A harmful MYH11 variant detected in a family with thoracic aortic dissection and patent ductus arteriosus.

Thoracic aortic dissection (TAD) is an important cause of sudden cardiac death and is characterized by high morbidity, mortality, and a poor prognosis. Patent ductus arteriosus (PDA) is a common congenital heart disease. The pathogenesis of both TAD and PDA has been reported to be related to genetic factors. The MYH11 gene, which encodes myosin heavy chain 11, has been reported in individuals with both TAD and PDA. Herein, we first detected a harmful MYH11 missense variant (c. T3728C, p. L1243P) in a TAD and PDA family. This missense variant co-segregated with the TAD/PDA phenotype in this family of four individuals, providing evidence of its harmfulness. Histopathological examinations revealed the presence of fragmented, broken, and lessened elastic fibers and the deposition of proteoglycans in the median of aortic dissection. Moreover, the immunofluorescence results showed that the labeled MYH11 protein in the tissue of the aortic dissection was weaker than that in the normal aorta. We present this familial case to stress the necessity of postmortem genetic testing in such cases among forensic practices. Identifying those culprit gene variants can direct effective genetic counseling and personalized health management in family members (especially first-degree relatives) with high-risk genotypes.

Novel pH-responsive E-selectin targeting natural polysaccharides hybrid micelles for diabetic nephropathy.

Diabetic nephropathy (DN) is an important complication of diabetes and is the main cause of end-stage renal disease. The pathogenesis of DN is complex, including glucose and lipid metabolism disorder, inflammation, and so on. Novel hybrid micelles loaded Puerarin (Pue) based on Angelica sinensis polysaccharides (ASP) and Astragalus polysaccharide (APS) were fabricated with pH-responsive ASP-hydrazone-ibuprofen (BF) materials (ASP-HZ-BF, SHB) and sialic acid (SA) modified APS-hydrazone-ibuprofen materials (SA/APS-HZ-BF, SPHB) by thin-film dispersion method. The SA in hybrid micelles can specifically bind to the E-selectin receptor which is highly expressed in inflammatory vascular endothelial cells. The loaded Pue could be accurately delivered to the inflammatory site of the kidney in response to the low pH microenvironment. Overall, this study provides a promising strategy for developing hybrid micelles based on natural polysaccharides for the treatment of diabetic nephropathy by inhibiting renal inflammatory reactions, and antioxidant stress.

Application of P/VB staining to identify antemortem injury in a decomposed cadaver.

It is challenging in forensic pathology to determine whether an injury is formed antemortem or postmortem in putrefied tissues. Hematoxylin-eosin (HE) staining fails to work in highly decomposed corpses. Ponceau/Victoria blue B (P/VB) staining is usually used to show collagen fibers and muscles. Here, we used P/VB to show antemortem laceration injury on the scalp in a severely decomposed cadaver 1.5 years after death. This method is a simple and alternative method for the diagnosis of antemortem injury.

High Precision Sea Surface Temperature Prediction of Long Period and Large Area in the Indian Ocean Based on the Temporal Convolutional Network and Internet of Things.

Impacted by global warming, the global sea surface temperature (SST) has increased, exerting profound effects on local climate and marine ecosystems. So far, investigators have focused on the short-term forecast of a small or medium-sized area of the ocean. It is still an important challenge to obtain accurate large-scale and long-term SST predictions. In this study, we used the reanalysis data sets provided by the National Centers for Environmental Prediction based on the Internet of Things technology and temporal convolutional network (TCN) to predict the monthly SSTs of the Indian Ocean from 2014 to 2018. The results yielded two points: Firstly, the TCN model can accurately predict long-term SSTs. In this paper, we used the Pearson correlation coefficient (hereafter this will be abbreviated as "correlation") to measure TCN model performance. The correlation coefficient between the predicted and true values was 88.23%. Secondly, compared with the CFSv2 model of the American National Oceanic and Atmospheric Administration (NOAA), the TCN model had a longer prediction time and produced better results. In short, TCN can accurately predict the long-term SST and provide a basis for studying large oceanic physical phenomena.

