Advanced micro/nano-electroporation for gene therapy: recent advances and future outlook.

Gene therapy is a promising disease treatment approach by editing target genes, and thus plays a fundamental role in precision medicine. To ensure gene therapy efficacy, the effective delivery of therapeutic genes into specific cells is a key challenge. Electroporation utilizes short electric pulses to physically break the cell membrane barrier, allowing gene transfer into the cells. It dodges the off-target risks associated with viral vectors, and also stands out from other physical-based gene delivery methods with its high-throughput and cargo-accelerating features. In recent years, with the help of advanced micro/nanotechnology, micro/nanostructure-integrated electroporation (micro/nano-electroporation) techniques and devices have significantly improved cell viability, transfection efficiency and dose controllability of the electroporation strategy, enhancing its application practicality especially in vivo. This technical advancement makes micro/nano-electroporation an effective and versatile tool for gene therapy. In this review, we first introduce the evolution of electroporation technique with a brief explanation of the perforation mechanism, and then provide an overview of the recent advancements and prospects of micro/nano-electroporation technology in the field of gene therapy. To comprehensively showcase the latest developments of micro/nano-electroporation technology in gene therapy, we focus on discussing micro/nano-electroporation devices and current applications at both in vitro and in vivo levels. Additionally, we outline the ongoing clinical studies of gene electrotransfer (GET), revealing the tremendous potential of electroporation-based gene delivery in disease treatment and healthcare. Lastly, the challenges and future directions in this field are discussed.

Baicalein improves renal interstitial fibrosis by inhibiting the ferroptosis in vivo and in vitro.

Evidence indicates that Baicalein can ameliorate renal interstitial fibrosis by inducing myofibroblast apoptosis and inhibit the RLS3-induced ferroptosis in melanocytes. However, the relationship between renal interstitial fibrosis and anti-ferroptosis affected by Baicalein remains unclear. In our study, the anti-fibrosis and anti-ferroptosis effects of Baicalein were assessed in a rat model induced by the UUO method in vivo, and the effects of Baicalein on Erastin-induced ferroptosis of renal MPC-5 cells were examined by Western blot of fibrosis-related and ferroptosis-related proteins in vitro. In the UUO-induced rat model, Baicalein decreased kidney weight loss, improved renal function assessed the biomarks of urinary albumin excretion, serum creatine, and BUN levels, and reduced renal tubular injury. Furthermore, Baicalein inhibited renal ferroptosis by reducing ROS and MDA levels and increasing SOD and GSH levels in the UUO rat model. In addition, Baicalein potently reduced the expression of fibrosis-related proteins such as TGF-ß1, a-SMA, and Smad-2 to prevent renal interstitial fibrosis, and increased the expression of ferroptosis-related proteins such as SLC7A11, GPX4, and FTH to inhibit ferroptosis both in vitro and in vivo. Taken together, Baicalein exerts anti-fibrosis activity by reducing the ferroptosis response on the UUO-induced rat model and renal MPC5 cells. Therefore, Baicalein, as a novel therapeutic method on kidney diseases with strong activity in suppressing ferroptosis, could be a potential alternative treatment for renal interstitial fibrosis.

Association between triglyceride glucose index (TyG) and psychotic symptoms in patients with first-episode drug-naïve major depressive disorder.

