Engineered exosomes with enhanced stability and delivery efficiency for glioblastoma therapy.

Due to the blood-brain barrier (BBB), the application of chemical drugs for glioblastoma treatment is severely limited. Recently, exosomes have been widely applied for drug delivery to the brain. However, the differences in brain targeting efficiency among exosomes derived from different cell sources, as well as the premature drug leakage during circulation, still limit the therapeutic efficacy. Here, we designed a functional oligopeptide-modified exosome loaded with doxorubicin (Pep2-Exos-DOX) for glioblastoma treatment. BV2 mouse microglial cell line was selected as the exosome source due to the favorable BBB penetration. To avoid drug release in the circulation, a redox-response oligopeptide was designed for incorporation into the membranes of exosomes to lock the drug during circulation. The enrichment of the drug in glioblastoma was confirmed. Pharmacodynamic evaluation showed Pep2-Exos-DOX possessed significant anti-cancer activity against glioblastoma as well as relative biosafety. This exosome-based drug delivery system modified with redox-response oligopeptides provides us a novel strategy for brain diseases treatment.

Influence of a Two-Dimensional Growth Mode on Electrical Properties of the GaN Buffer in an AlGaN/GaN High Electron Mobility Transistor.

An extensive study has been conducted on a series of AlGaN/GaN high electron mobility transistor (HEMT) samples using metalorganic vapour phase epitaxy, to investigate the influence of growth modes for GaN buffer layers on device performance. The unintentional doping concentration and screw dislocation density are significantly lower in the samples grown with our special two-dimensional (2D) growth approach, compared to a widely-used two-step method combining the 2D and 3D growth. The GaN buffer layers grown by the 2D growth approach have achieved an unintentional doping density of 2 × 1014 cm-3, two orders lower than 1016 cm-3 of the GaN samples grown using a conventional two-step method. High-frequency capacitance measurements show that the samples with lower unintentional doping densities have lower buffer leakage and higher breakdown limits. This series of samples have attained sub-nA/mm leakages, a high breakdown limit of 2.5 MV/cm, and a saturation current density of about 1.1 A/mm. It indicates that our special 2D growth approach can effectively lessen the unintentional doping in GaN buffer layers, leading to low buffer leakage and high breakdown limits of GaN/AlGaN HEMTs.

A Simple Approach to Achieving Ultrasmall III-Nitride Microlight-Emitting Diodes with Red Emission.

The microdisplays for augmented reality and virtual reality require ultrasmall micro light-emitting-diodes (µLEDs) with a dimension of ≤5 µm. Furthermore, the microdisplays also need three kinds of such µLEDs each emitting red, green, and blue emission. Currently, in addition to a great challenge for achieving ultrasmall µLEDs mainly based on III-nitride semiconductors, another fundamental barrier is due to an extreme difficulty in growing III-nitride-based red LEDs. So far, there has not been any effective approach to obtain high indium content InGaN as an active region required for a red LED while maintaining high optical performance. In this paper, we have demonstrated a selective epitaxy growth approach using a template featuring microhole arrays. This allows us to not only obtain the natural formation of ultrasmall µLEDs but also achieve InGaN with enhanced indium content at an elevated growth temperature, at which it is impossible to obtain InGaN-based red LEDs on a standard planar surface. By means of this approach, we have demonstrated red µLEDs (at an emission wavelength of 642 nm) with a dimension of 2 µm, exhibiting a high luminance of 3.5 × 107 cd/m2 and a peak external quantum efficiency of 1.75% measured in a wafer form (i.e., without any packaging to enhance an extraction efficiency). In contrast, an LED grown under identical growth conditions but on a standard planar surface shows green emission at 538 nm. This highlights that our approach provides a simple solution that can address the two major challenges mentioned above.

Simple Approach to Mitigate the Emission Wavelength Instability of III-Nitride µLED Arrays.

