Global Trends and Frontier in Research on Pancreatic Alpha Cells: A Bibliometric Analysis from 2013 to 2023.

PURPOSE: Over the past 20 years, much of the research on diabetes has focused on pancreatic beta cells. In the last 10 years, interest in the important role of pancreatic alpha cells in the pathogenesis of diabetes, which had previously received little attention, has grown. We aimed to summarize and visualize the hotspot and development trends of pancreatic alpha cells through bibliometric analysis and to provide research direction and future ideas for the treatment of diabetes and other islet-related diseases. METHODS: We used two scientometric software packages (CiteSpace 6.1.R6 and VOSviewer1.6.18) to visualize the information and connection of countries, institutions, authors, and keywords in this field. RESULTS: A total of 532 publications, published in 752 institutions in 46 countries and regions, were included in this analysis. The United States showed the highest output, accounting for 39.3% of the total number of published papers. The most active institution was Vanderbilt University, and the authors with highest productivity came from Ulster University. In recent years, research hotspots have concentrated on transdifferentiation, gene expression, and GLP-1 regulatory function. Visualization analysis shows that research hotspots mainly focus on clinical diseases as well as physiological and pathological mechanisms and related biochemical indicators. CONCLUSIONS: This study provides a review and summary of the literature on pancreatic alpha cells through bibliometric and visual methods and shows research hotspot and development trends, which can guide future directions for research.

Fractionated plasma separation and adsorption integrated with continuous veno-venous hemofiltration in patients with acute bipyridine herbicide poisoning.

OBJECTIVE: To evaluate the clinical efficacy and safety of fractionated plasma separation and adsorption combined with continuous veno-venous hemofiltration (FPSA-CVVH) treatment in patients with acute bipyridine herbicide poisoning. METHODS: A retrospective analysis of 18 patients with acute bipyridine herbicide poisoning was conducted, of which 9 patients were poisoned by diquat and 9 patients by paraquat. All patients underwent FPSA-CVVH treatment. The serum cytokine levels in pesticide-poisoned patients were assessed. The efficacy of FPSA-CVVH in eliminating cytokines, the 90-d survival rate of poisoned patients, and adverse reactions to the treatment were observed. RESULTS: Fourteen patients (77.8%) had acute kidney injuries and 10 (55.6%) had acute liver injuries. The serum cytokine levels of high mobility group protein B-1 (HMGB-1), interleukin-6 (IL-6), IL-8, interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1ß (MIP-1ß) were significantly elevated. A total of 41 FPSA-CVVH treatment sessions were administered. After a single 8-h FPSA-CVVH treatment, the decreases in HMGB-1, IL-6, IL-8, IP-10, MCP-1, and MIP-1ß were 66.0%, 63.5%, 73.3%, 63.7%, 53.9%, and 54.1%, respectively. During FPSA-CVVH treatment, one patient required a filter change due to coagulation in the plasma component separator, and one experienced a bleeding adverse reaction. The 90-d patient survival rate was 50%, with 4 patients with diquat poisoning and 5 patients with paraquat poisoning, and both liver and kidney functions were restored to normal. CONCLUSION: Cytokine storms may play a significant role in the progression of multiorgan dysfunction in patients with acute bipyridine herbicide poisoning. FPSA-CVVH can effectively reduce cytokine levels, increase the survival rate of patients with acute bipyridine herbicide poisoning, and decrease the incidence of adverse events.

Fugacity- and biotransformation-based mechanistic insights into the trophic transfer of organophosphate flame retardants in a subtropical coastal food web from the Northern Beibu Gulf of China.

