Switching ubiquitous and muscle-specific isoforms of mitochondrial respiratory complex IV in skeletal muscle fine-tunes complex IV activity.

Respiratory complex IV (CIV, cytochrome c oxidase) is the terminal enzyme of the mitochondrial electron transport chain. Some CIV subunits have two or more isoforms, which are ubiquitously expressed or are expressed in specific tissues like the lung, muscle, and testis. Among the tissue-specific CIV isoforms, the muscle-specific isoforms are expressed in adult cardiac and skeletal muscles. To date, the physiological and biochemical association between the muscle-specific CIV isoforms and aerobic respiration in muscles remains unclear. In this study, we profiled the CIV organization and expression pattern of muscle-specific CIV isoforms in different mouse muscle tissues. We found extensive CIV-containing supramolecular organization in murine musculature at advanced developmental stages, while a switch in the expression from ubiquitous to muscle-specific isoforms of CIV was also detected. Such a switch was confirmed during the in vitro differentiation of mouse C2C12 myoblasts. Unexpectedly, a CIV expression decrease was observed during C2C12 differentiation, which was probably due to a small increase in the expression of muscle-specific isoforms coupled with a dramatic decrease in the ubiquitous isoforms. We also found that the enzymatic activity of CIV containing the muscle-specific isoform COX6A2 was higher than that with COX6A1 in engineered HEK293T cells. Overall, our results indicate that switching the expression from ubiquitous to muscle-specific CIV isoforms is indispensable for optimized oxidative phosphorylation in mature skeletal muscles. We also note that the in vitro C2C12 differentiation model is not suitable for the study of muscular aerobic respiration due to insufficient expression of muscle-specific CIV isoforms.

Effect of biofeedback intervention on neurological characteristics of children with attention deficit hyperactivity disorder.

OBJECTIVE: To evaluate the effects of biofeedback intervention on the neurological characteristics of children with attention deficit hyperactivity disorder (ADHD). METHODS: 150 children aged 6-12 years with ADHD were divided into two groups according to the treatment method. The atomoxetine group received atomoxetine drug treatment, and the combined treatment group received EEG biofeedback therapy. Continuous performance test (CPT), SNAP-IV and WFIRS-P were used to assess attention and behavior, and functional magnetic resonance imaging (fMRI) was used to observe changes in brain activity. RESULTS: The response time, error times, error response rate and attention fluctuation index of CPT in the combined treatment group were significantly lower than those in the atomoxetine group (p < 0.05), and the correct response rate was higher than that in the atomoxetine group (p < 0.05). After intervention, SNAP-IV and WFIRS-P scores in the combined treatment group were significantly lower than those in the atomoxetine group (p < 0.001). fMRI results showed that the activity of the prefrontal, parietal, amygdala and hippocampus in the combined treatment group was significantly higher than that in the atomoxetine group (p < 0.001). CONCLUSION: Biofeedback intervention can significantly improve the attention and behavior of ADHD children and positively regulate the neural activity in related brain areas on the basis of drug treatment, suggesting that biofeedback therapy can be considered as a potential effective nondrug treatment option for ADHD children.

Effects of Talaromyces marneffei on Complete Blood Count by a Sysmex XN-9000 Analyzer.

BACKGROUND: Talaromyces marneffei (T. marneffei) infection detected in the peripheral blood smears has been described by several reports. We studied the effects of T. marneffei in peripheral blood samples on complete blood count (CBC) using a Sysmex XN-9000 analyzer. METHODS: In a simulated T. marneffei infection model, blood samples with and without infectious diseases were selected, with high, medium, and low levels of white blood cell (WBC) and platelet (PLT) count, respectively. All samples were detected immediately and after a warm bath of 37℃ for 2 hours. RESULTS: WBC count of all samples was significantly increased by T. marneffei from a certain concentration and higher. For all samples, the effect of T. marneffei on WBC count after warm bath was significantly reduced compared to that on immediate WBC count from 4 - 6 x 109/L T. Marneffei and higher (p < 0.05). The presence of T. marneffei in all blood samples did not affect the results of PLT count. For all samples, the obvious effects of T. marneffei on WBC differential (WDF) and white cell nucleated red blood cell (WNR) scatter plots were from 4 - 6 x 109 T Marneffei and higher. CONCLUSIONS: As a kind of intracellular yeast, T. marneffei may affect WBC count, NRBC count, and WBC differential count of peripheral blood samples when the yeast concentration is (4 - 6) x 109 T Marneffei and higher. Moreover, the unique scatter plot cloud on WDF and WNR scatter plots caused by T. marneffei, may become an important clue pointing toward T. marneffei in peripheral blood.

