Associations of Combined Exposure to Metabolic and Inflammatory Indicators with Thyroid Nodules in Adults: A Nested Case-Control Study.

Objective: To explore associations of combined exposure to metabolic/inflammatory indicators with thyroid nodules. Methods: We reviewed personal data for health screenings from 2020 to 2021. A propensity score matching method was used to match 931 adults recently diagnosed with thyroid nodules in a 1 : 4 ratio based on age and gender. Conditional logistic regression and Bayesian kernel machine regression (BKMR) were used to explore the associations of single metabolic/inflammatory indicators and the mixture with thyroid nodules, respectively. Results: In the adjusted models, five indicators (ORQ4 vs. Q1: 1.30, 95% CI: 1.07-1.58 for fasting blood glucose; ORQ4 vs. Q1: 1.30, 95% CI: 1.08-1.57 for systolic blood pressure; ORQ4 vs. Q1: 1.26, 95% CI: 1.04-1.53 for diastolic blood pressure; ORQ4 vs. Q1: 1.23, 95% CI: 1.02-1.48 for white blood cell; ORQ4 vs. Q1: 1.28, 95% CI: 1.07-1.55 for neutrophil) were positively associated with the risk of thyroid nodules, while high-density lipoproteins (ORQ3 vs. Q1: 0.75, 95% CI: 0.61-0.91) were negatively associated with the risk of thyroid nodules. Univariate exposure-response functions from BKMR models showed similar results. Moreover, the metabolic and inflammatory mixture exhibited a significant positive association with thyroid nodules in a dose-response pattern, with systolic blood pressure being the greatest contributor within the mixture (conditional posterior inclusion probability of 0.82). No interaction effects were found among the five indicators. These associations were more prominent in males, participants with higher age (≥40 years old), and individuals with abnormal body mass index status. Conclusions: Levels of the metabolic and inflammatory mixture have a linear dose-response relationship with the risk of developing thyroid nodules, with systolic blood pressure levels being the most important contributor.

Use of circulating tumor cells and microemboli to predict diagnosis and prognosis in diffuse glioma.

OBJECTIVE: Circulating tumor cell (CTC) detection is a promising noninvasive technique that can be used to diagnose cancer, monitor progression, and predict prognosis. In this study, the authors aimed to investigate the clinical utility of CTCs in the management of diffuse glioma. METHODS: Sixty-three patients with newly diagnosed diffuse glioma were included in this multicenter clinical cohort. The authors used a platform based on isolation by size of epithelial tumor cells (ISET) to detect and analyze CTCs and circulating tumor microemboli (CTMs) in the peripheral blood of patients both before and after surgery. Least absolute shrinkage and selector operation (LASSO) and Cox regression analyses were used to verify whether CTCs and CTMs are independent prognostic factors for diffuse glioma. RESULTS: CTC levels were closely related to the degree of malignancy, WHO grade, and pathological subtypes. Receiver operating characteristic curve analysis revealed that a high CTC level was a predictor for glioblastoma. The results also showed that CTMs originate from the parental tumor rather than from the circulation and are an independent prognostic factor for diffuse glioma. The postoperative CTC level is related to the peripheral immune system and patient survival. Cox regression analysis showed that postoperative CTC levels and CTM status are independent prognostic factors for diffuse glioma, and CTC- and CTM-based survival models had high accuracy in internal validation. CONCLUSIONS: The authors revealed a correlation between CTCs and clinical characteristics and demonstrated that CTCs and CTMs are independent predictors for the diagnosis and prognosis of diffuse glioma. Their CTC- and CTM-based survival models can enable clinicians to evaluate patients' response to surgery as well as their outcomes.