Reversibly Photoswitching Upconversion Nanoparticles for Super-Sensitive Photoacoustic Molecular Imaging.

Photoacoustic (PA) imaging uses light excitation to generate the acoustic signal for detection and improves tissue penetration depth and spatial resolution in the clinically relevant depth of living subjects. However, strong background signals from blood and pigments have significantly compromised the sensitivity of PA imaging with exogenous contrast agents. Here we report a nanoparticle-based probe design that uses light to reversibly modulate the PA emission to enable photoacoustic photoswitching imaging (PAPSI) in living mice. Such a nanoprobe is built with upconverting nanocrystals and photoswitchable small molecules and can be switched on by NIR light through upconversion to UV energy. Reversibly photoswitching of the nanoprobe reliably removed strong tissue background, increased the contrast-to-noise ratio, and thus improved imaging sensitivity. We have shown that PAPSI can image 0.05 nM of the nanoprobe in hemoglobin solutions and 104 labeled cancer cells after implantation in living mice using a commercial PA imager.

Core-Shell-Shell Upconversion Nanoparticles with Enhanced Emission for Wireless Optogenetic Inhibition.

Recent advances in upconversion technology have enabled optogenetic neural stimulation using remotely applied optical signals, but limited success has been demonstrated for neural inhibition by using this method, primarily due to the much higher optical power and more red-shifted excitation spectrum that are required to work with the appropriate inhibitory opsin proteins. To overcome these limitations, core-shell-shell upconversion nanoparticles (UCNPs) with a hexagonal phase are synthesized to optimize the doping contents of ytterbium ions (Yb3+) and to mitigate Yb-associated concentration quenching. Such UCNPs' emission contains an almost three-fold enhanced peak around 540-570 nm, matching the excitation spectrum of a commonly used inhibitory opsin protein, halorhodopsin. The enhanced UCNPs are utilized as optical transducers to develop a fully implantable upconversion-based device for in vivo tetherless optogenetic inhibition, which is actuated by near-infrared (NIR) light irradiation without any electronics. When the device is implanted into targeted sites deep in the rat brain, the electrical activity of the neurons is reliably inhibited with NIR irradiation and restores to normal level upon switching off the NIR light. The system is further used to perform tetherless unilateral inhibition of the secondary motor cortex in behaving mice, achieving control of their motor functions. This study provides an important and useful supplement to the upconversion-based optogenetic toolset, which is beneficial for both basic and translational neuroscience investigations.

Synthesis of Mesoporous ZIF-8 Nanoribbons and their Conversion into Carbon Nanoribbons for High-Performance Supercapacitors.

ZIF-8 nanoribbons, with tunable morphology and pore structure, were synthesized by using the tri-block co-polymer Pluronic F127 as a soft template. The as-synthesized ZIF-8 nanoribbons were converted into carbon nanoribbons by thermal transformation with largely preserved morphology and porosity. The resulting carbon nanoribbons feature both micro- and meso-pores with high surface areas of over 1000 m2 g-1 . In addition, nitrogen-doping in the carbon nanoribbons was achieved, as confirmed by XPS and EELS measurements. The hybrid carbon nanoribbons provide pseudo-capacitance that promotes electrochemical performance, rendering a high specific capacitance of up to 297 F g-1 at a current density of 0.5 A g-1 in a three-electrode system. A long cycle life was also demonstrated by recording a 90.26 % preservation of capacitance after 10 000 cycles of charge-discharge at a current density of 4.0 A g-1 . Furthermore, a symmetrical supercapacitor is fabricated by employing the carbon nanoribbons, which shows good electrochemical performance with respect to energy, power and cycle life.

Energy Migration Upconversion in Ce(III)-Doped Heterogeneous Core-Shell-Shell Nanoparticles.

