Enhanced brain-targeting and efficacy of cannabidiol via RVG-Exo/CBD nanodelivery system.

This study introduces an innovative brain-targeted drug delivery system, RVG-Exo/CBD, utilizing rabies virus glycoprotein (RVG)-engineered exosomes for encapsulating cannabidiol (CBD). The novel delivery system was meticulously characterized, confirming the maintenance of exosomal integrity, size, and successful drug encapsulation with a high drug loading rate of 83.0 %. Evaluation of the RVG-Exo/CBD's brain-targeting capability demonstrated superior distribution and retention in brain tissue compared to unmodified exosomes, primarily validated through in vivo fluorescence imaging. The efficacy of this delivery system was assessed using a behavioral sensitization model in mice, where RVG-Exo/CBD notably suppressed methamphetamine-induced hyperactivity more effectively than CBD alone, indicating a reduction in effective dose and enhanced bioavailability. Overall, the RVG-Exo/CBD system emerges as a promising strategy for enhancing the therapeutic efficacy and safety of CBD, particularly for neurological applications, highlighting its potential for addressing the limitations associated with traditional CBD administration in clinical settings.

PI3Kδ Mediates Fibrosis by Patient-Derived Vitreous.

The epithelial-mesenchymal transition (EMT) is a fundamental process in developing fibrotic diseases, including forming epiretinal membranes (ERMs). ERMs can result in irreversible vision loss. Previous research has demonstrated that vitreous (VIT) derived from patients with proliferative diabetic retinopathy can stimulate angiogenesis through the Axl/PI3K/Akt pathway. Building upon this knowledge, we aimed to explore the influence of VIT from patients with macular membranes in ARPE-19 cells. Our findings reveal that patient-derived VIT from individuals with macular membranes promotes EMT and phosphoinositide 3-kinase-delta (PI3Kδ) expression in ARPE-19 cells. To elucidate the function of PI3Kδ in the ERM, we conducted experiments involving the knockout of p110δ, a key subunit of PI3Kδ, and observed that its absence hinders EMT induced by patient-derived VIT. Moreover, p110δ depletion reduces cell proliferation and migration in ARPE-19 cells. Remarkably, these effects were further corroborated by applying the p110δ inhibitor idelalisib, which blocks fibrosis in the laser-induced fibrosis model. Collectively, our results propose that p110δ plays a critical role in the progression of ERMs. Consequently, targeting p110δ emerges as a promising therapeutic approach for mitigating fibrosis. These findings contribute to a better understanding of the underlying mechanisms involved in ERM formation and highlight the potential for p110δ-directed antifibrotic therapy in retinal diseases.

Redefining left bundle branch block from high-density electroanatomical mapping.

BACKGROUND: The existing ECG criteria for diagnosing left bundle branch block (LBBB) are insufficient to distinguish between true and false blocks accurately. METHODS: We hypothesized that the notch width of the QRS complex in the lateral leads (I, avL, V5, V6) on the LBBB-like ECG could further confirm the diagnosis of true complete left bundle branch block (t-LBBB). We conducted high-density, three-dimensional electroanatomical mapping in the cardiac chambers of 37 patients scheduled to undergo CRT. These patients' preoperative electrocardiograms met the ACC/AHA/HRS guidelines for the diagnosis of complete LBBB. If the left bundle branch potential could be mapped from the base of the heart to the apex on the left ventricular septum, it was defined as a false complete left bundle branch block (f-LBBB). Otherwise, it was categorized as a t-LBBB. We conducted a comparative analysis between the two groups, considering the clinical characteristics, real-time correspondence between the spread of ventricular electrical excitation and the QRS wave, QRS notch width of the lateral leads (I, avL, V5, V6), and the notch width/left ventricular end-diastolic diameter (Nw/LVd) ratio. We performed the ROC correlation analysis of Nw/LVd and t-LBBB to determine the sensitivity and specificity for diagnostic authenticity. RESULTS: Twenty-five patients were included in the t-LBBB group, while 12 patients were assigned to the f-LBBB group. Within the t-LBBB group, the first peak of the QRS notch correlated with the depolarization of the right ventricle and septum, the trough corresponded to the depolarization of the left ventricle across the left ventricle, and the second peak aligned with the depolarization of the left ventricular free wall. In contrast, within the f-LBBB group, the first peak coincided with the depolarization of the right ventricle and a majority of the left ventricle, the second peak occurred due to the depolarization of the latest, locally-activated myocardium in the left ventricle, and the trough was a result of delayed activation of the left ventricle that did not align with the usual peak timing. The QRS notch width (45.2 ± 12.3 ms vs. 52.5 ± 9.2 ms, P < 0.05) and the Nw/LVd ratio (0.65 ± 0.19 ms/mm vs. 0.81 ± 0.17 ms/mm, P < 0.05) were compared between the two groups. After conducting the ROC correlation analysis, a sensitivity of 56% and a specificity of 91.7% for diagnosing t-LBBB using Nw/LVd were obtained. CONCLUSION: By utilizing the current diagnostic criteria for LBBB, an increased Nw/LVd value can enhance the effectiveness of diagnosing LBBB.

