Anterior chamber and angle characteristics in Chinese children (6-11 years old) with different refractive status using swept-source optical coherence tomography.

BACKGROUND: The anatomic structure of the anterior chamber (AC) helps to explain differences in refractive status in school-aged children and is closely associated with primary angle closure (PAC). The aim of this study was to quantify and analyze the anterior chamber and angle (ACA) characteristics in Chinese children with different refractive status by swept-source optical coherence tomography (SS-OCT). METHODS: In a cross-sectional observational study, 383 children from two primary schools in Shandong Province, China, underwent a complete ophthalmic examination. First, the anterior chamber depth (ACD), anterior chamber width (ACW), angle-opening distance (AOD), and trabecular-iris space area (TISA) were evaluated automatically using a CASIA2 imaging device. AOD and TISA were measured at 500, 750 µm nasal (N1 and N2, respectively), and temporal (T1 and T2, respectively) to the scleral spur (SS). Cycloplegic refraction and axial length (AL) were then measured. According to spherical equivalent refraction (SER), the children were assigned to hyperopic (SER > 0.50D), emmetropic (-0.50D < SER ≤ 0.50D), and myopic groups (SER ≤ -0.50D). RESULTS: Out of the 383 children, 349 healthy children (160 girls) with a mean age of 8.23 ± 1.06 years (range: 6-11 years) were included. The mean SER and AL were - 0.10 ± 1.57D and 23.44 ± 0.95 mm, respectively. The mean ACD and ACW were 3.17 ± 0.24 mm and 11.69 ± 0.43 mm. The mean AOD were 0.72 ± 0.25, 0.63 ± 0.22 mm at N1, T1, and 0.98 ± 0.30, 0.84 ± 0.27 mm at N2, T2. The mean TISA were 0.24 ± 0.09, 0.22 ± 0.09mm2 at N1, T1, and 0.46 ± 0.16, 0.40 ± 0.14mm2 at N2, T2. The myopic group had the deepest AC and the widest angle. Compared with boys, girls had shorter AL, shallower ACD, narrower ACW, and ACA (all p < 0.05). By Pearson's correlation analysis, SER was negatively associated with ACD, AOD, and TISA. AL was positively associated with ACD, ACW, AOD, and TISA. In the multiple regression analysis, AOD and TISA were associated with deeper ACD, narrower ACW, and longer AL. CONCLUSION: In primary school students, the myopic eyes have deeper AC and wider angle. ACD, ACW, AOD, and TISA all increase with axial elongation. ACA is highly correlated with deeper ACD.

Disulfiram reduces the severity of mouse acute pancreatitis by inhibiting RIPK1-dependent acinar cell necrosis.

Acute pancreatitis (AP) is a frequent abdominal inflammatory disease. Despite the high morbidity and mortality, the management of AP remains unsatisfactory. Disulfiram (DSF) is an FDA-proved drug with potential therapeutic effects on inflammatory diseases. In this study, we aim to investigate the effect of DSF on pancreatic acinar cell necrosis, and to explore the underlying mechanisms. Cell necrosis was induced by sodium taurocholate or caerulein, AP mice model was induced by nine hourly injections of caerulein. Network pharmacology, molecular docking, and molecular dynamics simulation were used to explore the potential targets of DSF in protecting against cell necrosis. The results indicated that DSF significantly inhibited acinar cell necrosis as evidenced by a decreased ratio of necrotic cells in the pancreas. Network pharmacology, molecular docking, and molecular dynamics simulation identified RIPK1 as a potent target of DSF in protecting against acinar cell necrosis. qRT-PCR analysis revealed that DSF decreased the mRNA levels of RIPK1 in freshly isolated pancreatic acinar cells and the pancreas of AP mice. Western blot showed that DSF treatment decreased the expressions of RIPK1 and MLKL proteins. Moreover, DSF inhibited NF-κB activation in acini. It also decreased the protein expression of TLR4 and the formation of neutrophils extracellular traps (NETs) induced by damage-associated molecular patterns released by necrotic acinar cells. Collectively, DSF could ameliorate the severity of mouse acute pancreatitis by inhibiting RIPK-dependent acinar cell necrosis and the following formation of NETs.