Genome-wide identification and characterization of aquaporins in mangrove plant Kandelia obovata and its role in response to the intertidal environment.

Aquaporins (AQPs) play important roles in plant growth, development and tolerance to environmental stresses. To understand the role of AQPs in the mangrove plant Kandelia obovata, which has the ability to acquire water from seawater, we identified 34 AQPs in the K. obovata genome and analysed their structural features. Phylogenetic analysis revealed that KoAQPs are homologous to AQPs of Populus and Arabidopsis, which are evolutionarily conserved. The key amino acid residues were used to assess water-transport ability. Analysis of cis-acting elements in the promoters indicated that KoAQPs may be stress- and hormone-responsive. Subcellular localization of KoAQPs in yeast showed most KoAQPs function in the membrane system. That transgenic yeast with increased cell volume showed that some KoAQPs have significant water-transport activity, and the substrate sensitivity assay indicates that some KoAQPs can transport H2 O2 . The transcriptome data were used to analyze the expression patterns of KoAQPs in different tissues and developing fruits of K. obovata. In addition, real-time quantitative PCR analyses combined transcriptome data showed that KoAQPs have complex responses to environmental factors, including salinity, flooding and cold. Collectively, the transport of water and solutes by KoAQPs contributed to the adaptation of K. obovata to the coastal intertidal environment.

Immature Erythroid Precursors and/or Erythrocyte Dysplasia in Peripheral Blood.

BACKGROUND: With the progress of technology in automated hematology analyzers, in the vast majority of cases, nucleated red corpuscles (NRC) can be automatically identified by most types of automated hematology analyzers, thus correcting the leukocyte count and avoiding pseudoleukocytosis by the analyzers themselves. The objective of the study was to explore pseudoleukocytosis due to immature erythroid precursors and/or erythrocyte dysplasia in the peripheral blood resulting from different rare situations. METHODS: Four rare cases showing pseudoleukocytosis due to immature erythroid precursors and/or erythrocyte dysplasia in the peripheral blood were analyzed and the effects on complete blood count (CBC) performed on a Sysmex XN-2000 analyzer and microscopic morphological features of the peripheral blood were investigated. These cases were selected for their vital value in describing all pseudoleukocytosis due to immature erythroid pre-cursors and/or erythrocyte dysplasia in the peripheral blood. The causes of immature erythroid precursors and/or erythrocyte dysplasia in the peripheral blood were analyzed. RESULTS: In all these cases, proportions of NRC and leukocyte counts were affected to varying degrees by the presence of numerous immature erythroid precursors and/or obvious erythrocyte dysplasia in the peripheral blood. All cases associated with an alarm concerning NRC presentation, and abnormal scattergrams of WDF and WNR, thus leading to pseudoleukocytosis. CONCLUSIONS: Laboratory artifacts led by NRC may be an indicator towards the occurrence of numerous immature erythroid precursors and/or obvious erythrocyte dysplasia in the peripheral blood, and active extramedullary hematopoiesis, breakdown of the bone marrow barrier, and the stress response of acute bleeding and severe multiple infection.

Glutathione-Responsive Magnetic Nanoparticles for Highly Sensitive Diagnosis of Liver Metastases.

Liver metastasis (LM) occurs in various cancers, and its early and accurate diagnosis is of great importance. However, the detection of small LMs is still a great challenge because of the subtle differences between normal liver tissue and small metastases. Herein, we prepare glutathione (GSH)-responsive hyaluronic acid-coated iron oxide nanoparticles (HIONPs) for highly sensitive diagnosis of LMs through a facile one-pot method. HIONPs greatly enhance the signal of MRI in tumor metastases as T1 contrast agent (CA), whereas they substantially decrease the signal of liver as T2 CA as they aggregate into clusters upon the high GSH in liver. Consequently, MRI contrasted by HIONPs clearly distinguishes metastatic tumors (bright) from surrounding liver tissues (dark). HIONPs with superior LM contrasting capability and facile synthesis are very promising for clinical translation and indicate a new strategy to develop an ultrasensitive MRI CA for LM diagnosis that exploits high GSH level in the liver.