Novel potential lncRNA biomarker in B cells indicates essential pathogenic pathway activation in patients with SLE.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a highly heterogeneous disease, and B cell abnormalities play a central role in the pathogenesis of SLE. Long non-coding RNAs (lncRNAs) have also been implicated in the pathogenesis of SLE. The expression of lncRNAs is finely regulated and cell-type dependent, so we aimed to identify B cell-expressing lncRNAs as biomarkers for SLE, and to explore their ability to reflect the status of SLE critical pathway and disease activity. METHODS: Weighted gene coexpression network analysis (WGCNA) was used to cluster B cell-expressing genes of patients with SLE into different gene modules and relate them to clinical features. Based on the results of WGCNA, candidate lncRNA levels were further explored in public bulk and single-cell RNA-sequencing data. In another independent cohort, the levels of the candidate were detected by RT-qPCR and the correlation with disease activity was analysed. RESULTS: WGCNA analysis revealed one gene module significantly correlated with clinical features, which was enriched in type I interferon (IFN) pathway. Among non-coding genes in this module, lncRNA RP11-273G15.2 was differentially expressed in all five subsets of B cells from patients with SLE compared with healthy controls and other autoimmune diseases. RT-qPCR validated that RP11-273G15.2 was highly expressed in SLE B cells and positively correlated with IFN scores (r=0.7329, p<0.0001) and disease activity (r=0.4710, p=0.0005). CONCLUSION: RP11-273G15.2 could act as a diagnostic and disease activity monitoring biomarker for SLE, which might have the potential to guide clinical management.

A tough, reversible and highly sensitive humidity actuator based on cellulose nanofiber films by intercalation modulated plasticization.

Cellulose nanofiber was an ideal candidate for humidity actuators based on its wide availability, biocompatibility and excellent hydrophilicity. However, conventional cellulose nanofiber-based actuators faced challenges like poor water resistance, flexibility, and sensitivity. Herein, water-resistant, flexible, and highly sensitive cross-linked cellulose nanofibers (CCNF) single-layer humidity actuators with remarkable reversible humidity responsiveness were prepared by combining the green click chemistry modification and intercalation modulated plasticization (IMP). The incorporation of phenyl ring and the crosslinked network structure in CCNF films contributed to its improved water resistance and mechanical properties (with a stress increased from 85.9 ± 3.1 MPa to 141.2 ± 21.5 MPa). SEM analysis confirmed enhanced interlaminar sliding properties facilitated by IMP. This resulted in increased flexibility and toughness of CCNF films, with a strain of 11.5 % and toughness of 9.9 MJ/m3. These improvements efficiently enhanced humidity sensitivity for cellulose nanofiber, with a 4.8-fold increase in bending curvature and a response time of only 3.4 ± 0.1 s. Finally, the good humidity sensitivity of modified CNF can be easily imparted to carbon nanotubes (CNTs) via simple self-assembly method, thus leading to a high-performance humidity-responsive actuator. The click chemistry modification and IMP offer a new avenue to fabricate tough, reversible and highly sensitive humidity actuator based on cellulose nanofiber.

Study on the pharmacokinetics, tissue distribution and excretion of Penthorum chinense Pursh in normal and acute alcoholic liver injury rats using validated UPLC-MS/MS method.

Penthorum chinense Pursh (PCP), as a traditional medicine of Miao nationality in China, is often used for the treatment of various liver diseases. At present, information regarding the in vivo process of PCP is lacking. Herein, a sensitive and robust ultra-performance liquid chromatography tandem with mass spectrometry (UPLC-MS/MS) was developed and validated for the quantification of several components to study their pharmacokinetics, tissues distribution and excretion in normal and acute alcoholic liver injury (ALI) rats. Prepared samples were separated on a Thermo C18 column (4.6 mm × 50 mm, 2.4 µm) using water containing 0.1 % formic acid (A) and acetonitrile (B) as the mobile phase for gradient elution. Negative electrospray ionization was performed using multiple reaction monitoring (MRM) mode for each component. The validated UPLC-MS/MS assay gave good linearity, accuracy, precision, recovery rate, matrix effect and stability. This method was successfully applied to the pharmacokinetics, tissue distribution and excretion in normal and acute ALI rats. There were differences in pharmacokinetic process, tissue distribution and excretion characteristics, indicating that ALI had a significant influence on the in vivo process of PCP in rats. The research provided an experimental basis for the study of PCP quality control and further application in the clinic.

