[Application of ARHGAP8 in Predicting the Efficacy of Neoadjuvant Chemotherapy for Locally Advanced Mid-Low Rectal Cancer].

Objective To analyze the sensitivity of ARHGAP8 in predicting the efficacy of neoadjuvant chemotherapy in the patients with locally advanced mid-low colorectal cancer and provide accurate evidence for the treatment of advanced colorectal cancer. Methods The differentially expressed gene ARHGAP8 was screened out by bioinformatics analysis.Cancer tissue and rectal tissue of 68 patients with primary rectal cancer were selected.The rectal cancer tissue samples and the rectal tissue samples were collected for clinical validation of ARHGAP8 expression by quantitative real-time PCR,Western blotting,and immunohistochemistry.The clinical and pathological features such as gender,age,tumor stage,differentiation degree,and pathological type of the patients were collected for functional validation.Forty-four patients with locally advanced mid-low rectal cancer who received neoadjuvant chemotherapy were selected for immunohistochemical examination of ARHGAP8 expression.The expression level of ARHGAP8 was compared between before and after chemotherapy and among different efficacy groups. Results The bioinformatics analysis revealed differences in the expression level of ARHGAP8 between the cancer tissue and rectal tissue (P<0.001).The expression level of ARHGAP8 was correlated with tumor stage (P=0.024),lymph node metastasis (P=0.007),and age (P=0.005).Quantitative real-time PCR results showed that the mRNA level of ARHGAP8 in the cancer tissue was higher than that in the rectal tissue (P<0.001).Western blotting and immunohistochemistry results demonstrated that the protein level of ARHGAP8 in the cancer tissue was higher than that in the rectal tissue (P=0.011).The expression of ARHGAP8 was correlated with tumor size (P=0.010) and pathological stage (P=0.005),while it showed no significant association with tumor differentiation degree,lymph node metastasis,liver metastasis,Ki-67,or microsatellite instability expression level.The 44 patients receiving neoadjuvant chemotherapy included 13,8,8,and 15 patients of tumor regression grades 0,1,2,and 3,respectively.Among them,65.91% (29/44) patients showed responses to the treatment.After neoadjuvant chemotherapy,the expression of ARHGAP8 in the cancer tissue was down-regulated in the patients who responded to the chemotherapy (P<0.001).The response rate in the patients with low protein level of ARHGAP8 was 92.86%,which was higher than that (53.33%) in the patients with high protein level of ARHGAP8 (P=0.033). Conclusion ARHGAP8 is highly expressed in the rectal cancer tissue.The patients with locally advanced mid-low rectal cancer and low ARHGAP8 expression are more sensitive to neoadjuvant chemotherapy with the XELOX protocol.ARHGAP8 can serve as a potential biomarker for the occurrence and development of rectal cancer and an important index for evaluating the efficacy of neoadjuvant chemotherapy with the XELOX protocol in the patients with locally advanced mid-low rectal cancer.

Re-examination of the Claimed Isolation of Stable Noncyclic 1,2-Disulfoxides.

Re-examination of the claimed isolation and X-ray characterization of di-p-tolyl and dimesityl 1,2-disulfoxides from thermolysis of the corresponding aryl sulfinimines and thiosulfinates showed that the isolated disulfide dioxides are instead the well-known isomeric thiosulfonates, as confirmed by XAS, DART-MS, X-ray, IR and NMR methods. Concerns with the original X-ray structures are addressed. Our results agree with the DFT prediction of very weak diaryl 1,2-disulfoxide S-S bond dissociation enthalpies. For now, room-temperature-stable noncyclic 1,2-disulfoxides remain unknown.

Multichannel Lanthanide-Doped Nanoprobes for Serodiagnosis and Therapy.

In this account, we will highlight recent progress in the development of multichannel lanthanide-doped (MC-Ln) nanoprobes for highly efficient serodiagnosis and therapy, with a particular focus on our own work. First, we first provide a classification of the types of MC-Ln nanoprobes based on the contained type and number of signals. The merits of different types of nanoprobes and the reason using lanthanides are elucidated. Then, we provide an overview of the current uses of MC-Ln nanoprobes in serodiagnosis and therapy, focusing on the strategic exploration to improve the diagnostic and therapeutic performance from different perspectives. Finally, we present a prospective outlook on the future development and potential issues of next-generation MC-Ln nanoprobes. We hope that this timely account will update our understanding of MC-Ln and similar nanoprobes for bioapplications and provide helpful references for the state-of-the-art tools for serodiagnosis and therapy.