Epigenetic variation in maize agronomical traits for breeding and trait improvement.

Epigenetics-mediated breeding (Epibreeding) involves engineering crop traits and stress responses through the targeted manipulation of key epigenetic features to enhance agricultural productivity. While conventional breeding methods raise concerns about reduced genetic diversity, epibreeding propels crop improvement through epigenetic variations that regulate gene expression, ultimately impacting crop yield. Epigenetic regulation in crops encompasses various modes, including histone modification, DNA modification, RNA modification, non-coding RNA, and chromatin remodeling. This review summarizes the epigenetic mechanisms underlying major agronomic traits in maize and identifies candidate epigenetic landmarks in the maize breeding process. We propose a valuable strategy for improving maize yield through epibreeding, combining CRISPR/Cas-based epigenome editing technology and Synthetic Epigenetics (SynEpi). Finally, we discuss the challenges and opportunities associated with maize trait improvement through epibreeding.

The trxG protein ULT1 regulates Arabidopsis organ size by interacting with TCP14/15 to antagonize the LIM peptidase DA1 for H3K4me3 on target genes.

Plant organ size is an important agronomic trait that makes a significant contribution to plant yield. Despite its central importance, the genetic and molecular mechanisms underlying organ size control remain to be fully clarified. Here, we report that the trithorax group protein ULTRAPETALA1 (ULT1) interacts with the TEOSINTE BRANCHED1/CYCLOIDEA/PCF14/15 (TCP14/15) transcription factors by antagonizing the LIN-11, ISL-1, and MEC-3 (LIM) peptidase DA1, thereby regulating organ size in Arabidopsis. Loss of ULT1 function significantly increases rosette leaf, petal, silique, and seed size, whereas overexpression of ULT1 results in reduced organ size. ULT1 associates with TCP14 and TCP15 to co-regulate cell size by affecting cellular endoreduplication. Transcriptome analysis revealed that ULT1 and TCP14/15 regulate common target genes involved in endoreduplication and leaf development. ULT1 can be recruited by TCP14/15 to promote lysine 4 of histone H3 trimethylation at target genes, activating their expression to determine final cell size. Furthermore, we found that ULT1 influences the interaction of DA1 and TCP14/15 and antagonizes the effect of DA1 on TCP14/15 degradation. Collectively, our findings reveal a novel epigenetic mechanism underlying the regulation of organ size in Arabidopsis.

[Prediction of Spatial Distribution of Heavy Metals in Cultivated Soil Based on Multi-source Auxiliary Variables and Random Forest Model].

Spatial prediction of the concentrations of soil heavy metals (HMs) in cultivated land is critical for monitoring cultivated land contamination and ensuring sustainable eco-agriculture. In this study, 32 environmental variables from terrain, climate, soil attributes, remote-sensing information, vegetation indices, and anthropogenic activities were used as auxiliary variables, and random forest (RF), regression Kriging (RK), ordinary Kriging (OK), and multiple linear regression (MLR) models were proposed to predict the concentrations of As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn in cultivated soils. In comparison to those of RK, OK, and MLR, the RF model had the best prediction performance for As, Cd, Cr, Hg, Pb, and Zn, whereas the OK and RK models had highest prediction performance for Cu and Ni, respectively, showing that R2 was the highest, and mean absolute error (MAE) and root mean square error (RMSE) were the lowest. The prediction performance of the spatial distribution of soil HMs under different prediction methods was basically consistent. The high value areas of eight HMs concentrations were all distributed in the southern plain area. However, the RF model depicted the details of spatial prediction more prominently. Moreover, the importance ranking of influencing factors derived from the RF model indicated that the spatial variation in concentrations of the eight HMs in Lanxi City were mainly affected by the combined effects of Se, TN, pH, elevation, annual average temperature, annual average rainfall, distance from rivers, and distance from factories. Given the above, random forest models could be used as an effective method for the spatial prediction of soil heavy metals, providing scientific reference for regional soil pollution investigation, assessment, and management.