III-nitride semiconductors and their heterojunctions exhibit intrinsic polarization due to the asymmetry of their wurtzite structure, which determines all the fundamental properties of III-nitride optoelectronics. The intrinsic polarization-induced quantum-confined Stark effect leads to an emission wavelength shift with increasing injection current for III-nitride visible LEDs, forming an insurmountable barrier for the fabrication of a full color display. For instance, a yellow LED designed to produce yellow light emits green or blue light at an elevated current, while a green (blue) LED gives off blue (violet) light with increasing current. This color instability becomes a serious issue for a microdisplay such as the displays for augmented reality (AR)/virtual reality (VR) typically utilized at proximity to the eye, where human eyes are sensitive to a tiny change in light color. It is well-known that an optical mode wavelength for a microcavity is insensitive to injection current. In this work, we have demonstrated an approach to epitaxially integrating microLEDs (green microLEDs as an example, one of the key components for a full color microdisplay) and a microcavity. This allows the emission from the microLEDs to be coupled with the microcavity, leading to a negligible emission wavelength shift with increasing injection current. In contrast, identical microLEDs but without a microcavity show a large emission wavelength shift from 560 nm down to 510 nm, measured under identical conditions. This approach provides a simple solution to resolving the 30-year issue in the field of III-nitride optoelectronics.

Optimization of the vancomycin administration regimen by clinical pharmacists based on a population pharmacokinetics model: a prospective interventional study.

In vancomycin treatment, the rates of correct blood sampling and initial trough concentrations within the target range are very low. Studies of interventions by clinical pharmacists based on population pharmacokinetics (PPK) models are limited. This study aimed to evaluate the intervention effect of clinical pharmacist-mediated optimization of the vancomycin administration regimen based on a PPK model. Retrospectively enrolled patients constituted the control group, and prospectively enrolled patients constituted the intervention group. The vancomycin administration regimen, trough concentration, pharmacokinetic parameters, and clinical outcomes of the two groups were compared. The control and intervention groups comprised 236 and 138 patients, respectively. Compared with those in the control group, the therapeutic drug monitoring (TDM) and correct TDM sampling time rates in the intervention group were significantly higher (76.92% vs. 43.59%; 63.9% vs. 39.0%, both p < 0.001). The rates of an initial trough concentration within 10-20 mg/L and an adjusted regimen were also significantly higher in the intervention group (55.80% vs. 30.51%, 71.95% vs. 39.18%, both p < 0.001). The rate of an area under the curve (AUC) within 400-650 mg·h/L was higher in the intervention group than in the control group (52.7% vs. 36.6%, p < 0.001). The eradication rates of Gram-positive bacteria were 91.4% in the intervention group and 81.3% in the control group (p = 0.049). Eight patients developed acute kidney injury (AKI) in the control group; however, no AKI occurred in the intervention group (p = 0.029). Intervention by clinical pharmacists can increase the rate of correct sampling time. Using the PPK model combined with Bayesian estimation, clinical pharmacists can greatly increase the trough concentration and AUCs within the target range, especially for adjusted regimens. Higher PK/PD target rates resulted in better Gram-positive bacterial eradication and reduced renal toxicity of vancomycin.

Nearly Lattice-Matched GaN Distributed Bragg Reflectors with Enhanced Performance.

Heavy silicon-doping in GaN generally causes a rough surface and saturated conductivity, while heavily silicon-doped n++-AlGaN with ≤5% aluminum can maintain an atomically flat surface and exhibit enhanced conductivity. Given this major advantage, we propose using multiple pairs of heavily silicon-doped n++-Al0.01Ga0.99N and undoped GaN instead of widely used multiple pairs of heavily silicon-doped n++-GaN and undoped GaN for the fabrication of a lattice-matched distributed Bragg reflector (DBR) by using an electrochemical (EC) etching technique, where the lattice mismatch between Al0.01Ga0.99N and GaN can be safely ignored. By means of using the EC etching technique, the n++-layers can be converted into nanoporous (NP) layers whilst the undoped GaN remains intact, leading to a significantly high contrast in refractive index between NP-layer and undoped GaN and thus forming a DBR. Our work demonstrates that the NP-Al0.01Ga0.99N/undoped GaN-based DBR exhibits a much smoother surface, enhanced reflectivity and a wider stopband than the NP-GaN/undoped GaN-based DBR. Furthermore, the NP-Al0.01Ga0.99N/undoped GaN-based DBR sample with a large size (up to 1 mm in width) can be obtained, while a standard NP-GaN/undoped GaN-based DBR sample obtained is typically on a scale of a few 100 µm in width. Finally, a series of DBR structures with high performance, ranging from blue to dark yellow, was demonstrated by using multiple pairs of n++-Al0.01Ga0.99N and undoped GaN.