Performance in the Fundamentals of Laparoscopic Surgery: Does it reflect global rating scales in the Objective Structured Assessment of Technical Skills in porcine laparoscopic surgery?

Objective: To correlate the utility of the Fundamentals of Laparoscopic Surgery (FLS) manual skills program with the Objective Structured Assessment of Technical Skills (OSATS) global rating scale in evaluating operative performance. Methods: The Asian Urological Surgery Training and Educational Group (AUSTEG) Laparoscopic Upper Tract Surgery Course implemented and validated the FLS program for its usage in laparoscopic surgical training. Delegates' basic laparoscopic skills were assessed using three different training models (peg transfer, precision cutting, and intra-corporeal suturing). They also performed live porcine laparoscopic surgery at the same workshop. Live surgery skills were assessed by blinded faculty using the OSATS rating scale. Results: From March 2016 to March 2019, a total of 81 certified urologists participated in the course, with a median of 5 years of post-residency experience. Although differences in task time did not reach statistical significance, those with more surgical experience were visibly faster at completing the peg transfer and intra-corporeal suturing FLS tasks. However, they took longer to complete the precision cutting task than participants with less experience. Overall OSATS scores correlated weakly with all three FLS tasks (peg transfer time: r=-0.331, r 2=0.110; precision cutting time: r=-0.240, r 2=0.058; suturing with intra-corporeal knot time: r=-0.451, r 2=0.203). Conclusion: FLS task parameters did not correlate strongly with OSATS globing rating scale performance. Although FLS task models demonstrated strong validity, it is important to assimilate the inconsistencies when benchmarking technical proficiency against real-life operative competence, as evaluated by FLS and OSATS, respectively.

Phytochemical components analysis and hypolipidemic effect on hyperlipidemia mice of the aerial parts from Allium sativum.

Background: The bulbs of Allium sativum are widely used as food or seasoning (garlic), while they have also been utilized as a famous traditional medicine since ancient eras for the treatment of scabies, tuberculosis, pertussis, diarrhea and dysentery, etc. However, very few studies focus on their abundant aerial parts, which are normally discarded during the harvest season. Methods: The hyperlipidemic mice model has been used to study the lipid-lowering effect of the aerial parts in this article. 180 mice were randomly divided into 18 groups, including blank control (BC), model (Mod), positive control (PC), and low-, medium-, and high-dose groups of the crude extract, petroleum ether, ethyl acetate, n-butanol, and residual water extracts (corresponding to CE, PEE, EAE, NBE, WE), with 10 mice in each group. The preventive effects of the extracts on hyperlipidemic mice lasted for four weeks. Ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) and gas chromatography tandem mass spectrometry (GC-MS/MS) were used to analyze the chemical components of NBE and PEE respectively. Results: The results of the mice experiment showed that n-butanol extract (NBE) and petroleum ether extract (PEE) from the aerial parts could significantly reduce the contents of total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), alanine transaminase (ALT) and aspartate transaminase (AST) in serum of hyperlipidemic mice, and increase the contents of high density lipoprotein cholesterol (HDL-C). They could enhance the activity of superoxide dismutase (SOD) in liver and reduce the level of malondialdehyde (MDA). At the same time, they could improve steatosis and inflammation of liver cells. The results of phytochemical components analysis showed that NBE was rich in organic acids, flavonoids and nitrogen-containing constituents, while PEE contained organic sulfur compounds, aliphatic acids and derivatives, alkaloids, phytosterols, etc. Conclusion: These results support that the aerial parts of A. sativum are an interesting source of bioactive ingredients that may be useful in the prevention and treatment of hyperlipidemia.

Chemical reduction of π-expanded functionalized pentacene: cooperation of side group in alkali metal binding.