Evaluating the economic impacts of COVID-19 pandemic on shipping and port industry: A case study of the port of Shanghai.

The stability of shipping and port operations are crucial for international trade and global supply chain. However, the COVID-19 pandemic hit the shipping and port industry enormously in late 2019, and continues till now. It is important to identify the impacts of the pandemic on shipping and port operations and evaluate the potential economic impacts for better setting future development strategies and policies. A System Dynamics (SD) model is proposed to depict the impact transmission within the supply chain considering 5 sub-systems (shipping, port, transportation, manufacturing and social). Potential economic impacts which are represented by the shipping loss and port loss will be assessed. 6 scenarios with different epidemic durations and capacity recovery degrees have been set to investigate the economic impacts. The port of Shanghai, together with the container shipping business is selected as input for case study. Results indicate that in the first few months the port and carriers may suffer economic loss due to shrunken demand caused by COVID-19. But later carriers may enjoy an increase of income compared to non-pandemic scenario owing to strong recovery in most scenarios. Moreover, we found that manufacturing, transportation and port operation capacities would jointly affect the recovery process and economic impacts. The findings can facilitate policy makers in making port management and future industry development decisions.

Diffusion tensor imaging in evaluating testicular injury after unilateral testicular torsion and detorsion in rat model: A preliminary study.

Diffusion tensor imaging (DTI) is a functional magnetic resonance sequence based on the movement of water molecules. This study attempted to investigate the feasibility of DTI in evaluating testicular injury after testicular torsion and detorsion. Seventy-two rats were randomly divided into the sham group, torsion group and detorsion group. The left testis in the sham group was brought out through a scrotal incision for 1 hr, and that of the torsion group was twisted 720o clockwise for 1 hr and fixed to the scrotum, while the detorsion group was restored after being twisted 720° for 1 hr. Rats were further divided into four subgroups according to the set time, then performed DTI and histology analysis. The mean diffusion of the torsion and detorsion groups increased within 24 hr (p <.01), while it in the detorsion-1-week-group was lower than that in the detorsion-24-hr-group (p <.05). The fraction anisotropy of both experimental groups decreased in the acute phase (p <.01), while that of the detorsion-1-week-group increased (p <.01). Cosentino score in both experimental groups showed an increasing trend (p <.05). Besides, the spermatogenic ability of the detorsion-1-week-group decreased (p <.05). In conclusion, DTI was able to evaluate the injury after testicular torsion and detorsion.

Value of CT Imaging in the Differentiation of Gastric Leiomyoma From Gastric Stromal Tumor.

PURPOSE: To discuss significant computed tomography (CT) findings that differentiate gastric leiomyomas (GLs) from small gastric stromal tumors (GSTs). METHODS: One hundred sixty cases with pathologically proven GLs (n = 50) and GSTs (n = 110) with comprehensive CT images were enrolled in this retrospective study. Computed tomography findings (ie, size, location, contour, growth pattern, enhancement degree, necrosis, ulceration, calcification, and lymph nodes) were analyzed through the χ2 or Fisher exact test, independent T test, and multivariate (logistic regression) analysis. Sensitivity and specificity were also calculated. RESULTS: Features of cardia location, endophytic growth, homogeneous gradual enhancement, absent of necrosis, long diameter less than 24 mm, short diameter less than 20 mm, unenhanced CT value larger than 35.2 Hounsfield units (HU), portal venous phase CT value larger than 67.4 HU, and enhancement degree of arterial and venous phase less than 16.2 HU and 32.4 HU were found to be statistically significant between GLs and small GSTs (P < .05). On multivariate analysis, cardia location, endophytic growth, and homogeneous gradual enhancement were independent predictive factors for GLs and small GSTs. CONCLUSION: These 10 CT criteria are very helpful to differentiate GLs from small GSTs. Especially cardia location, endophytic growth, and homogeneous gradual enhancement are of high value in differential diagnosis.