A clinically feasible circulating tumor cell sorting system for monitoring the progression of advanced hepatocellular carcinoma.

BACKGROUND: Hematogenous metastasis is essential for the progression of advanced hepatocellular carcinoma (HCC) and can occur even after patients receive multidisciplinary therapies, including immunotherapy and hepatectomy; circulating tumor cells (CTCs) are one of the dominant components of the metastatic cascade. However, the CTC capture efficiency for HCC is low due to the low sensitivity of the detection method. In this study, epithelial cell adhesion molecule (EpCAM)/vimentin/Glypican-3 (GPC3) antibody-modified lipid magnetic spheres (LMS) were used to capture tumor cells with epithelial phenotype, mesenchymal phenotype and GPC3 phenotype, respectively, in order to capture more CTCs with a more comprehensive phenotype for monitoring tumor metastasis. RESULTS: The novel CTC detection system of Ep-LMS/Vi-LMS/GPC3-LMS was characterized by low toxicity, strong specificity (96.94%), high sensitivity (98.12%) and high capture efficiency (98.64%) in vitro. A sudden increase in CTC counts accompanied by the occurrence of lung metastasis was found in vivo, which was further validated by a clinical study. During follow-up, the rapid increase in CTCs predicted tumor progression in HCC patients. Additionally, genetic testing results showed common genetic alterations in primary tumors, CTCs and metastatic tissues. The proportion of patients predicted to benefit from immunotherapy with the CTC detection method was higher than that for the tissue detection method (76.47% vs. 41.18%, P = 0.037), guiding the application of clinical individualized therapy. CONCLUSIONS: The Ep-LMS/Vi-LMS/GPC3-LMS sequential CTC capture system is convenient and feasible for the clinical prediction of HCC progression. CTCs captured by this system could be used as a suitable alternative to HCC tissue detection in guiding immunotherapy, supporting the clinical application of CTC liquid biopsy.

An efficient method for identifying natural common homoisoflavonoid by 1H-NMR.

Homoisoflavone contains 16 carbon atoms in the skeleton. The homoisoflavonoid skeleton from natural products can be roughly divided into 13 kinds, among which 5 kinds of common skeletons contain a large amount of compounds and 8 kinds of abnormal skeletons comprise a small amount of compounds. In this article, the structure identification experience of homoisoflavonoids found in Caesalpinia mimosoides was used as references and an efficient 1H NMR spectroscopic method for identifying homoisoflavonoid structure has been established. Using the chemical shift differences of H-2, 3, 4 and 9, the common natural homoisoflavonoids can be quickly and conveniently determined.

Structural Analysis and Characterization of 4-F-α-PVP Analog 4-F-3-Methyl-α- PVP Hydrochloride.