Chemical reduction of a vertically expanded pentacene, TIPS-peri-pentacenopentacene (TIPS-PPP), with sodium metal in THF readily afforded a doubly-reduced product isolated as [{Na+(THF)3}2(TIPS-PPP2-)]. Single-crystal X-ray diffraction revealed the formation of a π-complex of TIPS-PPP2- with two {Na+(THF)3} moieties. The sodium ion is coordinated to three C-atoms at the most negatively charged edge sites and at the lateral ethynyl group. The delocalisation of the charge on the ethynyl function is accompanied by its notable elongation (Δ = 0.015 Å) coupled with the contraction of the adjacent single C-C bond (Δ = 0.033 Å). Bond length analysis supported by Harmonic Aromaticity Oscillator Model (HOMA) shows that the dianion can be written with four aromatic sextets in agreement with the Clar representation. Although TIPS-PPP2- has 36 π-electrons (4n), it does not show a global magnetic paratropic response. The rings with the most negative charge density have a very low paratropic response, while the other rings have a low diatropic response. Overall, the dianion is a non-aromatic molecule.

Two polymorph modifications of tris(hexafluoroacetylacetonato)iron(III) revealed: is that common for other trivalent metals?

A long-standing issue about the correct identification of an important starting reagent, iron(III) hexafluoroacetylacetonate, Fe(hfac)3 (1), has been resolved. The tris-chelated mononuclear complex was found to crystallize in two polymorph modifications which can be assigned as the low-temperature (1-L) monoclinic P21/n and the high-temperature (1-H) trigonal P-3. Low-temperature polymorph 1-L was found to transform to 1-H upon sublimation at 44 °C. Two modifications are clearly distinguished by powder X-ray diffraction (PXRD), single-crystal X-ray diffraction, differential scanning calorimetry (DSC), and melting-point measurements. On the other hand, the two forms share similar characteristics in direct analysis in real-time mass spectrometry (DART-MS), attenuated total reflection (ATR) spectroscopy, and some physical properties, such as color, volatility, sensitivity, and solubility. Analysis of the literature and some of our preliminary data strongly suggest that the appearance of two polymorph modifications for trivalent metal (both transition and main group) hexafluoroacetylacetonates is a common case for several largely used complexes not yet accounted for in the crystallographic databases.

Decoding the Molecular Mechanisms of BRAF V600E-Induced Nevi Formation.

Melanocytes derived from neural crest cells harbor the BRAF V600E mutation, which is the predominant driver of nevus formation in humans. This mutation leads to malignant cell proliferation and subsequent cell cycle arrest, culminating in oncogene-induced senescence and nevus development. Nevertheless, emerging evidence has highlighted the heterogeneity of cellular senescence markers in BRAF V600E-induced senescent melanocytes. Moreover, the capacity of melanocytes within nevi to regain their proliferative ability raises questions about the molecular mechanisms by which BRAF V600E, via the mitogen-activated protein kinase signaling pathway, triggers nevus formation. This study provides an overview and discussion of the molecular mechanisms underpinning BRAF V600E-induced melanocyte nevus formation and the relevant animal models employed for their elucidation. It also highlights the significance of elucidating dynamic changes in cytoplasmic and nuclear substrates that interact with phosphorylated extracellular signal-regulated protein kinases 1 and 2 and underscores the value of using targeted BRAF V600E animal models created through gene editing technologies.

Icanbelimod (CBP-307), a next-generation Sphingosine-1-phosphate receptor modulator, in healthy men: pharmacokinetics, pharmacodynamics, safety, and tolerability in a randomized trial in Australia.