Distinct genome-wide alternative polyadenylation during the response to silicon availability in the marine diatom Thalassiosira pseudonana.

The post-transcriptional regulation involved in the responses of diatoms to silicon is poorly understood. Using a poly(A)-tag sequencing (PAT-seq) technique that interrogates only the junctions of 3'-untranslated region (UTR) and the poly(A) tails at the transcriptome level, a comprehensive comparison of alternative polyadenylation (APA) was performed to understand the role of post-transcriptional regulation in various silicon-related cellular responses for the marine diatom Thalassiosira pseudonana. In total, 23 701 poly(A) clusters and 6894 APA genes, treated with silicon starvation and replenishment, were identified at nine time points. Significant APA was found in numerous genes (e.g. five cingulin genes) closely associated with the silicon-starvation response, girdle bands and valve synthesis, suggesting that many genes participated in the responses to silicon availability and biosilica formation through changes in transcript isoforms. The poly(A) site usage profiles were distinct during various stages of silicon biomineralization responses. Moreover, a correlation between APA and expression levels of APA switching genes was also discovered. This is an interesting study that presents a genome-wide profile of transcript ends in diatoms, which is distinct from that of higher plants, animals and other microalgae. This work provides an important resource to understand a different aspect of cell-wall synthesis.

Simple Analysis of the Computed Tomography Features of Gastric Schwannoma.

OBJECTIVE: The objective of this study was to assess the computed tomography (CT) findings of gastric schwannoma (GS) and identify the difference between large (> 5 cm) and small (≤ 5 cm) GS. MATERIALS AND METHODS: CT findings of 38 pathologically proven cases of GSs were retrospectively reviewed. The CT evaluation of GS included categorical variables (location, contour, growth pattern, enhancement pattern, necrosis, ulceration, calcification, and lymph nodes) and continuous variables (size, CT value of 3 phases, and enhancement degree). The lesion was divided into 2 groups (large [> 5 cm] and small [≤ 5 cm] GS) according to the tumor size. The Fisher exact test was used for categorical variables and the Student t or Mann-Whitney U test for continuous variables. RESULTS: Of the 38 patients, there were 32 women and 6 men. The median age was 54.5 years (range 39-79). Most of patients (65.8%, [25 of 38]) had nonspecific gastrointestinal symptoms such as abdominal or gastric pain, fullness and discomfort, bleeding, and melena. The tumors were mainly located in the stomach body (71.1% [27 of 38]), and the mean diameter was 3.7 cm (range 1.5 cm-10.3 cm), of which included large (> 5 cm) (n = 8) and small (≤ 5 cm) (n = 30). All of the GSs were benign, 9 of whom had palpable perigastric lymph nodes, which confirmed by pathology for the reactive inflammatory hyperplasia. Growth pattern, pattern of enhancement, necrosis, calcification, surface ulceration, and lymph node in the CT images were found to be significant variables for differentiating large (> 5 cm) and small (≤ 5 cm) GS (P < .05). CONCLUSION: GSs were predominantly located at the gastric body and occurred most frequently in women between the ages of 40-70 years, and showed gradual enhancement after contrast enhancement. Palpable perigastric lymph nodes could not be considered as malignant factor of GS. There 7 computed CT criteria are significant difference between large (> 5 cm) and small (≤ 5 cm) GS.

Transcriptional evidence for cross talk between JA and ET or SA during root-knot nematode invasion in tomato.

studies have demonstrated that jasmonic acid (JA) reduces root-knot nematode (RKN) infections in tomato plants. RKN invasion is sensed by roots, and root-derived JA signaling activates systemic defense responses, though this is poorly understood. Here, we investigate variations in the RKN-induced transcriptome in scion phloem between two tomato plant grafts: CM/CM ( Lycopersicum esculentum Mill. cv. Castlemart) and CM/ spr2 (a JA-deficient mutant). A total of 8,716 genes were differentially expressed in the scion phloem of the plants with JA-deficient rootstock via RNA sequencing. Among these genes, 535 upregulated and 153 downregulated genes with high copy numbers were identified as significantly differentially expressed. Among them, 34 predicted transcription factor genes were identified. Additionally, we used real-time quantitative PCR to analyze the expression patterns of 42 genes involved in the JA, ethylene, or salicylic acid pathway in phloem under RKN infection. The results suggested that in the absence of JA signaling, the ET signaling pathway is enhanced after RKN infection; however, alterations in the SA signaling pathway were not observed.