Epitaxial Integration of Multiple CdSe Quantum Dots in a Colloidal CdS Nanoplatelet.

Presynthesized CdSe/CdS core/shell quantum dots (QDs) are two-dimensionally (2D) and epitaxially fused in solution to form a CdS nanoplatelet with multiple epitaxially embedded CdSe QDs (CdSe@CdS coupled-dots@platelet). In addition to providing spatial confinement for the excitonic states of multiple CdSe QDs in a CdS nanoplatelet, the continuous and single-crystalline nanoplatelet with controlled thickness enables quantum coupling between the CdSe QDs, resulting in inhomogeneous-free optical properties for the colloidal CdSe@CdS coupled-dots@nanoplatelets with bright photoluminescence. The results here suggest that solution synthesis can offer a simple means to obtain semiconductor nanocrystals for realizing unique yet complex excitonic properties that are otherwise difficult to achieve.

Dose Optimization of Teicoplanin for Critically Ill Patients With Renal Dysfunction and Continuous Renal Replacement Therapy: Experience From a Prospective Interventional Study.

Background: Due to the lack of updated information on teicoplanin (TEI) for continuous renal replacement therapy (CRRT), no exact dosage regimen has been recommended. The aim of this study was to optimize the dosage regimen of TEI in renal dysfunction patients with or without CRRT, evaluate the influence factors of the eradication of Gram-positive bacteria, and evaluate the effect of CRRT on the clearance of TEI. Methods: Patients with renal dysfunction receiving TEI treatment in the ICU were prospectively recruited and divided into CRRT and non-CRRT groups. Logistic regression analysis was used to screen the factors affecting the eradication of Gram-positive bacteria. The filtrate concentration of the CRRT group was measured at the time of TEI Cmin, and the filtration coefficient of TEI was calculated to evaluate the effect of CRRT on the clearance of TEI. Results: A total of 106 patients were included, 40 cases in the CRRT group and 66 cases in the non-CRRT group. After giving high-loading doses of TEI, 75.8 and 70% of TEI Cmin in the non-CRRT and CRRT groups reached the range of 10-30 mg/L before the 3rd dose, respectively. The risk of G+ bacteria being uneradicated was higher while the APACHEⅡscore was higher than 22.5. The albumin level before the start of TEI administration and before the 6th-8th dose was lower than 32.8 g/L and 29.3 g/L, respectively, and Cmin before the 3rd dose and 6th-8th dose was lower than 13.2 mg/L and 17.1 mg/L, respectively, with the duration of TEI therapy shorter than 10.5 days. The correlation coefficient (r) was 0.6490 between Cmin before the 3rd dose and the albumin level (p < 0.001). The filtration coefficient of TEI was 10.7 ± 2.4% at Cmin and 11.1 ± 2.5% at Cmax. The GFR had no correlation with the filtration coefficient (r = -0.06204; r = -0.08059). The clearance of TEI in CRRT patients was negatively correlated with the albumin level (r = -0.6305, p = 0.0013). Conclusion: The early stage of the albumin level can significantly affect the initial Cmin and clinical efficacy of TEI, and also had effect on the clearance of TEI by CRRT. The filtration coefficient of TEI was stable, even with a higher ultrafiltration rate.

A Regression Model to Predict Linezolid Induced Thrombocytopenia in Neonatal Sepsis Patients: A Ten-Year Retrospective Cohort Study.