Background: Icanbelimod (formerly CBP-307) is a next-generation S1PR modulator, targeting S1PR1. In this first-in-human study, icanbelimod was investigated in healthy men in Australia. Methods: Participants were randomized 3:1, double-blind, to icanbelimod or placebo in four single-dose cohorts (0.1 mg, 0.25 mg, 0.5 mg [n=8 per cohort], 2.5 mg [n=4]) or for 28-days once-daily treatment in two cohorts (0.15 mg, 0.25 mg [n=8 per cohort]). Participants in the 0.25-mg cohort received 0.1 mg on Day 1. Treatments were administered orally after fasting; following one-week washout, icanbelimod was administered after breakfast in the 0.5-mg cohort. Results: Icanbelimod exposure increased rapidly and dose-dependently with single and multiple dosing (Tmax 4-7 hours). Lymphocyte counts decreased rapidly after single (-11%, 0.1 mg; -40%, 0.25 mg; -71%, 0.5 mg; -77%, 2.5 mg) and multiple doses (-49%, 0.15 mg; -75%, 0.25 mg), and recovered quickly, 7 days after dosing. After single-dose 0.5 mg, although a high-fat breakfast versus fasting did not affect maximal decrease, lymphocyte counts tended to be lower after breakfast across most timepoints up to 72 hours. Twenty-eight participants (63.6%) experienced mainly mild treatment-emergent adverse events (TEAEs). After single-dose icanbelimod, the most common TEAEs were headache (28.6%, n=6) and dizziness (19.0%, n=4). Three participants experienced transient bradycardia, with one serious, following single-dose 2.5 mg icanbelimod. After multiple-dose icanbelimod, the most common TEAEs were headache (50.0%, n=6) and lymphopenia (41.7%, n=5), and two participants withdrew due to non-serious TEAEs. Up-titration attenuated heart rate reductions. Conclusion: Icanbelimod was well-tolerated up to 0.5 mg and effectively reduced lymphocyte counts. Clinical trial registration: ClinicalTrials.gov, identifier NCT02280434.b.

Development and Evaluation of DOTA-FAPI-Maleimide as a Novel Radiotracer for Tumor Theranostic with Extended Circulation.

This study aimed to evaluate a novel albumin-binding strategy for addressing the challenge of insufficient tumor retention of fibroblast activation protein inhibitors (FAPIs). Maleimide, a molecule capable of covalent binding to free thiol groups, was modified to conjugate with FAPI-04 in order to enhance its binding to endogenous albumin, resulting in an extended blood circulation half-life and increased tumor uptake. DOTA-FAPI-maleimide was prepared and radiolabeled with Ga-68 and Lu-177, followed by cellular assays, pharmacokinetic analysis, PET/CT, and SPECT/CT imaging to assess the probe distribution in various tumor-bearing models. Radiolabeling of the modified probe was successfully achieved with a radiochemical yield of over 99% and remained stable for 144 h. Cellular assays showed that the ligand concentration required for 50% inhibition of the probe was 1.20 ± 0.31 nM, and the Kd was 0.70 ± 0.07 nM with a Bmax of 7.94 ± 0.16 fmol/cell, indicative of higher specificity and affinity of DOTA-FAPI-maleimide compared to other FAPI-04 variants. In addition, DOTA-FAPI-maleimide exhibited a persistent blood clearance half-life of 7.11 ± 0.34 h. PET/CT images showed a tumor uptake of 2.20 ± 0.44%ID/g at 0.5 h p.i., with a tumor/muscle ratio of 5.64 in HT-1080-FAP tumor-bearing models. SPECT/CT images demonstrated long-lasting tumor retention. At 24 h p.i., the tumor uptake of [177Lu]Lu-DOTA-FAPI-maleimide reached 5.04 ± 1.67%ID/g, with stable tumor retention of 3.40 ± 1.95%ID/g after 4 days p.i. In conclusion, we developed and evaluated the thiol group-attaching strategy, which significantly extended the circulation and tumor retention of the adapted FAPI tracer. We envision its potential application for clinical cancer theranostics.

The "appearing" and "disappearing" ascites in the treatment of colorectal cancer: a case report.

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. In the treatment of patients with CRC, oxaliplatin plays a pivotal role, with moderate side effects. Neurotoxicity, myelosuppression, ototoxicity, delayed hypersensitivity reactions, and rhabdomyolysis induced by oxaliplatin have been reported individually. However, the occurrence of oxaliplatin-induced ascites has not been reported previously. The objectives of this case report were to elaborate on the rare occurrence of ascites in a patient with CRC after oxaliplatin therapy and to explore its characteristics and causes. Case description: We report on a case of upper rectal cancer seen in a 65-year-old man who underwent robotic-assisted laparoscopic anterior rectal resection. The patient developed ascites during postoperative adjuvant therapy with oxaliplatin and capecitabine. We ruled out tumor recurrence by laparoscopy, intraoperative biopsy, and biochemistry of the ascites. The patient did not experience a recurrence of ascites after discontinuation of chemotherapy. Conclusion: This case suggests that chemotherapy with oxaliplatin might cause ascites. The mechanism of the oxaliplatin-induced liver injury was further discussed, which might have been the cause of ascite formation. When patients with CRC who underwent chemotherapy with oxaliplatin develop ascites, surgeons should actively determine whether this is a side effect of chemotherapy or is due to tumor recurrence in order to avoid unnecessary surgery.

