Manganese Amplifies Photoinduced ROS in Toluidine Blue Carbon Dots to Boost MRI Guided Chemo/Photodynamic Therapy.

The contrast agents and tumor treatments currently used in clinical practice are far from satisfactory, due to the specificity of the tumor microenvironment (TME). Identification of diagnostic and therapeutic reagents with strong contrast and therapeutic effect remains a great challenge. Herein, a novel carbon dot nanozyme (Mn-CD) is synthesized for the first time using toluidine blue (TB) and manganese as raw materials. As expected, the enhanced magnetic resonance (MR) imaging capability of Mn-CDs is realized in response to the TME (acidity and glutathione), and r1 and r2 relaxation rates are enhanced by 224% and 249%, respectively. In addition, the photostability of Mn-CDs is also improved, and show an efficient singlet oxygen (1 O2 ) yield of 1.68. Moreover, Mn-CDs can also perform high-efficiency peroxidase (POD)-like activity and catalyze hydrogen peroxide to hydroxyl radicals, which is greatly improved under the light condition. The results both in vitro and in vivo demonstrate that the Mn-CDs are able to achieve real-time MR imaging of TME responsiveness through aggregation of the enhanced permeability and retention effect at tumor sites and facilitate light-enhanced chemodynamic and photodynamic combination therapies. This work opens a new perspective in terms of the role of carbon nanomaterials in integrated diagnosis and treatment of diseases.

Rescue of nucleus pulposus cells from an oxidative stress microenvironment via glutathione-derived carbon dots to alleviate intervertebral disc degeneration.

The senescence of nucleus pulposus (NP) cells (NPCs), which is induced by the anomalous accumulation of reactive oxygen species (ROS), is a major cause of intervertebral disc degeneration (IVDD). In this research, glutathione-doped carbon dots (GSH-CDs), which are novel carbon dot antioxidant nanozymes, were successfully constructed to remove large amounts of ROS for the maintenance of NP tissue at the physical redox level. After significantly scavenging endogenous ROS via exerting antioxidant activities, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and total antioxidant capacity, GSH-CDs with good biocompatibility have been demonstrated to effectively improve mitochondrial dysfunction and rescue NPCs from senescence, catabolism, and inflammatory factors in vivo and in vitro. In vivo imaging data and histomorphological indicators, such as the disc height index (DHI) and Pfirrmann grade, demonstrated prominent improvements in the progression of IVDD after the topical application of GSH-CDs. In summary, this study investigated the GSH-CDs nanozyme, which possesses excellent potential to inhibit the senescence of NPCs with mitochondrial lesions induced by the excessive accumulation of ROS and improve the progression of IVDD, providing potential therapeutic options for clinical treatment.

Dried fruit intake can lower the risk of ulcerative colitis: evidence from a Mendelian randomization study.

BACKGROUND AND OBJECTIVES: This study aims to examine the causal relationship between dietary factors and ulcerative colitis (UC). METHODS AND STUDY DESIGN: The analysis utilized data from genome-wide association studies (GWAS). Dried fruit, vegetables, processed meat, fresh fruit, and cereal intake were examined as exposure factors. UC was considered the outcome. Two-sample Mendelian randomization (TSMR) analysis was performed using methods. Heterogeneity and horizontal pleiotropy assessments were conducted to ensure the robustness of our findings. Additionally, we applied False Discovery Rate (FDR) corrections for multiple tests. RESULTS: The analysis revealed a significant inverse causal relationship between dried fruit intake and UC risk (odds ratio [OR]: 0.488, 95% confidence interval [CI]: 0.261 to 0.915, p = 0.025). No significant association was observed between vegetable intake (OR: 1.742, 95% CI: 0.561 to 5.415, p = 0.337), processed meat intake (OR: 1.136, 95% CI: 0.552 to 2.339, p = 0.729), fresh fruit intake (OR: 0.977, 95% CI: 0.465 to 2.054, p = 0.952), cereal intake (OR: 1.195, 95% CI: 0.669 to 2.134, p = 0.547). The low heterogeneity observed across analyses and the confirmation of stability through leave-one-out analysis reinforce the reliability of these results. Moreover, after adjusting for multiple tests, none of the dietary factors reached a p-value below the conventional significance threshold of 0.05. CONCLUSIONS: This study provides evidence of a potential association between dried fruit intake and a reduced risk of UC. Further MR studies incorporating larger GWAS datasets are needed to confirm these findings.

