Combination of PEGylation and Cationization on Phospholipid-Coated Cyclosporine Nanosuspensions for Enhanced Ocular Drug Delivery.

Strong precorneal clearance mechanisms including reflex blink, constant tear drainage, and rapid mucus turnover constitute great challenges for eye drops for effective drug delivery to the ocular epithelium. In this study, cyclosporine A (CsA) for the treatment of dry eye disease (DED) was selected as the model drug. Two strategies, PEGylation for mucus penetration and cationization for potent cellular uptake, were combined to construct a novel CsA nanosuspension (NS@lipid-PEG/CKC) by coating nanoscale drug particles with a mixture of lipids, DSPE-PEG2000, and a cationic surfactant, cetalkonium chloride (CKC). NS@lipid-PEG/CKC with the mean size ∼173 nm and positive zeta potential ∼+40 mV showed promoted mucus penetration, good cytocompatibility, more cellular uptake, and prolonged precorneal retention without obvious ocular irritation. More importantly, NS@lipid-PEG/CKC recovered tear production and goblet cell density more efficiently than the commercial cationic nanoemulsion on a dry eye disease rat model. All results indicated that a combination of PEGylation and cationization might provide a promising strategy to coordinate mucus penetration and cellular uptake for enhanced drug delivery to the ocular epithelium for nanomedicine-based eye drops.

Construction of Ag-TiO2 Hierarchical Micro-/Nanostructures on a Ti Plate for Photocatalysts via Femtosecond Laser Hybrid Technology.

Titanium dioxide photocatalysts can break down pollutants using natural light. They possess notable light stability, chemical stability, and catalytic effects, thus leading to extensive research worldwide. However, the limited light absorption range of titanium dioxide and their inefficiencies in generating and transporting photogenerated carriers hinder the enhancement of their photocatalytic performance. In this study, we employ a femtosecond laser composite processing method to create an Ag-TiO2 nanoplate composite catalyst. This method doubles the catalytic efficiency compared with the structure processed solely with the femtosecond laser. The resulting Ag-TiO2 nanoplate composite catalysts show significant promise for addressing environmental and energy challenges, including the photodegradation of organic pollutants.

Quantitative and biosafe modification of bifunctional groups onto carbon dots by click chemistry.

Surface functionalization can effectively affect the properties of carbon dots (CDs), for example, improved solubility and dispersibility as well as enhanced selectivity and sensitivity. However, it is still a challenging task to tailor one or more specific functionalities of CDs via precise surface modification. In this study, click chemistry is applied to engineer CD surface functionalization, where the fluorescent molecule Rhodamine B (RhB) can be efficiently grafted onto the glucose-based bare CDs. The reaction process is quantitatively analyzed, which provides the basic theory for the functionalization of glucose-based CDs by double fluorescent molecules, namely RhB and Cy7. The fluorescence behavior of CDs can be accurately regulated by adjusting the molar ratio of the two molecules. The results of cell proliferation and apoptosis behavior of functionalized carbon dots show that the linkers (triazole structure) introduced by click chemistry have good biocompatibility. This quantitative and multifunctional modification method of CDs has undoubtedly greatly expanded its application field, especially in biological and medical aspects.

Predictive value of white blood cell to hemoglobin ratio for 30-day mortality in patients with severe intracerebral hemorrhage.

Aim: To explore the predictive value of white blood cell to hemoglobin ratio (WHR) for 30-day mortality in patients with intracerebral hemorrhage (ICH). Methods: In this cohort study, 2,848 patients with ICH were identified in the Medical Information Mart for Intensive Care (MIMIC)-III and MIMIC-IV. Least absolute shrinkage and selection operator (LASSO) regression screened covariates of 30-day mortality of ICH patients. COX regression analysis was used to study the association of different levels of WHR, white blood cell (WBC), and hemoglobin (Hb) with 30-day mortality. The median follow-up time was 30 (20.28, 30.00) days. Results: In total, 2,068 participants survived at the end of the follow-up. WHR was negatively correlated with the Glasgow Coma Score (GCS) (spearman correlation coefficient = -0.143, p < 0.001), and positively associated with the Sepsis-related Organ Failure Assessment (SOFA) score (spearman correlation coefficient = 0.156, p < 0.001), quick SOFA (qSOFA) score (spearman correlation coefficient = 0.156, p < 0.001), and Simplified Acute Physiology Score II (SAPS-II) (spearman correlation coefficient = 0.213, p < 0.001). After adjusting for confounders, WHR >0.833 (HR = 1.64, 95%CI: 1.39-1.92) and WBC >10.9 K/uL (HR = 1.49, 95%CI: 1.28-1.73) were associated with increased risk of 30-day mortality of patients with ICH. The area under the curve (AUC) value of the prediction model based on WHR and other predictors was 0.78 (95%CI: 0.77-0.79), which was higher than SAPSII (AUC = 0.75, 95%CI: 0.74-0.76), SOFA score (AUC = 0.69, 95%CI: 0.68-0.70) and GCS (AUC = 0.59, 95%CI: 0.57-0.60). Conclusion: The level of WHR was associated with 30-day mortality in patients with severe ICH, and the WHR-based prediction model might provide a tool to quickly predict 30-day mortality in patients with ICH.