Adaptive real-time single-pixel imaging.

For most imaging systems, there is a trade-off between spatial resolution, temporal resolution, and signal-to-noise ratio. Such a trade-off is particularly severe in single-pixel imaging systems, given the limited throughput of the only one available pixel. Here we report a real-time single-pixel imaging method that can adaptively balance the spatial resolution, temporal resolution, and signal-to-noise ratio of the imaging system according to the changes in the target scene. When scene changes are detected, the dynamic imaging mode will be activated. The temporal resolution will be given high priority and real-time single-pixel imaging will be conducted at a video frame rate (30 frames/s) to visualize the object motion. When no scene changes are detected, the static imaging mode will be activated. The spatial resolution and the signal-to-noise ratio will be progressively built up to resolve fine structures and to improve image quality. The proposed method not only adds practicability to single-pixel imaging, but also generates a new, to the best of our knowledge, insight in data redundancy reduction and information capacity improvement for other computational imaging schemes.

Loneliness Trajectories Predict Risks of Cardiovascular Diseases in Chinese Middle-Aged and Older Adults.

OBJECTIVES: Loneliness is considered a risk factor for cardiovascular diseases (CVD), but related evidence is mixed. Examining trajectories of loneliness over time, as compared to the assessment of loneliness at a single time point, can be useful to better understand the risks for CVD. The present study aimed to examine loneliness trajectories and their impacts on CVD in Chinese middle-aged and older adults. METHODS: The sample included 9235 adults aged 45 years and above from four waves of the China Health and Retirement Longitudinal Survey from 2011 to 2018. Loneliness was assessed by a single-item question with a four-point scale. CVD events were measured by self-reports of heart diseases and stroke in 2018. RESULTS: Group-based trajectory modeling showed that three loneliness trajectories emerged: stable low, moderate increasing, and high increasing loneliness. Binary logistic regression showed that loneliness trajectories were significantly associated with the risk of having CVD after controlling for all covariates. Specifically, compared to the group with stable low loneliness, people with moderate increasing had a higher risk of having stroke, and people with high increasing loneliness had higher risks of having both heart diseases and stroke. In contrast, loneliness at a single time point was not independently associated with the risk of having CVD. DISCUSSION: The present study identified groups of people vulnerable to CVD from the perspective of social connections in terms of loneliness trajectories. Middle-aged and older adults showing increasing loneliness may need social and emotional support to protect their cardiovascular health.

Low-frequency band noise generated by industrial recirculating aquaculture systems exhibits a greater impact on Micropterus salmoidess.

The effect of underwater noise environment generated by equipment in industrial recirculating aquaculture systems (RAS) on fish is evident. However, different equipment generate noise in various frequency ranges. Understanding the effects of different frequency ranges noise on cultured species is important for optimizing the underwater acoustic environment in RAS. Given this, the effects of underwater noise across various frequency bands in RAS on the growth, physiology, and collective behavior of juvenile largemouth bass (Micropterus salmoides) were comprehensively evaluated here. In this study, three control groups were established: low-frequency noise group (80-1000 Hz, 117 dB re 1µPa RMS), high-frequency noise group (1-19 kHz, 117 dB re 1µPa RMS), and ambient group. During a 30-day experiment, it was found that: 1) industrial RAS noise with different frequency bands all had a certain inhibitory effect on the growth of fish, which the weight gain rate and product of length and depth of caudal peduncle in the ambient group were significantly higher than those of the two noise groups, with the low-frequency noise group showing significantly lower values than the high-frequency noise group; 2) industrial RAS noise had a certain degree of adverse effect on the digestive ability of fish, with the low-frequency noise group being more affected; 3) industrial RAS noise affected the collective feeding behavior of fish, with the collective feeding signal propagation efficiency and feeding intensity of the noise groups being significantly lower than those of the ambient group, and the high-frequency noise group performing better than the low-frequency noise group as a whole therein. From the above, the underwater noise across different frequency bands generated by equipment operation in industrial RAS both had an impact on juvenile largemouth bass, with the low-frequency noise group being more severely affected.

