Effect of four chitinase genes on the female fecundity in Sogatella furcifera (Horváth).

BACKGROUND: The white-backed planthopper (WPH), Sogatella furcifera (Horváth), is a destructive rice pest with strong reproductive capacity. To gain insights into the roles of chitinases in the reproductive process of this insect species, this study represents the first-ever endeavor to conduct an in-depth exploration into the reproductive functions of four chitinase genes. RESULTS: In this study, it was observed that four chitinase genes were expressed in female adults, with a relatively high expression level in the ovaries. SfCht2 and SfIDGF1 were highly expressed during later ovarian development. while SfENGase increased and then decreased with ovarian development. SfCht2, SfCht6-2 and SfENGase were highly expressed in fat body on the first and second days after eclosion, whereas SfIDGF1 highest on day 7. Compared with control group, Silencing four chitinase genes inhibited ovarian development and significantly shortened the oviposition period of S. furcifera, reducing egg-laying capacity but not affecting egg hatching. The detection demonstrated that the expression levels of SfVg, SfVgR and 70-90% juvenile hormone (JH) signaling pathway-related reproductive genes was significantly down-regulated. Moreover, SfCht6-2 and SfENGase significantly affected the expression levels of Target of Rapamycin (TOR) signaling pathway genes. SfENGase had the ability to impact nutrient signaling pathways and fatty acid metabolism, repressing vitellogenin synthesis and ultimately influencing ovarian development of S. furcifera. CONCLUSIONS: Overall, this study provides insight into the function of chitinases in insect fecundity and is of great significance for enriching the cognition of insect chitinase function. They will become the suitable target genes for controlling the most destructive rice planthoppers. © 2023 Society of Chemical Industry.

Buprofezin affects the molting process by regulating nuclear receptors SfHR3 and SfHR4 in Sogatella furcifera.

Nuclear receptors play a crucial role in various signaling and metabolic pathways, such as insect molting and development. Buprofezin (2-tert-butylimino-3-isopropyl-5-phenyl-perhydro-1, 3, 5-thiadiazin-4-one), a chitin synthesis inhibitor, causes molting deformities and slow death in insects by inhibiting chitin synthesis and interfering with their metabolism. This study investigated whether buprofezin affects insect ecdysteroid signaling pathway. The treatment of buprofezin significantly suppressed the transcription levels of SfHR3 and SfHR4, two nuclear receptor genes, in third-instar nymphs of Sogatella furcifera. Meanwhile, the transcription levels of SfHR3 and SfHR4 in first-day fifth-instar nymphs were induced at 12 h after 20E treatment. In addition, the silencing of SfHR3 and SfHR4 genes in first-day fifth-instar nymphs caused severe developmental delay and molting failure, resulting in a significant reduction of survival rates at 7.36% and 2.99% on the eighth day, respectively. Further analysis showed that the silencing SfHR3 and SfHR4 significantly inhibited the transcription levels of chitin synthesis and degradation-related genes. These results indicate that buprofezin can inhibits chitin synthesis and degradation by suppressing the signal transduction of 20E through SfHR3 and SfHR4, leading to molting failure and death. This study not only expands our understanding of the molecular mechanism of buprofezin in pest control but also lays a foundation for developing new control strategies of RNAi by targeting SfHR3 and SfHR4.

Reactive Oxygen Species Scavenging Nanozymes: Emerging Therapeutics for Acute Liver Injury Alleviation.

Acute liver injury (AIL), a fatal clinical disease featured with a swift deterioration of hepatocyte functions in the short term, has emerged as a serious public health issues that warrants attention. However, the effectiveness of existing small molecular antioxidants and anti-inflammatory medications in alleviating AIL remains uncertain. The unique inherent structural characteristics of liver confer it a natural propensity for nanoparticle capture, which present an opportunity to exploit in the formulation of nanoscale therapeutic agents, enabling their selective accumulation in the liver and thereby facilitating targeted therapeutic interventions. Significantly increased reactive oxygen species (ROS) accumulation and inflammation response have been evidenced to play crucial roles in occurrence and development of AIL. Nanozymes with ROS-scavenging capacities have demonstrated considerable promise in ROS elimination and inflammation regulation, thereby offering an appealing therapeutic instrument for the management of acute liver injury. In this review, the mechanisms of different type of ALI were summarized. In addition, we provide a comprehensive summary and review of the available ROS-scavenging nanozymes, including transition metal-based nanozymes, noble metal nanozymes, carbon-based nanozymes, and some other nanozymes. Furthermore, the challenges still need to be solved in the field of ROS-scavenging nanozymes for ALI alleviation are also discussed.