Flexible Piezoelectric and Pyroelectric Nanogenerators Based on PAN/TMAB Nanocomposite Fiber Mats for Self-Power Multifunctional Sensors.

Self-powered wearable electronics to convert mechanical and thermal energy into electrical energy are important for biomedical monitoring, which highly require good flexibility, comfortability, signal sensitivity, and accuracy. In this work, composite nanofiber mats of polyacrylonitrile (PAN) and trimethylamine borane (TMAB) were prepared by electrospinning, which exhibited excellent piezoelectric and pyroelectric abilities in harvesting mechanical and thermal energy. The PAN/TMAB-4 nanofiber mats not only generated a high voltage of up to 2.56 V and a high power of 0.19 µW upon shape deformation but also exhibited linear voltage response to thermal gradient. The hybrid piezoelectric and pyroelectric output signals were successfully integrated together and have been applied to precisely monitor human vital signs, including elbow bending angles, foot posture, and breathing status, in real time by attaching the flexible sensors to proper human body parts. Overall, good flexibility, bifunctional sensing ability, and self-power make PAN-/TMAB-type sensors very attractive in fabricating high-performance electronics for detecting motion, monitoring health, and making portable microelectronics.

Trigone ventricular glioblastoma multiforme with trapped temporal horn: A case report.

Background: Intraventricular glioblastoma multiforme (GBM) is extremely rare, especially in the trigone region. This report presents a case of trigone ventricular GBM with trapped temporal horn (TTH). Case presentation: A 59-year-old woman was admitted to our department with a 1-month history of rapidly progressive headache, nausea, and weakness in the right lower extremity. Head non-contrast computed tomography and enhanced magnetic resonance imaging (MRI) revealed a trigone ventricular mass lesion with TTH and heterogeneous enhancement. The lesion was found 18 months ago as a small asymptomatic tumor mimicking ependymoma. This neoplasm was removed subtotally through the right parieto-occipital approach guided by neuroendoscopy. A ventriculoperitoneal shunt was subsequently performed to relieve TTH. The final pathological diagnosis was GBM. Unfortunately, 36 days after the first surgery, the patient died due to her family's decision to refuse therapy. Conclusion: This rare case shows that GBM should be considered in the differential diagnosis of trigonal tumors. In this case, the tumor possibly originated from the neural stem cells in the subventricular zone. Patients with intraventricular GBM have a worse prognosis, and careful follow-up and early surgery for small intraventricular tumors are necessary, even for those with ependymoma-like radiological findings.

Discovery of Chitin Deacetylase Inhibitors through Structure-Based Virtual Screening and Biological Assays.

Chitin deacetylase (CDA) inhibitors were developed as novel antifungal agents because CDA participates in critical fungal physiological and metabolic processes and increases virulence in soilborne fungal pathogens. However, few CDA inhibitors have been reported. In this study, 150 candidate CDA inhibitors were selected from the commercial Chemdiv compound library through structure-based virtual screening. The top-ranked 25 compounds were further evaluated for biological activity. The compound J075-4187 had an IC50 of 4.24 ± 0.16 µM for AnCDA. Molecular docking calculations predicted that compound J075-4187 binds to the amino acid residues, including active sites (H101, D48). Furthermore, compound J075-4187 inhibited food spoilage fungi and plant pathogenic fungi, with minimum inhibitory concentration (MIC) at 260 µg/ml and minimum fungicidal concentration (MFC) at 520 µg/ml. Therefore, compound J075-4187 is a good candidate for use in developing antifungal agents for fungi control.

Dispersion-assisted tunable fluorescence from carbon dots.