Progress and Outlook on Electrochemical Sensing of Lung Cancer Biomarkers.

Electrochemical biosensors have emerged as powerful tools for the ultrasensitive detection of lung cancer biomarkers like carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and alpha fetoprotein (AFP). This review comprehensively discusses the progress and potential of nanocomposite-based electrochemical biosensors for early lung cancer diagnosis and prognosis. By integrating nanomaterials like graphene, metal nanoparticles, and conducting polymers, these sensors have achieved clinically relevant detection limits in the fg/mL to pg/mL range. We highlight the key role of nanomaterial functionalization in enhancing sensitivity, specificity, and antifouling properties. This review also examines challenges related to reproducibility and clinical translation, emphasizing the need for standardization of fabrication protocols and robust validation studies. With the rapid growth in understanding lung cancer biomarkers and innovations in sensor design, nanocomposite electrochemical biosensors hold immense potential for point-of-care lung cancer screening and personalized therapy guidance. Realizing this goal will require strategic collaboration among material scientists, engineers, and clinicians to address technical and practical hurdles. Overall, this work provides valuable insight for developing next-generation smart diagnostic devices to combat the high mortality of lung cancer.

Bio-electrocatalytic alkene reduction using ene-reductases with methyl viologen as electron mediator.

Asymmetric hydrogenation of alkene moieties is important for the synthesis of chiral molecules, but achieving high stereoselectivity remains a challenge. Biocatalysis using ene-reductases (EReds) offers a viable solution. However, the need for NAD(P)H cofactors limits large-scale applications. Here, we explored an electrochemical alternative for recycling flavin-containing EReds using methyl viologen as a mediator. For this, we built a bio-electrocatalytic setup with an H-type glass reactor cell, proton exchange membrane, and carbon cloth electrode. Experimental results confirm the mediator's electrochemical reduction and enzymatic consumption. Optimization showed increased product concentration at longer reaction times with better reproducibility within 4-6 h. We tested two enzymes, Pentaerythritol Tetranitrate Reductase (PETNR) and the Thermostable Old Yellow Enzyme (TOYE), using different alkene substrates. TOYE showed higher productivity for the reduction of 2-cyclohexen-1-one (1.20 mM h-1), 2-methyl-2-cyclohexen-1-one (1.40 mM h-1) and 2-methyl-2-pentanal (0.40 mM h-1), with enantiomeric excesses ranging from 11% to 99%. PETNR outperformed TOYE in terms of enantioselectivity for the reduction of 2-methyl-2-pentanal (ee 59±7% (S)). Notably, TOYE achieved promising results also in reducing ketoisophorone, a challenging substrate, with similar enantiomeric excess compared to published values using NADH.

Unveil cis-acting combinatorial mRNA motifs by interpreting deep neural network.

SUMMARY: Cis-acting mRNA elements play a key role in the regulation of mRNA stability and translation efficiency. Revealing the interactions of these elements and their impact plays a crucial role in understanding the regulation of the mRNA translation process, which supports the development of mRNA-based medicine or vaccines. Deep neural networks (DNN) can learn complex cis-regulatory codes from RNA sequences. However, extracting these cis-regulatory codes efficiently from DNN remains a significant challenge. Here, we propose a method based on our toolkit NeuronMotif and motif mutagenesis, which not only enables the discovery of diverse and high-quality motifs but also efficiently reveals motif interactions. By interpreting deep-learning models, we have discovered several crucial motifs that impact mRNA translation efficiency and stability, as well as some unknown motifs or motif syntax, offering novel insights for biologists. Furthermore, we note that it is challenging to enrich motif syntax in datasets composed of randomly generated sequences, and they may not contain sufficient biological signals. AVAILABILITY AND IMPLEMENTATION: The source code and data used to produce the results and analyses presented in this manuscript are available from GitHub (https://github.com/WangLabTHU/combmotif).

