Persistent Luminescence Nanoplatform for Autofluorescence-Free Tracking of Submicrometer Plastic Particles in Plant.

The uptake of plastic particles by plants and their transport through the food chain make great risks to biota and human health. Therefore, it is important to trace plastic particles in the plant. Traditional fluorescence imaging in plants usually suffers significant autofluorescence background. Here, we report a persistent luminescence nanoplatform for autofluorescence-free imaging and quantitation of submicrometer plastic particles in plant. The nanoplatform was fabricated by doping persistent luminescence nanoparticles (PLNPs) onto polystyrene (PS) nanoparticles. Cr3+-doped zinc gallate PLNP was employed as the dopant for autofluorescence-free imaging due to its persistent luminescence nature. In addition, the Ga element in PLNP was used as a proxy to quantify the PS in the plant by inductively coupled plasma mass spectrometry (ICP-MS). Thus, the developed nanoplatform allows not only dual-mode autofluorescence-free imaging (persistent luminescence and laser-ablation ICP-MS) but also ICP-MS quantitation for tracking PS in plant. Application of this nanoplatform in a typical plant model Arabidopsis thaliana revealed that PS mainly distributed in the root (>99.45%) and translocated very limited (<0.55%) to the shoot. The developed nanoplatform has great potential for quantitative tracing of submicrometer plastic particles to investigate the environmental process and impact of plastic particles.

Risperidone for the Treatment of Dementia-Related Psychosis: A Systematic Review and Meta-Analysis.

INTRODUCTION: Risperidone is one of the atypical antipsychotics that has been used for the treatment of dementia-related psychosis (DRP). However, the findings concerning its efficacy and safety in DRP are contradictory. METHODS: We conducted a systematic review and meta-analysis to address the effects of risperidone on the alleviation of DRP. We searched Medline via PubMed, Scopus, Web of Science, Google Scholar, and PsychINFO from the inception until May 2024. Appropriate statistical tests were used to test the study hypothesis. RESULTS: The study included 17 articles and 2311 patients with DRP. Risperidone alleviated DRP with a standardized mean difference (SMD) of 0.355 (95%CI, 0.170 to 0.541, p=0.000). The impact of treatment was positively associated with treatment duration (slope p = 0.038) and dose (slope p= 0.000). Six studies (n=354) reported the data for the effects of risperidone on cognitive function. Analysis showed that risperidone treatment deteriorated cognitive function in DRP patients with an SMD of -0.185 (95%CI, -0.349 to -0.020, p=0.028). The mean effect size was 0.36 with a 95% CI of 0.17 to 0.54. However, the true effect size in 95% of all comparable populations fell in the interval of -0.37 to 1.08. This revealed a high heterogeneity among the included publications as the prediction interval showed a wider range of expected treatment effects than CI. CONCLUSION: Our meta-analysis provides evidence for the effectiveness of risperidone in the management of DRP. However, because of safety concerns and high data heterogeneity, risperidone use should be individualized for each patient.

Effects of comprehensive nursing intervention on quality of life, Self-efficacy, gastrointestinal reaction and immune function of patients with breast cancer undergoing chemotherapy.

Objective: To assess the effects of comprehensive nursing intervention on quality of life, self-efficacy, gastrointestinal reaction and immune function of patients with breast cancer undergoing chemotherapy. Methods: This was a retrospective study. One hundred and twenty patients receiving chemotherapy after breast cancer surgery were randomly divided into the experimental group and the control group(n=60) from January 2021 to January 2023. Patients in the perioperative period, the experimental group were given comprehensive nursing intervention, while those in the control group were given conventional specialist nursing intervention. The differences in quality of life, self-efficacy, gastrointestinal reaction, immune function and patient satisfaction between the two groups were compared and analyzed. Results: After the intervention, the SF-36 scores in the experimental group were significantly higher than those in the control group (P=0.00), the efficacy indicators were significantly improved compared to the control group(P=0.00); the scores of gastrointestinal symptoms in the experimental group were significantly lower than those in the control group after the intervention(P<0.05). The indexes of CD3+, CD4+ and CD4+/CD8+ in the experimental group after the intervention were significantly higher than those in the control group(P=0.00); The patient satisfaction in the experimental group was 100%, which was significantly higher than 92% in the control group, with statistically significant differences(P=0.02). Conclusion: Comprehensive nursing intervention leads to a variety of benefits in the treatment of patients with breast cancer during postoperative chemotherapy, such as relieving patients' gastrointestinal reactions, improving their immune function and quality of life, besides effectively improving their self-efficacy, which is worthy of clinical application.