Patient and Family Member Factors Influencing Outcomes of Poststroke Inpatient Rehabilitation.

OBJECTIVE: To investigate how family members' attitudes toward functional regain, and patients' knowledge and intention of independence influence poststroke rehabilitation. DESIGN: Cross-sectional study. SETTING: Three rehabilitation inpatient settings. PARTICIPANTS: Younger (n=79) and older (n=84) poststroke patients, along with their family members (spouses, n=104; children, n=59). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Custom-designed questionnaires were used to tap into the patients' knowledge about rehabilitation (Patient's Rehabilitation Questionnaire-Knowledge About Rehabilitation) and intention of independence (Patient's Rehabilitation Questionnaire-Intention of Independence), and family members' attitudes toward patients in performing basic activities of daily living (BADL) (Family Member Attitudes Questionnaire-BADL) and instrumental activities of daily living (Family Member Attitudes Questionnaire-instrumental activities of daily living). The rehabilitation outcomes included gains in motor, cognitive, and emotional functions, and self-care independence, measured with common clinical instruments. RESULTS: The Family Member Attitudes Questionnaire-BADL predicted cognitive outcome and the Patient's Rehabilitation Questionnaire-Intention of Independence predicted motor outcome for both groups. Differential age-related effects were revealed for the Patient's Rehabilitation Questionnaire-Intention of Independence in predicting emotional outcome only for the younger group, and self-care independence only for the older group. CONCLUSIONS: Patients' intention of independence positively affected motor recovery, while family members' positive attitudes promoted cognitive regain. The findings suggested plausible age-related differences in how patients' intentions affect emotion versus self-care independence outcomes. Future studies should explore strategies for promoting positive attitudes toward independence among patients and family members during poststroke rehabilitation.

Gadolinium deposition in the liver and brain in a rat model with liver fibrosis after intravenous administration of gadoxetate disodium.

Objectives: To investigate gadolinium deposition in the liver and brain in a rat model with liver fibrosis (LF) after intravenous administration of gadoxetate disodium (GD) and the histological effects of gadolinium deposition in the liver and brain. Methods: Adult male Sprague-Dawley rats were randomly assigned to one of the three groups: 1) LF group received intraperitoneal injection of carbon tetrachloride (CCl4) for 9 weeks alone; 2) LF&GD group received CCl4 and intravenous administration of GD (for 5 consecutive days); 3) GD group received olive oil and GD. Seven days after the final injection of GD, the deep cerebellar nuclei (DCN) and liver were excised to determine gadolinium concentrations via inductively coupled plasma mass spectrometry, and histologic staining was performed. Bonferroni's post-hoc test and Wilcoxon rank sum test were used to compare the differences between the three groups. Results: The concentrations of retained gadolinium in the liver in the LF&GD group (2.18 ± 0.44 µg/g) were significantly greater compared to the LF group (0.02 ± 0.01 µg/g, P < 0.001) and GD group (0.37 ± 0.11 µg/g, P < 0.001). Also, the concentrations of retained gadolinium in DCN were increased in the LF&GD group (0.13 ± 0.06 µg/g) compared to the LF group (0.01 ± 0.00 µg/g, P < 0.001) and GD group (0.06 ± 0.02 µg/g, P = 0.019). No histopathological alterations were detected in the liver and DCN between LF&GD group and LF group. Conclusions: LF aggravated gadolinium deposition in the liver and DCN after administration of GD. However, no significant acute histological alterations were observed due to gadolinium deposition.

Integrin-Targeted Theranostic Nanoparticles for Clinical MRI-Traceable Treatment of Liver Fibrosis.