In this study, carbon dots (CDs) synthesized by hydrothermal method with amino-rich surface exhibit tunable fluorescence across entire visible range by simply controlling the concentration. A comprehensive comparison has been performed for the first time between concentration-induced aggregation of the single-type CDs and electrostatic-induced agglomeration of opposite-charged CDs in terms of their fluorescence properties. Experimental results show that both the aggregation of CDs and internal absorption filtration are possible causes of the concentration-dependent fluorescence emission. Subsequently, the inter distance of adjacent CDs in their aggregates was enlarged by forming rigid double-stranded DNA (dsDNA) between adjacent CDs through base pairing. It is clear that the contact of CDs induces the changes of fluorescence emission and light absorption. Through a better understanding of the mechanisms behind concentration-induced multicolor emission, this work can provide a novel strategy to develop the advanced applications of CDs.

The Phase Structural Evolution and Gas Separation Performances of Cellulose Acetate/Polyimide Composite Membrane from Polymer to Carbon Stage.

Blending and heat-treatment play significant roles in adjusting gas separation performances of membranes, especially for incorporating thermally labile polymers into carbon molecular sieve membranes (CMSMs). In this work, cellulose acetate (CA) is introduced into polyimide (PI) as a sacrificial phase to adjust the structure and gas separation performance from polymer to carbon. A novel result is observed that the gas permeability is reduced, even when the immiscible CA phase decomposes and forms pores after heat treatment at 350 °C. After carbonization at 600 °C, the miscible CA has changed without contribution, while the role of the immiscible CA phase has changed from original hindrance to facilitation, the composite-based CMSM at a CA content of 10 wt.% shows highest performances, a H2 permeability of ~5300 Barrer (56% enhancement) with a similar H2/N2 permselectivity of 42. The structural analyses reveal that the chain interactions and phase separation behaviors between CA and PI play critical roles on membrane structures and gas diffusion, and the corresponding phase structural evolutions during heat treatment and carbonization determine gas separation properties.

Ratiometric dual-emission of Rhodamine-B grafted carbon dots for full-range solvent components detection.

Quick and visual detection of component contents, such as water, in a mixed solvent is important for many practical applications, and a full range detection is especially preferred. In this work, a carbon dots based ratiometric fluorescent sensor was synthesized by grafting fluorescent group (Rhodamine B, RhB) on carbon dots, and the dual emission peaks exhibited a linear ratiometric response with the change of polarity and hydrogen bond of Solvent Hansen solubility parameters. This responsive behavior is attributed to surface state photoluminescence mechanisms, and has been used for the quantitative detection of water content in ethanol with an excellent linear relationship (R2 = 0.996), a low detection limit (0.2%), and a full detection range (0-100%). Furthermore, a paper-based ratiometric fluorescence sensing strip is also demonstrated, which exhibits good storage stability and sensitivity. This study suggests that RhB grafted carbon dots could be feasibly and effectively used as ratiometric fluorescent sensors for solvent content detection.

The response of tartary buckwheat and 19 bZIP genes to abscisic acid (ABA).

Tartary buckwheat is a kind of plant which can be used as medicine as well as edible. Abscisic acid (ABA) signaling plays an important role in the response of plants such as tartary buckwheat to drought and other stress. However, there are not many studies on tartary buckwheat by ABA treatment. In this study, the germination, root length, stoma, and anthocyanin accumulation of tartary buckwheat were all significantly affected by ABA. ABA signaling is important for plants to respond to drought and other stresses, the bZIP gene family is an important member of the ABA signaling pathway. Through the analysis of the origin relationship between tartary buckwheat bZIP family and its related species, 19 bZIP genes in tartary buckwheat were found to be relatively conserved, which laid a foundation for further study of bZIP family. The qRT-PCR results showed that most of the group members were induced by ABA treatment, including 0, 15, 30, 50, 70 µM ABA and 0, 0.5, 2, 4, 8, 16, 24 h ABA treatment. These results suggested that ABA could affect the growth and development of tartary buckwheat, and FtbZIPs might have different functions in the response of tartary buckwheat to drought. This study will be helpful to further analyze the genetic breeding and economic value of tartary buckwheat resistance.

Interface-Controlled Thermal Rectification Phenomenon of Monolayer Graphene/Boron Nitride Heterosheet.

Thermal rectification (TR) in graphene/boron nitride (GBN) monolayer heterosheets containing various types of interfacial structures has been studied using molecular dynamic simulations. The TR effect is ascribed to the asymmetric heat flow caused by mismatched PDOS of graphene and BN in the boundary. Additionally, the dependences of TR effects on boundary structures and defects are discussed. At a temperature difference of 240 K and interfacial chirality angle of 30°, a TR ratio as high as 334% is obtained. Our studies prove that the TR effect of GBN could be effectively regulated by controlling the interfacial structures and defects, and our analyses provide guidance on the structural designs of unique thermal management materials.