Enhancing thromboprophylaxis after colorectal cancer surgery in China: Bridging the gap between evidence and implementation through pathway optimization.

BACKGROUND: The CRC-VTE trial conducted in China revealed a significant occurrence of venous thromboembolism (VTE) in patients following colorectal cancer (CRC) surgery, raising concerns about implementing thromboprophylaxis measures. The present study aimed to identify and analyze inappropriate aspects of current thromboprophylaxis practices. METHODS: This study performed an analysis of the CRC-VTE trial, a prospective multicenter study that enrolled 1836 patients who underwent CRC surgery. The primary objective was to identify independent risk factors for VTE after CRC surgery using multivariate logistic regression analysis. Furthermore, among the cases in which VTE occurred, the appropriateness of thromboprophylaxis was assessed based on several factors, including pharmacologic prophylaxis, time to initiate prophylaxis, drug selection, drug dosage, and duration of pharmacologic prophylaxis. Based on the analysis of the current state of thromboprophylaxis and relevant clinical guidelines, a modified Delphi method was used to develop a clinical pathway for VTE prophylaxis after CRC surgery. RESULTS: In this analysis of 1836 patients, 205 (11.2%) were diagnosed with VTE during follow-up. The multifactorial analysis identified several independent risk factors for VTE, including age (≥70 years), female sex, varicose veins in the lower extremities, intraoperative blood transfusion, and the duration of immobilization exceeding 24 h. None of the patients diagnosed with VTE in the CRC trial received adequate thromboprophylaxis. The main reasons for this inappropriate practice were the omission of thromboprophylaxis, delayed initiation, and insufficient duration of thromboprophylaxis. We developed a specialized clinical pathway for thromboprophylaxis after CRC surgery to address these issues. CONCLUSIONS: This study offers a comprehensive nationwide evaluation of existing thromboprophylaxis practices in patients after CRC surgery in China. A specialized clinical pathway was developed to address the identified gaps and improve the quality of care. This clinical pathway incorporates explicit, tailored, detailed recommendations for thromboprophylaxis after CRC surgery.

Trickier than It Looks: Isomerization between Five- and Six-Coordinated Zinc in Heterometallic Li2Zn2 Molecule.

This report describes the synthesis and characterization of two heterobimetallic Li-Zn coordination isomers [Li2Zn2(tbaoac)6] (tbaoac = tert-butyl acetoacetato) that have been isolated separately by the same stoichiometric reaction run in different organic solvents. The 6-coordinated zinc isomer (6-Zn) was synthesized in acetone with high yield, while the 5-coordinated one (5-Zn) was readily obtained from ethanol. The 5-Zn isomer has a low solubility in organic solvents such as alkanes and haloalkanes, while its 6-Zn counterpart exhibits a good solubility in almost all common solvents. Two isomeric molecules feature similar centrosymmetric tetranuclear cyclic assemblies, which are different in their arrangement of tbaoac ligands. While all ligands act as µ2-type in the structure of 5-Zn, the two tbaoac groups chelating Li appear as µ3-type in 6-Zn, thus providing an additional coordination for Zn ions. However, the real structural transformation between these isomers was shown to be more complex than simply making or breaking a couple of Zn-O bonds. X-ray single-crystal structure analysis, powder X-ray diffraction, multinuclear NMR, DART mass spectrometry, ICP-OES analysis, and TGA have been employed for the characterization of the isomers. The combination of powder X-ray diffraction and 1H NMR investigation revealed that 6-Zn isomer can be quantitatively transformed to 5-Zn in ethanol, while the reverse conversion instantly takes place in acetone.

Improving the efficiency and environmental safety of emamectin benzoate through a pH-responsive metal-organic framework microencapsulation strategy.