OBJECTIVES: To identify 1-(4-fluorophenyl)-2-(1-pyrrolidinyl) pentan-1-one (4-F-α-PVP) analog 1-(4-fluoro-3-methyl phenyl)-2-(1-pyrrolidinyl) pentan-1-one (4-F-3-Methyl-α-PVP) hydrochloride without reference substance. METHODS: The direct-injection electron ionization-mass spectrometry (EI-MS), GC-MS, electrospray ionization-high resolution mass spectrometry (ESI-HRMS), ultra-high performance liquid chromatography-high resolution tandem mass spectrometry (UPLC-HRMS/MS), nuclear magnetic resonance (NMR), ion chromatography and Fourier transform infrared spectroscopy (FTIR) were integrated utilized to achieve the structural analysis and characterization of the unknown compound in the sample, and the cleavage mechanism of the fragment ions was deduced by EI-MS and UPLC-HRMS/MS. RESULTS: By analyzing the direct-injection EI-MS, GC-MS, ESI-HRMS and UPLC-HRMS/MS of the compound in the samples, it was concluded that the unknown compound was a structural analog of 4-F-α-PVP, possibly with one more methyl group in the benzene ring. According to the analysis results of 1H-NMR and 13C-NMR, it was further proved that the methyl group is located at the 3-position of the benzene ring. Since the actual number of hydrogen in 1H-NMR analysis was one more than 4-F-3-Methyl-α-PVP neutral molecule, it was inferred that the compound existed in the form of salt. Ion chromatography analysis results showed that the compound contained chlorine anion (content 11.14%-11.16%), with the structural analysis of main functional group information by FTIR, the unknown compound was finally determined to be 4-F-3-Methyl-α-PVP hydrochloride. CONCLUSIONS: A comprehensive method using EI-MS, GC-MS, ESI-HRMS, UPLC-HRMS/MS, NMR, ion chromatography and FTIR to identify 4-F-3-Methyl-α-PVP hydrochloride in samples is established, which will be helpful for the forensic science laboratory to identify this compound or other analog compounds.

Transcriptome and metabolome reveal the accumulation of secondary metabolites in different varieties of Cinnamomum longepaniculatum.

BACKGROUND: Cinnamomum longepaniculatum (Gamble) N. Chao ex H. W. Li, whose leaves produce essential oils, is a traditional Chinese medicine and economically important tree species. In our study, two C. longepaniculatum varieties that have significantly different essential oil contents and leaf phenotypes were selected as the materials to investigate secondary metabolism. RESULT: The essential oil content and leaf phenotypes were different between the two varieties. When the results of both transcriptome and metabolomic analyses were combined, it was found that the differences were related to phenylalanine metabolic pathways, particularly the metabolism of flavonoids and terpenoids. The transcriptome results based on KEGG pathway enrichment analysis showed that pathways involving phenylpropanoids, tryptophan biosynthesis and terpenoids significantly differed between the two varieties; 11 DEGs (2 upregulated and 9 downregulated) were associated with the biosynthesis of other secondary metabolites, and 12 DEGs (2 upregulated and 10 downregulated) were related to the metabolism of terpenoids and polyketides. Through further analysis of the leaves, we detected 196 metabolites in C. longepaniculatum. The abundance of 49 (26 downregulated and 23 upregulated) metabolites differed between the two varieties, which is likely related to the differences in the accumulation of these metabolites. We identified 12 flavonoids, 8 terpenoids and 8 alkaloids and identified 4 kinds of PMFs from the leaves of C. longepaniculatum. CONCLUSIONS: The combined results of transcriptome and metabolomic analyses revealed a strong correlation between metabolite contents and gene expression. We speculate that light leads to differences in the secondary metabolism and phenotypes of leaves of different varieties of C. longepaniculatum. This research provides data for secondary metabolite studies and lays a solid foundation for breeding ideal C. longepaniculatum plants.

Coactivation of NF-κB and Notch signaling is sufficient to induce B-cell transformation and enables B-myeloid conversion.

NF-κB and Notch signaling can be simultaneously activated in a variety of B-cell lymphomas. Patients with B-cell lymphoma occasionally develop clonally related myeloid tumors with poor prognosis. Whether concurrent activation of both pathways is sufficient to induce B-cell transformation and whether the signaling initiates B-myeloid conversion in a pathological context are largely unknown. Here, we provide genetic evidence that concurrent activation of NF-κB and Notch signaling in committed B cells is sufficient to induce B-cell lymphomatous transformation and primes common progenitor cells to convert to myeloid lineage through dedifferentiation, not transdifferentiation. Intriguingly, the converted myeloid cells can further transform, albeit at low frequency, into myeloid leukemia. Mechanistically, coactivation of NF-κB and Notch signaling endows committed B cells with the ability to self renew. Downregulation of BACH2, a lymphoma and myeloid gene suppressor, but not upregulation of CEBPα and/or downregulation of B-cell transcription factors, is an early event in both B-cell transformation and myeloid conversion. Interestingly, a DNA hypomethylating drug not only effectively eliminated the converted myeloid leukemia cells, but also restored the expression of green fluorescent protein, which had been lost in converted myeloid leukemia cells. Collectively, our results suggest that targeting NF-κB and Notch signaling will not only improve lymphoma treatment, but also prevent the lymphoma-to-myeloid tumor conversion. Importantly, DNA hypomethylating drugs might efficiently treat these converted myeloid neoplasms.