Statins inhibit protein kinase D (PKD) activation in intestinal cells and prevent PKD1-induced growth of murine enteroids.

We examined the impact of statins on protein kinase D (PKD) activation by G protein-coupled receptor (GPCR) agonists. Treatment of intestinal IEC-18 cells with cerivastatin inhibited PKD autophosphorylation at Ser916 induced by angiotensin II (ANG II) or vasopressin in a dose-dependent manner with half-maximal inhibition at 0.2 µM. Cerivastatin treatment inhibited PKD activation stimulated by these agonists for different times (5-60 min) and blunted HDAC5 phosphorylation, a substrate of PKD. Other lipophilic statins, including simvastatin, atorvastatin, and fluvastatin also prevented PKD activation in a dose-dependent manner. Using IEC-18 cell lines expressing PKD1 tagged with EGFP (enhanced green fluorescent protein), cerivastatin or simvastatin blocked GPCR-mediated PKD1-EGFP translocation to the plasma membrane and its subsequent nuclear accumulation. Similar results were obtained in IEC-18 cells expressing PKD3-EGFP. Mechanistically, statins inhibited agonist-dependent PKD activation rather than acting directly on PKD catalytic activity since exposure to cerivastatin or simvastatin did not impair PKD autophosphorylation or PKD1-EGFP membrane translocation in response to phorbol dibutyrate, which bypasses GPCRs and directly stimulates PKC and PKD. Furthermore, cerivastatin did not inhibit recombinant PKD activity determined via an in vitro kinase assay. Using enteroids generated from intestinal crypt-derived epithelial cells from PKD1 transgenic mice as a model of intestinal regeneration, we show that statins oppose PKD1-mediated increase in enteroid area, complexity (number of crypt-like buds), and DNA synthesis. Our results revealed a previously unappreciated inhibitory effect of statins on receptor-mediated PKD activation and in opposing the growth-promoting effects of PKD1 on intestinal epithelial cells.

Genetic factors define CPO and CLO subtypes of nonsyndromicorofacial cleft.

Nonsyndromic orofacial cleft (NSOFC) is a severe birth defect that occurs early in embryonic development and includes the subtypes cleft palate only (CPO), cleft lip only (CLO) and cleft lip with cleft palate (CLP). Given a lack of specific genetic factor analysis for CPO and CLO, the present study aimed to dissect the landscape of genetic factors underlying the pathogenesis of these two subtypes using 6,986 cases and 10,165 controls. By combining a genome-wide association study (GWAS) for specific subtypes of CPO and CLO, as well as functional gene network and ontology pathway analysis, we identified 18 genes/loci that surpassed genome-wide significance (P < 5 × 10-8) responsible for NSOFC, including nine for CPO, seven for CLO, two for both conditions and four that contribute to the CLP subtype. Among these 18 genes/loci, 14 are novel and identified in this study and 12 contain developmental transcription factors (TFs), suggesting that TFs are the key factors for the pathogenesis of NSOFC subtypes. Interestingly, we observed an opposite effect of the genetic variants in the IRF6 gene for CPO and CLO. Moreover, the gene expression dosage effect of IRF6 with two different alleles at the same single-nucleotide polymorphism (SNP) plays important roles in driving CPO or CLO. In addition, PAX9 is a key TF for CPO. Our findings define subtypes of NSOFC using genetic factors and their functional ontologies and provide a clue to improve their diagnosis and treatment in the future.

Graphene Quantum Dots Disrupt Embryonic Stem Cell Differentiation by Interfering with the Methylation Level of Sox2.