Herein, we developed a technique for loading nanopesticides onto Metal-Organic Frameworks (MOFs) to control Spodoptera litura. The average short-axis length of the synthesized carrier emamectin benzoate@PCN-222 @hyaluronic acid (EB@PCN-222 @HA) was ∼40 nm, with an average long-axis length of ∼80 nm. This enabled the manipulation of its size, contact angle, and surface tension on the surface of leaves. Pesticide-loading capacity, determined via thermogravimetric analysis, was measured at ∼16 %. To ensure accurate pesticide release in the alkaline intestine of Spodoptera litura, EB@PCN-222 @HA was engineered to decompose under alkaline conditions. In addition, the carrier delayed the degradation rate of EB, enhancing EB's stability. Loading Nile red onto PCN-222 @HA revealed potential entry into the insect body through feeding, which was supported by bioassay experiments. Results demonstrated the sustained-release performance of EB@PCN-222 @HA, extending its effective duration. The impact of different carrier concentrations on root length, stem length, fresh weight, and germination rate of pakchoi and tomato were assessed. Promisingly, the carrier exhibited a growth-promoting effect on the fresh weight of both the crops. Furthermore, cytotoxicity experiments confirmed its safety for humans. In cytotoxicity assays, PCN-222 @HA showed minimal toxicity at concentrations up to 100 mg/L, with cell survival rates above 80 %. Notably, the EB@PCN-222 @HA complex demonstrated reduced cytotoxicity compared to EB alone, supporting its safety for human applications. This study presents a safe and effective approach for pest control using controlled-release pesticides with extended effective durations.

Dual-loaded nano pesticide system based on industrial grade scaleable carrier materials with combinatory efficacy and improved safety.

Repeated and widespread use of single chemical pesticides raises concerns about efficiency and safety, developing multi-component synergistic pesticides provides a new route for efficient control of diseases. Most commercial compound formulations are open systems with non-adjustable released rates, resulting in a high frequency of applications. Meanwhile, although nano pesticide delivery systems constructed with different carrier materials have been extensively studied, realizing their actual scale-up production still has important practical significance due to the large-scale field application. In this study, a boscalid and pyraclostrobin dual-loaded nano pesticide system (BPDN) was constructed with industrial-grade carrier materials to facilitate the realization of large-scale production. The optimal industrial-scale preparation mechanism of BPDN was studied with surfactants as key factors. When agricultural emulsifier No.600 and polycarboxylate are used as the ratio of 1:2 in the preparation process, the BPDN has a spherical structure with an average size of 270 nm and exhibits superior physical stability. Compared with commercial formulation, BPDN maintains rate-stabilized release up to 5 times longer, exhibits better dispersion and spreading performance on foliar, has more than 20% higher deposition amounts, and reduces loss. A single application of BPDN could efficiently control tomato gray mold during the growing period of tomatoes due to extended duration and combinatory effectiveness, reducing two application times and labor costs. Toxicology tests on various objects systematically demonstrated that BPDN has improved safety for HepG2 cells, and nontarget organism earthworms. This research provides insight into creating safe, efficient, and environmentally friendly pesticide production to reduce manual operation times and labor costs. Accompanied by production strategies that can be easily scaled up industrially, this contributes to the efficient use of resources for sustainable agriculture.

Epilepsy detection based on multi-head self-attention mechanism.

CNN has demonstrated remarkable performance in EEG signal detection, yet it still faces limitations in terms of global perception. Additionally, due to individual differences in EEG signals, the generalization ability of epilepsy detection models is week. To address this issue, this paper presents a cross-patient epilepsy detection method utilizing a multi-head self-attention mechanism. This method first utilizes Short-Time Fourier Transform (STFT) to transform the original EEG signals into time-frequency features, then models local information using Convolutional Neural Network (CNN), subsequently captures global dependency relationships between features using the multi-head self-attention mechanism of Transformer, and finally performs epilepsy detection using these features. Meanwhile, this model employs a light multi-head attention mechanism module with an alternating structure, which can comprehensively extract multi-scale features while significantly reducing computational costs. Experimental results on the CHB-MIT dataset show that the proposed model achieves accuracy, sensitivity, specificity, F1 score, and AUC of 92.89%, 96.17%, 92.99%, 94.41%, and 96.77%, respectively. Compared to the existing methods, the method proposed in this paper obtains better performance along with better generalization.