Self-Propelled Ultrasmall AuNPs-Tannic Acid Hybrid Nanozyme with ROS-Scavenging and Anti-Inflammatory Activity for Drug-Induced Liver Injury Alleviation.

Developing nanomedicines with superior reactive oxygen species (ROS) scavenging capability has emerged as a promising strategy in treating ROS-related diseases, for example, drug-induced liver injury. However, designing nanoscavengers with the self-propelling ability to scavenge ROS actively remains challenging. Here, a self-propelled silica-supported ultrasmall gold nanoparticles-tannic acid hybrid nanozyme (SAuPTB) is designed that can effectively alleviate acetaminophen (APAP)-induced liver injury by scavenging excessive ROS and regulating inflammation. SAuPTB exhibits multienzyme activity and displays significantly enhanced diffusion under hydrogen peroxide (H2 O2 ). This in vitro research shows that SAuPTB can effectively eliminate ROS, increasing the viability of H2 O2 -stimulated cells and reducing the cytotoxicity of APAP/H2 O2 -treated AML12 cells. The in vivo studies show that SAuPTB can accumulate at inflammatory sites in mouse liver, resulting in the decrease of alanine aminotransferase, aspartate aminotransferase, and ROS, reduction in pro-inflammatory cytokines and chemokines, hence reduced hepatocyte necrosis, liver injury, and mortality. Furthermore, SAuPTB activates the nuclear erythroid 2-related factor 2 pathway to upregulate antioxidative genes and reduce oxidative stress. Finally, the liver shows decreased high mobility group box 1 and F4/80+ macrophages, suggesting an anti-inflammatory response. This work provides a novel design strategy of nanozymes for ROS-related disease treatment.

Central nervous system injury meets nanoceria: opportunities and challenges.

Central nervous system (CNS) injury, induced by ischemic/hemorrhagic or traumatic damage, is one of the most common causes of death and long-term disability worldwide. Reactive oxygen and nitrogen species (RONS) resulting in oxidative/nitrosative stress play a critical role in the pathological cascade of molecular events after CNS injury. Therefore, by targeting RONS, antioxidant therapies have been intensively explored in previous studies. However, traditional antioxidants have achieved limited success thus far, and the development of new antioxidants to achieve highly effective RONS modulation in CNS injury still remains a great challenge. With the rapid development of nanotechnology, novel nanomaterials provided promising opportunities to address this challenge. Within these, nanoceria has gained much attention due to its regenerative and excellent RONS elimination capability. To promote its practical application, it is important to know what has been done and what has yet to be done. This review aims to present the opportunities and challenges of nanoceria in treating CNS injury. The physicochemical properties of nanoceria and its interaction with RONS are described. The applications of nanoceria for stroke and neurotrauma treatment are summarized. The possible directions for future application of nanoceria in CNS injury treatment are proposed.

Identification and profiling of Sogatella furcifera microRNAs and their potential roles in regulating the developmental transitions of nymph-adult.

Sogatella furcifera is one of the most serious insect pests that affect rice in Asia. One class of small RNAs (sRNAs; ~22 nt long) is miRNAs, which participate in various biological processes by regulating the expression of target genes in a spatiotemporal manner. However, the role of miRNAs in nymph-to-adult transition in S. furcifera remains unknown. In this study, we sequenced sRNA libraries of S. furcifera prepared from individuals at three different developmental stages (pre-moult, moulting and early adult). A total of 253 miRNAs (134 known and 119 novel) were identified, of which 12 were differentially expressed during the nymph-to-adult developmental transition. Moreover, Real time quantitative PCR (RT-qPCR) analysis revealed that all 12 miRNAs were differentially expressed among five different nymph tissues and 14 different developmental stages (first to fifth instar nymphs and 1-day-old adults). Injection of miR-2a-2 mimic/antagomir and miR-305-5p-1 mimic/antagomir into 1-day-old fifth instar nymphs significantly increased the mortality rate. In addition, a defective moulting phenotype was observed in nymphs injected with miR-2a-2 and miR-305-5p-1, suggesting that these miRNAs are involved in S. furcifera nymph-adult transition. In conclusion, these results reveal the function of critical miRNAs in S. furcifera nymph-adult transition, and also provide novel potential targets of insecticides for the long-term sustainable management of S. furcifera.