The bioaccumulation and trophic transfer of organophosphate flame retardants (OPFRs) in marine ecosystems have attracted great attention in recent research, but our understanding of the trophic transfer mechanisms involved is limited. In this study, we investigated the trophodynamics of OPFRs and their metabolites in a subtropical coastal food web collected from the northern Beibu Gulf, China, and characterized their trophodynamics using fugacity- and biotransformation-based approaches. Eleven OPFRs and all seven metabolites were simultaneously quantified in the shellfish, crustacean, pelagic fish, and benthic fish samples, with total concentrations ranging from 164 to 4.11 × 104 and 4.56-4.28 × 103 ng/g lipid weight, respectively. Significant biomagnification was observed only for tris (phenyl) phosphate (TPHP) and tris (2-ethylhexyl) phosphate (TEHP), while other compounds except for tris(2-chloroethyl) phosphate (TCEP) displayed biomagnification trends based on Monte Carlo simulations. Using a fugacity-based approach to normalize the accumulation of OPFRs in biota to their relative biological phase composition, storage lipid is the predominant biological phase for the mass distribution of 2-ethylhexyl diphenyl phosphate (EHDPHP) and TPHP. The water content and structure protein are equally important for TCEP, whereas lipid and structure protein are the two most important phases for other OPFRs. The mass distribution of these OPFRs along with TLs can explain their trophodynamics in the food web. The organophosphate diesters (as OPFR metabolites) also displayed biomagnification trends based on bootstrapped estimation. The correlation analysis and Korganism-water results jointly suggested the metabolites accumulation in high-TL organisms was related to biotransformation processes. The metabolite-backtracked trophic magnification factors for tri-n­butyl phosphate (TNBP) and TPHP were both greater than the values that accounted for only the parent compounds. This study highlights the incorporation of fugacity and biotransformation analysis to characterize the trophodynamic processes of OPFRs and other emerging pollutants in food webs.

Novel MRI-Based Pedicle Bone Quality Score Independently Predicts Pedicle Screw Loosening after Degenerative Lumbar Fusion Surgery.

Pedicle screw loosening after posterior lumbar fusion is associated with poor bone quality, which often determines screw pull-out strength, insertion torque, and vertebral body loading characteristics. Magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score were associated with poor bone quality. Current evidence suggests that pedicle bone quality (PBQ) has a greater impact on screw stability. However, the correlation between MRI-based PBQ score and screw loosening has not been reported. PURPOSE: To introduce and evaluate an MRI-based PBQ score to determine its effectiveness in predicting pedicle screw loosening following lumbar fusion surgery. METHODS: The retrospective study analyzed 244 patients who underwent posterior lumbar interbody fusion (PLIF) with pedicle screws between December 2017 and December 2021, with CT and MRI imaging before surgery. Data collected included patient demographics and preoperative radiological data. Radiographic screw loosening was measured at 12 months postoperatively. Clinical assessments included pain visual analog scale (VAS) and Oswestry Disability Index (ODI) scores. The PBQ score was measured using MRI scans. We use univariate analysis for preliminary screening of the risk factors of screw loosening. Subsequent analysis involved multivariate logistic regression to identify independent predictive factors for screw loosening. We constructed the receiver operating characteristic (ROC) curve to ascertain the discriminative capacity of the PBQ score. The area under the curve (AUC) quantified its predictive accuracy. Additionally, we evaluated the association between PBQ score and screw loosening using Spearman's correlation analysis. RESULTS: Overall, 244 patients who underwent PLIF with pedicle screw fixation participated in this study, including 35 in the loosening group and 209 in the non-loosening group. PBQ score in the loosening group was significantly higher than that in the non-loosening group. On multivariate logistic regression, the higher PBQ score (OR = 8.481, 95% CI: 3.158-22.774; p < 0.001) and the lower mean Hounsfield unit (HU) value of L1-4 (OR = 0.967, 95% CI 0.951-0.984; p < 0.001) were the variables that significantly predicted screw loosening. The AUC for the PBQ score and HU value were 0.751 (95% CI: 0.673-0.828) and 0.702 (95% CI: 0.612-0.791). The PBQ score optimal cutoff to differentiate patients with loosening and with non-loosening was calculated as 3.045 with a sensitivity of 85.7% and specificity of 76.9%, while the optimal cutoff of the HU value was 151.5 with a sensitivity of 64.6% and specificity of 89.5%. CONCLUSIONS: The association between the PBQ score and the propensity for lumbar pedicle screw loosening was found to be substantial. As a predictive measure, the PBQ score outperformed the HU value in forecasting the likelihood of screw loosening post-posterior lumbar fusion.

Anti-IL-17 Inhibits PINK1/Parkin Autophagy and M1 Macrophage Polarization in Rheumatic Heart Disease.