One major challenge in upconversion research is to develop new materials and structures to expand the emission spectrum. Herein, a heterogeneous core-shell-shell nanostructure of NaYbF4 :Gd/Tm@NaGdF4 @CaF2 :Ce is developed to realize efficient photon upconversion in Ce3+ ions through a Gd-mediated energy migration process. The design takes advantage of CaF2 host that reduces the 4f-5d excitation frequency of Ce3+ to match the emission line of Gd3+ . Meanwhile, CaF2 is isostructural with NaGdF4 and can form a continuous crystalline lattice with the core layer. As a result, effective Yb3+ → Tm3+ → Gd3+ → Ce3+ energy transfer can be established in a single nanoparticle. This effect enables efficient ultraviolet emission of Ce3+ following near infrared excitation into the core layer. The Ce3+ upconversion emission achieved in the core-shell-shell nanoparticles features broad bandwidth and long lifetime, which offers exciting opportunities of realizing tunable lasing emissions in the ultraviolet spectral region.

A General Strategy for Ligand Exchange on Upconversion Nanoparticles.

Lanthanide-doped upconversion nanoparticles with a suitable surface coating are appealing for biomedical applications. Because high-quality upconversion nanoparticles are typically prepared in an organic solvent and passivated by hydrophobic oleate ligands, a convenient and reliable method for the surface modification of upconversion nanoparticles is thus highly desired to satisfy downstream biological investigations. In this work, we describe a facile and versatile strategy for displacing native oleate ligands on upconversion nanoparticles with a diversity of hydrophilic molecules. The ligand-exchange procedure involves the removal of original oleate ligands followed by the attachment of new ligands in a separate step. The successful coating of relevant ligands was confirmed by Fourier transform infrared spectroscopy, thermogravimetry analysis, and ζ-potential measurement. The surface-modified nanoparticles display high stability and good biocompatibility, as revealed by electron microscopy, photoluminescence spectroscopy, and cytotoxicity assessment. Our study demonstrates that functional biomolecules such as biotin can be directly immobilized on the nanoparticle surface using this approach for the quick and effective detection of streptavidin.

Shielding Upconversion by Surface Coating: A Study of the Emission Enhancement Factor.

Surface coating is a commonly used strategy to enhance upconversion emissions by shielding the luminescent core from surface quenching. In this work, we provide insights into the effect of surface coating on upconversion by investigating NaYF4 :Yb/Er nanoparticles and the corresponding NaYF4 :Yb/Er@NaYF4 core-shell nanoparticles, as a function of dopant concentration of Yb(3+) and excitation power. We observe declining emission enhancement factors with decreasing Yb(3+) concentration and increasing excitation power. Our mechanistic investigations suggest that the phenomenon originates from stepwise excitation in the upconversion process, as well as energy hopping among the Yb(3+) dopants. This increased understanding of the effect of surface coating on upconversion should be important towards the rational design of lanthanide-doped core-shell nanoparticles for various applications.

Multimodal Upconversion Nanoplatform with a Mitochondria-Targeted Property for Improved Photodynamic Therapy of Cancer Cells.

Upconversion nanoparticles (UCNPs) with the capacity to emit high-energy visible or UV light under low-energy near-infrared excitation have been extensively explored for biomedical applications including imaging and photodynamic therapy (PDT) against cancer. Enhanced cellular uptake and controlled subcellular localization of a UCNP-based PDT system are desired to broaden the biomedical applications of the system and to increase its PDT effect. Herein, we build a multimodal nanoplatform with enhanced therapeutic efficiency based on 808 nm excited NaYbF4:Nd@NaGdF4:Yb/Er@NaGdF4 core-shell-shell nanoparticles that have a minimized overheating effect. The photosensitizer pyropheophorbide a (Ppa) is loaded onto the nanoparticles capped with biocompatible polymers, and the nanoplatform is functionalized with transcriptional activator peptides as targeting moieties. Significantly increased cellular uptake of the nanoparticles and dramatically elevated photocytotoxicity are achieved. Remarkably, colocalization of Ppa with mitochondria, a crucial subcellular organelle as a target of PDT, is proven and quantified. The subsequent damage to mitochondria caused by this colocalization is also confirmed to be significant. Our work provides a comprehensively improved UCNP-based nanoplatform that maintains great biocompatibility but shows higher photocytotoxicity under irradiation and superior imaging capabilities, which increases the biomedical values of UCNPs as both nanoprobes and carriers of photosensitizers toward mitochondria for PDT.