[Effects of Supplementation of Different Amendments on Soil Heavy Metals and Enzyme Activities in Coastal Saline Land].

The supplementation of soil amendments may not only improve the soil physical and chemical properties but also lead to the accumulation of heavy metals in soil. This experiment included six treatments:control (CK), organic manure (OM), polyacrylamide+organic manure (PAM+OM), straw mulching+organic manure (SM+OM), buried straw+organic manure (BS+OM), and bio-organic manure+organic manure (BM+OM) to explore the effects of different soil amendments on heavy metals and soil enzyme activities in coastal saline land and the relationship between them. The results revealed that compared with that in the CK treatment, the contents of soil Cr, Cu, Ni, and Pb exhibited an upward trend after the supplementation of soil amendments, among which the SM+OM and PAM+OM treatments had the most significant effects on the contents of soil Cr and Cu, respectively, whereas the BM+OM treatment had the most significant effects on the contents of soil Ni and Pb. Compared with those in the CK treatment, the activities of soil invertase and urease increased significantly following supplementation of soil amendments, and the BM+OM treatment had the best effect. The alkaline phosphatase activity exhibited a slightly upward trend after the supplementation of soil amendments, whereas the catalase activity did not change significantly. The redundancy analysis revealed that the first two axes cumulatively accounted for 70.3% of the variability in enzyme activities, and the importance of single soil heavy metals on soil enzyme activity was as follows:Ni>Cu>Cr>Pb.

[Clinical Features and Prognostic Factors of Patients with Primary Cutaneous Lymphoma].

OBJECTIVE: To retrospectively analyze the clinical characteristics and prognostic factors of patients with primary cutaneous lymphoma. METHODS: The clinical data of 22 patients with primary cutaneous lymphoma admitted to Xinjiang Hotan District People's Hospital, Heji Hospital affiliated to Changzhi Medical College and the Fifth Medical Center of PLA General Hospital from January 2013 to June 2021 were retrospectively analyzed. RESULTS: The incidence of primary cutaneous T cell and NK/T cell lymphoma was about 91.9/100 000, and the incidence of primary cutaneous B cell lymphoma was about 14.5/100 000. The overall survival (OS) of patients aged ≥65 years was significantly shorter than that of patients younger than 65 years (P <0.05). Patients with elevated ß2-microglobulin (ß2-MG) had shorter OS and progression-free survival (PFS) (both P <0.05). Patients who achieved complete/partial response after initial treatment had longer OS than those with stable or progressive disease (P <0.05). There were significant differences in OS and PFS among patients with different pathological types of primary cutaneous lymphoma that originated from T and NK/T cells, the OS and PFS of patients with mycosis fungoides were longer than those of patients with other pathological types (both P <0.05). In addition, disease stage might also affect the PFS of the patients (P =0.056). CONCLUSION: The age, disease stage, ß2-MG level, pathological type and remission state after treatment of the patients were related to the clinical prognosis.

Insular dysfunction of interoception in major depressive disorder: from the perspective of neuroimaging.

Interoception plays a crucial role in maintaining bodily homeostasis and promoting survival, and is considered the basis of human emotion, cognition, and self-formation. A malfunction of interoception is increasingly suggested to be a fundamental component of different mental health conditions, and depressive disorders have been especially closely associated. Interoceptive signaling and processing depends on a system called the "interoceptive pathway," with the insula, located in the deep part of the lateral fissure, being the most important brain structure in this pathway. Neuroimaging studies have revealed alterations in the structure and function of the insula in a large number of individuals with depression, yet the precise relationship between these alterations and interoceptive dysfunction remains unclear. The goal of this review is to examine the evidence that exists for dysfunction of interoception in people with Major Depressive Disorder (MDD), and to determine the associated specific alterations in the structure and function of the insula revealed by neuroimaging. Overall, three aspects of the potential relationship between interoceptive dysfunction and alterations in insular function in people with depression have been assessed, namely clinical symptoms, quantitative measures of interoceptive function and ability, and interoceptive modulation. To conclude, several specific limitations of the published studies and important lines of enquiry for future research are offered.