Au-Fe3O4 heterodimer multifunctional nanoparticles-based platform for ultrasensitive naked-eye detection of Salmonella typhimurium.

In this work, we developed an ultrasensitive colorimetry for Salmonella typhimurium detection with multifunctional Au-Fe3O4 dumbbell-like nanoparticles (DBNPs) which possessed easy bio-modifiability, excellent LSPR characteristics, superparamagnetic properties and super peroxidase-like activity. In the detection, the anti-S. typhimurium antibody modified DBNPs (IDBNPs) bound with S. typhimurium and aggregated on their surfaces in a large number, which showed much quicker magnetic response than free IDBNPs. By controlling appropriate separation conditions, IDBNPs@S. typhimurium composites were captured, while free IDBNPs were remained in the supernatant. Therefore, by detecting the absorbance of the supernatant, quantitative detection was achieved from 10 to 1000 CFU/mL. Moreover, utilizing the peroxidase-like activity of IDBNPs, we further realized semi-quantitative naked-eye detection. By adding ABTS into the above supernatant, which was oxidized to green chelate (OxABTS), colorimetric signal was amplified significantly, and meanwhile, the green chelates and the wine-red IDBNPs engendered mixed color, enhancing the range of color gradation and greatly improving the visual resolution. Finally, a detection limit (10 CFU/mL) comparable with that of above spectrum measurement was achieved. Besides, our method exhibited efficient capture capability (nearly 100% even for rare S. typhimurium), and had good stability and specificity, and acceptable anti-interference ability in fetal bovine serum and milk samples.

Juvenile Hormone Synthesis Pathway Gene SfIPPI Regulates Sogatella furcifera Reproduction.

The juvenile hormone (JH) is crucial for insect reproduction, and isopentenyl pyrophosphate isomerase (IPPI) is a key enzyme in the JH synthesis pathway. However, few studies have investigated how IPPI regulates insect reproduction. This study identifies and characterizes the IPPI gene (SfIPPI) from the important agricultural pest Sogatella furcifera. A phylogenetic analysis reveals a high homology of SfIPPI with the IPPI amino acid sequences of Laodelphax striatellus and Nilaparvata lugens (Stål). Furthermore, SfIPPI is expressed at various developmental stages and in various tissues of S. furcifera, and is significantly higher on the 5th day of adult emergence and in integument tissue, while lower levels are found on the 3rd day of adult emergence and in fat body and gut tissue. After silencing SfIPPI using RNA interference, the ovarian development is significantly inhibited and the fecundity is significantly reduced when compared with the control group. Additionally, SfIPPI silencing significantly decreases the expression levels of downstream JH signal transduction pathway genes (SfJHAMT, SfFAMeT, and SfKr-h1) and SfVg. Our findings are helpful in elucidating the molecular mechanism underlying the regulation of insect reproduction through genes in the JH synthesis pathway, and they provide a theoretical basis for the development of pest control treatments targeting SfIPPI.

Targeting visualization of malignant tumor based on the alteration of DWI signal generated by hTERT promoter-driven AQP1 overexpression.

PURPOSE: To specifically diagnose malignant tumors in DWI using the human telomerase reverse transcriptase (hTERT) promoter-driven AQP1 expression. METHODS: The human telomerase reverse transcriptase (hTERT) promoter-driven AQP1 gene overexpression lentivirus system (hTERT-AQP1) and cytomegalovirus (CMV) promoter-driven AQP1 gene overexpression lentivirus system (CMV-AQP1) were prepared, and transduced into telomerase-positive and -negative cells. The AQP1 expression and DWI signal intensity (SI) change in transduced cells were analyzed. Balb/C nude mice subcutaneous xenograft models derived from lentivirus-transduced telomerase-positive and -negative cells were used to evaluate AQP1 expression and DWI SI change in vivo. We further established another group of subcutaneous xenograft model using pristine telomerase-positive and -negative cells, followed by injecting the lentiviral vectors intratumorally or intravenously, to determine the malignant tumor-targeted imaging of hTERT-AQP1. RESULTS: The hTERT-AQP1 and CMV-AQP1 were successfully prepared. After transduction, hTERT-AQP1 could induce the specific overexpression of AQP1 in telomerase-positive cells. Compared with untransduced cells, all CMV-AQP1-pretransduced cells and hTERT-AQP1-pretransduced telomerase-positive cells showed decreased SI and increased apparent diffusion coefficient (ADC) in DWI, while hTERT-AQP1-pretransduced telomerase-negative cells showed no obvious SI and ADC change. Correspondingly, hTERT-AQP1-transduced telomerase-positive tumors and CMV-AQP1-transduced telomerase-positive and -negative tumors showed decreased DWI SI and increased ADC, while hTERT-AQP1-transduced telomerase-negative tumor had no SI and ADC changes. After intratumoral or intravenous injection, CMV-AQP1 could upregulate AQP1 expression and induce DWI SI and ADC alteration in both telomerase-positive and -negative tumors, while hTERT-AQP1 worked in telomerase-positive tumors specifically. CONCLUSION: Cancers can be specifically visualized based on the DWI signal alteration which triggered by hTERT-AQP1 lentivirus system that combined AQP1 gene and hTERT promoter.