Programmable patterning fabrication of laser-induced graphene-MXene composite electrodes for flexible planar supercapacitors.

The development of laser-induced graphene (LIG) has been regarded as an effective method for satisfying the substantial requirements for the scalable fabrication of graphene-based electrode materials. Despite the rapid progress in fabricating LIG-based supercapacitors, the incompatibility between material modification and the device planarization process remains a challenging problem to be resolved. In this study, we demonstrate the attributes of novel LIG-MXene (LIG-M) composite electrodes for flexible planar supercapacitors fabricated by direct laser writing (DLW) of MXene-coated polyimide (PI) films. During the DLW process, PI was transformed into LIG, while MXene was simultaneously introduced to produce LIG-M. Combining the porous structure of LIG and the high conductivity of MXene, the as-prepared LIG-M-based supercapacitor exhibited superior specific capacitance, five times higher than that of the pristine LIG-based supercapacitor. The enhanced capacitance of LIG-M also benefited from the pseudocapacitive performance of the abundant active sites offered by MXene. Moreover, the planar LIG-M-based device delivered excellent cycling stability and flexibility. No significant performance degradation was observed after bending tests. Arbitrary electrode patterns could be obtained using the DLW technique. The patterned in-series LIG-M supercapacitor was able to power a light-emitting diode, demonstrating significant potential for practical applications.

124I-Labeled Monoclonal Antibody and Fragment for the Noninvasive Evaluation of Tumor PD-L1 Expression In Vivo.

Lung cancer is a highly heterogeneous cancer and is divided broadly into small and nonsmall cell lung cancer (SCLC or NSCLC). In all NSCLC patients, it is estimated that 50%-60% are programmed cell death ligand 1 (PD-L1) positive, and anti-PD-1/PD-L1 therapies have shown their clinical application prospects in advanced NSCLC. To avoid unnecessary adverse effects and provide anti-PD-1/PD-L1 therapy to the most appropriate patient population, the PD-L1 expression in patients preparing for treatment must be evaluated accurately and in real time. In this study, we noninvasively evaluate the PD-L1 expression in an NSCLC xenograft using 124I-labeled F(ab')2 fragments of durvalumab (Durva) and compared it with the 124I-labeled intact antibody in terms of the biodistribution and dosimetry. The aim is to develop a nuclide labeled molecular probe with better performance for PD-L1 immunoPET imaging. After cleaving using IdeS protease, the F(ab')2 fragments of Durva were labeled with 124I. The radioligand showed a high radiochemical purity (>96%) and outstanding stability. Western blot, quantitative real-time polymerase chain reaction, and flow cytometry were performed on the two selected NSCLC cell lines to measure the in vitro PD-L1 expression. The H460 cells showed a much higher PD-L1 expression than the A549 cells, both at the protein level and the mRNA level. In the following cell binding experiment and binding specificity assay, the labeled radioligand showed good affinity to high PD-L1 expression cells and could be blocked with excess unlabeled intact Durva. The results of the biodistribution and the positron emission tomography (PET) image showed that the peak tumor uptake of 124I-Durva-F(ab')2 was close to 124I-Durva, but much earlier (5.29 ± 0.42% ID/g for 124I-Durva-F(ab')2 at 12 h vs 5.18 ± 0.73% ID/g for 124I-Durva at 48 h). Compared with 124I-Durva, an accelerated blood clearance was observed for 124I-Durva-F(ab')2. The faster blood clearance allowed for a higher tumor-to-background ratio, which was reflected on the image in contrast. The H460 tumors showed excellent contrast as early as 4 h after injection with 124I-Durva-F(ab')2, and for 124I-Durva, the xenograft could not be distinguished clearly until 24 h after injection. Interestingly, 124I-Durva-F(ab')2 showed lower accumulations compared to other metal isotopes labeled PD-L1 antibodies in bone, liver, spleen etc., which will be beneficial for metastasis detection. Another benefit of accelerated blood clearance was a reduction in the radiation dose. According to the results of the OLINDA/EXM, the effective dose for the total body of 124I-Durva was 4.25-times greater than that of 124I-Durva-F(ab')2 (186 µSv/MBq vs 43.8 µSv/MBq). All of these data indicated that 124I-Durva-F(ab')2 is a promising immunoPET tracer for evaluating the in vivo PD-L1 levels in an NSCLC model and is expected to be successful in future clinical application.