Background: Linezolid-induced thrombocytopenia (LIT) is the main factor limiting the clinical application of linezolid (LZD). The incidence and risk factors of LIT in neonatal patients were possibly different from other populations based on pathophysiological characteristics. The purpose of this study was to establish a regression model for predicting LIT in neonatal sepsis patients. Methods: We retrospectively included 518 patients and divided them into the LIT group and the non-LIT group. A logistic regression analysis was used to analyze the factors related to LIT, and a regression model was established. A receiver operating characteristic (ROC) curve was drawn to evaluate the model's predictive value. We prospectively collected 39 patients' data to validate the model and evaluate the effect of LZD pharmacokinetics on LIT. Results: Among the 518 patients, 103 patients (19.9%) developed LIT. The Kaplan-Meier plot revealed that the overall median time from the initiation of LZD treatment to the onset of LIT in preterm infants was much shorter when compared with term infants [10 (6, 12) vs. 13 (9.75, 16.5), p = 0.004]. Multiple logistic regression analysis indicated that the independent risk factors of LIT were lower weight at medication, younger gestational ages, late-onset sepsis, necrotizing enterocolitis, mechanical ventilation, longer durations of LZD treatment, and lower baseline of platelet level. We established the above seven-variable prediction regression model and calculated the predictive probability. The ROC curve showed that the predicted probability of combined body weight, gestational age, duration of LZD treatment, and baseline of platelet had better sensitivity (84.4%), specificity (74.2%), and maximum AUC (AUC = 0.873). LIT occurred in 9 out of 39 patients (23.1%), and the accuracies of positive and negative predictions of LIT were 88.9 and 76.7%, respectively. Compared with the non-LIT patients, the LIT patients had higher trough concentration [11.49 (6.86, 15.13) vs. 5.51 (2.80, 11.61) mg/L; p = 0.028] but lower apparent volume of distribution (Vd) [0.778 (0.687, 1.421) vs. 1.322 (1.099, 1.610) L; p = 0.010]. Conclusion: The incidence of LIT was high in neonatal sepsis patients, especially in preterm infants. LIT occurred earlier in preterm infants than in term infants. The regression model of seven variables had a high predictive value for predicting LIT. LIT was correlated with higher trough concentration and lower Vd.

Vancomycin in neonatal sepsis: predictive performance of a Chinese neonatal population pharmacokinetic model and clinical efficacy evaluation.

BACKGROUND: In the neonatal population, individual calculation and adjustment of vancomycin (VCM) doses has been recommended based on population pharmacokinetics (PPK) methods. OBJECTIVE: Our previous study established a Chinese neonatal VCM PPK model. The main goal of this study was to evaluate the predictive performance of this PPK model for VCM trough concentration. METHODS: The data on neonatal severe infection patients treated with VCM were retrospectively collected. The predictive performance of this PPK model was expressed using mean prediction error (MPE), mean absolute prediction error (MAPE), sensitivity and specificity. Linear regression analysis was used to compare predicted and measured VCM concentrations. We drew the receiver operating characteristic (ROC) curve to evaluate the predictive efficacy of the ratio of area under the concentration-time curve over 24 hours to minimum inhibitory concentration (AUC0-24/MIC) and trough concentration for clinical efficacy. RESULTS: A total of 40 neonates with Gram-positive bacterial sepsis were included. After VCM treatment, 32 (80%) neonates were clinically cured. Eight cases were a clinical failure: the trough concentrations and AUC0-24 were lower than that of the clinical cure patients (8.70±4.30 vs 14.30±4.50 mg/L, p=0.003; 404.30±122.80 vs 515.40±131.70, p=0.037). The measured and predicted trough concentration were 11.16 (5.96, 16.53) mg/L and 10.13 (6.61, 15.73) mg/L, respectively. The MPE and MAPE were 4.62% and 13.26% (5.30%, 25.88%), respectively. The proportion of MAPE <30% in the adjusted regimen was higher than the initial regimen (89.66% vs 65.00%, p=0.039). Predictions of sensitivity and specificity by this PPK model were 88.24% and 94.29%, respectively. The coefficients of determination of linear regression analysis were 0.9171 and 0.9009 for the initial and adjusted regimen, respectively. The AUC0-24 was correlated with the trough concentration (r=0.587, p<0.001). The ROC curve indicated that the optimal cut-off points for predicting clinical efficacy were AUC0-24/MIC >425.47 and trough concentration >9.45 mg/L. CONCLUSION: This PPK model has good predictive performance in Chinese neonatal patients. Both AUC0-24/MIC and trough concentration can predict the clinical efficacy of antibacterial treatment.