Collective Plasmon Coupling in Gold Nanoparticle Clusters for Highly Efficient Photothermal Therapy.

Plasmonic nanomaterials with strong absorption at near-infrared frequencies are promising photothermal therapy agents (PTAs). The pursuit of high photothermal conversion efficiency has been the central focus of this research field. Here, we report the development of plasmonic nanoparticle clusters (PNCs) as highly efficient PTAs and provide a semiquantitative approach for calculating their resonant frequency and absorption efficiency by combining the effective medium approximation (EMA) theory and full-wave electrodynamic simulations. Guided by the theoretical prediction, we further develop a universal strategy of space-confined seeded growth to prepare various PNCs. Under optimized growth conditions, we achieve a record photothermal conversion efficiency of up to ∼84% for gold-based PNCs, which is attributed to the collective plasmon-coupling-induced near-unity absorption efficiency. We further demonstrate the extraordinary photothermal therapy performance of the optimized PNCs in in vivo application. Our work demonstrates the high feasibility and efficacy of PNCs as nanoscale PTAs.

Subcortical Volume Changes in Early Menopausal Women and Correlation With Neuropsychological Tests.

Background: The aging process and declining estradiol levels are two important factors that cause structural brain alterations. Many prior studies have investigated these two elements and revealed controversial results in menopausal women. Here, a cross-sectional study was designed to individually evaluate estradiol-related structural changes in the brain. Methods: A total of 45 early menopausal women and 54 age-matched premenopausal controls were enrolled and subjected to magnetic resonance imaging (MRI) scans, blood biochemistry tests, and neuropsychological tests. MRI structural images were analyzed using FreeSurfer to detect changes in subcortical and cortical volumes as well as cortical thickness. Finally, structural brain data as well as clinical and neuropsychological data were used for Pearson's correlation analyses to individually determine estradiol-related structural and functional changes in the brains of early menopausal women. Results: Compared with the premenopausal controls, the early menopausal women showed significant subcortical volumetric loss in the left amygdala and right amygdala, higher serum follicle-stimulating hormone (FSH) levels, more recognizable climacteric and depressive symptoms, decreased quality of sleep, and decreased working memory and executive functions. Simultaneously, FSH levels were related to lower working memory accuracy and longer working memory reaction time. Decreased subcortical volume in the bilateral amygdala was also related to lower working memory accuracy and longer executive reaction time in early menopausal women. Conclusion: The data suggest that estradiol deficiency in early menopausal women can lead to subcortical volume and functional brain changes, which may contribute to further understanding the neurobiological role of declined estradiol levels in early menopausal women.

Synergistic Theranostics of Magnetic Resonance Imaging and Photothermal Therapy of Breast Cancer Based on the Janus Nanostructures Fe3O4-Aushell-PEG.

