein-negative hepatocellular carcinoma based on serological biomarkers.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Serum biomarkers play an important role in the early diagnosis and prognosis of HCC. Because a certain percentage of HCC patients are negative for alpha-fetoprotein (AFP), the diagnosis of AFP-negative HCC is essential to improve the detection rate of HCC. AIM: To establish an effective model for diagnosing AFP-negative HCC based on serum tumour biomarkers. METHODS: A total of 180 HCC patients were enrolled in this study. The expression levels of GP73, des-γ-carboxyprothrombin (DCP), CK18-M65, and CK18-M30 were detected by a fully automated chemiluminescence analyser. The variables were selected by logistic regression analysis. Several models were constructed using stepwise backward logistic regression. The performance of the models was compared using the C statistic, integrated discrimination improvement, net reclassification improvement, and calibration curves. The clinical utility of the nomogram was assessed using decision curve analysis (DCA). RESULTS: The results showed that the expression levels of GP73, DCP, CK18-M65, and CK18-M30 were significantly greater in AFP-negative HCC patients than in healthy controls (P < 0.001). Multivariate logistic regression analysis revealed that GP73, DCP, and CK18-M65 were independent factors for diagnosing AFP-negative HCC. By comparing the diagnostic performance of multiple models, we included GP73 and CK18-M65 as the model variables, and the model had good discrimination ability (area under the curve = 0.946) and good goodness of fit. The DCA curves indicated the good clinical utility of the nomogram. CONCLUSION: Our study identified GP73 and CK18-M65 as serum biomarkers with certain application value in the diagnosis of AFP-negative HCC. The diagnostic nomogram based on CK18-M65 combined with GP73 demonstrated good performance and effectively identified high-risk groups of patients with HCC.

Main focus of parents of children with attention deficit hyperactivity disorder and the effectiveness of early clinical screening.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common mental and behavioral disorder among children. AIM: To explore the focus of attention deficit hyperactivity disorder parents and the effectiveness of early clinical screening. METHODS: This study found that the main directions of parents seeking medical help were short attention time for children under 7 years old (16.6%) and poor academic performance for children over 7 years old (12.1%). We employed a two-stage experiment to diagnose ADHD. Among the 5683 children evaluated from 2018 to 2021, 360 met the DSM-5 criteria. Those diagnosed with ADHD underwent assessments for letter, number, and figure attention. Following the exclusion of ADHD-H diagnoses, the detection rate rose to 96.0%, with 310 out of 323 cases identified. RESULTS: This study yielded insights into the primary concerns of parents regarding their children's symptoms and validated the efficacy of a straightforward diagnostic test, offering valuable guidance for directing ADHD treatment, facilitating early detection, and enabling timely intervention. Our research delved into the predominant worries of parents across various age groups. Furthermore, we showcased the precision of the simple exclusion experiment in discerning between ADHD-I and ADHD-C in children. CONCLUSION: Our study will help diagnose and guide future treatment directions for ADHD.

Colonization ability and uniformity of resources and environmental factors determine biological homogenization of soil protists in human land-use systems.

Humans have substantially transformed the global land surface, resulting in the decline in variation in biotic communities across scales, a phenomenon known as "biological homogenization." However, different biota are affected by biological homogenization to varying degrees, but this variation and the underlying mechanisms remain little studied, particularly in soil systems. To address this topic, we used metabarcoding to investigate the biogeography of soil protists and their prey/hosts (prokaryotes, fungi, and meso- and macrofauna) in three human land-use ecosystem types (farmlands, residential areas, and parks) and natural forest ecosystems across subtropical and temperate regions in China. Our results showed that the degree of community homogenization largely differed between taxa and functional groups of soil protists, and was strongly and positively linked to their colonization ability of human land-use systems. Removal analysis showed that the introduction of widespread, generalist taxa (OTUs, operational taxonomic units) rather than the loss of narrow-ranged, specialist OTUs was the major cause of biological homogenization. This increase in generalist OTUs seemingly alleviated the negative impact of land use on specialist taxa, but carried the risk of losing functional diversity. Finally, homogenization of prey/host biota and environmental conditions were also important drivers of biological homogenization in human land-use systems, with their importance being more pronounced in phagotrophic than parasitic and phototrophic protists. Overall, our study showed that the variation in biological homogenization strongly depends on the colonization ability of taxa in human land-use systems, but is also affected by the homogenization of resources and environmental conditions. Importantly, biological homogenization is not the major cause of the decline in the diversity of soil protists, and conservation and study efforts should target at taxa highly sensitive to local extinction, such as parasites.