Objective: Major depressive disorder (MDD) sufferers frequently have psychotic symptoms, yet the underlying triggers remain elusive. Prior research suggests a link between insulin resistance (IR) and increased occurrence of psychotic symptoms. Hence, this study sought to investigate the potential association between psychotic symptoms in Chinese patients experiencing their first-episode drug-naïve (FEDN) MDD and the triglyceride glucose (TyG) index, an alternative measure of insulin resistance (IR). Methods: Between September 2016 and December 2018, 1,718 FEDN MDD patients with an average age of 34.9 ± 12.4 years were recruited for this cross-sectional study at the First Hospital of Shanxi Medical University in China. The study collected clinical and demographic data and included assessments of anxiety, depression, and psychotic symptoms using the 14-item Hamilton Anxiety Rating Scale (HAMA), the 17-item Hamilton Depression Rating Scale (HAMD-17), and the positive subscales of the Positive and Negative Syndrome Scale (PANSS), respectively. Measurements of metabolic parameters, fasting blood glucose (FBG), and thyroid hormones were also gathered. To assess the correlation between the TyG index and the likelihood of psychotic symptoms, the study used multivariable binary logistic regression analysis. Additionally, two-segmented linear regression models were employed to investigate possible threshold effects in case non-linearity relationships were identified. Results: Among the patients, 9.95% (171 out of 1,718) exhibited psychotic symptoms. Multivariable logistic regression analysis showed a positive correlation between the TyG index and the likelihood of psychotic symptoms (OR = 2.12, 95% CI: 1.21-3.74, P = 0.01) after adjusting for confounding variables. Moreover, smoothed plots revealed a nonlinear relationship with the TyG index, revealing an inflection point at 8.42. Interestingly, no significant link was observed to the left of the inflection point (OR = 0.50, 95% CI: 0.04-6.64, P = 0.60), whereas beyond this point, a positive correlation emerged between the TyG index and psychotic symptoms (OR = 2.42, 95% CI: 1.31-4.48, P = 0.01). Particularly, a considerable 142% rise in the probability of experiencing psychotic symptoms was found with each incremental elevation in the TyG index. Conclusions: Understanding the non-linear link between the TyG index and the risk of psychotic symptoms in Chinese patients with FEDN MDD highlights the potential for targeted therapeutic approaches. By acknowledging the threshold effect observed, there is an opportunity to mitigate risk factors associated with IR-related psychiatric comorbidities through tailored interventions. These preliminary results stress the need for further longitudinal research to solidify these insights and contribute to more effective therapeutic strategies.

Palladium-Catalyzed Sequential Cross-Coupling/Annulation of ortho-Vinyl Bromobenzene with Aryl Bromide: Bimetallic Pathway versus Pd(II)-Pd(IV) Pathway: A DFT Investigation.

The palladium-catalyzed sequential cross-coupling/annulation of ortho-vinyl bromobenzenes with aryl bromides generating phenanthrenes was characterized by density functional theory (DFT). The Pd(II)-Pd(IV) pathway (Path V) is shown to be less probable than the bimetallic pathway (Path I), the latter proceeding via the following six steps: oxidative addition, vinyl-C(sp2)-H activation, Pd(II)-Pd(II) transmetalation, C-C coupling, aryl-C(sp2)-H activation, and reductive elimination. The aryl-C(sp2)-H activation process acts as the rate-determining step (RDS) of the entire chemical transformation, with an activation free energy barrier of ca. 27.4-28.8 kcal·mol-1, in good agreement with the corresponding experimental data (phenanthrenes' yields of ca. 65-90% at 130 °C after 5 h of reaction). The K2CO3 additive effectively reduces the activation free energy barrier of the RDS through direct participation in the reaction while preferentially modulating the charge distributions and increasing the stability of corresponding intermediates and complexes along the reaction path. Furthermore, bonding and electronic structure analyses of the key structures indicate that the chemo- and regioselectivities of the reaction are strongly influenced by both electronic effects and steric hindrance.

Single-cell transcriptomics reveals colonic immune perturbations during amyloid-ß driven Alzheimer's disease in mice.

The "gut-brain axis" is emerging as an important target in Alzheimer's disease (AD). However, immunological mechanisms underlying this axis remain poorly understood. Using single-cell RNA sequencing of the colon immune compartment in the 5XFAD amyloid-ß (Aß) mouse model, we uncovered AD-associated changes in ribosomal activity, oxidative stress, and BCR/plasma cell activity. Strikingly, levels of colon CXCR4 + antibody secreting cells (ASCs) were significantly reduced. This corresponded with accumulating CXCR4 + B cells and gut-specific IgA + cells in the brain and dura mater, respectively. Consistently, a chemokine ligand for CXCR4, CXCL12, was expressed at higher levels in 5XFAD glial cells and in in silico analyzed human brain studies, supporting altered neuroimmune trafficking. An inulin prebiotic fiber diet attenuated AD markers including Aß plaques and overall frailty. These changes corresponded to an expansion of gut IgA + cells and rescued peripheral T regs levels. Our study points to a key glia-gut axis and potential targets against AD. Study Highlights: AD is associated with altered immune parameters in the gut of 5XFAD mice. 5 XFAD colon has reduced ASCs, including CXCR4 + cells with a migratory gene signature. 5XFAD brain gliosis includes increased CXCL12 expression. CXCR4 + B cells and gut-specific IgA + ASCs accumulate in the 5XFAD brain and/or dura mater. Inulin diet attenuates AD disease parameters while boosting IgA + cell and T reg levels.