The tremendous potential for graphene quantum dots (GQDs) in biomedical applications has led to growing concerns of their health risks in human beings. However, present studies mainly focused on oxidative stress, apoptosis, and other general toxicity effects; the knowledge on the developmental toxicity and the related regulatory mechanisms is still far from sufficient. Our study revealed the development retardation of mouse embryonic stem cells (mESCs) caused by GQDs with a novel DNA methylation epigenetic mechanism. Specifically, GQDs were internalized into cells mainly via energy-dependent endocytosis, and a significant fraction of internalized GQDs remained in the cells even after a 48-h clearance period. Albeit with unobservable cytotoxicity or any influences on cell pluripotency, significant retardation was found in the in vitro differentiation of the mESCs into embryoid bodies (EBs) with the upregulation of Sox2 levels in GQD pretreatment groups. Importantly, this effect could be contributed by GQD-induced inhibition in CpG methylation of Sox2 through altering methyltransferase and demethyltransferase transcriptional expressions, and the demethyltransferase inhibitor, bobcat339 hydrochloride, reduced GQD-induced upregulation of Sox2. The current study first demonstrated that GQDs compromised the differentiation program of the mESCs, potentially causing development retardation. Exposure to this nanomaterial during gestation or early developmental period would cause adverse health risks and is worthy of more attention.

Unambiguous Acquisition/Tracking Technique Based on Sub-Correlation Functions for GNSS Sine-BOC Signals.

The autocorrelation function (ACF) of the Binary Offset Carrier modulation (BOC) signal for Global Navigation Satellite System (GNSS) has multiple peaks, ambiguity is easily generated during the synchronization of the baseband signal. Some methods have been proposed to remove the ambiguity, but the performance is not suitable for high-order BOC signals or does not maintain narrow correlation characteristics. This paper proposes a sub-function reconstruction synchronization algorithm to solve this problem, of which the key is to design a new local auxiliary code: the local Pseudo-Random Noise (PRN) code is divided into several new codes with different delays. The auxiliary code performs a coherent integration operation with the received signal. Then, a correlation function without any positive side peaks is obtained by multiplying the two correlation results to make the acquisition/tracking completely unambiguous. The paper gives a design scheme of navigation signal acquisition/tracking and deduces the theoretical analysis of detection performance. The phase discrimination function is provided. The performance of the method is analyzed from both theoretical and simulation aspects. Compared with the Binary phase shift keying-like (BPSK-LIKE) method, Subcarrier Phase Cancellation (SCPC) method and the Autocorrelation Side-Peak Cancellation Technique (ASPeCT) method, the proposed method has the best detection probability for the acquisition, which is 0.5 dB-Hz better than ASPeCT. For tracking, the proposed method performs best in terms of phase-detection curve, anti-multipath performance, and anti-noise performance. For high-order BOC signals, the SRSA technique successfully removes the false lock points, and there is only one multipath error envelope, and the code tracking error is almost the same as the ASPeCT method.

Effects of Sodium Valproate Combined with Lamotrigine on Quality of Life and Serum Inflammatory Factors in Patients with Poststroke Secondary Epilepsy.

BACKGROUND: We sought to explore the effects of sodium valproate combined with lamotrigine on quality of life and serum inflammatory factors in patients with poststroke secondary epilepsy. METHODS: A total of 145 patients with post-stroke secondary epilepsy admitted to our hospital from January 2017 to June 2018 were collected: 76 treated with sodium valproate combined with lamotrigine (study group) and 69 patients treated with sodium valproate alone (control group). The levels of serum high-mobility group protein B1, matrix metalloproteinase 9, and interleukin 6 were detected before and after treatment, and the therapeutic efficacy and adverse reactions were compared between the 2 groups. RESULTS: The total effective rate of the study group was higher than that of the control group. Both groups decreased in epileptiform discharges or in the number of involved leads after treatment, with the results of the study group being lower than those of the control group. The quality of life scores in both groups was increased after treatment, albeit the scores of the study group were higher than those of the control group. In terms of the levels of serum inflammatory factors, the 2 groups were reduced after treatment; the levels of the study group were lower than those of the control group. Regarding the incidence of adverse reactions, no significant difference was seen between the 2 groups. CONCLUSIONS: Sodium valproate combined with lamotrigine has better clinical efficacy and higher safety in the treatment of poststroke secondary epilepsy and is able to reduce the expression levels of serum inflammatory factors.