Role of 18F-FDG PET/CT imaging in cardiac and pericardial masses.

BACKGROUND: Considering the few reported cardiac masses, PET/CT in the imaging workup of cardiac masses is not well established. This retrospective study analyzed the role of 18F-FDG PET/CT imaging in cardiac/pericardial masses. METHODS AND RESULTS: Fifty-nine patients with newly diagnosed cardiac/pericardial masses who underwent PET/CT and transthoracic echocardiography (TTE) were recruited. Echocardiographic and PET/CT characteristics were evaluated for predictive value in differentiating malignant and non-malignant lesions using histologic confirmation as the gold standard. The McNemar test was used to test the differences in sensitivity between PET/CT and TTE. 18F-FDG PET/CT had higher sensitivity in determining the malignancy of cardiac/pericardial masses compared to TTE (sensitivity, 96.6% vs 72.4%, P = .039). However, when pericardial masses were excluded from the analysis, the difference in sensitivity between the two was not statistically significant (sensitivity, 95.6% vs 78.3%, P = .219). 18F-FDG PET/CT identified two malignant pericardial masses missed on TTE, changed the diagnostic orientation of TTE in 15 patients, and found seven patients with extracardiac lesions in 29 malignant patients. CONCLUSIONS: PET/CT was an effective additional image modality in patients with suspected malignant cardiac mass for further confirmation and to screen for potential metastasis.

Coordination-Assembly of Lanthanide Supramolecular Hydrogels with Luminescent Multi-stimulus Response.

Luminescent supramolecular hydrogels have shown extensive potential for a variety of applications due to their unique optical properties and biocompatibility. Coordination self-assembly provides a promising strategy for the preparation of supramolecular hydrogels. In this contribution, a series of luminescent lanthanide (Ln) supramolecular hydrogels HG-Ln2nL3n1/2 are synthesized by coordination self-assembly of Ln ions and V shaped bis-tetradentate ligands (H4L1 and H4L2) with different bent angles (∠B). Two rigid conjugated ligands H4L1 and H4L2 with bent angles (∠B ≈ 150°) featuring a 2,6-pyridine bitetrazolate chelating moiety were designed and synthesized, which generated hydrogels via the deprotonation self-assembly with lanthanide ions. Characteristic Eu3+ and Yb3+ emissions were realized in the corresponding hydrogels, with intriguing multi-stimulus response behaviors. The luminescence of the HG-Eu2nL3n1 hydrogel can be enhanced or quenched when stimulated by diverse metal ions, attributed to the replacement of the coordinated lanthanide ions and changes in the intersystem crossing efficiency of the ligand. Furthermore, pH-responsive emission of the HG-Eu2nL3n1 hydrogel has also been observed. Our work provides potential strategies for the design of next-generation smart responsive hydrogel materials with variable structures.

Particle electrode materials dependent tetrabromobisphenol A degradation in three-dimensional biofilm electrode reactors.