Eucalyptol-loaded microcapsules combined with Cynanchum komarovii extracts provide long-term and low-risk management of Chinese wolfberry (Lycium barbarum L.).

Realizing eco-friendly, long-term, and low-risk aphid control on Lycium barbarum (medicinal cash crop) using a Cynanchum komarovii extracts and eucalyptus oil-loaded microcapsules (EOMCs) formulation compositions is viable. In this study, the aim is to optimize the composition of Cynanchum komarovii extracts and EOMCs formulation for effective control of aphids, the release of EOMCs was controlled by changing the cross-linking degree of the shell to match the aphid control characteristics of Cynanchum komarovii extracts. Four types of polyamines were used as cross-linking agents for the preparation of EOMCs by interfacial polymerization. The bioactivity, wettability, and field application efficacy of Cynanchum komarovii extracts and different EOMCs formulation compositions were evaluated. These EOMCs exhibited an encapsulation efficiency exceeding 85 %. The control efficiency of the formulation compositions of microcapsules with a moderate release rate and Cynanchum komarovii extracts on aphids remained at 62.86 %, while the control efficiency of the combination of microcapsules with the fastest and slowest rates with Cynanchum komarovii extracts was only 48.62 % and 57.11 %, respectively. The formulation compositions of Cynanchum komarovii extracts with all four types of EOMCs were found to be safe for Chinese wolfberry plants. Overall, by selecting appropriate polyamines during fabrication, the release rate can be effectively controlled to achieve sustainable and low-risk aphid control in Lycium barbarum through compounding with selected microcapsules.

Breaking boundaries in radiology: redefining AI diagnostics via raw data ahead of reconstruction.

Objective.In the realm of utilizing artificial intelligence (AI) for medical image analysis, the paradigm of 'signal-image-knowledge' has remained unchanged. However, the process of 'signal to image' inevitably introduces information distortion, ultimately leading to irrecoverable biases in the 'image to knowledge' process. Our goal is to skip reconstruction and build a diagnostic model directly from the raw data (signal).Approach. This study focuses on computed tomography (CT) and its raw data (sinogram) as the research subjects. We simulate the real-world process of 'human-signal-image' using the workflow 'CT-simulated data- reconstructed CT,' and we develop a novel AI predictive model directly targeting raw data (RCTM). This model comprises orientation, spatial, and global analysis modules, embodying the fusion of local to global information extraction from raw data. We selected 1994 patients with retrospective cases of solid lung nodules and modeled different types of data.Main results. We employed predefined radiomic features to assess the diagnostic feature differences caused by reconstruction. The results indicated that approximately 14% of the features had Spearman correlation coefficients below 0.8. These findings suggest that despite the increasing maturity of CT reconstruction algorithms, they still introduce perturbations to diagnostic features. Moreover, our proposed RCTM achieved an area under the curve (AUC) of 0.863 in the diagnosis task, showcasing a comprehensive superiority over models constructed from secondary reconstructed CTs (0.840, 0.822, and 0.825). Additionally, the performance of RCTM closely resembled that of models constructed from original CT scans (0.868, 0.878, and 0.866).Significance. The diagnostic and therapeutic approach directly based on CT raw data can enhance the precision of AI models and the concept of 'signal-to-image' can be extended to other types of imaging. AI diagnostic models tailored to raw data offer the potential to disrupt the traditional paradigm of 'signal-image-knowledge', opening up new avenues for more accurate medical diagnostics.

Traditional Chinese medicines treat ischemic stroke and their main bioactive constituents and mechanisms.

Ischemic stroke (IS) remains one of the leading causes of death and disability in humans. Unfortunately, none of the treatments effectively provide functional benefits to patients with IS, although many do so by targeting different aspects of the ischemic cascade response. The advantages of traditional Chinese medicine (TCM) in preventing and treating IS are obvious in terms of early treatment and global coordination. The efficacy of TCM and its bioactive constituents has been scientifically proven over the past decades. Based on clinical trials, this article provides a review of commonly used TCM patent medicines and herbal decoctions indicated for IS. In addition, this paper also reviews the mechanisms of bioactive constituents in TCM for the treatment of IS in recent years, both domestically and internationally. A comprehensive review of preclinical and clinical studies will hopefully provide new ideas to address the threat of IS.