Rheumatic heart disease (RHD) is an important and preventable cause of cardiovascular death and disability, but the lack of clarity about its exact mechanisms makes it more difficult to find alternative methods or prevention and treatment. We previously demonstrated that increased IL-17 expression plays a crucial role in the development of RHD-related valvular inflammatory injury. Macrophage autophagy/polarization may be a pro-survival strategy in the initiation and resolution of the inflammatory process. This study investigated the mechanism by which IL-17 regulates autophagy/polarization activation in macrophages. A RHD rat model was generated, and the effects of anti-IL-17 and 3-methyladenine (3-MA) were analyzed. The molecular mechanisms underlying IL-17-induced macrophage autophagy/polarization were investigated via in vitro experiments. In our established RHD rat model, the activation of the macrophage PINK1/Parkin autophagic pathway in valve tissue was accompanied by M1 macrophage infiltration, and anti-IL-17 treatment inhibited autophagy and reversed macrophage inflammatory infiltration, thereby attenuating endothelial-mesenchymal transition (EndMT) in the valve tissue. The efficacy of 3-MA treatment was similar to that of anti-IL-17 treatment. Furthermore, in THP-1 cells, the pharmacological promotion of autophagy by IL-17 induced M1-type polarization, whereas the inhibition of autophagy by 3-MA reversed this process. Mechanistically, silencing PINK1 in THP-1 blocked autophagic flux. Moreover, IL-17-induced M1-polarized macrophages promoted EndMT in HUVECs. This study revealed that IL-17 plays an important role in EndMT in RHD via the PINK1/Parkin autophagic pathway and macrophage polarization, providing a potential therapeutic target.

Conductive/Insulating Bioinks with Multitechnology Compatibility and Adjustable Performance.

Conducting/insulating inks have received significant attention for the fabrication of a wide range of additive manufacturing technology. However, current inks often demonstrate poor biocompatibility and face trade-offs between conductivity and mechanical stiffness under physiological conditions. Here, conductive/insulating bioinks based on two-dimensional materials are proposed. The conductive bioink, graphene (GR)-poly(lactic-co-glycolic acid) (PLGA), is prepared by introducing conductive GR into a degradable polymer matrix, PLGA, while the insulating bioink, boron nitride (BN)-PLGA, is synthesized by adding insulating BN. By optimizing the material ratios, this work achieves precise control of the electromechanical properties of the bioinks, thereby enabling the flexible construction of conductive networks according to specific requirements. Furthermore, these bioinks are compatible with a variety of manufacturing technologies such as 3D printing, electrospinning, spin coating, and injection molding, expanding their application range in the biomedical field. Overall, the results suggest that these conducting/insulating bioinks offer improved mechanical, electronic, and biological properties for various emerging biomedical applications.

Discovery of NO Donor-Aurovertin Hybrids as Dual Ferroptosis and Apoptosis Inducers for Treating Triple Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a highly lethal malignancy, and its clinical management encounters severe challenges due to its high metastatic propensity and the absence of effective therapeutic targets. To improve druggability of aurovertin B (AVB), a natural polyketide with a significant antiproliferative effect on TNBC, a series of NO donor/AVB hybrids were synthesized and tested for bioactivities. Among them, compound 4d significantly inhibited the proliferation and metastasis of TNBC in vitro and in vivo with better safety than that of AVB. The structure-activity relationship analysis suggested that the types of NO donor and the linkers had considerable effects on the activities. Mechanistic investigations unveiled that 4d induced apoptosis and ferroptosis by the reduction of mitochondrial membrane potential and the down-regulation of GPX4, respectively. The antimetastatic effect of 4d was associated with the upregulation of DUSP1. Overall, these compelling results underscore the tremendous potential of 4d for treating TNBC.

Improvement of accumulated dose distribution in combined cervical cancer radiotherapy with deep learning-based dose prediction.