BACKGROUND: Satisfactory prognosis of breast cancer (BC) is limited by difficulty in early diagnosis and insufficient treatment. The combination of molecular imaging and photothermal therapy (PTT) may provide a solution. METHODS: Fe3O4-Aushell nanoparticles (NPs) were prepared by thermal decomposition, seeded growth and galvanic replacement and were comprehensively characterized. After conjugated to PEG, NPs were used as MRI and PTT agents in vitro and in vivo. RESULTS: Fe3O4-Aushell NPs which had uniform Janus-like morphology were successfully synthesized. The Fe3O4 had a size of 18 ± 2.2 nm, and the Aushell had an outer diameter of 25 ± 3.3 nm and an inner diameter of 20 ± 2.9 nm. The NPs showed superparamagnetism, a saturation magnetization of 36 emu/g, and an optical absorption plateau from 700 to 808 nm. The Fe3O4-Aushell NPs were determined to possess good biocompatibility. After PEG coating, the zeta potential of NPs was changed from -23.75 ± 1.37 mV to -13.93 ± 0.55 mV, and the FTIR showed the characteristic C-O stretching vibration at 1113 cm-1. The NPs' MR imaging implied that the T2 can be shortened by Fe3O4-Aushell NPs in a concentration-dependent manner, and the Fe3O4-Aushell NPs coated with PEG at the molar ratio of 160 (PEG: NPs) showed the highest transverse relaxivity (r 2) of 216 mM-1s-1. After irradiation at 0.65 W/cm2 for 5 min, all cells incubated with the Fe3O4-Aushell-PEG160 NPs (Fe: 30 ppm, Au: 70 ppm) died. After administrated intratumorally, Fe3O4-Aushell-PEG160 notably decreased the signal intensity of tumor in T2WI images. Under the same irradiation, the temperature of tumors injected with Fe3O4-Aushell-PEG160 quickly rose to 54.6°C, and the tumors shrank rapidly and were ablated in 6 days. CONCLUSION: Fe3O4-Aushell-PEG NPs show good r 2 and PTT performance and are promising synergistic theranostic agents of MRI and PTT for BC.

Identification and RNAi-Based Functional Analysis of Four Chitin Deacetylase Genes in Sogatella furcifera (Hemiptera: Delphacidae).

Chitin deacetylases (CDAs) are chitin-degrading enzymes that play a key role in insect molting. In this study, we identified and characterized four full-length cDNAs of CDAs from Sogatella furcifera (Horváth). Developmental expression showed that SfCDA1 and SfCDA2 were expressed at all nymph developmental stages, SfCDA3 and SfCDA4 were mainly expressed in the third-instar to fifth-instar nymph stages, whereas tissue-specific analyses indicated that four CDA genes were mainly high expressed in the integument and head during the fifth-instar nymph. RNA interference (RNAi) results revealed that SfCDA1, SfCDA2, and SfCDA4 are associated with molting defect and high mortality with nymph-adult molting. Furthermore, transcripts of chitin synthase 1 variants (SfCHS1, SfCHS1a, and SfCHS1b) were significantly downregulated and causing significant changes in the expression levels of trehalases (TRE1 and TRE2) in the SfCDA1, SfCDA2, and SfCDA4 dsRNA treatment groups. By contrast, no significant phenotypic characteristics were observed after dsSfCDA3 injection. Taken together, our results suggest that SfCDA1, SfCDA2, and SfCDA4 play a vital role in nymph-adult transition, and these genes could regulate chitin biosynthesis expression levels.

pH-Driven Reversible Assembly and Disassembly of Colloidal Gold Nanoparticles.

Owing to the localized surface plasmon resonance (LSPR), dynamic manipulation of optical properties through the structure evolution of plasmonic nanoparticles has been intensively studied for practical applications. This paper describes a novel method for direct reversible self-assembly and dis-assembly of Au nanoparticles (AuNPs) in water driven by pH stimuli. Using 3-aminopropyltriethoxysilane (APTES) as the capping ligand and pH-responsive agent, the APTES hydrolyzes rapidly in response to acid and then condenses into silicon. On the contrary, the condensed silicon can be broken down into silicate by base, which subsequently deprotonates the APTES on AuNPs. By controlling condensation and decomposition of APTES, the plasmonic coupling among adjacent AuNPs could be reversible tuned to display the plasmonic color switching. This study provides a facile and distinctive strategy to regulate the reversible self-assembly of AuNPs, and it also offers a new avenue for other plasmonic nanoparticles to adjust plasmonic properties via reversible self-assembly.

Fluorine-mediated synthesis of anisotropic iron oxide nanostructures for efficient T2-weighted magnetic resonance imaging.