The completely biological degradation of Tetrabromobisphenol A (TBBPA) contaminant is challenging. Bio-electrochemical systems are efficient to promote electrons transfer between microbes and pollutants to improve the degradation of refractory contaminants. In particular, three-dimensional biofilm electrode reactors (3DBERs), integrating the biofilm with particle electrodes, represent a novel bio-electrochemical technology with superior treatment performances. In this study, the electroactive biofilm is cultured and acclimated on two types of particle electrodes, granular activated carbon (GAC) and granular zeolite (GZ), to degrade the target pollutant TBBPA in 3DBERs. Compared to GZ, GAC materials are more favorable for biofilm formation in terms of high specific surface area and good conductivity. The genus of Thauera is efficiently enriched on both GAC and GZ particles, whose growth is promoted by the electricity. By applying 5 V voltage, TBBPA can be removed by over 95% in 120 min whether packing GAC or GZ particle electrodes in 3DBERs. The synergy of electricity and biofilm in TBBPA degradation was more significant in GAC packed 3DBER, because the improved microbial activity by electrical stimulation accelerates debromination rate and hence the decomposition of TBBPA. Applying electricity also promotes TBBPA degradation in GZ packed 3DBER mainly due to the enhanced electrochemical effects. Roles of particle electrode materials in TBBPA removal are distinguished in this work, bringing new insights into refractory wastewater treatment by 3DBERs.

Down-regulation of lncRNA CASC9 aggravates sepsis-induced acute lung injury by regulating miR-195-5p/PDK4 axis.

BACKGROUND: Long non-coding RNA (lncRNA) cancer susceptibility candidate 9 (CASC9) is reported to be linked to cancers. This research aims to explore the role and possible mechanism of CASC9 in lung injury induced by sepsis. METHODS: Lipopolysaccharide (LPS) induced human small airway epithelial cells (HSAECs) were established in vitro to mimic sepsis-induced lung injury. The effects of CASC9 and miR-195-5p on HSAECs viability were studied by CCK-8 assay. Interactions between CASC9 and miR-195-5p were determined by bioinformatics analysis, RT-PCR, dual luciferase reporter assay, and RNA immunoprecipitation assay. Pyruvate dehydrogenase kinase 4 (PDK4) and apoptosis-related molecules including Bcl2 and Bad were detected by western blot. Additionally, sepsis-induced lung injury model in rats was established by intraperitoneal injection of LPS in vivo to validate the demonstrations of in vitro studies. RESULTS: CASC9 was markedly down-regulated while miR-195-5p was significantly up-regulated in HSAECs treated by LPS and lung tissues of rats with sepsis. CASC9 interacted with miR-195-5p, and negatively regulated its expression level. Overexpression of CASC9 or transfection of miR-195-5p inhibitors significantly promoted the viability of HSAECs. The transfection of miR-195-5p mimics effected oppositely. For mechanism, miR-195-5p targeted the 3'UTR of pyruvate dehydrogenase kinase 4 (PDK4) gene and depressed the protein level, and PDK4 was regulated indirectly by CASC9. Restoration of CASC9 in the lung tissues of rats with sepsis ameliorated lung injury. CONCLUSION: CASC9 protects lung epithelial cells from sepsis-induced injury via regulating miR-195-5p/PDK4 axis.

A pilot-scale three-dimensional electrochemical reactor combined with anaerobic-anoxic-oxic system for advanced treatment of coking wastewater.

Coking wastewater is highly concentrated and extremely toxic, greatly challenging the treatment technologies. Conventional biological technology such as anaerobic-anoxic-oxic (A2O) system is inefficient, since various biological reactions are inhibited by toxicants in coking wastewater. In this work, a pilot-scale three-dimensional electrochemical reactor (3DER) is integrated into the A2O system as a pretreatment unit to improve the treatment efficiency of coking wastewater. The results indicate that 3DER pretreatment increased the biodegradability of coking wastewater, promoting the degradation of coking wastewater in A2O system. The integrated 3DER-A2O system can remove 94.4% of COD and 76.2% of TN from coking wastewater, and the energy consumption was only 0.22 kWh/kg COD and 4.69 kWh/kg TN. The components of coking wastewater were significantly simplified and the acute toxicity was reduced from 99% to 12% after the treatment. The integrated 3DER-A2O system provides a new solution for coking wastewater treatment, showing a promising application potential.