Short-term effects of heatwaves on clinical and subclinical cardiovascular indicators in Chinese adults: A distributed lag analysis.

AIMS: Previous studies have related heat waves to morbidity and mortality of cardiovascular diseases; however, potential mechanisms remained limited. Our aims were to investigate the short-term effects of heat waves on a series of clinical/subclinical indicators associated with cardiovascular health. METHODS: Our study used 80,574 health examination records from the Health Management Center of Nanjing Zhongda Hospital during the warm seasons of 2019-2021, including 62,128 participants. A total of 11 recognized indicators of cardiovascular risk or injury were assessed. Air pollution and meteorological data were obtained from the Nanjing Ecological Environment Bureau and the China Meteorological Data Network, respectively. Heat waves were defined as a daily average temperature over the 95th percentile for three or more consecutive days from May to September. We used a combination of linear mixed effects models and distributed lag nonlinear models to assess the lagged effects of heat waves on clinical and subclinical cardiovascular indicators. Stratified analyses based on individuals' characteristics, including gender, age, body mass index (BMI), diabetes, and hypertension, were also performed. RESULTS: Heat waves were related to significant changes in most indicators, with the magnitude of effects generally peaking at a lag of 0 to 3 days. Moreover, the cumulative percentage changes over lag 0-7 days were -0.82 % to -2.55 % in blood pressure, 1.32 % in heart rate, 0.20 % to 2.66 % in systemic inflammation markers, 0.36 % in a blood viscosity parameter, 9.36 % in homocysteine, and 1.35 % to 3.25 % in injuring myocardial enzymes. Interestingly, females and males showed distinct susceptibilities in different indicators. Stronger effects were also found in participants aged 50 years or over, individuals with abnormal BMI status, and patients with diabetes. CONCLUSION: Short-term exposure to heat waves could significantly alter clinical/subclinical cardiovascular indicator profiles, including blood pressure changes, increased heart rate, acute systemic inflammation, elevated blood viscosity, and myocardial injury.

Copper-doped bismuth oxychloride nanosheets assembled into sphere-like morphology for improved photocatalytic inactivation of drug-resistant bacteria.

The devastating microbiological contamination as well as emerging drug-resistant bacteria has posed severe threats to the ecosystem and public health, which propels the continuous exploitation of safe yet efficient disinfection products and technology. Here, copper doping engineered bismuth oxychloride (Cu-BiOCl) nanocomposite with a hierarchical spherical structure was successfully prepared. It was found that due to the exposure of abundant active sites for the adsorption of both bacteria cells and molecular oxygen in the structure, the obtained Cu-BiOCl with nanosheets assembled into sphere-like morphology exhibited remarkable photocatalytic antibacterial effects. In particular, compared to the pure BiOCl, composite Cu-BiOCl possessed improved antibacterial effects against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Methicillin-resistant Staphylococcus aureus (MRSA). The combination of physicochemical characterizations and theoretical calculations has revealed that copper doping significantly promoted the light absorbance, inhibited the recombination of electron-hole pairs, and enhanced molecular oxygen adsorption, which resulted in more generation of active species including reactive oxygen species (ROS) and h+ to achieve superior photocatalytic bacterial inactivation. Finally, transcriptome analysis on MRSA pinpointed photocatalytic inactivation induced by Cu-BiOCl may retard largely the development of drug-resistance. Therefore, the built spherical Cu-BiOCl nanocomposite has provided an ecofriendly, economical and robust strategy for the efficient removal of drug-resistant bacteria with promising potentials for environmental and healthcare utilizations.