Bushen Tianjing Recipe inhibits human ovarian granulosa cell line KGN apoptosis induced by miR-23a through the regulation of the sirtuin family.

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Tianjing Recipe (BTR) is a tonic-kidney formula of Traditional Chinese Medicine (TCM) with good therapeutic effects in clinical settings. It was mainly applied to inhibit the decrease of ovarian reserve function in patients. However, the anti-apoptosis mechanism of BTR remains unknown. AIM OF THE STUDY: The formula of BTR is composed of prepared rehmannia root, debark peony root, carapax testudinis and asiatic cornelian cherry fruit. All four components contain the essences of nourishing yin and tonic-kidney. In the theory of TCM, the kidneys store the essence and are primarily responsible for reproduction and development. Hence, we speculated that BTR had some effect on women's reproductive system. In our research, rat serum contains BTR resolved into culture medium for incubation with miR-23a-induced KGN cells to test and determine our hypothesis. MATERIALS AND METHODS: BTR was prepared by the traditional decoction method to collect concentrated liquids for oral administration to rats (15.00 g/kg) for 14 days. The group with miR-23a-induced KGN cells was selected as the positive control, while the mimic one was the control. Pro-apoptosis and anti-apoptosis biomarkers were detected and analyzed by western blot together with upstream transcription factors and intracellular apoptotic signal pathways. RESULTS: The medium- and high-concentration of BRT greatly reduced the apoptosis of miR-23a-induced KGN cells both in mitochondria and cytoplasm. It showed the up-regulation of SIRT1 and SIRT3, the down-regulation of pro-apoptosis factor Bax and apoptotic-related proteins Caspase 3, 8, 9, and the reduction of phosphorylation of ERK1/2 and NF-κB. however, there was no consistency in the group with a low concentration of BTR, compared with those of other groups. CONCLUSION: Our research verified that BTR had a positive effect on women's reproductive system under medium or high concentration, illuminated the intrinsic mechanism at molecular levels, and convinced its potential application values in clinical settings.

Face preference detection task based on EEG energy analysis in the source domain.

Facial stimulation can produce specific event-related potential (ERP) component N170 in the fusiform gyrus region. However, the role of the fusiform gyrus region in facial preference tasks is not clear at present, and the current research of facial preference analysis based on EEG signals is mostly carried out in the scalp domain. This paper explores whether the region of the fusiform gyrus is involved in processing face preference emotions in terms of the distribution of energy over the source domain, and finds that the pars orbitalis cortex is most energetically active in the face preference task and that there are significant differences between the left and right hemispheres.Clinical Relevance- The role of pars orbitalis in facial preference may help doctors determine whether the pars orbitalis cortex is lost in clinical practice.

Using Determinant Point Process in Generative Adversarial Networks for SSVEP Signals Synthesis.

Steady-state visual evoked potential (SSVEP) is one of the main paradigms of brain-computer interface (BCI). However, the acquisition method of SSVEP can cause subject fatigue and discomfort, leading to the insufficiency of SSVEP databases. Inspired by generative determinantal point process (GDPP), we utilize the determinantal point process in generative adversarial network (GAN) to generate SSVEP signals. We investigate the ability of the method to synthesize signals from the Benchmark dataset. We further use some evaluation metrics to verify its validity. Results prove that the usage of this method significantly improved the authenticity of generated data and the accuracy (97.636%) of classification using deep learning in SSVEP data augmentation.

Case report: Differential diagnosis of highly amplified anti-CD5 CAR T cells and relapsed lymphoma cells in a patient with refractory ALK positive anaplastic large cell lymphoma.