Determination of pyraclostrobin dynamic residual distribution in tilapia tissues by UPLC-MS/MS under acute toxicity conditions.

As a lipophilic fungicide, pyraclostrobin is highly toxic to aquatic organisms, especially to fish. In recent years, research has mainly focused on the pyraclostrobin residue in fish tissues under chronic toxicity, but less is known about its distribution in fish tissues under acute toxicity conditions. In this study, the distribution of pyraclostrobin in fish tissues (blood, liver, muscle and gill) was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The purification effects of different purification materials [1) mixtures of PSA, C18 and MgSO4; 2) QuEChERS-PC; and 3) Oasis HLB SPE] were compared for the detection of pyraclostrobin in fish tissues. Finally, the quick and easy clean-up tool of the Oasis HLB SPE procedure was selected. Under optimum conditions, the linearities had a good relationship (determination coefficient R2 > 0.999). The mean recoveries of the analyte for all tested concentrations ranged from 86.94% to 108.81% with RSDs of 0.7%-4.9%. The pyraclostrobin residue amount was much different in fish tissues. Furthermore, the pyraclostrobin residue in different fish tissues increased initially and then decreased gradually. The concentrations in each tissue were initially ranked before 120 min in the following order: gill > liver > blood > muscle. These phenomena may be attributed to the stress response of fish under acute poisoning. This is the first study to document the distribution of pyraclostrobin in fish tissues under acute toxicity conditions, and it provides reference for the management of agrochemicals in terms of aquatic ecological risks.

Comparative ecotoxicity of neonicotinoid insecticides to three species of Trichogramma parasitoid wasps (Hymenoptera: Trichogrammatidae).

Compatibility of neonicotinoid insecticides with the natural enemies has been concerned for decades. This study aims to evaluate and compare the acute and sublethal toxicity effects of neonicotinoid insecticides on three species of Trichogramma parasitoid wasps (i.e. Trichogramma dendrolimi, T. ostriniae and T. confusum) with broad distribution and great relevance to integrated pest management (IPM) strategies. A residual contact bioassay demonstrated that nitenpyram had the greatest intrinsic toxicity to T. dendrolimi and T. ostriniae with LC50 values of 0.060 (0.056-0.065) and 0.066 (0.050-0.087) mg a.i. L-1, respectively. But for T. confusum, the most toxic neonicotinoid insecticide is dinotefuran with a LC50 value of 0.065 (0.055-0.078) mg a.i. L-1. Furthermore, based on the risk quotient estimation, acetamiprid was considered to be the only safe neonicotinoid insecticide (Class 1, RQ＜50). A dipped egg contact bioassay showed that neonicotinoid insecticides induced significant toxic effects on the parasitism of three Trichogramma spp. at low-lethal concentrations. Additionally, emergence probability of the unexposed offspring was also significantly reduced by neonicotinoids. According to the estimated EC50 values, acetamiprid possessed the least toxicity to the parasitism and emergence of T. dendrolimi and T. ostriniae, and for T. confusum, the least toxic neonicotinoid insecticide was thiacloprid. Overall, among the test neonicotinoid insecticides, acetamiprid and thiacloprid may exhibit the less ecotoxicity to the test Trichogramma species.

Bioactivity, physiological characteristics and efficacy of the SDHI fungicide pydiflumetofen against Sclerotinia sclerotiorum.

Sclerotinia sclerotiorum, which can cause Sclerotinia stem rot, is a devastating plant pathogen. This study aimed to assess the potential of pydiflumetofen, a new-generation succinate dehydrogenase inhibitor (SDHI) fungicide, to control Sclerotinia stem rot. Pydiflumetofen exhibited favorable bioactivity in suppressing mycelial growth, sclerotial production and morphological changes, and the myceliogenic and carpogenic germination of sclerotia. Treatment with pydiflumetofen increased the cell membrane permeability of S. sclerotiorum and decreased oxalic acid production. In addition, inoculation tests demonstrated that the protective activity of 40 µg/mL pydiflumetofen against the fungus was better than its curative activity. Under natural infection conditions, the spraying of pydiflumetofen at 200 g a.i. ha-1 significantly reduced the incidence and severity of Sclerotinia stem rot. In addition, the sensitivity baseline to pydiflumetofen was established using 171 isolates collected from various crops in China. The results showed that the frequency distribution of the EC50 values of pydiflumetofen was a unimodal curve with a mean EC50 value of 0.0095 ±â€¯0.0005 µg/mL. This study confirmed the favorable bioactivity of pydiflumetofen against S. sclerotiorum at various developmental stages and its high effectiveness under natural infection conditions, which indicates that pydiflumetofen is a promising tool for the management of Sclerotinia stem rot.