Acupoint nanocomposite hydrogel for simulation of acupuncture and targeted delivery of triptolide against rheumatoid arthritis.

BACKGROUND: Attenuating inflammatory response and relieving pain are two therapeutic therapeutical goals for rheumatoid arthritis (RA). Anti-inflammatory and analgesic drugs are often associated with many adverse effects due to nonspecific distribution. New drug delivery systems with practical targeting ability and other complementary strategies urgently need to be explored. To achieve this goal, an acupoint drug delivery system that can target deliver anti-inflammatory drugs and simulate acupuncture in relieving pain was constructed, which can co-deliver triptolide (TP) and 2-chloro-N (6)-cyclopentyl adenosine (CCPA). RESULTS: We have successfully demonstrated that acupoint nanocomposite hydrogel composed of TP-Human serum album nanoparticles (TP@HSA NPs) and CCPA could effectively treat RA. The result shows that CCPA-Gel can enhance analgesic effects specifically at the acupoint, while the mechanical and thermal pain threshold was 4.9 and 1.6 times compared with non-acupoint, respectively, and the nanocomposite gel further enhanced. Otherwise, the combination of acupoint and nanocomposite hydrogel exerted synergetic improvement of inflammation, bone erosion, and reduction of systemic toxicity. Furthermore, it could regulate inflammatory factors and restore the balance of Th17/Treg cells, which provided a novel and effective treatment strategy for RA. Interestingly, acupoint administration could improve the accumulation of the designed nanomedicine in arthritic paws (13.5% higher than those in non-acupoint at 48 h), which may explain the better therapeutic efficiency and low toxicity. CONCLUSION: This novel therapeutic approach-acupoint nanocomposite hydrogel, builds a bridge between acupuncture and drugs which sheds light on the combination of traditional and modern medicine.

Multifunctional nanorods based on self-assembly of biomimetic apolipoprotein E peptide for the treatment of Alzheimer's disease.

Targeting a single molecule or a single pathway and poor drug delivery to the brain hamper the therapy of Alzheimer's disease (AD) based on abnormal metabolism of amyloid-ß (Aß). To solve these problems, we designed and synthesized a multi - strategy peptide (MOP), an ingenious apolipoprotein E mimetic peptide, which could reduce Aß deposition via inhibiting Aß aggregation and at the same time accelerate Aß clearance. Meanwhile, MOP could be self-assembled into different nanostructure, thus we constructed a multifunctional delivery system (APND-3) based on MOP self-assembled nanorods (aspect ratios of 3) that was a favorable morphology to enhance the permeation across the blood brain barrier (BBB) to address the poor delivery to brain issues. Besides, the drug delivery system introduces polydopamine (PDA) and COG1410 ligand as a shell to keep the favorable morphology of core and enhance the BBB targeting efficiency. As a result, the delivery system significantly enhances the delivery of MOP to the brain, thus reducing Aß deposition, mitigating the memory deficits, and ameliorating neurologic damage in AD model mice. Our findings suggest that our drug and carrier integrated multifunctional delivery system has the potential for AD treatment.

A Regression Model to Predict Augmented Renal Clearance in Critically Ill Obstetric Patients and Effects on Vancomycin Treatment.