Whole-brain mapping of monosynaptic afferent inputs to the CRH neurons in the medial prefrontal cortex of mice.

Corticotropin-releasing hormone (CRH) neurons are densely distributed in the medial prefrontal cortex (mPFC), which plays a crucial role in integrating and processing emotional and cognitive inputs from other brain regions. Therefore, it is important to know the neural afferent patterns of mPFCCRH neurons, which are still unclear. Here, we utilized a rabies virus-based monosynaptic retrograde tracing system to map the presynaptic afferents of the mPFCCRH neurons throughout the entire brain. The results show that the mPFCCRH neurons receive inputs from three main groups of brain regions: (1) the cortex, primarily the orbital cortex, somatomotor areas, and anterior cingulate cortex; (2) the thalamus, primarily the anteromedial nucleus, mediodorsal thalamic nucleus, and central medial thalamic nucleus; and (3) other brain regions, primarily the basolateral amygdala, hippocampus, and dorsal raphe nucleus. Taken together, our results are valuable for further investigations into the roles of the mPFCCRH neurons in normal and neurological disease states. These investigations can shed light on various aspects such as cognitive processing, emotional modulation, motivation, sociability, and pain.

MiniMounter: A low-cost miniaturized microscopy development toolkit for image quality control and enhancement.

Head-mounted miniaturized fluorescence microscopy (Miniscope) has emerged as a significant tool in neuroscience, particularly for behavioral studies in awake rodents. However, the challenges of image quality control and standardization persist for both Miniscope users and developers. In this study, we propose a cost-effective and comprehensive toolkit named MiniMounter. This toolkit comprises a hardware platform that offers customized grippers and four-degree-of-freedom adjustment for Miniscope, along with software that integrates displacement control, image quality evaluation, and enhancement of 3D visualization. Our toolkit makes it feasible to accurately characterize Miniscope. Furthermore, MiniMounter enables auto-focusing and 3D imaging for Miniscope prototypes that possess solely a 2D imaging function, as demonstrated in phantom and animal experiments. Overall, the implementation of MiniMounter effectively enhances image quality, reduces the time required for experimental operations and image evaluation, and consequently accelerates the development and research cycle for both users and developers within the Miniscope community.

A Proteomic Analysis of Human Follicular Fluid: Proteomic Profile Associated with Embryo Quality.

Embryo selection is a key point of in vitro fertilization (IVF). The most commonly used method for embryo selection is morphological assessment. However, it is sometimes inaccurate. Follicular fluid (FF) contains a complex mixture of proteins that are essential for follicle development and oocyte maturation. Analyzing human FF proteomic profiles and identifying predictive biomarkers might be helpful for evaluating embryo quality. A total of 22 human FF samples were collected from 19 infertile women who underwent IVF/intracytoplasmic sperm injection (ICSI) treatment between October 2021 and November 2021. FFs were grouped into two categories on the basis of the day 3 embryo quality, grade I or II in the hqFF group and grade III in the nhqFF group. FF was analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). The key differentially expressed proteins (DEPs) were validated by parallel reaction monitoring (PRM) and enzyme-linked immunosorbent assay (ELISA). Differentially expressed proteins were further analyzed using DAVID software. A total of 558 proteins were identified, of which 50 proteins were differentially expressed in the hqFF versus nhqFF group, including 32 upregulated proteins (> 1.20-fold, P < 0.05) and 18 downregulated proteins (< 0.67-fold, P < 0.05). Bioinformatics analyses showed that the upregulated DEPs were enriched in components of the coagulation and complement systems and negative regulation of peptidase activity, while the downregulated DEPs were enriched in molecular function of extracellular matrix structural and constituent collagen binding. Our results suggested that a number of protein biomarkers in FF were associated with embryo quality. It may help develop an effective and noninvasive method for embryo selection.