ZmBELL10 interacts with other ZmBELLs and recognizes specific motifs for transcriptional activation to modulate internode patterning in maize.

Plant height is an important agronomic trait that affects crop yield. Elucidating the molecular mechanism underlying plant height regulation is also an important question in developmental biology. Here, we report that a BELL transcription factor, ZmBELL10, positively regulates plant height in maize (Zea mays). Loss of ZmBELL10 function resulted in shorter internodes, fewer nodes, and smaller kernels, while ZmBELL10 overexpression increased plant height and hundred-kernel weight. Transcriptome analysis and chromatin immunoprecipitation followed by sequencing showed that ZmBELL10 recognizes specific sequences in the promoter of its target genes and activates cell division- and cell elongation-related gene expression, thereby influencing node number and internode length in maize. ZmBELL10 interacted with several other ZmBELL proteins via a spatial structure in its POX domain to form protein complexes involving ZmBELL10. All interacting proteins recognized the same DNA sequences, and their interaction with ZmBELL10 increased target gene expression. We identified the key residues in the POX domain of ZmBELL10 responsible for its protein-protein interactions, but these residues did not affect its transactivation activity. Collectively, our findings shed light on the functions of ZmBELL10 protein complexes and provide potential targets for improving plant architecture and yield in maize.

Endoplasmic reticulum stress mediates environmental particle-induced inflammatory response in bronchial epithelium.

While the detailed mechanisms for how particulate matter (PM) causes adverse health effects in the lungs remain largely unknown, endoplasmic reticulum (ER) stress has been implicated in PM-induced lung injury. The present study was undertaken to examine how/if ER stress might regulate PM-induced inflammation, and to begin to define potential underlying molecular mechanisms. Here, ER stress hallmarks were examined in human bronchial epithelial (HBE) cells exposed to PM. To confirm roles of certain pathways, siRNA targeting ER stress genes and an ER stress inhibitor were employed. Expression of select inflammatory cytokines and related signaling pathway components by the cells were assessed as well. The results showed that PM exposure induced elevations in two ER stress hallmarks, i.e. GRP78 and IRE1α, in time-and/or dose-related manners in the HBE cells. Inhibition of ER stress by siRNA for GRP78 or IRE1α significantly alleviated the PM-induced effects. Further, ER stress appeared to regulate PM-induced inflammation - likely through downstream autophagy and NF-κB pathways - as implied by studies showing that inhibition of ER stress by siRNA of GRP78 or IRE1α caused significant amelioration of PM-induced autophagy and subsequent activation of NF-κB pathways. Moreover, the ER stress inhibitor 4-PBA were used to confirm the protective effects against PM-induced outcomes. Together, the results suggest ER stress plays a deleterious role in PM-induced airway inflammation, possibly through activation of autophagy and NF-κB signaling. Accordingly, protocols/treatments that could lead to inhibited ER stress could potentially be effective for treatment of PM-related airway disorders.

The relationship between processing speed and remodeling spatial patterns of intrinsic brain activity in the elderly with different sleep duration.

Objective: Brain neuroplasticity in which sleep affects the speed of information processing in the elderly population has not been reported. Therefore, this study was conducted to explore the effects of sleep on information processing speed and its central plasticity mechanism in the elderly. Methods: A total of 50 individuals aged 60 and older were enrolled in this case control study. All subjects were divided into two groups according to the sleep time: short sleep duration (< 360 min) (6 men and 19 women; mean age: 66.96 ± 4.28 years old), and non-short sleep duration (> 360 min) (13 men and 12 women). Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected, and the amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) were calculated for each participant. Two-sample t-tests were performed to compare the ALFF, ReHo, and DC maps between the two groups. Then, the relationships among clinical features, fMRI and cognitive function were analyzed using general linear model. Results: Short sleep duration group showed significantly increased ALFF value in the bilateral middle frontal gyrus and right insula; significantly increased ReHo value in the left superior parietal gyrus, and decreased ReHo value in the right crebellum; significantly decreased DC value in the left inferior occipital gyrus, left superior parietal gyrus and right cerebellum (p < 0.05, AlphaSim correction). The ALFF value of right insula is significantly associated with symbol digit modalities test (SDMT) score (ß = -0.363, p = 0.033). Conclusion: Short sleep duration and processing speed are significantly associated with remodeling spatial patterns of intrinsic brain activity in the elderly.