Favorable Bioactivity of the SDHI Fungicide Benzovindiflupyr Against Sclerotinia sclerotiorum Mycelial Growth, Sclerotial Production, and Myceliogenic and Carpogenic Germination of Sclerotia.

Sclerotinia sclerotiorum, which can cause Sclerotinia stem rot, is a prevalent plant pathogen. This study aims to evaluate the application potential of benzovindiflupyr, a new generation of succinate dehydrogenase inhibitor (SDHI), against S. sclerotiorum. In our study, 181 isolates collected from different crops (including eggplant [n = 34], cucumber [n = 27], tomato [n = 29], pepper [n = 35], pumpkin [n = 32], and kidney bean [n = 25]) in China were used to establish baseline sensitivity to benzovindiflupyr. The frequency distribution of the 50% effective concentration (EC50) values of benzovindiflupyr was a unimodal curve, with mean EC50 values of 0.0260 ± 0.011 µg/ml, and no significant differences in mean EC50 existed among the various crops (P > 0.99). Benzovindiflupyr can effectively inhibit mycelial growth, sclerotial production, sclerotial shape, and myceliogenic and carpogenic germination of the sclerotia of S. sclerotiorum. In addition, benzovindiflupyr showed good systemic translocation in eggplant. Using benzovindiflupyr at 100 µg/ml yielded efficacies of 71.3 and 80.5% for transverse activity and cross-layer activity, respectively, which were higher than those of acropetal and basipetal treatments (43.6 and 44.7%, respectively). Greenhouse experiments were then carried out at two experimental sites for verification. Applying benzovindiflupyr at 200 g a.i. ha-1 significantly reduced the disease incidence and severity of Sclerotinia stem rot. Overall, the results demonstrated that benzovindiflupyr is a potential alternative product to control Sclerotinia stem rot.

The Chemotherapeutic Effect of Docetaxel, Cisplatin and Fluorouracil Regimen on Gastric Cancer Stem Cells.

In recent years, chemotherapy targeting cancer stem cells has increasingly garnered interest from the scientists and clinicians. In this study, we explored both in vitro and in vivo if a chemotherapy regimen could arrest gastric tumor growth via demolishing CD24+ and CD44+ cancer stem cells (CSC) in the tumor mass. To facilitate the tumorigenesis in the subcutaneous xenograft model, we employed an electrospun scaffold comprising polydioxanone and gelatin for the delivery of tumor cells. The scaffold sported a highly porous micro-structure and promoted the in vitro and in vivo tumorigenesis without inducing apoptosis. in vivo studies confirmed that the tumor enjoyed an increase of volume by 56.21% and weight by 71.29%, respectively, in a 12-week period. Interestingly, populations of CD24+ and CD44+ cells in the tumor increased by 37% and 274%, respectively. No phenotypic change during tumorigenesis was observed due to the presence of the scaffold. Thereafter, we studied the chemotherapeutic effectiveness of a regimen comprising docetaxel, cisplatin and fluorouracil (DCF) in the scaffold model. The study showed that this regimen demonstrated a strong capability to demolish the CD44+ subpopulation in the tumor. This discovery warrants further study of the DCF regimen for gastric cancer. Moreover, the scaffold offers cancer scientists an accelerated in vivo platform for mechanistic chemotherapy study.

Activity, Translocation, and Persistence of Isopyrazam for Controlling Cucumber Powdery Mildew.