Three-Dimensional Chromosomal Landscape Revealing miR-146a Dysfunctional Enhancer in Lupus and Establishing a CRISPR-Mediated Approach to Inhibit the Interferon Pathway.

OBJECTIVE: The diminished expression of microRNA-146a (miR-146a) in systemic lupus erythematosus (SLE) contributes to the aberrant activation of the interferon pathway. Despite its significance, the underlying mechanism driving this reduced expression remains elusive. Considering the integral role of enhancers in steering gene expression, our study seeks to pinpoint the SLE-affected enhancers responsible for modulating miR-146a expression. Additionally, we aim to elucidate the mechanisms by which these enhancers influence the contribution of miR-146a to the activation of the interferon pathway. METHODS: Circular chromosome conformation capture sequencing and epigenomic profiles were applied to identify candidate enhancers of miR-146a. CRISPR activation was performed to screen functional enhancers. Differential analysis of chromatin accessibility was used to identify SLE-dysregulated enhancers, and the mechanism underlying enhancer dysfunction was investigated by analyzing transcription factor binding. The therapeutic value of a lupus-related enhancer was further evaluated by targeting it in the peripheral blood mononuclear cells (PBMCs) of patients with SLE through a CRISPR activation approach. RESULTS: We identified shared and cell-specific enhancers of miR-146a in distinct immune cells. An enhancer 32.5 kb downstream of miR-146a possesses less accessibility in SLE, and its chromatin openness was negatively correlated with SLE disease activity. Moreover, CCAAT/enhancer binding protein α, a down-regulated transcription factor in patients with SLE, binds to the 32.5-kb enhancer and induces the epigenomic change of this locus. Furthermore, CRISPR-based activation of this enhancer in SLE PBMCs could inhibit the activity of interferon pathway. CONCLUSION: Our work defines a promising target for SLE intervention. We adopted integrative approaches to define cell-specific and functional enhancers of the SLE critical gene and investigated the mechanism underlying its dysregulation mediated by a lupus-related enhancer.

Association between liver fibrosis and stroke recurrence in young patients with ischemic stroke.

BACKGROUND AND AIM: Stroke incidence rates are rising among young adults. Liver fibrosis has recently been recognized as a risk factor for cardiovascular events and stroke in the general population. It remains unclear whether liver fibrosis influences the prognosis of stroke. We aimed to evaluate the association between liver fibrosis and stroke recurrence in young stroke patients. METHODS AND RESULTS: Young adults with first-ever ischemic stroke were enrolled from a prospective stroke registry and were followed up for stroke recurrence. Liver fibrosis was evaluated by Fibrosis-4 (FIB-4) score and was stratified into three categories. Cox regression analysis was performed to assess the relationship between liver fibrosis and stroke recurrence. Over a median follow-up of 3.1 (1.7-4.6) years, 72 (11.6%) recurrent strokes occurred among 621 patients. According to the FIB-4 score, 73 (11.7%) patients had indeterminate fibrosis, while 11 (1.8%) had advanced fibrosis. Univariate Cox analysis revealed that patients with a high FIB-4 score were more likely to experience stroke recurrence than those with a low FIB-4 score (hazard ratio 3.748, 95% confidence interval 1.359-10.332, P = 0.011). After adjusting for potential confounders in the multivariate analysis, FIB-4 score remained an independent risk factor. CONCLUSIONS: Young stroke patients with advanced liver fibrosis were at a greater risk of stroke recurrence. Evaluating liver fibrosis may provide valuable information for stroke risk stratification, and the FIB-4 score could serve as a useful tool.

Optimizing the Buried Interface in Flexible Perovskite Solar Cells to Achieve Over 24% Efficiency and Long-Term Stability.