Background: Augmented renal clearance (ARC) risk factors and effects on vancomycin (VCM) of obstetric patients were possibly different from other populations based on pathophysiological characteristics. Our study was to establish a regression model for prediction of ARC and analyze the effects of ARC on VCM treatment in critically ill obstetric patients. Methods: We retrospectively included 427 patients, grouped into ARC and non-ARC patients. Logistic regression analysis was used to analyze the factors related to ARC. Receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of the model for ARC. Patients who received VCM therapy were collected. The published VCM population pharmacokinetic (PPK) model was used to calculate pharmacokinetic parameters. A linear regression analysis was made between the predicted and measured concentrations. Results: Of the 427 patients, ARC was present in 201 patients (47.1%). The independent risk factors of ARC were heavier, greater gestational age, higher albumin level, fewer caesarean section, severe preeclampsia and vasoactive drug; more infection, hypertriglyceridemia and acute pancreatitis. We established the above nine-variable prediction regression model and calculated the predicted probability. ROC curve showed that the predicted probability of combined weight, albumin and gestational age had better sensitivity (70.0%) and specificity (89.8%) as well as the maximal area under the curve (AUC, AUC = 0.863). 41 cases received VCM; 21 cases (51.2%) had ARC. The initial trough concentration in ARC patients was lower than in non-ARC patients (7.9 ± 3.2 mg/L vs 9.5 ± 3.3 mg/L; p = 0.033). Comparing the predicted trough concentration of two published VCM PPK models with the measured trough concentration, correlation coefficients (r) were all more than 0.8 in the ARC group and non-ARC group. AUC was significantly decreased in the ARC group (p = 0.003; p = 0.013), and clearance (CL) increased in the ARC group (p < 0.001; p = 0.008) when compared with the non-ARC group. Conclusion: ARC is a common state in critically ill obstetric patients. The regression model of nine variables had high predictive value for predicting ARC. The published VCM PPK models had good predictive performance for predicting trough concentrations of obstetric patients. Pharmacokinetic parameters of VCM are different in ARC obstetric patients, which results in enhanced VCM clearance and decreased trough concentration.

An injectable peptide hydrogel with excellent self-healing ability to continuously release salvianolic acid B for myocardial infarction.

Drug-loaded hydrogels can improve blood supply and inhibit extracellular matrix degradation after myocardial infarction. However, due to the continual dynamic motion of cardiac tissue, the hydrogel structure cannot be reconstructed in time, causing accelerated degradation and drug burst release. Here, a novel, superior, self-healing elastin-mimic peptide hydrogel (EMH) was fabricated for the local delivery of salvianolic acid B (SaB). The self-healing ability of EMH is enhanced by SaB-loaded polydopamine nanoparticles (SaB-PDA). In vitro, the pre-hydrogel (SaB-PDA/pre-EMH) is endowed with excellent biocompatibility and a low viscosity, making it suitable for intramyocardial injection. Once injected into the myocardial infarction (MI) region, SaB-PDA/pre-EMH can form SaB-PDA/EMH with great mechanical strength under the action of upregulated transglutaminase (TGase) in heart tissue post-MI. The superior self-healing ability of SaB-PDA/EMH allows for an increase in retention time in the beating ventricular wall. Therefore, with long-term release of SaB, SaB-PDA/EMH can inhibit ventricular remodeling and promote angiogenesis for MI treatment.

Comparison of LBM and FVM in the estimation of LAD stenosis.

The finite volume method (FVM)-based computational fluid dynamics (CFD) technology has been applied in the non-invasive diagnosis of coronary artery stenosis. Nonetheless, FVM is a time-consuming process. In addition to FVM, the lattice Boltzmann method (LBM) is used in fluid flow simulation. Unlike FVM solving the Navier-Stokes equations, LBM directly solves the simplified Boltzmann equation, thus saving computational time. In this study, 12 patients with left anterior descending (LAD) stenosis, diagnosed by CTA, are analysed using FVM and LBM. The velocities, pressures, and wall shear stress (WSS) predicted using FVM and LBM for each patient is compared. In particular, the ratio of the average and maximum speed at the stenotic part characterising the degree of stenosis is compared. Finally, the golden standard of LAD stenosis, invasive fractional flow reserve (FFR), is applied to justify the simulation results. Our results show that LBM and FVM are consistent in blood flow simulation. In the region with a high degree of stenosis, the local flow patterns in those two solvers are slightly different, resulting in minor differences in local WSS estimation and blood speed ratio estimation. Notably, these differences do not result in an inconsistent estimation. Comparison with invasive FFR shows that, in most cases, the non-invasive diagnosis is consistent with FFR measurements. However, in some cases, the non-invasive diagnosis either underestimates or overestimates the degree of stenosis. This deviation is caused by the difference between physiological and simulation conditions that remains the biggest challenge faced by all CFD-based non-invasive diagnostic methods.