Background: Anaplastic Large Cell Lymphoma (ALCL) is one of the most common subtypes of T-cell lymphoma. Among these, refractory and relapsed (r/r) ALK positive ALCL lacks effective therapies. The chimeric antigen receptor-modified T (CAR-T) cell therapy holds great promise as a therapeutic strategy for this disease. However, it is not known yet whether anti-CD5 CAR-T cells are sufficient for the definitive treatment of relapsed ALK+ ALCL, nor the role of accurate laboratory-based diagnoses during CAR-T treatment. Case presentation: The adolescent patient received autologous T cells containing sequences encoding VH domains specific to CD5. Following the infusion, there was an increase in both the copy number and proportion of CAR-T cells in peripheral blood. IL-6 and ferritin levels in the patient exhibited significant fluctuations, with increases of 13 and 70 folds respectively, compared to baseline after the treatment. Additionally, adverse effects were observed, including grade 4 rash, grade 1 headache, nausea, and neck-pain. Surprisingly, a relapsed disease phenotype was identified based on the results of PET/CT and histopathological analysis of the inguinal lymph node biopsy. After conducting a thorough diagnostic assessment, which included flow cytometry, next-generation sequencing (NGS), examination of immune-related gene rearrangements, and analysis of the immune repertoire of T-cell receptors (TCR), we conclusively determined that the hyperplastic T cells identified in the lymph node were the result of an expansion of CAR-T cells. Ultimately, the patient has attained complete remission (CR) and has sustained a disease-free survival state for 815 days as of the cutoff date on August 30, 2023. Conclusion: Taken together, the results demonstrate that anti-CD5 CAR-T cells can induce a clinical response in r/r ALK+ ALCL patient. Furthermore, this case underscores the importance of utilizing advanced technologies with high sensitivity and accuracy for biological detection in clinical laboratory diagnosis and prognosis in CAR-T cell treatment. Trial registration number: NCT04767308.

A novel tumor purity and immune infiltration-related model for predicting distant metastasis-free survival in prostate cancer.

BACKGROUND: umor cells, immune cells and stromal cells jointly modify tumor development and progression. We aim to explore the potential effects of tumor purity on the immune microenvironment, genetic landscape and prognosis in prostate cancer (PCa). METHODS: Tumor purity of prostate cancer patients was extracted from The cancer genome atlas (TCGA). Immune cellular proportions were calculated by the CIBERSORT. To identify critical modules related to tumor purity, we used weighted gene co-expression network analysis (WGCNA). Using STRING and Cytoscape, protein-protein interaction (PPI) networks were constructed and analyzed. A Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Disease Ontology (DO), and Gene Set Enrichment Analysis (GSEA) enrichment analysis of identified modules was conducted. To identify the expression of key genes at protein levels, we used the Human Protein Atlas (HPA) platform. RESULTS: A model of tumor purity score (TPS) was constructed in the gene expression omnibus series (GSE) 116,918 cohort. TCGA cohort served as a validation set and was employed to validate the TPS. TPS model, as an independent prognostic factor of distant metastasis-free survival (DMFS) in PCa. Patients had higher tumor purity and better prognosis in the low-TPS group. Tumor purity was related to the infiltration of mast cells and macrophage cells positively, whereas related to the infiltration of dendritic cells, T cells and B cells negatively in PCa. The nomogram based on TPS, Age, Gleason score and T stage had a good predictive value and could evaluate the prognosis of PCa metastasis. GO and KEGG enrichment analyses showed that hub genes mainly participate in T cell activation and T-helper lymphocytes (TH) differentiation. Hub genes were mainly enriched in primary immunodeficiency disease, according to DO analysis. SLAMF8 was identified as the most critical gene by Cytoscape and HPA analysis. CONCLUSIONS: Dynamic changes in the immune microenvironment associated with tumor purity could correlate with a poor DMFS of low-purity PCa. The TPS can predict the DMFS of PCa. In addition, prostate cancer metastases may be related to immunosuppression caused by a disorder of the immune microenvironment.

Residue dissipation dynamics and dietary risk assessment of emamectin benzoate, chlorantraniliprole, chlorfenapyr, and lufenuron in cabbage.