Purpose: Difficulties remain in dose optimization and evaluation of cervical cancer radiotherapy that combines external beam radiotherapy (EBRT) and brachytherapy (BT). This study estimates and improves the accumulated dose distribution of EBRT and BT with deep learning-based dose prediction. Materials and methods: A total of 30 patients treated with combined cervical cancer radiotherapy were enrolled in this study. The dose distributions of EBRT and BT plans were accumulated using commercial deformable image registration. A ResNet-101-based deep learning model was trained to predict pixel-wise dose distributions. To test the role of the predicted accumulated dose in clinic, each EBRT plan was designed using conventional method and then redesigned referencing the predicted accumulated dose distribution. Bladder and rectum dosimetric parameters and normal tissue complication probability (NTCP) values were calculated and compared between the conventional and redesigned accumulated doses. Results: The redesigned accumulated doses showed a decrease in mean values of V50, V60, and D2cc for the bladder (-3.02%, -1.71%, and -1.19 Gy, respectively) and rectum (-4.82%, -1.97%, and -4.13 Gy, respectively). The mean NTCP values for the bladder and rectum were also decreased by 0.02‰ and 0.98%, respectively. All values had statistically significant differences (p < 0.01), except for the bladder D2cc (p = 0.112). Conclusion: This study realized accumulated dose prediction for combined cervical cancer radiotherapy without knowing the BT dose. The predicted dose served as a reference for EBRT treatment planning, leading to a superior accumulated dose distribution and lower NTCP values.

[Phenotypic drug discovery promotes research and development of innovative drugs based on traditional Chinese medicine].

Traditional Chinese medicine with rich resources in China and definite therapeutic effects on complex diseases demonstrates great development potential. However, the complex composition, the unclear pharmacodynamic substances and mechanisms of action, and the lack of reasonable methods for evaluating clinical safety and efficacy have limited the research and development of innovative drugs based on traditional Chinese medicine. The progress in cutting-edge disciplines such as artificial intelligence and biomimetics, especially the emergence of cell painting and organ-on-a-chip, helps to identify and characterize the active ingredients in traditional Chinese medicine based on the changes in model characteristics, thus providing more accurate guidance for the development and application of traditional Chinese medicine. The application of phenotypic drug discovery in the research and development of innovative drugs based on traditional Chinese medicine is gaining increasing attention. In recent years, the technology for phenotypic drug discovery keeps advancing, which improves the early discovery rate of new drugs and the success rate of drug research and development. Accordingly, phenotypic drug discovery gradually becomes a key tool for the research on new drugs. This paper discusses the enormous potential of traditional Chinese medicine in the discovery and development of innovative drugs and illustrates how the application of phenotypic drug discovery, supported by cutting-edge technologies such as cell painting, deep learning, and organ-on-a-chip, propels traditional Chinese medicine into a new stage of development.

Diagnosis and treatment of secondary nephrotic syndrome with rash as the first symptom: a case report.

BACKGROUND: Membranous nephropathy (MN) is a common type of nephrotic syndrome (NS) in adults, accounting for about 20-30% of cases. Although secondary to specific factors, the coexistence of MN and mantle cell lymphoma (MCL) has been scarcely reported in clinical literature. CASE PRESENTATION: A 59-year-old Chinese male was admitted to the hospital with a generalized pruritic rash with bilateral lower extremity edema, which did not improve significantly after symptomatic treatment. He had undergone renal biopsy, and the diagnosis was thought to be secondary MN (SMN), therefore, we did a lymph node biopsy on the patient and found that MN was complicated with MCL. Soon after, the patient was admitted to the hematology department for a BR chemotherapy regimen (composed of bendamustine 90 mg/m2 BSA (body surface area), rituximab 375 mg/m2 BSA and dexamethasone 5 mg), and during the post-treatment follow-up, both his symptoms and renal function improved. CONCLUSIONS: The mechanism underlying the combination of SMN and MCL remains elusive and exceedingly rare, consequently often overlooked in clinical practice. This case serves to offer valuable clinical insights for diagnosis and treatment, while emphasizing the pivotal role of renal pathology in clinical assessment.

Construction and antibacterial activities of walnut green husk polysaccharide based silver nanoparticles (AgNPs).

In this paper, the size-controllable nano­silver particles (AgNPs) were synthesized from walnut green husk polysaccharide, and its cytotoxicity and antibacterial activity were evaluated. Firstly, acidic polysaccharide WGHP2 was extracted from walnut green husk, and then the silver ion in AgNO3 was reduced in WGHP2 aqueous solution using NaBH4, so as to synthesize the nano­silver composite. The nano­silver composite was characterized by transmission electron microscope, Fourier infrared spectroscopy, ultraviolet-visible spectrometer, scanning electron microscope, inductively coupled plasma mass spectrometry and X-ray photoelectron spectroscopy. The results show that AgNPs stabilized by WGHP2 are mainly regular spheres with an average particle size distribution of 15.04-19.23 nm. The particle size distribution and morphology of AgNPs changed with the concentration of silver precursor, which is related to the dispersion of silver precursor in polysaccharide aqueous solution and the formation of AgO coordination bond between silver precursor and polysaccharide molecules. These coordination bonds changed the ability of nanoparticles to produce and release Ag+, and thus regulated their antibacterial activity and cytotoxicity, as evidenced by the experimental result of the cytotoxicity of the nano­silver particle against PC12 cells and the bacteriostatic effect on E.coli and S.aureus. Conclusively, WGHP2-Ag has good stability, antibacterial activity and low cytotoxicity.