Herein, we developed a novel strategy for the shape-controlled synthesis of iron oxide nanostructures with superior r2 values through the introduction of fluoride ions as a morphology controlling agent and dopant. The selective adsorption of fluoride ions onto the specified crystal planes of iron oxide nanocrystals leads to the formation of octapod nanoparticles (ONPs) and cubic nanocrystal clusters (CNCs). Both ONPs and CNCs present high r2 values (526.5 and 462.2 mM-1 s-1, respectively) due to the synergistic effect of a larger effective radius, clustering and fluorine doping. The in vivo MRI results show significant enhancement in T2-weighted images of the liver after the intravenous injection of ONPs and CNCs, suggesting their great potential as efficient T2-weighted MRI contrast agents. This new approach of achieving anisotropic fluorine-doped iron oxide nanostructures with high r2 relaxivity provides an alternative strategy for the development of highly sensitive T2 contrast agents for MRI.

Role of SfJHAMT and SfFAMeT in the reproductive regulation of Sogatella furcifera and its expression under insecticide stress.

The isoprene branching pathway is a unique downstream synthesis pathway of juvenile hormone (JH) in arthropods, which plays an important role in the growth, development, and reproduction of insects. Juvenile hormone acid O-methyltransferase (JHAMT) and farnesoic acid O-methyltransferase (FAMeT) are two key proteins that are regulated in the isoprene branching pathway. Based on the available transcriptomic and genomic data of Sogatella furcifera, full-length cDNAs of SfJHAMT and SfFAMeT were identified. In vitro injection of dsRNA targeted to silence SfJHAMT and SfFAMeT inhibited the fecundity, ovarian development, and transcription levels of SfKr-h1 and SfVg significantly. Of note, The transcription levels of SfJHAMT and SfFAMeT are regulated mutually; i.e., silencing of SfJHAMT causes an increase in the SfFAMeT transcription level and vice versa, and the negative effect of simultaneous silencing on reproduction is greater. The results revealed a coordinated effect of SfJHAMT and SfFAMeT on the reproductive capabilities of S. furcifera. Furthermore, a JH analog (methoprene) partially rescued the negative effect of simultaneous silencing by SfJHAMT and SfFAMeT on reproduction. In addition, the expression profile analysis after insecticide stress showed that triazophos (LC25) can induce the transcription of SfMet and SfKr-h1 to promote JH signal transduction, which affects the transcription of SfVg and ultimately promotes the reproduction of S. furcifera. The results of the present study lay a foundation to further explain the isoprene branch pathway function in insect reproduction and can open up new avenues for sustainable pest control while expanding the current understanding of molecular mechanisms through which insecticides stimulate reproduction and lead to pest resurgence.

Metabolic Conversion and Removal of Manganese Ferrite Nanoparticles in RAW264.7 Cells and Induced Alteration of Metal Transporter Gene Expression.

BACKGROUND: Manganese Ferrite Nanoparticles (Mn-IONPs) are widely used in biomedical field and their cytotoxicity has been initially explored, but the mechanism remains obscure. The nano-bio interactions are believed to be crucial for cytotoxicity mechanism, while little data have been acquired. METHODS: Mn-IONPs were synthesized by thermal decomposition of acetylacetonate precursor. After physicochemical characterization, we analyzed the metabolic conversion and removal of Mn-IONPs in RAW264.7 cells by Prussian blue staining, TEM, HRTEM and elemental quantitative analysis, followed by gene expression evaluation using quantitative RT-PCR. RESULTS: Mn-IONPs were successfully synthesized. Both the uptake and cytotoxicity of Mn-IONPs on RAW264.7 cells were time- and dose-dependent. After internalized, Mn-IONPs were passed to daughter cells with passages on. Meanwhile, Mn-IONPs were exocytosed and digested to metal ions and further excreted out, resulted in the labeling rate and ions contents decreased gradually. As ion influx related genes, the expressions of ZIP14, IRP2, FtH and DMT1 were suppressed within 24 hours but overexpressed to a plateau at the 48th hour in a dose-dependent manner. At the 72nd hour, ZIP14 and DMT1 mRNA levels decreased toward normal, while IRP2 and FtH kept up-regulated. As efflux related genes, FPN, SLC30A10 and Hamp2 genes were up-regulated within 24-72 hours; SPCA1 was suppressed at the 24th and 72nd hour, while overexpressed at the 48th hour. All the efflux related genes' mRNA had a dose-dependent increasing manner at the corresponding time points. CONCLUSION: Mn-IONPs showed time- and dose-dependent cytotoxicity and cell labeling rate in RAW264.7 cells. Accompanying with the intracellular catabolic breakdown and exocytosis of Mn-IONPs, RAW264.7 cells also secreted and re-uptook manganese and iron ions to maintain intracellular homeostasis in the succeeding passages. And the metabolic conversion of Mn-IONPs in RAW264.7 cells can affect the expression of ZIP14, DMT1, FPN, SLC30A10, IRP2, FtH, Hamp2 and SPCA1 genes.