Efficient Prodrug Activator Gene Therapy by Retroviral Replicating Vectors Prolongs Survival in an Immune-Competent Intracerebral Glioma Model.

Prodrug activator gene therapy mediated by murine leukemia virus (MLV)-based retroviral replicating vectors (RRV) was previously shown to be highly effective in killing glioma cells both in culture and in vivo. To avoid receptor interference and enable dual vector co-infection with MLV-RRV, we have developed another RRV based on gibbon ape leukemia virus (GALV) that also shows robust replicative spread in a wide variety of tumor cells. We evaluated the potential of GALV-based RRV as a cancer therapeutic agent by incorporating yeast cytosine deaminase (CD) and E. coli nitroreductase (NTR) prodrug activator genes into the vector. The expression of CD and NTR genes from GALV-RRV achieved highly efficient delivery of these prodrug activator genes to RG-2 glioma cells, resulting in enhanced cytotoxicity after administering their respective prodrugs 5-fluorocytosine and CB1954 in vitro. In an immune-competent intracerebral RG-2 glioma model, GALV-mediated CD and NTR gene therapy both significantly suppressed tumor growth with CB1954 administration after a single injection of vector supernatant. However, NTR showed greater potency than CD, with control animals receiving GALV-NTR vector alone (i.e., without CB1954 prodrug) showing extensive tumor growth with a median survival time of 17.5 days, while animals receiving GALV-NTR and CB1954 showed significantly prolonged survival with a median survival time of 30 days. In conclusion, GALV-RRV enabled high-efficiency gene transfer and persistent expression of NTR, resulting in efficient cell killing, suppression of tumor growth, and prolonged survival upon CB1954 administration. This validates the use of therapeutic strategies employing this prodrug activator gene to arm GALV-RRV, and opens the door to the possibility of future combination gene therapy with CD-armed MLV-RRV, as the latter vector is currently being evaluated in clinical trials.

Yishenhuoxue formula regulates TGF-ß/Smad signal transduction to protect rats against Diabetic kidney disease injury.

TGF-ß signal pathway activation is vital in the pathogenesis of DKD. We aim to investigate the role of Yishenhuoxue formula on TGF-ß/Smad signal transduction in DKD rats. 60 male adult Wistar rats were enrolled and randomly allocated into four groups: N group, M group (given STZ 60mg/kg, ip), H group (given Yishenhuoxue formula 1.0g/kg/day, ig) and L group (given Yishenhuoxue formula 0.5g/kg/day, ig). The levels of BW, 24h UV, SCr, UCr, mALB were measured after 8 weeks treatment, while the levels of KW/BW index, CCr and UAER were calculated by relevant formula. The rats' left kidneys were harvested to detect histological changes by PAS staining and right kidneys were harvested to detect the levels of TGF-ß, Smad2/3, phosphorylated Smad 2/3, Smad 7 and CTGF by western blot analysis. We found that Yishenhuoxue formula treatment can protect kidneys from DKD injury, which is illustrated with following criteria: 1) a significant decrement in KW/BW index, 24h UV, SCr, mALB and UAER, while a significant increment in BW, UCr, CCr (p<0.05 vs. M group); 2) minor and segmental changes as slight expansion of the glomerular basement membrane compared with M group; 3) an apparent decrease in levels of TGF-ß1, phosphorylated Smad 2/3 and CTGF, while an apparent increase in levels of Smad 2/3 and Smad7 compared with M group (p<0.05). The studies confirm that Yishenhuoxue formula has strong inhibitory effect on TGF-ß/Smad signal transduction in DKD rats' kidneys by decreasing expression of TGF-ß1, weakening of Smad 2/3 phosphorylation and increasing expression of Smad 7.