Co-infection of H9N2 subtype avian influenza virus and QX genotype live attenuated infectious bronchitis virus increase the pathogenicity in SPF chickens.

Avian influenza virus (AIV) infection and vaccination against live attenuated infectious bronchitis virus (aIBV) are frequent in poultry worldwide. Here, we evaluated the clinical effect of H9N2 subtype AIV and QX genotype aIBV co-infection in specific-pathogen-free (SPF) white leghorn chickens and explored the potential mechanisms underlying the observed effects using by 4D-FastDIA-based proteomics. The results showed that co-infection of H9N2 AIV and QX aIBV increased mortality and suppressed the growth of SPF chickens. In particular, severe lesions in the kidneys and slight respiratory signs similar to the symptoms of virulent QX IBV infection were observed in some co-infected chickens, with no such clinical signs observed in single-infected chickens. The replication of H9N2 AIV was significantly enhanced in both the trachea and kidneys, whereas there was only a slight effect on the replication of the QX aIBV. Proteomics analysis showed that the IL-17 signaling pathway was one of the unique pathways enriched in co-infected chickens compared to single infected-chickens. A series of metabolism and immune response-related pathways linked with co-infection were also significantly enriched. Moreover, co-infection of the two pathogens resulted in the enrichment of the negative regulation of telomerase activity. Collectively, our study supports the synergistic effect of the two pathogens, and pointed out that aIBV vaccines might increased IBV-associated lesions due to pathogenic co-infections. Exacerbation of the pathogenicity and mortality in H9N2 AIV and QX aIBV co-infected chickens possibly occurred because of an increase in H9N2 AIV replication, the regulation of telomerase activity, and the disturbance of cell metabolism and the immune system.

Exploring the association between sleep duration and cancer risk in middle-aged and older Chinese adults: observations from a representative cohort study (2011-2020).

BACKGROUND: This prospective cohort study aimed to investigate the relationship between sleep duration and cancer incidence among 9996 participants over a median follow-up period of 9 years. METHODS: Participants without cancer at baseline were followed for over 88,790 person-years. The incidence of cancer and sleep duration was self-reported. The relationship between sleep duration and cancer incidence was analyzed using Cox proportional hazards models adjusted for various confounding factors, including age, gender, lifestyle factors, and comorbidities. RESULTS: During the follow-up, 325 participants were diagnosed with incident cancer, resulting in an incidence rate of 20.49 per 1000 person-years. After adjusting for confounders, a total sleep duration of less than 6 h was significantly associated with an increased risk of cancer (HR: 1.27; 95% CI: 1.01-1.61). This association was particularly strong for cancers in the digestive and respiratory systems (HR: 1.41; 95% CI: 1.03-1.93). Longer sleep durations (> 9 h) showed a potential increase in cancer risk, but results were not consistently significant. Age-stratified analyses revealed a similar significant increase in cancer incidence among individuals aged 60 years or younger with less than 6 h of sleep per day, showing a 35% increase in overall cancer risk and an 83% increase in digestive and respiratory system cancer. No significant association was found between nocturnal sleep durations or daytime naps and cancer incidence. However, a significant interaction was observed between daytime naps longer than 30 min and cancer incidence in women (p = 0.041). CONCLUSIONS: We observed that short sleep duration may increase the risk of cancer, particularly cancers in the digestive and respiratory systems. Additionally, while longer sleep durations might also increase cancer risk, this finding requires validation with larger sample sizes.

A N-doped carbon substrate makes the Ru-Co alloy an efficient electrocatalyst for pH-universal seawater splitting.

Designing electrocatalysts for seawater splitting remains challenging. A Ru-Co alloy supported by an N-doped carbon substrate catalyst has been designed using etching and a low-temperature treatment method. Studies show that the superior performance of this catalyst is related to the hollow-structured N-doped carbon frame and surface reconstruction of the Ru-Co alloy.

Mechanism and therapeutic potential of traditional Chinese medicine extracts in sepsis.