Emamectin benzoate (EB), chlorantraniliprole (CTP), chlorfenapyr (CFP), and lufenuron (LFR) are widely used to control Spodoptera exigua on cabbage. This study is aimed at establishing a universal, sensitive, accurate, and efficient method for the determination of these pesticide residues in cabbage using QuEChERS pretreatment combined with ultra-performance liquid chromatography or gas chromatography-tandem mass spectrometry (UPLC‒MS/MS or GC‒MS/MS). The recoveries of these pesticides (containing metabolites) in cabbage detected by the optimized method ranged between 80.9% and 99.9%, with relative standard deviations (RSDs) of 0.164-12.5%. The limit of quantification (LOQ) of the four pesticides was determined to be 0.01 mg/kg. The standard curve, accuracy, precision, and LOQ of the analysis method all met the requirements of pesticide residue detection. The optimized method was used to detect the dissipation dynamics and terminal residues in 12 regions. The dissipation half-lives of CTP, CFP, and LFR were 3.35-7.01 d, 2.29-4.75 d, and 3.24-6.80 d, respectively. The terminal residues of all these pesticides were below the maximum residue limits (MRLs). The dietary risk assessment indicated that the dietary risk probabilities for EB, CTP, CFP, and LFR were all less than 1 and were within the acceptable range. This study provides a comprehensive assessment of the residues and dietary risks of EB, CTP, CFP, and LFR for the scientific use of pesticides.

Functional diversification and dynamics of CAR-T cells in patients with B-ALL.

Understanding of cellular evolution and molecular programs of chimeric antigen receptor-engineered (CAR)-T cells post-infusion is pivotal for developing better treatment strategies. Here, we construct a longitudinal high-precision single-cell transcriptomic landscape of 7,578 CAR-T cells from 26 patients with B cell acute lymphoblastic leukemia (B-ALL) post-infusion. We molecularly identify eight CAR-T cell subtypes, including three cytotoxic subtypes with distinct kinetics and three dual-identity subtypes with non-T cell characteristics. Remarkably, long-term remission is coincident with the dominance of cytotoxic subtypes, while leukemia progression is correlated with the emergence of subtypes with B cell transcriptional profiles, which have dysfunctional features and might predict relapse. We further validate in vitro that the generation of B-featured CAR-T cells is induced by excessive tumor antigen stimulation or suppressed TCR signaling, while it is relieved by exogenous IL-12. Moreover, we define transcriptional hallmarks of CAR-T cell subtypes and reveal their molecular changes along computationally inferred cellular evolution in vivo. Collectively, these results decipher functional diversification and dynamics of peripheral CAR-T cells post-infusion.

TET3 plays a critical role in white adipose development and diet-induced remodeling.

Maintaining healthy adipose tissue is crucial for metabolic health, requiring a deeper understanding of adipocyte development and response to high-calorie diets. This study highlights the importance of TET3 during white adipose tissue (WAT) development and expansion. Selective depletion of Tet3 in adipose precursor cells (APCs) reduces adipogenesis, protects against diet-induced adipose expansion, and enhances whole-body metabolism. Transcriptomic analysis of wild-type and Tet3 knockout (KO) APCs unveiled TET3 target genes, including Pparg and several genes linked to the extracellular matrix, pivotal for adipogenesis and remodeling. DNA methylation profiling and functional studies underscore the importance of DNA demethylation in gene regulation. Remarkably, targeted DNA demethylation at the Pparg promoter restored its transcription. In conclusion, TET3 significantly governs adipogenesis and diet-induced adipose expansion by regulating key target genes in APCs.

Self-assembly of eugenol-loaded particles to regulate the adhesion of carriers on leaves for efficient foliar applications and ecotoxicological safety.

Currently, there is a pressing need to develop an agrochemical-loaded system that is both uncomplicated and efficient, thereby enhancing the adhesion of agrochemical to leaf surfaces and optimizing their insecticidal efficacy, while concurrently mitigating environmental risks. The flexible eugenol-loaded particles were synthesized via a one-step polyurethane self-assembly reaction, utilizing polyethylene glycol (PEG) as the soft segment and 4,4-diphenylmethane diisocyanate (MDI) as the hard segment. The increase in the length of the soft segment enhances the flexibility of the particles, thereby improving the contact area and adhesion with the foliar surface. When flexible particles are applied on the foliar surface, they can achieve satisfactory resistance to rainfall erosion. When the PEG molecular weight is 800, the residual concentration of eugenol can still reach 42.11% after 6 washes. The carrier protects the active ingredients and improves the resistance to ultraviolet irradiation. After 5 h of ultraviolet irradiation, the concentration of eugenol remained at 59.03% when PEG with a molecular weight of 200 was employed. Greenhouse experiments showed that the flexible transformation of particles greatly enhanced the application effect of spray on the foliar surface of particles. After undergoing three washes, the mortality of the particles can be enhanced by 5.4-8.4 times compared to that of emulsion concentrate (EC) sample. The enhancement of leaf retention performance reduces environmental risks caused by pesticide loss. Meanwhile, the controlled release of particles also reduces the acute toxicity to zebrafish. The toxicity selection pressure of the EUG@P800-Ps sample is 10.6 times that of the EC sample. In conclusion, the preparation process of the system is simple, and the flexible transformation is an effective strategy to improve the foliar application effect of spray and improve the environmental safety.