A cotyledon bioassay was conducted to assess the activity of isopyrazam against Podosphaera xanthii (Castagne) U. Braun & N. Shishkoff, causal agent of cucumber powdery mildew. Results showed that isopyrazam has protective and curative activity against P. xanthii, with EC50 values of 0.04 and 0.05 mg liter-1, respectively. These activities are higher than those for hexaconazole, difenoconazole, pyraclostrobin, kresoxim-methyl, and azoxystrobin, fungicides currently used against cucumber powdery mildew. Isopyrazam at 0.5 mg liter-1 damaged conidiophores. Results of inoculation tests in greenhouse pots indicate that isopyrazam demonstrates a level of systemic movement in cucumber plants, especially regarding translaminar and transverse translocation. Efficacy following translaminar and transverse translocations on cotyledons and leaves treated with 60 mg liter-1 was 94.40% and 88.96%, and 95.26% and 82.83%, respectively. In addition, isopyrazam at 60 mg liter-1 exhibited a long duration of efficacy against cucumber powdery mildew, almost 2 to 3 weeks longer than that of triazoles and strobilurins. Similar trends in residual durations were observed during 2014 and 2015 greenhouse trials. Isopyrazam at 30 and 60 a.i. g ha-1 provided efficacy ranging from 83.27 to 90.83% 20 days following treatment. In conclusion, isopyrazam has translaminar and transverse translocation in cucumber leaves, and long duration of activity against cucumber powdery mildew.

[Design and Realization of Personalized Corneal Analysis Software Based on Corneal Topography System].

As the most important refraction part in the optical system,cornea possesses characteristics which are important parameters in ophthalmology clinical surgery.During the measurement of the cornea in our study,we acquired the corneal data of Orbscan Ⅱ corneal topographer in real time using the Hook technology under Windows,and then took the data into the corneal analysis software.We then further analyzed and calculated the data to obtain individual Q-value of overall corneal 360semi-meridian.The corneal analysis software took Visual C++ 6.0as development environment,used OpenGL graphics technology to draw three-dimensional individual corneal morphological map and the distribution curve of the Q-value,and achieved real-time corneal data query.It could be concluded that the analysis would further extend the function of the corneal topography system,and provide a solid foundation for the further study of automatic screening of corneal diseases.

Investigation and assessment of heavy metals in surface sediments of Ganjiang River, China.

Surface sediment samples were collected from four sampling areas (Ganzhou nonferrous metal processing zones (GZ), Jian city sewage discharge areas (JA), Non city areas (NC) and Zhangshu middle-city areas (ZS)) to investigate the degree and chemical partitioning of heavy metals. Samples were analyzed for Cu, Zn, Pb, Cd, Cr, As and Ni using sequential extraction scheme. Based on geo-statistics analyses, the results showed maximum values of Cu (131.84 µg g(-1)), Zn (290.68 µg g(-1)), Cd (99.57 µg g(-1)), Cr (53.75 µg g(-1)), As (25.58 µg g(-1)) and Ni (64.75 µg g(11)) were in sediments dated at GZ areas, while ZS areas had the highest concentrations of Pb (128.51 µg g(-1)). Almost all metal values were higher than their corresponding background values in the following order: Ni < Cr < Zn < Pb < As < Cu < Cd. Meanwhile, sediments showed that heavy metals were predominantly occured in Fe-Mn oxide, residual, organic, exchangeable and carbonate fractions respectively. It was found that concentration in carbonate fractions were generally low for most of the studied metals. The geo-accumulation index and sediment quality values were used to determine the potential risk of heavy metal contamination. The results of geo-accumulation index indicated that contamination degree ranged from uncontaminated to extremely contaminated degrees. When metal partitioning characteristics were also considered, over 60% of metals showed potential bioavailability and toxic effects were probable.

The effects of childhood trauma on nonsuicidal self-injury and depressive severity among adolescents with major depressive disorder: The different mediating roles of positive and negative coping styles.