The buried interface of the perovskite layer has a profound influence on its film morphology, defect formation, and aging resistance from the outset, therefore, significantly affects the film quality and device performance of derived perovskite solar cells. Especially for FAPbI3 , although it has excellent optoelectronic properties, the spontaneous transition from the black perovskite phase to nonperovskite phase tends to start from the buried interface at the early stage of film formation then further propagate to degrade the whole perovskite. In this work, by introducing ─NH3 + rich proline hydrochloride (PF) with a conjugated rigid structure as a versatile medium for buried interface, it not only provides a solid α-phase FAPbI3 template, but also prevents the phase transition induced degradation. PF also acts as an effective interfacial stress reliever to enhance both efficiency and stability of flexible solar cells. Consequently, a champion efficiency of 24.61% (certified 23.51%) can be achieved, which is the highest efficiency among all reported values for flexible perovskite solar cells. Besides, devices demonstrate excellent shelf-life/light soaking stability (advanced level of ISOS stability protocols) and mechanical stability.

The flower of Abelmoschus manihot (L.) medik exerts antioxidant effects by regulating the Nrf2 signalling pathway in scald injury.

Scald is a common skin injury in daily life. It is well known that skin burns are associated with inflammation and oxidative stress. In our previous study, we found that Abelmoschus manihot (L.) medik had excellent therapeutic effects on scald-induced inflammation, but its effect on scald-induced oxidative stress was not reported. In this study, a deep second-degree scald model in mice was established, and the wound healing rate, healing time, malondialdehyde (MDA) and total superoxide dismutase (T-SOD) levels, and nuclear factor erythroid 2-related Factor 2 (Nrf2) expression in wound tissue were measured to evaluate the scald wound healing performance of extraction from A. manihot (L.) medik (EAM). Scalding activity in mice was examined in vivo by hot water-induced finger swelling. The treatment scald activities were also examined in vivo by subjecting mice to thermal water-induced digit swelling. Additionally, the antioxidant effect of EAM on fibroblasts was also used to determine the mechanism in vitro. The results showed that EAM not only decreased the wound healing time but also effectively regulated the levels of oxidising, MDA and T-SOD in wound tissue. Concurrently, EAM suppressed digit swelling and hyperalgesia. Furthermore, EAM had a significant protective effect on NIH-3T3 cells after H2 O2 injury by regulating the Nrf2 signalling pathway against oxidative injury. Therefore, EAM is a promising drug for the treatment of scald-induced inflammation.

Morroniside-mediated mitigation of stem cell and endothelial cell dysfunction for the therapy of glucocorticoid-induced osteonecrosis of the femoral head.

BACKGROUND: Prolonged use of glucocorticoids (GCs) potentially lead to a condition known as GCs-induced osteonecrosis of the femoral head (GIONFH). The primary mechanisms underlying this phenomenon lies in stem cells and endothelial cells dysfunctions. Morroniside, an iridoid glycoside sourced from Cornus officinalis, possesses numerous biological capabilities, including combating oxidative stress, preventing apoptosis, opposing ischemic effects, and promoting the regeneration of bone tissue. PURPOSE: This study aimed to analyze the impact of Morroniside on Dexamethasone (DEX)-induced dysfunction in stem cells and endothelial cells, and its potential as a therapeutic agent for GIONFH in rat models. METHODS: ROS assay, JC-1 assay, and TUNEL assay were used to detect oxidative stress and apoptosis levels in vitro. For the evaluation of the osteogenic capability of bone marrow-derived mesenchymal stem cells, we employed ALP and ARS staining. Additionally, the angiogenic ability of endothelial cells was assessed using tube formation assay and migration assay. Microcomputed tomography analysis, hematoxylin-eosin staining, and immunohistochemical staining were utilized to evaluate the in vivo therapeutic efficacy of Morroniside. RESULTS: Morroniside mitigates DEX-induced excessive ROS expression and cell apoptosis, effectively reducing oxidative stress and alleviating cell death. In terms of osteogenesis, Morroniside reverses DEX-induced osteogenic impairment, as evidenced by enhanced ALP and ARS staining, as well as increased osteogenic protein expression. In angiogenesis, Morroniside counteracts DEX-induced vascular dysfunction, demonstrated by an increase in tube-like structures in tube formation assays, a rise in the number of migrating cells, and elevated levels of angiogenic proteins. In vivo, our results further indicate that Morroniside alleviates the progression of GIONFH. CONCLUSION: The experimental findings suggest that Morroniside concurrently mitigates stem cell and endothelial cell dysfunction through the PI3K/AKT signaling pathway both in vitro and in vivo. These outcomes suggest that Morroniside serves as a potential therapeutic agent for GIONFH.