Sepsis is a complex syndrome characterized by multi-organ dysfunction, due to the presence of harmful microorganisms in blood which could cause mortality. Complications associated with sepsis involve multiple organ dysfunction. The pathogenesis of sepsis remains intricate, with limited treatment options and high mortality rates. Traditional Chinese medicine (TCM) has consistently demonstrated to have a potential on various disease management. Its complements include reduction of oxidative stress, inhibiting inflammatory pathways, regulating immune responses, and improving microcirculation. Traditional Chinese medicine can mitigate or even treat sepsis in a human system. This review examines progress on the use of TCM extracts for treating sepsis through different pharmacological action and its mechanisms. The potential targets of TCM extracts and active ingredients for the treatment of sepsis and its complications have been elucidated through molecular biology research, network pharmacology prediction, molecular docking analysis, and visualization analysis. Our aim is to provide a theoretical basis and empirical support for utilizing TCM in the treatment of sepsis and its complications while also serving as a reference for future research and development of sepsis drugs.

Selective Activation of Cascade Assembly Amplification for DNA Methyltransferase Detection Using a Double-Loop Interlocked DNA Circuit.

Precise and reliable monitoring of DNA adenine methyltransferase (Dam) activity is essential for disease diagnosis and biological analysis. However, existing techniques for detecting Dam activity often rely on specific DNA recognition probes that are susceptible to DNA degradation and exhibit limited target sensitivity and specificity. In this study, we designed and engineered a stable and dynamic DNA nanodevice called the double-loop interlocked DNA circuit (DOOR) that enables the sensitive and selective monitoring of Dam activity in complex biological environments. The DOOR incorporates two interlocked specialized sequences: a palindromic sequence for Dam identification and an initiator sequence for signal amplification. In the presence of Dam, the DOOR is cleaved by double-stranded DNA phosphodiesterase I endonuclease, generating massive double-stranded DNA (dsDNA) units. These units can self-assemble into a long dsDNA scaffold, thereby enhancing the subsequent reaction kinetics. The dsDNA scaffold further triggers a hyperbranched hybrid chain reaction to produce a fluorescent 3D DNA nanonet, enabling more precise monitoring of the Dam activity. The DOOR device exhibits excellent sensitivity, specificity, and stability, rendering it a powerful tool for studying DNA methylation in various biological processes and diseases.

[Research Progress of Functional Materials for Conversion of Agricultural Biomass Wastes].

Excess agricultural biomass waste is increasing rapidly, leading to many environmental and governance issues. Therefore, increased attention has been paid to the recycling and value-added application of agricultural biomass waste. In recent years, the research of agricultural biomass waste utilization and derived functional materials has mainly included the following two aspects： ① the extraction of natural polymers and value-added applications and ② the direct preparation of new carbon-based materials, including adsorption, catalysis, energy storage electrode, and composite functional materials. The conversion of agricultural biomass waste into functional materials has been gradually realized and widely used. To enable industrial-scale production and the quality and safety of agricultural biomass waste derivatives and to develop highly feasible and cost-effective biomass waste conversion methods should be the focus of future studies.

Rapid Detection of Uropathogens Using an Integrated Multiplex Digital Nucleic Acid Detection Assay Powered by a Digital-to-Droplet Microfluidic Device.

The digital nucleic acid detection assay features the capability of absolute quantitation without the need for calibration, thereby facilitating the rapid identification of pathogens. Although several integrated digital nucleic acid detection techniques have been developed, there are still constraints in terms of automation and analysis throughput. To tackle these challenges, this study presents a digital-to-droplet microfluidic device comprising a digital microfluidics (DMF) module at the bottom and a droplet microfluidics module at the top. Following sample introduction, the extraction of nucleic acid and the dispensation of nucleic acid elution for mixing with the multiple amplification reagents are carried out in the DMF module. Subsequently, the reaction droplets are transported to the sample inlet of the droplet microfluidic module via a liquid outlet, and then droplet generation in four parallel units within the droplet microfluidics module is actuated by negative pressure generated by a syringe vacuum. The digital-to-droplet microfluidic device was employed to execute an integrated multiplex digital droplet nucleic acid detection assay (imDDNA) incorporating loop-mediated isothermal amplification (LAMP). This assay was specifically designed to enable simultaneous detection of four uropathogens, namely, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterococcus faecalis. The entire process of the imDDNA is completed within 75 min, with a detection range spanning 5 orders of magnitude (9.43 × 10-2.86 × 104 copies µL-1). The imDDNA was employed for the detection of batched clinical specimens, showing a consistency of 91.1% when compared with that of the conventional method. The imDDNA exhibits simplicity in operation and accuracy in quantification, thus offering potential advantages in achieving rapid pathogen detection.