Liver fibrosis is the critical stage in the development of chronic liver disease (CLD), from simple injury to irreversible cirrhosis. Timely detection and intervention of liver fibrosis are crucial for preventing CLD from progressing into a fatal condition. Herein, we developed iron oxide (Fe3O4) nanoparticles (IONPs) and ferulic acid (FA) coencapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), followed by surface modification with cRGD peptides (cRGD-PLGA/IOFA) for integrin-targeted clinical magnetic resonance imaging (MRI)-traceable treatment of liver fibrosis. The cRGD peptide linked on the surface of the PLGA/IOFA NPs could specifically bind to the overexpressed integrin αvß3 on activated hepatic stellate cells (HSCs) in the fibrotic liver, enabling the high-sensitive clinical MR imaging (3 T) and precise staging of liver fibrosis. The FA encapsulated in cRGD-PLGA/IOFA showed excellent efficacy in reducing oxidative stress and inhibiting the activation of HSCs through the transforming growth factor-ß (TGF-ß)/Smad pathway. Notably, the IONPs encapsulated in cRGD-PLGA/IOFA NPs could alleviate liver fibrosis by regulating hepatic macrophages through the NF-κB pathway, lowering the proportion of Ly6Chigh/CD86+, and degrading collagen fibers. The FA and IONPs in the cRGD-PLGA/IOFA produced a synergistic enhancement effect on collagen degradation, which was more effective than the IONPs treatment alone. This study demonstrates that cRGD-PLGA/IOFA NPs could effectively relieve liver fibrosis by acting on macrophages and HSCs and provide a new strategy for the clinical MRI-traceable treatment of liver fibrosis.

Metagenomic insight of fluorene-boosted sludge acidogenic fermentation: Metabolic transformation of amino acids and monosaccharides.

Fluorene (Flu) occurs widely in various environments and its toxicity to organisms is well-known. However, the impact of Flu on complicated biochemical processes involving functional microbial community has been reported rarely. In this study, the facilitation of Flu on the volatile fatty acids (VFAs) generation executed by acidogenic microbial population during sludge acidogenic fermentation (37 °C, SRT = 8 d, pH = 10.0) was investigated. The accumulation of VFAs (particularly acetic acid) increased initially and then declined with the increasing of Flu concentration (0-500 mg/kg dry sludge), which reached a maximum (3211.1 mg COD/L) as Flu content was 200 mg/kg dry sludge. The Flu-enhanced VFAs production was primarily attributed to the shift of hydrolysis/acidification, as well as the corresponding functional microbial community and the activity of enzymes. Based on the metagenomics analysis, the conversion of organic substrates, i.e. amino acid and monosaccharide, into VFAs embraced in hydrolysis/acidification shaped by Flu was constructed at the genetic level. The relative abundances of genes included in aminotransfer and deamination process of amino acid and glycolysis of monosaccharide into VFA-precursors (pyruvate, acetyl-CoA and propionyl-CoA), and the further formation of VFAs were improved due to the Flu presence. This study shed light on the Flu-affected microbial processes at the molecular biology level during acidogenic fermentation and was of great significance in resource recovery of sludge containing persistent organic pollutants.

Supramolecular metal-organic frameworks as host-guest nanoplatforms for versatile and customizable biomedical applications.

Molecular imaging of disease with multifunctional nanoparticles has improved specificity and sensitivity but also raises the complexity, potential toxicity, and cost. Here, we show a facile and degradable self-assembly ß-cyclodextrin metal-organic framework (ß-CD-MOF) nanoplatform for customizable multifunctional imaging. These ß-CD-MOF nanoparticles were obtained with favorable morphology and size by controlling the degradation time. The ß-CD-MOF were used as nanoplatforms for facile functionalization with adamantane (Ad)-modified probes through host-guest interactions between the surface ß-CD units and Ad molecules. We demonstrated the method's feasibility and capability by developing various contrast agents for multiple biomedical imaging, including fluorescence imaging, magnetic resonance imaging (MRI), and computed tomography (CT) imaging. The nanoprobes showed superior performance compared to the corresponding small molecular probes, including better physio-chemical properties (e.g., about 5 times of T1 relaxivity for MRI, 1.2 times of Hounsfield units for CT), improved pharmacokinetics, effective tissue imaging capability, and low safety concerns. These ß-CD-MOF-based nanoparticles are promising host-guest nanoplatforms for developing multifunctional and safe imaging probes. STATEMENT OF SIGNIFICANCE: Molecular imaging of disease with multifunctional nanoparticles has improved specificity and sensitivity but also raises the complexity, potential toxicity, and cost. Here, we introduce facile and degradable self-assembly ß-cyclodextrin metal-organic framework (ß-CD-MOF) nanoplatforms for customizable multifunctional imaging. The significance of this work includes: 1) This work reports the tailoring of MOFs nanoparticles with suitable sizes and shapes for biomedical applications through controllable morphological transition and degradation; 2) The ß-CD-MOF-based host-guest nanoplatforms are facile and feasible for developing multifunctional nanoparticular contrast agents for effective tissue imaging; 3) The nanoparticular contrast agents show low safety concerns with a long-term tissue deposition similar to the small molecular probes.