Causality of particulate matter on cardiovascular diseases and cardiovascular biomarkers.

Background: Previous observational studies have shown that the prevalence of cardiovascular diseases (CVDs) is related to particulate matter (PM). However, given the methodological limitations of conventional observational research, it is difficult to identify causality conclusively. To explore the causality of PM on CVDs and cardiovascular biomarkers, we conducted a Mendelian randomization (MR) analysis. Method: In this study, we obtained summary-level data for CVDs and cardiovascular biomarkers including atrial fibrillation (AF), heart failure (HF), myocardial infarction (MI), ischemic stroke (IS), stroke subtypes, body mass index (BMI), lipid traits, fasting glucose, fasting insulin, and blood pressure from several large genome-wide association studies (GWASs). Then we used two-sample MR to assess the causality of PM on CVDs and cardiovascular biomarkers, 16 single nucleotide polymorphisms (SNPs) for PM2.5 and 6 SNPs for PM10 were obtained from UK Biobank participants. Inverse variance weighting (IVW) analyses under the fixed effects model were used as the main analytical method to calculate MR Estimates, followed by multiple sensitivity analyses to confirm the robustness of the results. Results: Our study revealed increases in PM2.5 concentration were significantly related to a higher risk of MI (odds ratio (OR), 2.578; 95% confidence interval (CI), 1.611-4.127; p = 7.920 × 10-5). Suggestive evidence was found between PM10 concentration and HF (OR, 2.015; 95% CI, 1.082-3.753; p = 0.027) and IS (OR, 2.279; 95% CI,1.099-4.723; p = 0.027). There was no evidence for an effect of PM concentration on other CVDs. Furthermore, PM2.5 concentration increases were significantly associated with increases in triglyceride (TG) (OR, 1.426; 95% CI, 1.133-1.795; p = 2.469 × 10-3) and decreases in high-density lipoprotein cholesterol (HDL-C) (OR, 0.779; 95% CI, 0.615-0.986; p = 0.038). The PM10 concentration increases were also closely related to the decreases in HDL-C (OR, 0.563; 95% CI, 0.366-0.865; p = 8.756 × 10-3). We observed no causal effect of PM on other cardiovascular biomarkers. Conclusion: At the genetic level, our study suggested the causality of PM2.5 on MI, TG, as well HDL-C, and revealed the causality of PM10 on HF, IS, and HDL-C. Our findings indicated the need for continued improvements in air pollution abatement for CVDs prevention.

A multidimensional optimization strategy of pyraclostrobin-loaded microcapsules to improve the selectivity between toxicological risk in zebrafish and efficacy in controlling rice blast.

Developing microcapsules (MCs) delivery systems can effectively mitigate toxicological risk of highly active/toxic pesticides; whereas the controlled release functions also limiting their practical effectiveness. Therefore, designing a precise regulating strategy to balance the toxicity and bioactivity of MCs is urgently needed. Here, we prepared a series of pyraclostrobin-loaded MCs with different wall materials, particle sizes, core density and shell compactness using interfacial polymerization. The results showed that the MCs released more slowly in water with increasing particle sizes and capsule compactness, and they sunk more quickly with the increasing particle sizes and core density. Additionally, MCs with slower release speed was always accompanied with lower acute toxicity levels to zebrafish. When the release dynamics slowed down to the threshold dose on demand for disease control, facilitating settlement of MCs can further reduce toxicity within spatial and temporal dimensions. The poor accumulation of MCs with larger particle sizes or dense shell in gills was closely related to their efficient detoxification. Importantly, seven of the MCs samples possessed superior selectivity between bio-performance in controlling rice blast and toxicological hazard to fish compared to commercial formulations. The results provide a comprehensive guidance for developing an efficient and safe pesticide delivery system.