Fatal hyperthermia among children in school buses: Analysis of 47 cases in China.

The school bus is an important mode of transportation for school-age children, and safety-related issues are always the focus of public concern. Fatal hyperthermia occurring in school buses is an uncommon type of school bus-related injury. An internet search using Chinese internet search engines based on various combinations of keywords including 'vehicles', 'school bus', 'children or babies', 'hyperthermia or heat stroke' and 'death' was performed. Forty-seven cases of fatal hyperthermia in children which occurred in school buses were retrieved in the study. High ambient temperature, younger age and poor management were identified as risk factors. There is a lack of consensus regarding the legal nature and liability for fatal hyperthermia occurring in school buses. Pre-employment education should be focused on awareness of the dangers of leaving children alone in a school bus. Most importantly, the relevant legislation and regulations on school buses should be implemented. An internal alarm-raising system is recommended to avoid this kind of tragedy.

Resveratrol nanocrystals based dissolving microneedles with highly efficient for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common immune disease characterized mainly by erosive arthritis with extensive clinical sequelae. Resveratrol (Res) has pharmacological effects in the treatment of RA, but it has not been widely used in the clinic due to its poor water solubility and low bioavailability. In this study, a drug delivery system (Res-NC MNs) of dissolved microneedles (MNs) loaded with Res nanocrystals (NC) was designed for the treatment of RA. Res-NC MNs can improve the drawbacks of long-term oral drug delivery with toxic side effects and low compliance associated with intra-articular drug delivery. In this study, Res-NC was prepared by media milling and loaded into soluble microneedles prepared from hyaluronic acid (HA) by vacuum casting for the treatment of RA. HA has high mechanical strength and can penetrate the cuticle layer of the skin for effective drug delivery. In in vivo pharmacodynamic experiments, Res-NC MNs achieved better therapeutic efficacy in the treatment of RA compared with oral Res. These findings suggest that Res-NC MNs may be an effective and promising drug delivery strategy for the treatment of RA.

Multifunctional composite soluble microneedle patch based on "one stone, three birds" strategy for promoting the healing of infectious wounds.

The colonisation of microorganisms such as bacteria forms a biofilm barrier on the wound's surface, preventing or delaying the penetration of antibacterial drugs. At the same time, continuous bacterial infection can cause oxidative stress and an inflammatory response and hinder angiogenesis, resulting in difficult wound healing. Based on the "one stone, three birds" strategy, a multi-functional nanoparticle composite soluble microneedle was designed and developed to solve this dilemma better. Ginsenoside-liposomes(R-Lipo) were prepared by ginsenoside Rg3, which had the effect of promoting repair, instead of cholesterol, and loaded with berberine (Ber), the antibacterial component of Coptis, together with polydopamine (PDA), which had anti-inflammatory and antioxidant properties, into microneedles based on hyaluronic acid (PDA/R-Lipo@BerMN). PDA/R-Lipo@BerMN tip can penetrate and destroy the integrity of the biofilm, dissolve under the action of hyaluronidase in the skin, and gradually release the drug to achieve rapid antibacterial, anti-inflammatory, antioxidant, and proliferation. As expected, the PDA/R-Lipo@BerMN patch effectively cleared ROS during wound closure, further promoted M2 macrophage polarisation, eradicated bacterial infection, and regulated the immune microenvironment, promoting inflammation suppression, collagen deposition, angiogenesis, and tissue regeneration.

Guillain Barré syndrome after combined diphtheria, tetanus, and acellular pertussis (DTaP) vaccine: A rare pediatric case report and review of literature.