OBJECTIVE: We aimed to examine whether positive and negative coping styles mediated the influences of childhood trauma on NSSI or depressive severity in adolescents with major depressive disorder (MDD). METHODS: The Children's Depression Inventory (CDI), the Ottawa Self-Injury Inventory Chinese Revised Edition (OSIC), the short-form Childhood Trauma Questionnaire (CTQ-SF), and the Simplified Coping Style Questionnaire (SCSQ) were evaluated in 313 adolescents with MDD. RESULTS: MDD adolescents with NSSI had higher CTQ-SF total score, emotional and sexual abuse subscale scores, but lower CDI total and subscale scores compared to the patients without NSSI. The multiple linear regression analysis revealed that emotional abuse (ß = 0.075, 95 % CI: 0.042-0.107) and ineffectiveness (ß = -0.084, 95 % CI: -0.160 âˆ¼ -0.009) were significantly associated with the frequency of NSSI in adolescents with MDD, but emotional abuse (ß = 0.884, 95 % CI: 0.570-1.197), sexual abuse (ß = 0.825, 95 % CI: 0.527-1.124) and negative coping style (ß = 0.370, 95 % CI: 0.036-0.704) were independently associated with the depressive severity in these adolescents. Furthermore, the mediation analysis demonstrated that positive coping style partially mediates the effect of childhood trauma on NSSI (Indirect effect = 0.002, 95 % bootCI: 0.001-0.004), while the negative coping style partially mediates the relationship between childhood trauma and depressive severity (Indirect effect = 0.024, 95 % bootCI: 0.005-0.051) in adolescents with MDD. LIMITATIONS: A cross-sectional design, the retrospective self-reported data, the small sample size. CONCLUSION: Our findings suggest that coping styles may serve as mediators on the path from childhood trauma to NSSI or depressive severity in MDD adolescents.

Dual network composite hydrogels with robust antibacterial and antifouling capabilities for efficient wound healing.

Wound dressings play a critical role in the wound healing process; however, conventional dressings often address singular functions, lacking versatility in meeting diverse wound healing requirements. Herein, dual-network, multifunctional hydrogels (PSA/CS-GA) have been designed and synthesized through a one-pot approach. The in vitro and in vivo experiments demonstrate that the optimized hydrogels have exceptional antifouling properties, potent antibacterial effects and rapid hemostatic capabilities. Notably, in a full-thickness rat wound model, the hydrogel group displays a remarkable wound healing rate exceeding 95% on day 10, surpassing both the control group and the commercial 3M group. Furthermore, the hydrogels exert an anti-inflammatory effect by reducing inflammatory factors interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), enhance the release of the vascular endothelial growth factor (VEGF) to promote blood vessel proliferation, and augment collagen deposition in the wound, thus effectively accelerating wound healing in vivo. These innovative hydrogels present a novel and highly effective approach to wound healing.

Rescuing Nucleus Pulposus Cells from ROS Toxic Microenvironment via Mitochondria-Targeted Carbon Dot-Supported Prussian Blue to Alleviate Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is invariably accompanied by excessive accumulation of reactive oxygen species (ROS), resulting in progressive deterioration of mitochondrial function and senescence in nucleus pulposus cells (NPCs). Significantly, the main ROS production site in non-immune cells is mitochondria, suggesting mitochondria is a feasible therapeutic target to reverse IVDD. Triphenylphosphine (TPP), which is known as mitochondrial-tropic ligands, is utilized to modify carbon dot-supported Prussian blue (CD-PB) to scavenge superfluous intro-cellular ROS and maintain NPCs at normal redox levels. CD-PB-TPP can effectively escape from lysosomal phagocytosis, permitting efficient mitochondrial targeting. After strikingly lessening the ROS in mitochondria via exerting antioxidant enzyme-like activities, such as superoxide dismutase, and catalase, CD-PB-TPP rescues damaged mitochondrial function and NPCs from senescence, catabolism, and inflammatory reaction in vitro. Imaging evaluation and tissue morphology assessment in vivo suggest that disc height index, mean grey values of nucleus pulposus tissue, and histological morphology are significantly improved in the IVDD model after CD-PB-TPP is locally performed. In conclusion, this study demonstrates that ROS-induced mitochondrial dysfunction and senescence of NPCs leads to IVDD and the CD-PB-TPP possesses enormous potential to rescue this pathological process through efficient removal of ROS via targeting mitochondria, supplying a neoteric strategy for IVDD treatment.

Vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication in Chinese population: A prospective, multicenter, randomized, two-stage study.