Exceptional high thermal conductivity of inter-connected annular graphite structures.

Based on the experimentally observed templating effects in CNTs containing carbon fibers, new types of inter-connected annular graphite structures are proposed and designed in order to significantly improve the cross-plane thermal conductivity of graphite. The calculations of the thermal conductivity of the newly designed structures were carried out by combining macroscopic continuous equations and microscopic molecular dynamic (MD) simulations. First, MD simulation was used to examine the influence of bending curvature on the in-plane thermal conductivity of a graphene sheet along and perpendicular to the rolling direction. Next, various types of annular graphite structures with single and inter-connected double/triple multi-layered graphite sheets were designed. Finally, finite element analysis was used to calculate the effective out of plane thermal conductivities of these structural models. The cross-plane thermal conductivity of a common graphite film is 2-3 orders of magnitude lower than its in-plane thermal conductivity, which strongly restricts its heat dissipation ability. However, the formation of annular graphite structures and the inter-connections of the outer layers lead to a dramatic improvement of effective out of plane thermal conductivity from 2.3 W m-1 K-1 to 799.8 W m-1 K-1 in this work, which is superior to common metal materials, especially considering the relatively lower density of carbon materials. These results would be valuable for designing and fabricating highly thermally conductive carbon materials for heat dissipation and temperature management.

Incorporation of Alkali Lignin in Polyacrylonitrile: Phase Separation, Coagulation, and Cyclization Kinetics.

In this study, we systematically investigated the phase separation behaviors of polyacrylonitrile (PAN)/alkali lignin (AL)/dimethyl sulfoxide (DMSO) systems and found that the addition of AL causes phase separation and the systems form sea (PAN)/island (AL) types of structures. Interestingly, the AL-rich domains are very stable even after a long time of storage up to 15 days. Additionally, how the phase separation affected the solution rheology, the coagulation process and PAN cyclization were explored. The addition of AL in PAN/DMSO solutions changes the solution viscosity and gelation behaviors. Also, the existence of AL-rich domains accelerates the coagulation rate of the PAN solution in water. Because AL degrades at a lower temperature than PAN, it reduces the PAN cyclization temperature but leads to a higher cyclization activation energy, which could be caused by their different initiation mechanisms. These results would be useful to understand how the addition of AL affects the PAN solution structures, solution rheology, solution coagulation behaviors, and PAN stabilization reactions.

Long-Term Survival and Prognostic Factors of Pulmonary Metastasectomy in Liver Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Lung is the most common extrahepatic metastatic organ of liver cancer. Surgical resection is a common local treatment for pulmonary metastasis. But the long-term prognosis of pulmonary metastasectomy varies greatly due to the small sample size and different results of previous studies. Therefore, we conducted this meta-analysis to evaluate the combined 5-year overall survival (OS) rate and prognostic factors after pulmonary metastasectomy in liver cancer. METHODS: Key words such as liver cancer pulmonary metastasis and metastasectomy were retrieved firstly in PubMed, Cochrane Library, Embase and Chinese Wanfang databases. Eligible studies were identified by manual searches. Each included study should report 5-year OS rate and/or prognostic factors of pulmonary metastasectomy. Newcastle-Ottawa Scale was used for quality assessment, and heterogeneity was estimated by I2. We calculated the combined 5-year survival rates and determined the prognostic factors for OS by the hazard ratios (HR) and number of events. RESULTS: Seventeen cohort studies with a total of 513 patients were included in this meta-analysis. The combined 5-year survival rates after pulmonary metastasectomy were 33% [95% confidence interval (95% CI) 29-37%]. The poor prognostic factors were disease-free interval (DFI) < 12 months (HR = 2.421 95% CI 1.384 4.236) and existence of cirrhosis (HR = 1.936 95% CI 1.031 3.636). CONCLUSION: The 5-year OS rate of patients with pulmonary metastasectomy after resection of primary liver cancer is 33%. DFI < 12 months and existence of cirrhosis are probably poor prognostic factors.

Regenerated cellulose I from LiCl·DMAc solution.

The regeneration of cellulose from microcrystalline cellulose/DMAc·LiCl solutions through thermal induced sol-gel transition and longtime gelation resulted in the formation of wholly cellulose I with a crystallinity as high as 84.7%.