Direct Epitaxial Approach to Achieve a Monolithic On-Chip Integration of a HEMT and a Single Micro-LED with a High-Modulation Bandwidth.

Visible light communications (VLC) require III-nitride visible micro-light-emitting diodes (µLEDs) with a high-modulation bandwidth. Such µLEDs need to be driven at a high injection current density on a kA/cm2 scale, which is about 2 orders of magnitude higher than those for normal visible LED operation. µLEDs are traditionally fabricated by dry-etching techniques where dry-etching-induced damages are unavoidable, leading to both a substantial reduction in performance and a great challenge to viability at a high injection current density. Furthermore, conventional biasing (which is simply applied across a p-n junction) is good enough for normal LED operation but generates a great challenge for a single µLED, which needs to be modulated at a high injection current density and at a high frequency. In this work, we have proposed a concept for an epitaxial integration and then demonstrated a completely different method that allows us to achieve an epitaxial integration of a single µLED with a diameter of 20 µm and an AlGaN/GaN high-electron-mobility transistor (HEMT), where the emission from a single µLED is modulated by tuning the gate voltage of its HEMT. Furthermore, such a direct epitaxial approach has entirely eliminated any dry-etching-induced damages. As a result, we have demonstrated an epitaxial integration of monolithic on-chip µLED-HEMT with a record modulation bandwidth of 1.2 GHz on industry-compatible c-plane substrates.

The impact of pre-evacuation ultrasound examination in histologically confirmed hydatidiform mole in missed abortion.

BACKGROUND: Early detecting hydatidiform mole in missed abortion is challenge. In this retrospective observational study, we analysed the sensitivity of detecting hydatidiform mole by pre-evacuation ultrasound examination or naked eye after surgical uterine evacuation in missed abortion. METHODS: Data on 577 cases with histologically confirmed hydatidiform mole were collected over a 10-year period and analysed. Data included serum ß-hCG level before surgical evacuation, the ultrasound examination findings, histology findings and naked eye findings. In addition, serum ß-hCG level on 2398 cases without hydatidiform mole was also collected. RESULTS: The median maternal age was 29 (range, 17-53) years and the range of gestational age was 6 to 12 weeks. The sensitivity of detecting hydatidiform mole by ultrasound examination or by naked eye was 25% or 60% respectively. This sensitivity was not increased by the combination of ultrasound and naked eye. There was no difference in the sensitivity of detecting subtypes of hydatidiform mole. The higher ß-hCG level was seen in cases with hydatidiform mole, compared to cases without hydatidiform mole. However, there was a lot of overlap in the distributions of ß-hCG between the two groups. CONCLUSIONS: In this study, we found lower sensitivity of detecting hydatidiform mole by ultrasound in missed abortion. ß-hCG level was higher in hydatidiform mole than in non- hydatidiform mole in missed abortion. Although higher sensitivity of detecting hydatidiform mole is seen by naked eye (60%), in order to minimise missed opportunity of detecting hydatidiform mole, our study suggests that routine histopathological examination is necessary in missed abortion.

A Novel Nanoparticle Preparation to Enhance the Gastric Adhesion and Bioavailability of Xanthatin.

OBJECTIVE: To prepare xanthatin (XA)-loaded polydopamine (PDA) nanoparticles (PDA-XA-NPs) and to investigate their adhesion and bioavailability. MATERIALS AND METHODS: PDA-XA-NPs were synthesized and characterized using transmission electron microscopy, zeta potential analysis and encapsulation efficiency analysis. Their in vitro release kinetics and inhibitory effects on gastric cancer were studied. The adhesion of PDA-XA-NPs was evaluated by in vivo imaging atlas. The pharmacokinetics of PDA-XA-NPs and XA was compared. RESULTS: PDA-XA-NPs had a spherical shape, a particle size of about 380 nm, an encapsulation efficiency of (82.1 ± 0.02) % and a drug loading capacity of (5.5 ± 0.1)%. The release of PDA-XA-NPs in PBS was stable and slow, without being affected by pH. The adhesion capacity of PDA-XA-NPs for mucin was significantly higher than that of bulk drug. The gastric mucosal retention of PDA-XA-NPs reached 89.1% which significantly exceeded that of XA. In vivo imaging showed that PDA-XA-NPs targeting the stomach were retained for a period of time. The pharmacokinetics study showed that PDA-XA-NPs had a longer retention time and a slower drug release than those of XA. In vitro experiments confirmed that PDA-XA-NPs exerted similar inhibitory effects on gastric cancer to those of XA, which lasted for a period of time. CONCLUSION: High-adhesion NPs were constructed. Gastric cancer was targeted by orally administered PDA-XA-NPs, as a potentially feasible therapy. Eventually, the bioavailability of XA was increased.