A randomized controlled comparative study of different fluid exchange modes in urgent-start peritoneal dialysis in patients with end-stage renal disease: automated peritoneal dialysis combined with manual fluid exchange vs. manual fluid exchange alone.

During urgent-start peritoneal dialysis (USPD) in end-stage renal disease (ESRD) patients, both adequate dialysis and skill training for fluid exchange are essential. However, automated peritoneal dialysis (APD) alone or manual fluid exchange peritoneal dialysis (MPD) alone could meet the above demands. Therefore, our study combined APD with MPD (A-MPD), and compared A-MPD with MPD, aiming to find the most appropriate treatment mode. This was a single-center, prospective, randomized controlled study. All eligible patients were randomized into the MPD and A-MPD groups. All patients underwent a five-day USPD treatment 48 h after catheter implantation, and they were followed up for six months after discharge. Overall, 74 patients were enrolled in this study. Among these, 14 and 60 patients quit due to complications during USPD and completed the study (A-MPD = 31, MPD = 29), respectively. Compared with MPD, the A-MPD treatment mode had a better effect on removing serum creatinine, blood urea nitrogen, and potassium and improving serum carbon dioxide combining power levels; it had less time expenditure on the fluid exchange by nurses (p < 0.05). In addition, patients in the A-MPD group had higher scores on the skill tests than those in the MPD group (p = 0.002). However, no significant differences in short-term peritoneal dialysis (PD) complications, PD technical survival rate, or mortality were found between the two groups. Therefore, the A-MPD mode could be recommended as an adoptable and suitable PD modality for USPD in the future.

[Effect of Spartina alterniflora Invasion on Soil C:N:P Stoichiometry in Coastal Wetland of Hangzhou Bay].

The invasion of Spartina alterniflora poses a great threat to coastal wetland ecosystems. In this study, the stoichiometric characteristics of soil carbon, nitrogen, and phosphorus under a Spartina alterniflora invasion were explored using ANOVA in a coastal wetland in Hangzhou Bay, and the driving coupling relationship between soil environmental factors and soil C:N:P stoichiometric characteristics of the coastal wetland were further explored based on the redundancy analysis (RDA), boosted regression tree (BRT), and partial least squares-structural equation (PLS-SEM) model. The results showed that:① after the invasion of Spartina alterniflora, soil N:P and total nitrogen (TN) in the wetland increased significantly, and with the increase in invasion time, TN and N:P decreased significantly, whereas soil organic carbon (SOC), C:N, and C:P increased significantly. ② The RDA model revealed that the main factors affecting the stoichiometric characteristics of topsoil C:N:P were SOC>electrical conductivity (EC)>TN in winter and SOC>bulk density (BD)>TN in summer. ③ The BRT model showed that under the invasion of Spartina alterniflora, TN was the key factor affecting soil C:N and N:P, and SOC was the key factor affecting C:P. ④ The PLS-SEM model showed that clay and water content directly affected SOC, thus affecting C:N and C:P; the clay and EC directly affected total phosphorus (TP), thus affecting N:P and C:P; and the EC directly affected TN, thus affecting C:N and N:P. In conclusion, the invasion of Spartina alterniflora had a significant impact on soil C:N:P stoichiometric characteristics in the study area. Soil physical properties and nutrient content directly or indirectly affected soil C:N:P stoichiometric characteristics to varying degrees.

Nintedanib prevents TGF-ß2-induced epithelial-mesenchymal transition in retinal pigment epithelial cells.

Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a key fibrosis pathogenesis in proliferative vitreoretinopathy (PVR). However, few medicines can prevent proliferative membranes and cell proliferation in the clinic. Nintedanib, a tyrosine kinase inhibitor, has been shown to prevent fibrosis and be anti-inflammatory in multiple organ fibrosis. In our study, 0.1, 1, 10 µM nintedanib was added to 20 ng/mL transforming growth factor beta 2 (TGF-ß2)-induced EMT in ARPE-19 cells. Western blot and immunofluorescence assay showed that 1 µM nintedanib suppressed TGF-ß2-induced E-cadherin expression decreased and Fibronectin, N-cadherin, Vimentin, and α-SMA expression increased. Quantitative real-time PCR results showed that 1 µM nintedanib decreased TGF-ß2-induced increase in SNAI1, Vimentin, and Fibronectin expression and increased TGF-ß2-induced decrease in E-cadherin expression. In addition, the CCK-8 assay, wound healing assay, and collagen gel contraction assay also showed that 1 µM nintedanib ameliorated TGF-ß2-induced cell proliferation, migration, and contraction, respectively. These results suggested that nintedanib inhibits TGF-ß2-induced EMT in ARPE-19 cells, which may be a potential pharmacological treatment for PVR.

Integration of high-throughput phenotyping, GWAS, and predictive models reveals the genetic architecture of plant height in maize.

Plant height (PH) is an essential trait in maize (Zea mays) that is tightly associated with planting density, biomass, lodging resistance, and grain yield in the field. Dissecting the dynamics of maize plant architecture will be beneficial for ideotype-based maize breeding and prediction, as the genetic basis controlling PH in maize remains largely unknown. In this study, we developed an automated high-throughput phenotyping platform (HTP) to systematically and noninvasively quantify 77 image-based traits (i-traits) and 20 field traits (f-traits) for 228 maize inbred lines across all developmental stages. Time-resolved i-traits with novel digital phenotypes and complex correlations with agronomic traits were characterized to reveal the dynamics of maize growth. An i-trait-based genome-wide association study identified 4945 trait-associated SNPs, 2603 genetic loci, and 1974 corresponding candidate genes. We found that rapid growth of maize plants occurs mainly at two developmental stages, stage 2 (S2) to S3 and S5 to S6, accounting for the final PH indicators. By integrating the PH-association network with the transcriptome profiles of specific internodes, we revealed 13 hub genes that may play vital roles during rapid growth. The candidate genes and novel i-traits identified at multiple growth stages may be used as potential indicators for final PH in maize. One candidate gene, ZmVATE, was functionally validated and shown to regulate PH-related traits in maize using genetic mutation. Furthermore, machine learning was used to build predictive models for final PH based on i-traits, and their performance was assessed across developmental stages. Moderate, strong, and very strong correlations between predictions and experimental datasets were achieved from the early S4 (tenth-leaf) stage. Colletively, our study provides a valuable tool for dissecting the spatiotemporal formation of specific internodes and the genetic architecture of PH, as well as resources and predictive models that are useful for molecular design breeding and predicting maize varieties with ideal plant architectures.

CeO2@NC nanozyme with robust dephosphorylation ability of phosphotriester: A simple colorimetric assay for rapid and selective detection of paraoxon.

Enzyme-mediated dephosphorylation reaction is the important approach to realize the inactivation and detection of hazardous phosphate chemicals. To date, many phosphatases-like nanozymes (e.g., CeO2) have demonstrated the catalytic hydrolysis ability of the phosphomonoesters, rather than phosphotriester, and the CeO2 nanozyme only work under relatively harsh conditions of high temperature, and large dosage. Thus, exploration of efficient nanozymes for the rapid dephosphorylation of phosphotriester under mild conditions remains a challenge. Here, a novel CeO2@NC nanozyme is developed with excellent phosphatases-like activity based on substrate synergistic effect, in which, CeO2 nanoparticles embedded in N-doped carbon (NC) material. Taking paraoxon as the model substrate, such CeO2@NC nanozyme can drive rapid dephosphorylation of phosphotriester over a broad temperature range, which not only significantly outperforms natural phosphatases and neat CeO2, but also can preserve >80% of the optimal activity after exposure of harsh conditions, such as strong acidic/basic medium, high temperature of up to 80 °C. The excellent catalytic performance could be due to that Ce(IV)/Ce(III) species act as the active sites to realize the polarization and hydrolysis of P-O bond while NC template works as the synergistic group to adsorb the substrate. Furthermore, a simple colorimetric assay is developed for the rapid and selective detection of paraoxon. Overall, this work not only develops a highly efficient phosphatases-like nanozyme via substrate synergetic strategy, but also opens an interesting avenue for the rapid detection of organophosphorus pesticides.

miR-155-5p/FOXO3a promotes pulmonary fibrosis in rats by mediating NLRP3 inflammasome activation.