Self-Assembled nanoparticles of natural bioactive molecules enhance the delivery and efficacy of paclitaxel in glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common primary malignant tumor in the central nervous system. Paclitaxel (PTX) is a well-established and highly effective anti-cancer drug for peripheral solid tumors. However, the application of PTX in GBM is hindered by several limitations, including poor water solubility, restricted entry across the blood-brain barrier (BBB), and enhanced excretion by efflux transporters. P-glycoprotein (P-gp) is a crucial efflux transporter that is abundantly present in cerebral vascular endothelial cells and GBM cells. It plays a significant role in the exocytosis of PTX within tumor tissues. METHODS: Recently, we have developed a novel technique for creating self-assembled nanoparticles utilizing a range of natural bioactive molecules. These nanoparticles can encapsulate insoluble drugs and effectively cross the BBB. In additional, we revealed that certain nanoparticles have the potential to act as P-gp inhibitors, thereby reducing the excretion of PTX. In this study, we conducted a screening of bioactive molecular nanoparticles to identify those that effectively inhibit the function of P-gp transporters. RESULTS: Among the candidates, we identified ursolic acid nanoparticles (UA NPs) as the P-gp inhibitors. Furthermore, we prepared co-assembled UA NPs embedded with paclitaxel, referred to as UA-PTX NPs. Our results demonstrate that UA-PTX NPs can enhance the blood concentration of PTX, facilitate its entry into the BBB, and inhibit the function of P-gp, resulting in a decrease in the excretion of PTX. This discovery effectively addressed the above three issues associated with the use of PTX in glioma treatment. CONCLUSIONS: UA-PTX NPs demonstrate strong anti-tumor effects and show great potential for treating GBM.

Enhancing visual perceptual learning using transcranial electrical stimulation: Transcranial alternating current stimulation outperforms both transcranial direct current and random noise stimulation.

Diverse strategies can be employed to enhance visual skills, including visual perceptual learning (VPL) and transcranial electrical stimulation (tES). Combining VPL and tES is a popular method that holds promise for producing significant improvements in visual acuity within a short time frame. However, there is still a lack of comprehensive evaluation regarding the effects of combining different types of tES and VPL on enhancing visual function, especially with a larger sample size. In the present study, we recruited four groups of subjects (26 subjects each) to learn an orientation discrimination task with five daily training sessions. During training, the occipital region of each subject was stimulated by one type of tES-anodal transcranial direct current stimulation (tDCS), alternating current stimulation (tACS) at 10 Hz, high-frequency random noise stimulation (tRNS), and sham tACS-while the subject performed the training task. We found that, compared with the sham stimulation, both the high-frequency tRNS and the 10-Hz tACS facilitated VPL efficiently in terms of learning rate and performance improvement, but there was little modulatory effect in the anodal tDCS condition. Remarkably, the 10-Hz tACS condition exhibited superior modulatory effects compared with the tRNS condition, demonstrating the strongest modulation among the most commonly used tES types for further enhancing vision when combined with VPL. Our results suggest that alpha oscillations play a vital role in VPL. Our study provides a practical guide for vision rehabilitation.