BACKGROUND: The efficacy of Vonoprazan-amoxicillin dual therapy (VAT) in the treatment of Helicobacter pylori (H. pylori) is controversial. AIM: To evaluate the efficacy of VAT in the Chinese population. METHODS: This prospective, multicenter, randomized, open-label, and two-stage study was conducted at 23 centers in Fujian, China (May 2021-April 2022). H. pylori-infected patients were randomized to bismuth quadruple therapy (BQT), BQT-Vonoprazan (BQT-V), seven-day VAT (VAT-7), ten-day VAT (VAT-10), and fourteen-day VAT (VAT-14) groups. The primary endpoint was the H. pylori eradication rate. The secondary endpoint was the frequency of adverse events. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2100045778. RESULTS: In the first stage, VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated. In the second stage, the eradication rates for BQT, VAT-10, and VA-14 were 80.2% [95% confidence interval (95%CI): 71.4%-86.8%], 93.2% (86.6%-96.7%), 92.2% (85.3%-96.0%) in the intention-to-treat (ITT) analysis, and 80.9% (95%CI: 71.7%-87.5%), 94.0% (87.5%-97.2%), and 93.9% (87.4%-97.2%) in the per-protocol analysis. The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group (P = 0.022 and P = 0.046, respectively). The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group (25.27% and 13.73% vs 37.62%, respectively; P < 0.001). CONCLUSION: VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT, with a more tolerable safety profile in H. pylori-infected patients in Fujian.

Antibiotic resistance profile of Helicobacter pylori to 14 antibiotics: a multicenter study in Fujian, China.

Background and aim: Efficacy of Helicobacter pylori (H. pylori) eradication is related to the local antimicrobial resistance epidemiology. We aimed to investigate the antibiotic resistance of H. pylori in Fujian, China. Methods: H. pylori-infected patients in four centers were enrolled in the study from Oct 2019 to Jan 2022. The bacteria were isolated, cultured and identified from the biopsy of patients' gastric mucosa samples. Antimicrobial susceptibility testing was performed by a modified broth microdilution method for H. pylori to seven guideline-recommended antibiotics and seven potential choices for H. pylori eradication. Results: A total of 205 H. pylori strains were isolated. The resistance rates of amoxicillin (AMX), amoxicillin and clavulanate potassium (AMC), cefixime (CFM), gentamicin (GEN), tetracycline (TET), doxycycline (DOX), azithromycin (AZM), clarithromycin (CLR), levofloxacin (LVFX), sparfloxacin (SPFX), metronidazole (MTZ), tinidazole (TID), rifampicin (RFP) and furazolidone (FZD) were 11.22%, 12.20%, 7.32%, 12.20%, 4.88%, 4.39%, 44.39%, 43.90%, 30.24%, 21.46%, 40.98%, 45.85%, 5.37% and 10.24%, respectively. The rates of pan-sensitivity, single, double, triple and multiple resistance for seven guideline-recommended antibiotics were 32.68%, 30.24%, 13.17%, 7.76%, and 14.15%, respectively. The main double-resistance patterns were CLR+MTZ (10/205, 5%) and CLR+LVFX (9/205, 4%). The main triple-resistance pattern was CLR+MTZ+ LVFX (15/205, 7%). Conclusions: In Fujian, the prevalence of H. pylori resistance to AZM, CLR, LVFX, SPFX, MTZ, and TID was high, whereas that to AMX, AMC, GEN, CFM, TET, DOX, RFP and FZD was relatively low. CFM and DOX are promising new choices for H. pylori eradication.

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.

CFTR potentiator ivacaftor protects against noise-induced hair cell loss by increasing Nrf2 and reducing oxidative stress.