The viral trends and genotype diversity of norovirus in the wastewater of Shenzhen, China.

Norovirus (NoV) is the primary cause of acute gastroenteritis (AGE) on a global scale. Numerous studies have demonstrated the immense potential of wastewater surveillance in monitoring the prevalence and spread of NoV within communities. This study employed a one-step reverse transcription-quantitative PCR to quantify NoV GI/GII in wastewater samples (n = 2574), which were collected once or twice a week from 38 wastewater treatment plants from March 2023 to February 2024 in Shenzhen. The concentrations of NoV GI and GII ranged from 5.0 × 104 to 1.7 × 106 copies/L and 4.1 × 105 to 4.5 × 106 copies/L, respectively. The concentrations of NoV GII were higher than those of NoV GI. Spearman's correlation analysis revealed a moderate correlation between the concentration of NoV in wastewater and the detection rates of NoV infections in sentinel hospitals. Baseline values were established for NoV concentrations in Shenzhen's wastewater, providing a crucial reference point for implementing early warning systems and nonpharmaceutical interventions to mitigate the impact of potential outbreaks. A total of 24 NoV genotypes were identified in 100 wastewater samples by sequencing. Nine genotypes of NoV GI were detected, with the major genotypes being GI.4 (38.6 %) and GI.3 (21.8 %); Fifteen genotypes of NoV GII were identified, with GII.4 (53.6 %) and GII.17 (26.0 %) being dominant. The trends in the relative abundance of NoV GI/GII were significantly different, and the trends in the relative abundance of NoV GII.4 over time were similar across all districts, suggesting a potential risk of cross-regional spread. Our findings underscore the effectiveness of wastewater surveillance in reflecting population-level NoV infections, capturing the diverse array of NoV genotypes, and utilizing NoV RNA in wastewater as a specific indicator to supplement clinical surveillance data, ultimately enhancing our ability to predict the timing and intensity of NoV epidemics.

PARP1-driven repair of topoisomerase IIIα DNA-protein crosslinks by FEN1.

Persistent DNA-protein crosslinks formed by human topoisomerase IIIα (TOP3A-DPCs) interfere with DNA metabolism and lead to genome damage and cell death. Recently, we demonstrated that such abortive TOP3A-DPCs are ubiquitylated and proteolyzed by Spartan (SPRTN). Here, we identify transient poly(ADP-ribosylation) (PARylation) in addition to ubiquitylation as a signaling mechanism for TOP3A-DPC repair and provide evidence that poly(ADP-ribose) polymerase 1 (PARP1) drives the repair of TOP3A-DPCs by recruiting flap endonuclease 1 (FEN1) to the TOP3A-DPCs. We find that blocking PARylation attenuates the interaction of FEN1 and TOP3A and that TOP3A-DPCs accumulate in cells with compromised PARP1 activity and in FEN1-deficient cells. We also show that PARP1 suppresses TOP3A-DPC ubiquitylation and that inhibiting the ubiquitin-activating enzyme E1 (UBE1) increases TOP3A-DPCs, consistent with ubiquitylation serving as a signaling mechanism for TOP3A-DPC repair mediated by SPRTN and TDP2. We propose that two concerted pathways repair TOP3A-DPCs: PARylation-driven FEN1 excision and ubiquitylation-driven SPRTN-TDP2 excision.

Association of oxidative balance score with epilepsy and moderate to severe depression: Insights from the NHANES study.