Novel manganese and polyester dendrimer-based theranostic nanoparticles for MRI and breast cancer therapy.

Therapeutic nanoplatforms are widely used in the diagnosis and treatment of breast cancer due to the merits of enabling high soft-tissue resolution and the availability of numerous therapeutic nanoparticles. It is thus vital to develop multifunctional theranostic nanoparticles for the visualization and dynamic monitoring of tumor therapy. In this study, we designed a manganese-based and hypericin-loaded polyester dendrimer nanoparticle (MHD) for magnetic resonance imaging (MRI) and hypericin-based photodynamic therapy (PDT) enhancement. We found that MHD could greatly enhance MRI contrast with a longitudinal relaxivity of 5.8 mM-1 s-1 due to the Mn-based paramagnetic dendrimer carrier. Meanwhile, the MRI-guided PDT inhibition of breast tumors could be achieved by the hypericin-carrying MHD and further improved by Mn2+-mediated alleviation of the hypoxic microenvironment and the enhancement of cellular ROS. Besides, MHD showed excellent biocompatibility and biosafety with liver and kidney clearance mechanisms. Thus, the high efficiency in MRI contrast enhancement and excellent tumor-inhibiting effects indicate MHD's potential as a novel, stable, and multifunctional nanotheranostic agent for breast cancer.

Photodegradation of fleroxacin by g-C3N4/PPy/Ag and HPLC-MS/MS analysis of degradation pathways.

To improve the photocatalytic activity of g-C3N4, graphitic phase carbon nitride was prepared using melamine as the substrate and modified with PPy and Ag nanoparticles. The structure, morphology, and optical properties of the photocatalysts were investigated using various characterization methods such as XRD, FT-IR, TEM, XPS, and UV-vis DRS. The degradation of fleroxacin, a common quinolone antibiotic, was isolated and measured using the HPLC-MS/MS technique to trace its intermediates and deduce the main degradation pathways. The results showed that g-C3N4/PPy/Ag had high photocatalytic activity and a degradation rate of more than 90%. The fleroxacin degradation reactions were primarily oxidative ring opening of the N-methyl piperazine ring structure, defluorination reactions on fluoroethyl, HCHO, and N-methyl ethylamine removal reactions.

Single-Molecule Dendritic MRI Nanoprobes Reveal the Size-Dependent Tumor Entrance.

The tumor entrance of drug delivery systems, including therapeutic proteins and nanomedicine, plays an essential role in affecting the treatment outcome. Nanoparticle size is a critical but contradictory factor in making a trade-off among blood circulation, tumor accumulation, and penetration. Here, this work designs a series of single-molecule gadolinium (Gd)-based magnetic resonance imaging (MRI) nanoprobes with well-defined sizes to precisely explore the size-dependent tumor entrance in vivo. The MRI nanoprobes obtained by divergent synthesis contain a core molecule of macrocyclic Gd(III)-chelate and different layers of dendritic lysine units, mimicking globular protein. This work finds that the r1 relaxivity and MR imaging signals increase with the nanoparticle size. The nanoprobe with a lower limit of critical size threshold ≈8.0 nm achieves superior tumor accumulation and penetration. These single-molecule MRI nanoprobes can be served to precisely examine the size-related nanoparticle-biological interactions.