[Cloning of AhWRKY33 from Asarum heterotropoides and its genetic transformation in Arabidopsis].

The WRKY family genes, which play an important role in plant morphogenesis and stress response, were selected based on the data of the full-length transcriptome of Asarum heterotropoides. Using AtWRKY33, which regulates the synthesis of the camalexin in the model plant Arabidopsis to compare homologous genes in A. heterotropoides, primers were designed to amplify the open reading frame(ORF) fragment of AhWRKY33 gene by RT-PCR using total RNA of A. heterotropoides leaves as template. Real-time PCR results showed that there was a significant difference between the aerial part and the underground part of A. heterotropoides, the toxic aristolochic acid content is highly expressed in the leaves higher than the root. After verification, the WRKY33 gene of A. heterotropoides is ORF long 1 686 bp, encoding 561 amino acids.AhWRKY33 had two conserved WRKYGQK domains. According to the classical classification, it belongs to group Ⅰ WRKY transcription factor. A. heterotropoides WRKY33 had some homology with amino acids of other species. The study successfully constructed the plant eukaryotic expression vector PHG-AhWRKY33 and transformed Arabidopsis thaliana, the transgenic Arabidopsis was obtained by PCR detection and hygromycin resistant plate screening. It found that the germination of transgenic Arabidopsis seeds was accelerated and the stress resistance was increased. It laid a foundation for further analysis of WRKY transcription factor in the growth and development of A. heterotropoides and the synthesis of secondary metabolites.

Programmable Self-Assembly of Protein-Scaffolded DNA Nanohydrogels for Tumor-Targeted Imaging and Therapy.

DNA hydrogels are biocompatible and are suitable for many biomedical applications. However, to be useful imaging probes or drug carriers, the ordinary bulk size of DNA hydrogels must be overcome. Here we put forward a new strategy for fabricating a novel and simple protein-scaffolded DNA nanohydrogel, constructed through a direct DNA self-assembly using three types of streptavidin (SA)-based DNA tetrad for the activation of imaging and targeting therapy of cancer cells. The DNA nanohydrogels are easily prepared, and we show that by varying the initial concentration of DNA tetrad, it is possible to finely control their size within nanoscale range, which are favorable as carriers for intracellular imaging and transport. By further incorporating therapeutic agents and tumor-targeting MUC1 aptamer, these multifunctionalized SA-scaffolded DNA nanohydrogels (SDH) can specifically target cancer cells and selectively release the preloaded therapeutic agents via a structure switching when in an ATP-rich intracellular environment, leading to the activation of the fluorescence and efficient treatment of cancer cells. With the advantages of facile modular design and assembly, effective cellular uptake, and excellent biocompatibility, the method reported here has the potential for the development of new tunable DNA nanohydrogels with multiple synergistic functionalities for biological and biomedical applications.

Thrombophilia risk is not increased in children after perinatal stroke.