BACKGROUND: Depression is a significant public health issue, closely associated with epilepsy and oxidative stress (OS). This study aims to explore the level of OS in patients with epilepsy and its relationship with moderate to severe depression (MSD). METHODS: This cross-sectional study includes 10,819 participants aged 20-80 from the National Health and Nutrition Examination Survey (NHANES) database (2013-2020 pre-pandemic). Depression symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), and epilepsy was diagnosed based on antiepileptic drug use in the past 30 days. The oxidative balance score (OBS) was calculated from dietary recall and lifestyle habits over the previous 24 h. RESULTS: Compared to non-epileptic subjects, epileptic patients have a significantly higher prevalence of depression. Epileptic patients exhibit lower OBS and Dietary Oxidative Balance Scores (DOBS), while there is no significant difference in Lifestyle Oxidative Balance Scores (LOBS). Depressed patients show lower OBS, DOBS, and LOBS. The mediation model indicates that DOBS mediates 3.44 % of epilepsy-related MSD. CONCLUSIONS: Epileptic patients exhibit significantly higher levels of OS and consume more pro-oxidant foods compared to the general population. However, their lifestyle habits do not differ significantly from those of the control group. Additionally, epileptic patients are at a higher risk of developing MSD. Although a pro-oxidant diet may be associated with epilepsy-mediated MSD, its mediating effect is relatively weak.

Clinical Pharmacokinetics of Semaglutide: A Systematic Review.

Purpose: The aim of this review was to provide all the pharmacokinetic data for semaglutide in humans concerning its pharmacokinetics after subcutaneously and oral applications in healthy and diseased populations, to provide recommendations for clinical use. Methodology: The PubMed and Embase databases were searched to screen studies associated with the pharmacokinetics of semaglutide. The pharmacokinetic parameters included area under the curve plasma concentrations (AUC), maximal plasma concentration (Cmax), time to Cmax, half-life (t1/2), and clearance. The systematic literature search retrieved 17 articles including data on pharmacokinetic profiles after subcutaneously and oral applications of semaglutide, and at least one of the above pharmacokinetic parameter was reported in all included studies. Results: Semaglutide has a predictable pharmacokinetic profile with a long t1/2 that allows for once-weekly subcutaneous administration. The AUC and Cmax of both oral and subcutaneous semaglutide increased with dose. Food and various dosing conditions including water volume and dosing schedules can affect the oral semaglutide exposure. There are limited drug-drug interactions and no dosing adjustments in patients with upper gastrointestinal disease, renal impairment or hepatic impairment. Body weight may affect semaglutide exposure, but further studies are needed to confirm this. Conclusion: This review encompasses all the pharmacokinetic data for subcutaneous and oral semaglutide in both healthy and diseased participants. The existing pharmacokinetic data can assist in developing and evaluating pharmacokinetic models of semaglutide and will help clinicians predict semaglutide dosages. In addition, it can also help optimize future clinical trials.

Recent trends: Retractions of articles in the oncology field.

Background: In recent years, there has been a surge in media reports on articles being retracted after publication. This issue has gained significant attention, particularly due to the consecutive large-scale retractions carried out by renowned international publishers, which have aroused widespread concern in the society. Objective: To analyze the data of retracted articles and retraction trends. Methods: The publications were searched through Web of Science Core Collection (WoSCC) database and imported into CiteSpace in plain text format, and visual analysis of countries, institutions, keywords, and subject areas were performed to reveal the trends of retracted articles and the worst areas of retraction. Results: From 1990 to 2022, 21,568 retracted articles were retrieved, among which the number of retracted articles increased year by year. China is the country with the highest number of retracted articles; Islamic Azad University is the institution with the highest number of retracted articles. In the analysis of all retracted articles across different subject areas, the number of retracted articles in the field of oncology was the highest; In the keyword cluster analysis of retracted articles within the field of oncology, the most prominent category of retracted articles were related to pancreatic cancer. Conclusions: Scientific and systematic analysis of retracted articles is conducive to improving the quality of papers, raising the level of human research, and cleaning up the research environment.

Myricetin ameliorates cognitive impairment in 3×Tg Alzheimer's disease mice by regulating oxidative stress and tau hyperphosphorylation.