Over-production of reactive oxygen species (ROS) in the inner ear can be triggered by a variety of pathological events identified in animal models after traumatic noise exposure. Our previous research found that inhibition of the AMP-activated protein kinase alpha subunit (AMPKα) protects against noise-induced cochlear hair cell loss and hearing loss by reducing ROS accumulation. However, the molecular pathway through which AMPKα exerts its antioxidative effect is still unclear. In this study, we have investigated a potential target of AMPKα and ROS, cystic fibrosis transmembrane conductance regulator (CFTR), and the protective effect against noise-induced hair cell loss of an FDA-approved CFTR potentiator, ivacaftor, in FVB/NJ mice, mouse explant cultures, and HEI-OC1 cells. We found that noise exposure increases phosphorylation of CFTR at serine 737 (p-CFTR, S737), which reduces wildtype CFTR function, resulting in oxidative stress in cochlear sensory hair cells. Pretreatment with a single dose of ivacaftor maintains CFTR function by preventing noise-increased p-CFTR (S737). Furthermore, ivacaftor treatment increases nuclear factor E2-related factor 2 (Nrf2) expression, diminishes ROS formation, and attenuates noise-induced hair cell loss and hearing loss. Additionally, inhibition of noise-induced AMPKα activation by compound C also diminishes p-CFTR (S737) expression. In line with these in-vivo results, administration of hydrogen peroxide to cochlear explants or HEI-OC1 cells increases p-CFTR (S737) expression and induces sensory hair cell or HEI-OC1 cell damage, while application of ivacaftor halts these effects. Although ivacaftor increases Nrf2 expression and reduces ROS accumulation, cotreatment with ML385, an Nrf2 inhibitor, abolishes the protective effects of ivacaftor against hydrogen-peroxide-induced HEI-OC1 cell death. Our results indicate that noise-induced sensory hair cell damage is associated with p-CFTR. Ivacaftor has potential for treatment of noise-induced hearing loss by maintaining CFTR function and increasing Nrf2 expression for support of redox homeostasis in sensory hair cells.

CD99 triggers upregulation of miR-9-modulated PRDM1/BLIMP1 in Hodgkin/Reed-Sternberg cells and induces redifferentiation.

CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene. Our study was carried out to examine the role of CD99 in tumor progression of classical Hodgkin lymphoma (cHL). Here, we showed that lowly expressed CD99 protein in cHL cell lines and primary cHL cases correlates with the deficient expression of the positive regulatory domain 1 (PRDM1/BLIMP1). In addition, cHL cell lines showed high levels of miR-9 expression. We determined that the upregulation of CD99 induced expression of transcription factor PRDM1, a master regulator of plasma-cell differentiation, which is also a target for miR-9-mediated downregulation. Indeed, inhibition of miR-9 also triggered upregulation of PRDM1 expression. Furthermore, overexpression of CD99 resulted in changed growth features and reorganization of actin cytoskeleton. As upregulation of CD99 led to a decrease in cHL diagnosis marker CD30 and CD15 and an increase in plasma-cell differentiation marker CD38 and the restoration of B-cell makers PAX5, CD79α and CD19, we suggest that downregulated CD99 leads to the prevention of plasma-cell differentiation in Hodgkin/Reed-Sternberg (H/RS) cells. Furthermore, these data indicate that CD99 may control miR-9 expression, which directly targets PRDM1. Altogether, these results reveal a CD99-miR-9-PRDM1 molecule axis in lymphomagenesis of cHL and suggest that upregulation of CD99 in H/RS cells induces terminal B-cell differentiation, which may provide a novel therapeutic strategies for cHL.

Construction of Bifidobacterium infantis as a live oral vaccine that expresses antigens of the major fimbrial subunit (CfaB) and the B subunit of heat-labile enterotoxin (LTB) from enterotoxigenic Escherichia coli.

We sought to develop Bifidobacterium infantis (BI) as a vehicle for the expression of heterologous antigens. Two proteins of enterotoxigenic Escherichia coli (ETEC) were expressed in BI: CfaB, a major fimbrial subunit protein, and LTB, the B subunit of heat-labile enterotoxin. The expression of CfaB and LTB in BI was verified by electrophoretic analysis. Sprague-Dawley rats were then subjected to intragastric immunization with BI-CfaB and BI-LTB systems both separately and together. ELISA was used to characterize the serum and mucosal immune responses against ETEC antigens. The immunized rats were intraperitoneally challenged with wild-type ETEC H10407 to study the immune response in vivo. The serum titres of IgG and faecal IgA antibodies in the BI-CfaB plus BI-LTB mixed vaccination group were significantly greater than those in the other two groups, which were immunized with a single vaccine (P<0.05). However, no significant difference was seen between the two groups that received a single immunization. These results suggest that expressing CfaB and LTB in BI provides a probiotic system with immunogenic properties. Furthermore, the expression of LTB in BI preserved its mucosal adjuvant effect. So this study confirms that BI can be used as a novel oral vaccine expression system for a heterologous antigen and BI-LTB can provide mucosal adjuvant properties.