Morphological transformation enhances Tumor Retention by Regulating the Self-assembly of Doxorubicin-peptide Conjugates.

Rationale: Both spatial accuracy and temporal persistence are crucial in drug delivery, especially for anti-tumor intravenous nanomedicines, which have limited persistence due to their small particle sizes and easy removal from tumors. The present study takes advantage of morphological transformation strategy to regulate intravenous nanomedicines to display different sizes in different areas, achieving high efficient enrichment and long retention in lesions. Methods: We designed and synthesized functional doxorubicin-peptide conjugate nanoparticles (FDPC-NPs) consisting of self-assembled doxorubicin-peptide conjugates (DPCs) and an acidic-responsive shielding layer named the functional polylysine graft (FPG), which can regulate the assembly morphology of the DPCs from spherical DPC nanoparticles (DPC-NPs) to DPC-nanofibers (DPC-NFs) by preventing the assembly force from π-π stacking and hydrogen bond between the DPC-NPs. The morphology transformation and particle changes of FDPC-NPs in different environments were determined with DLS, TEM and SEM. We used FRET to explore the enhanced retention effect of FDPC-NPs in tumor site in vivo. HPLC-MS/MS analytical method was established to analyze the biodistribution of FDPC-NPs in H22 hepatoma xenograft mouse model. Finally, the antitumor effect and safety of FDPC-NPs was evaluated. Results: The FDPC-NPs were stable in blood circulation and responsively self-assembled into DPC-NFs when the FDPC-NPs underwent the acid-sensitive separation of the shielding layer in a mildly acidic microenvironment. The FDPC-NPs maintained a uniform spherical size of 80 nm and exhibited good morphological stability in neutral aqueous solution (pH 7.4) but aggregated into a long necklace-like chain structure or a crosslinked fiber structure over time in a weakly acidic solution (pH 6.5). These acidity-triggered transformable FDPC-NPs prolonged the accumulation in tumor tissue for more than 5 days after a single injection and improved the relative uptake rate of doxorubicin in tumors 31-fold. As a result, FDPC-NPs exhibited a preferable anti-tumor efficacy and a reduced side effect in vivo compared with free DOX solution and DOX liposomes. Conclusions: Morphology-transformable FDPC-NPs represent a promising therapeutic approach for prolonging the residence time of drugs at the target site to reduce side effect and enhance therapeutic efficacy. Our studies provide a new and simple idea for the design of long-term delivery systems for intravenous chemotherapeutic drugs.

Nonpolar (112Ì 0) GaN Metal-Semiconductor-Metal Photodetectors with Superior Performance on Silicon.

This article reports a nonpolar GaN metal-semiconductor-metal (MSM) photodetector (PD) with an ultrahigh responsivity and an ultrafast response speed in the ultraviolet spectral region, which was fabricated on nonpolar (112̅0) GaN stripe arrays with a major improvement in crystal quality grown on patterned (110) silicon substrates by means of using our two-step processes. Our nonpolar GaN MSM-PD exhibits a responsivity of 695.3 A/W at 1 V bias and 12628.3 A/W at 5 V bias, both under 360 nm ultraviolet illumination, which are more than 20 times higher and 4 orders of magnitude higher compared to the current state-of-the-art photodetector, respectively. The nonpolar GaN MSM-PD displays a rise time and a fall time of 66 and 43 µs, respectively, which are 3 orders of magnitude faster compared to the current state-of-the-art photodetector.