Dynamic Self-Stiffening and Structural Evolutions of Polyacrylonitrile/Carbon Nanotube Nanocomposites.

The self-stiffening under external dynamic strain has been observed for some artificial materials, especially for nanocomposites. However, few systematic studies have been carried out on their structural evolutions, and the effect of the types of nanofillers was unclear. In this study, we used a semicrystalline polymer, polyacrylonitrile (PAN), and various types of carbon nanomaterials including C60, carbon nanotube (CNT), and graphene oxide (GO). An external uniaxial dynamic strain at small amplitude of 0.2% was applied on the prepared nanocomposite films. It was observed that PAN/CNT exhibited significant self-stiffening behavior, whereas PAN/GO showed no response. Systematic characterizations were performed to determine the structural evolutions of PAN/CNT film during dynamic strain testing, and it was found that the external dynamic strain not only induced the crystallization of PAN chains but also aligned CNT along the strain direction.

A high-yield and versatile method for the synthesis of carbon dots for bioimaging applications.

A facile and versatile molten-salt method was developed to prepare hydrosoluble carbon dots (CDs) from various precursors, in high yields and on a large scale. Citric acid-based CDs (CA-CDs) were obtained in a maximum yield of 39.6% and exhibited a high fluorescence quantum yield of 20.8% without any passivation. The CA-CDs showed little cytotoxicity even at a concentration as high as 800 µg mL-1. In addition, CA-CDs could be used as multicolour fluorescence imaging agents in vitro with blue, green, and red fluorescence emissions at excitation wavelengths of 405, 488, and 543 nm, respectively. Moreover, the CA-CDs could be chelated with gadolinium ions (Gd3+) to construct Gd-CA-CDs for dual-mode magnetic resonance and fluorescence imaging. The Gd-CA-CDs showed good water dispersibility, excellent biocompatibility, a strong fluorescence quantum yield of 13.1%, and a high magnetic resonance relaxivity of 22.45 mM-1 s-1. The molten-salt method was demonstrated to be applicable to other precursors, such as sodium lignosulphonate, sucrose, glucose, and p-phenylenediamine, and the maximum yield of the four as-prepared CDs was as high as 66.7%, which is much higher than the value reported in previous studies. This study proves that the molten-salt synthesis is a versatile method to obtain CDs in high yields, which will promote the application of CDs in the field of bioimaging.

In situ synthesis of NIR-light emitting carbon dots derived from spinach for bio-imaging applications.

Near infrared (NIR)-light emitting fluorescent probes have attracted extensive research attention in the bioimaging field due to their deep tissue penetration, minimal auto-fluorescence and lower emission light damage to bio-tissues. Herein, we designed and prepared NIR-light emitting CDs (R-CDs) from spinach by a one-step solvothermal method. The R-CDs exhibited good water solubility, a maximum fluorescence emission peak at 680 nm, a high quantum yield of 15.34%, remarkable photo-stability and resistance to metal ions in a body-simulating environment, excellent compatibility, negligible toxicity, and superior labelling capability in vitro and in vivo. These findings significantly highlight the design of NIR-light emitting CDs and exploit their bio-imaging applications.

Resveratrol sensitizes glioblastoma-initiating cells to temozolomide by inducing cell apoptosis and promoting differentiation.

Glioblastoma-initiating cells play crucial roles in the origin, growth, and recurrence of glioblastoma multiforme. The elimination of glioblastoma-initiating cells is believed to be a key strategy for achieving long-term survival of glioblastoma patients due to the highly resistant property of glioblastoma-initiating cells to temozolomide. Resveratrol, a naturally occurring polyphenol, has been widely studied as a promising candidate for cancer prevention and treatment. Whether resveratrol could enhance the sensitivity of glioblastoma-initiating cells to temozolomide therapy has not yet been reported. Here, using patient-derived glioblastoma-initiating cell lines, we found that resveratrol sensitized glioblastoma-initiating cells to temozolomide both in vitro and in vivo. Furthermore, we showed that resveratrol enhanced glioblastoma-initiating cells to temozolomide-induced apoptosis through DNA double-stranded breaks/pATM/pATR/p53 pathway activation, and promoted glioblastoma-initiating cell differentiation involving p-STAT3 inactivation. Our results propose that temozolomide and resveratrol combination strategy may be effective in the management of glioblastoma patients, particularly for those patients who have been present with a high abundance of glioblastoma-initiating cells in their tumors and show slight responsiveness to temozolomide.