BACKGROUND: Alzheimer's disease is characterized by abnormal ß-amyloid (Aß) plaque accumulation, tau hyperphosphorylation, reactive oxidative stress, mitochondrial dysfunction and synaptic loss. Myricetin, a dietary flavonoid, has been shown to exert neuroprotective effects in vitro and in vivo. Here, we aimed to elucidate the mechanism and pathways involved in the protective effect of myricetin. METHODS: The effect of myricetin was assessed on Aß42 oligomer-treated neuronal SH-SY5Y cells and in 3×Tg mice. Behavioral tests were performed to assess the cognitive effects of myricetin (14 days, ip) in 3×Tg mice. The levels of beta-amyloid precursor protein (APP), synaptic and mitochondrial proteins, glycogen synthase kinase3ß (GSK3ß) and extracellular regulated kinase (ERK) 2 were assessed via Western blotting. Flow cytometry assays, immunofluorescence staining, and transmission electron microscopy were used to assess mitochondrial dysfunction and reactive oxidative stress. RESULTS: We found that, compared with control treatment, myricetin treatment improved spatial cognition and learning and memory in 3×Tg mice. Myricetin ameliorated tau phosphorylation and the reduction in pre- and postsynaptic proteins in Aß42 oligomer-treated neuronal SH-SY5Y cells and in 3×Tg mice. In addition, myricetin reduced reactive oxygen species generation, lipid peroxidation, and DNA oxidation, and rescued mitochondrial dysfunction via the associated GSK3ß and ERK 2 signalling pathways. CONCLUSIONS: This study provides new insight into the neuroprotective mechanism of myricetin in vitro in cell culture and in vivo in a mouse model of Alzheimer's disease.

Conserved microRNAs miR-8-3p and miR-2a-3 targeting chitin biosynthesis to regulate the molting process of Sogatella furcifera (Horváth)(Hemiptera: Delphacidae).

Molting is a key solution to growth restriction in insects. The periodic synthesis and degradation of chitin, one of the major components of the insect epidermis, is necessary for insect growth. MicroRNA (miRNA) have been implicated in molting regulation, yet their involvement in the interplay interaction between the chitin synthesis pathway and 20-hydroxyecdysone signaling remains poorly understood. In this study, soluble trehalase (Tre1) and phosphoacetylglucosamine mutase (PAGM) were identified as targets of conserved miR-8-3p and miR-2a-3, respectively. The expression profiles of miR-8-3p-SfTre1 and miR-2a-3-SfPAGM exhibited an opposite pattern during the different developmental stages, indicating a negative regulatory relationship between them. This relationship was confirmed by an in vitro dual-luciferase reporter system. Overexpression of miR-8-3p and miR-2a-3 by injection of mimics inhibited the expression of their respective target genes and increased mortality, leading to death in the pre-molting, and molting death phenomena. They also caused a decrease in chitin content and expression levels of key genes in the chitin synthesis pathway (SfTre1, SfTre2, SfHK, SfG6PI, SfGFAT, SfGNA, SfPAGM, SfUAP, SfCHS1, SfCHS1a, and SfCHS1b). Conversely, the injection of miRNA inhibitors resulted in the upregulation of the expression levels of these genes. Following 20E treatment, the expression levels of miR-8-3p and miR-2a-3 decreased significantly, while their corresponding target genes increased significantly. These results indicate that miR-8-3p and miR-2a-3 play a regulatory role in the molting of Sogatella furcifera by targeting SfTre1 and SfPAGM, respectively. These findings provide new potential targets for the development of subsequent new control strategies.

Design of Ultrasound-Driven Charge Interference Therapy for Wound Infection.

Wound infections, especially those caused by pathogenic bacteria, present a considerable public health concern due to associated complications and poor therapeutic outcomes. Herein, we developed antibacterial nanoparticles, namely, PGTP, by coordinating guanidine derivatives with a porphyrin-based sonosensitizer. The synthesized PGTP nanoparticles, characterized by their strong positive charge, effectively disrupted the bacterial biosynthesis process through charge interference, demonstrating efficacy against both Gram-negative and Gram-positive bacteria. Additionally, PGTP nanoparticles generated reactive oxygen species under ultrasound stimulation, resulting in the disruption of biofilm integrity and efficient elimination of pathogens. RNA-seq analysis unveiled the detailed mechanism of wound healing, revealing that PGTP nanoparticles, when coupled with ultrasound, impair bacterial metabolism by interfering with the synthesis and transcription of amino acids. This study presents a novel approach to combatting wound infections through ultrasound-driven charge-interfering therapy, facilitated by advanced antibacterial nanomaterials.