OBJECTIVE: Pulmonary fibrosis (PF) is regarded as progressive lung disease. miR-155-5p depletion exerts anti-fibrotic effects in silicotic mice. This study explored the effect and possible mechanism of miR-155-5p in PF rats, hoping to find a new target for PF management. METHODS: Bleomycin-induced PF rat model was established. Alveolar structure and collagen fiber deposition were observed by HE and Elastica-Masson staining. Alveolitis and PF scores were evaluated using the method of Szapiel. Total collagen content was detected using the Sircol method. PF rats were intraperitoneally injected with NLRP3 inhibitor MCC950 or intravenously injected with miR-155-5p antagomir and si-FOXO3a lentivirus plasmids. Binding sites of miR-155-5p and FOXO3a were predicted using bioinformatics analysis and dual-luciferase reporter assay. The expressions of miR-155-5p, NLRP3, ASC, caspase-1, IL-1ß, IL-18, and FOXO3a were detected by RT-qPCR, Western blot, and ELISA. RESULTS: MCC950 treatment inhibited NLRP3 inflammasome, alleviated alveolar hemorrhage and alveolitis, and reduced blue collagen fiber deposition, scores of alveolitis and PF, and levels of NLRP3, ASC, caspase-1, IL-1ß, and IL-18 in PF rats. miR-155-5p was elevated in lung tissues of PF rats. Inhibition of miR-155-5p downregulated levels of NLRP3, ASC, caspase-1, IL-1ß, and IL-18 in lung tissues of PF rats. miR-155-5p targeted FOXO3a. miR-155-5p inhibition and silencing FOXO3a exacerbated alveolitis and PF in rats and increased levels of NLRP3, ASC, caspase-1, IL-1ß, and IL-18. CONCLUSIONS: miR-155-5p aggravated alveolitis and promoted PF by targeting FOXO3a and prompting the activation of NLRP3 inflammasome and then inducing IL-1ß and IL-18 release.

Clinical observation of Jipei dilong ointment combined with diacerein in the treatment of knee osteoarthritis in the early and mid-term stage / 中国药房

OBJECTIVE To investigate clinical efficacy and safety of Jipei dilong ointment combined with diacerein in the treatment of knee osteoarthritis （KOA） in the early and mid-term stage. METHODS Totally 100 KOA patients were randomly divided into control group and trial group， with 50 cases in each group. Control group received Diacerein capsules orally， 50 mg every time， bid. Trial group additionally received Jipei dilong ointment， once a day， on the basis of control group. Both groups had a treatment course of 4 weeks， and were followed up for 3 months after treatment. The clinical efficacy of 2 groups， visual analogue scale （VAS）， Western Ontario and McMaster University osteoarthritis index （WOMAC） score， Lysholm scores before and after treatment， at 3-month follow-up after treatment were all observed； the levels of tumor necrosis factor-α （TNF-α）， interleukin 1β （IL-1β）， IL-6， superoxide dismutase （SOD）， malondialdehyde （MDA）， nitric oxide （NO）， cartilage oligomeric matrix protein （COMP）， matrix metalloproteinase-13 （MMP-13） and C-telopeptide of type Ⅱ collagen （CTX-Ⅱ） were detected in knee joint fluid. The incidence of adverse drug reactions was recorded. RESULTS After 4 weeks of treatment， total effective rate was 96.0% in trial group and 90.0% in control group， without statistical significance between 2 groups （P＞0.05）. At 3- 2019YFC1712500） month follow-up after treatment， total effective rate of trial group was 94.0%， and was higher than 62.0% of control group（P＜0.05）. After 4 weeks of treatment and at 3-month follow-up after treatment， VAS score， WOMAC score，the contents ofTNF-α， IL-1β， IL-6， MDA， NO， COMP， MMP-13 and CTX-Ⅱ in knee joint fluid of two groups were significantly lower than before； Lysholm score and SOD activity of knee joint fluid were significantly higher than before， and the trial group was significantly better than the control group during the same period （P＜0.05）. And there was no statistical significance in the incidence of adverse drug reactions between two groups（P＞0.05）. CONCLUSION For the treatment of KOA in early and mid- term stage， Jipei dilong ointment combined with diacerein relieve pain， improve knee function by inhibiting inflammatory reaction， reducing oxidative stress and inhibiting chondrocyte and matrix degradation， and have low incidence of adverse drug reactions.