Perinatal stroke causes cerebral palsy and lifelong disability. Specific diseases are definable, but mechanisms are poorly understood. Evidence suggests possible associations between arterial perinatal stroke and prothrombotic disorders, but population-based, controlled, disease-specific studies are limited. Understanding thrombophilia in perinatal stroke informs pathogenesis models and clinical management. We conducted a population-based, prospective, case-control study to determine the association of specific perinatal stroke diseases with known thrombophilias. Children with idiopathic magnetic resonance imaging-classified neonatal arterial ischemic stroke (NAIS), arterial presumed perinatal ischemic stroke (APPIS), or fetal periventricular venous infarction (PVI) were recruited. Standardized thrombophilia evaluations were performed after 12 months of age on stroke cases and controls, including quantified proteins C and S, antithrombin, factors VIII/IX/XI, fibrinogen, lipoprotein(a), homocysteine, lupus anticoagulant, anticardiolipin antibodies and genotyping of factor V Leiden (FVL), factor II G20210A (FII), and methylenetetrahydrofolate reductase C677T. A total of 212 children were studied: 46 with NAIS, 34 with APPIS, 55 with PVI, and 77 controls (male, 53%; median age, 4.8 years). Of 14 parameters, no differences were observed in 12, including all common thrombophilias. Mean prothrombin time was shorter in arterial strokes (P < .001). Rates of antiphospholipid antibodies were low, comparable to those in controls, and resolved on repeat testing. FVL and FII rates were comparable to population norms. Total number of possible abnormalities did not differ between cases and controls. Our prospective, population-based, controlled, disease-specific study suggests minimal association between perinatal stroke and thrombophilia. This does not exclude the possibility of disordered coagulation at the time of stroke but suggests testing in childhood is not indicated.

Hierarchically structuring and synchronous photoreduction of graphene oxide films by laser holography for supercapacitors.

Herein, we report a simple laser holography technology for hierarchically structuring and synchronous photoreduction of graphene oxides (GO), toward the development of efficient graphene-based electrodes for supercapacitor applications in cost effectively manners. Hierarchical micro-nanostructures, formed due to laser treatment induced photoreduction and ablation effect. Interestingly, both the morphology and reduction degree of the laser holography reduced GO (LHRGO) show strong dependence on the laser intensity, providing the feasibility for controlling the micro-nanostructures, chemical composition, and the conductivity of the graphene electrodes. Furthermore, the supercapacitors based on LHRGO show higher capacitance values and better electrochemical performance compared to that based on thermal reduced GO (TRGO) of same reduction level. Photoredution and micro-nanostructuring of GO using laser holography may hold great promise for production of effective carbon-based electrodes towards practical applications in energy storage devices.

Systematic analysis of gene expression profiles reveals prognostic stratification and underlying mechanisms for muscle-invasive bladder cancer.

BACKGROUND: Muscle-invasive bladder cancer (MIBC) is originated in the muscle wall of the bladder, and is the ninth most common malignancy worldwide. However, there are no reliable, accurate and robust gene signatures for MIBC prognosis prediction, which is of the importance in assisting oncologists to make a more accurate evaluation in clinical practice. METHODS: This study used univariable and multivariable Cox regression models to select gene signatures and build risk prediction model, respectively. The t-test and fold change methods were used to perform the differential expression analysis. The hypergeometric test was used to test the enrichment of the differentially expressed genes in GO terms or KEGG pathways. RESULTS: In the present study, we identified three prognostic genes, KLK6, TNS1, and TRIM56, as the best subset of genes for muscle-invasive bladder cancer (MIBC) risk prediction. The validation of this stratification method on two datasets demonstrated that the stratified patients exhibited significant difference in overall survival, and our stratification was superior to three other stratifications. Consistently, the high-risk group exhibited worse prognosis than low-risk group in samples with and without lymph node metastasis, distant metastasis, and radiation treatment. Moreover, the upregulated genes in high-risk MIBC were significantly enriched in several cancer-related pathways. Notably, PDGFRB, a receptor for platelet-derived growth factor of PI3K-Akt signaling pathway, and TUBA1A were identified as two targets of multiple drugs. In addition, the angiogenesis-related genes, as well as two marker genes of M2 macrophage, CD163 and MRC1, were highly upregulated in high-risk MIBC. CONCLUSIONS: In summary, this study investigated the underlying molecular mechanism and potential therapeutic targets associated with worse prognosis of high-risk MIBC, which could improve our understanding of progression of MIBC and provide new therapeutic strategies for the MIBC patients.