Activatable NIR-II Plasmonic Nanotheranostics for Efficient Photoacoustic Imaging and Photothermal Cancer Therapy.

Precise manipulation of optical properties through the structure-evolution of plasmonic nanoparticles is of great interest in biomedical fields including bioimaging and phototherapy. However, previous success has been limited to fixed assembled structures or visible-NIR-I absorption. Here, an activatable NIR-II plasmonic theranostics system based on silica-encapsulated self-assembled gold nanochains (AuNCs@SiO2 ) for accurate tumor diagnosis and effective treatment is reported. This transformable chain structure breaks through the traditional molecular imaging window, whose absorption can be redshifted from the visible to the NIR-II region owing to the fusion between adjacent gold nanoparticles in the restricted local space of AuNCs@SiO2 triggered by the high H2 O2 level in the tumor microenvironment (TME), leading to the generation of a new string-like structure with strong NIR-II absorption, which is further confirmed by finite-difference-time-domain (FDTD) simulation. With the TME-activated characteristics, AuNCs@SiO2 exhibits excellent properties for photoacoustic imaging and a high photothermal conversion efficiency of 82.2% at 1064 nm leading to severe cell death and remarkable tumor growth inhibition in vivo. These prominent intelligent TME-responsive features of AuNCs@SiO2 may open up a new avenue to explore optical regulated nano-platform for intelligent, accurate, and noninvasive theranostics in NIR-II window.

Educational impact of the mini-Clinical Evaluation Exercise in resident standardization training: a comparative study between resident and professional degree postgraduate trainees.

OBJECTIVE: We aimed to explore differences in the educational impact of the mini-Clinical Evaluation Exercise (mini-CEX) on resident (RE) and professional degree postgraduate (PDPG) trainees, as well as influencing factors, to provide suggestions for hospital managers, trainers, and trainees. METHODS: We performed a retrospective analysis of all scores among first-year resident standardization training trainees registered during 2017 to 2019 at Xinqiao Hospital of Army Medical University, to identify differences in mini-CEX outcomes between REs and PDPGs. RESULTS: We collected data of 154 registered trainees for retrospective analysis, including 57 PDPG trainees and 97 RE trainees. The mean (standard deviation) overall performance score of PDPGs was 84.18 (4.25), which was higher than that of REs (81.48 (3.35)). In terms of domain analysis, PDPG trainees performed significantly better than REs in history taking, physical examination, clinical diagnosis/treatment regimen, and the knowledge examination; communication skills/humanistic care were comparable between the groups. CONCLUSIONS: PDPGs performed better than REs in overall competency, history taking, physical examination, clinical diagnosis/treatment regimen, and the knowledge examination. A better knowledge base, supervisor-dominated one-to-one teaching mode, higher self-esteem and learning goals, and more sophisticated responses to feedback were potential contributors to a superior educational impact of the mini-CEX.

Dysregulation within the salience network and default mode network in hyperthyroid patients: a follow-up resting-state functional MRI study.

This study investigated the aberrant connectivity of the salience network (SN) and default mode network (DMN) and the relevance between these abnormalities and symptom improvement in hyperthyroid patients using resting-state functional magnetic resonance imaging (rs-fMRI). Seed-based functional connectivity (FC) analyses were performed on state fMRI data to reveal possible differences in critical node connectivity in the SN and DMN between 41 new-onset, untreated hyperthyroid patients and 41 healthy controls. Subsequently, follow-up data were available for 25 patients treated with methimazole for one month. Compared with the healthy controls, the patients exhibited abnormal internetwork FC from the SN to the DMN and the executive control network (ECN) and decreased intra-network FC within the SN. Relative to the hyperthyroid state, the antithyroid therapy induced reversible connectivity of the left insula to the dorsal anterior cingulate cortex(dACC)and ECN, and persistently increased connectivity between the SN and DMN in patients with improved thyroid function. Finally, Pearson's correlation analyses were performed among the abnormal FC, neuropsychological assessment and serum free triiodothyronine(FT3)level data. The results indicated that aberrant intra- and internetwork FC in the SN and DMN might underlie the pathogenesis of hyperthyroidism, and antithyroid treatment could regulate the FC of certain key brain regions within the SN and DMN in hyperthyroid patients.