A 20-month-old girl was diagnosed with Guillain - Barré syndrome (GBS) based on progressive muscle weakness, areflexia, and albuminocytologic dissociation of the cerebrospinal fluid. Despite timely and systematic treatment, she eventually became paralyzed. There is a temporal correlation between the girl's GBS and the DTaP vaccination, but the exact causal relationship between the two is still debatable. Furthermore, we summarized clinical features of other 45 published GBS cases after DTP vaccines (or vaccine substances containing tetanus) through a systematic review. The mean onset age, sex distribution, onset time after vaccination, detection of antiganglioside antibodies, and other basic clinical features of GBS after DTP vaccination (or vaccine substances containing tetanus) were analyzed. The temporal pattern of GBS after vaccination was similar to that of GBS after infection. Herein, we report this rare case of presumptive pediatric GBS after DTaP vaccination and review similar cases to draw the attention of medical personnel to similar events after vaccination. An association between DTP vaccines and GBS has been proposed, and the causal relationship between these two incidents are worthy further exploration. Moreover, surveillance and vigilance for GBS after vaccination are highly recommended.

Wearable Hydrogel-Based Epidermal Sensor with Thermal Compatibility and Long Term Stability for Smart Colorimetric Multi-Signals Monitoring.

Hydrogel-based wearable epidermal sensors (HWESs) have attracted widespread attention in health monitoring, especially considering their colorimetric readout capability. However, it remains challenging for HWESs to work at extreme temperatures with long term stability due to the existence of water. Herein, a wearable transparent epidermal sensor with thermal compatibility and long term stability for smart colorimetric multi-signals monitoring is developed, based on an anti-freezing and anti-drying hydrogel with high transparency (over 90% transmittance), high stretchability (up to 1500%) and desirable adhesiveness to various kinds of substrates. The hydrogel consists of polyacrylic acid, polyacrylamide, and tannic acid-coated cellulose nanocrystals in glycerin/water binary solvents. When glycerin readily forms strong hydrogen bonds with water, the hydrogel exhibits outstanding thermal compatibility. Furthermore, the hydrogel maintains excellent adhesion, stretchability, and transparency after long term storage (45 days) or at subzero temperatures (-20 °C). For smart colorimetric multi-signals monitoring, the freestanding smart colorimetric HWESs are utilized for simultaneously monitoring the pH, T and light, where colorimetric signals can be read and stored by artificial intelligence strategies in a real time manner. In summary, the developed wearable transparent epidermal sensor holds great potential for monitoring multi-signals with visible readouts in long term health monitoring.

Intraorbital self-inflating hydrogel expander implantation with a modified technique in congenital microphthalmia.

PURPOSE: To investigate the long-term outcomes of intraorbital self-inflating hydrogel expander implantation with optic nerve transection in children with congenital microphthalmia. METHODS: The medical records of unilaterally blind microphthalmic pediatric patients undergoing intraconal hydrogel expander implantation with optic nerve transection were reviewed retrospectively. For each patient, the microphthalmic eye was preserved. The orbital volume and globe volume were measured and analyzed based on computed tomography scans taken preoperatively and 36 months postoperatively. The palpebral length was measured between the medial and lateral canthus at every follow-up. Surgical complications were also recorded. RESULTS: Twelve patients were included (median age, 44.25 ± 17.5 months). At 36 months postoperatively, the microphthalmic and contralateral orbital volumes increased by 3.07 ± 0.77 ml and 2.03 ± 0.67 ml, respectively. The mean microphthalmic/contralateral ratio (MCR) of the orbital volume increased significantly from 76.60% ± 5.46% to 83.81% ± 5.41% (P < 0.001). The microphthalmic palpebral length increased by 6.17 ± 1.85 mm, whereas the contralateral palpebral length increased by 2.67 ± 1.44 mm. Significant changes were observed in the palpebral length MCR (68.00% ± 4.83% vs 85.07% ± 3.87%; P < 0.001). There was no significant change in the microphthalmic globe volume at 36 months postoperatively (P = 0.215). For the fellow eye, the globe volume increased significantly by 0.53 ± 0.34 ml (P < 0.001). During the follow-up period, 2 patients developed a sunken prosthesis. One patient had difficulty opening the eye after wearing the conformer. There were no cases of expander rejection or extrusion. CONCLUSIONS: In this small cohort of patients with congenital microphthalmia, intraorbital self-expanding hydrogel expander implantation with optic nerve transection led to excellent osseous and eyelid growth throughout the 36-month follow-up period.

3D Upconversion Barcodes for Combinatory Wireless Neuromodulation in Behaving Animals.

Upconversion techniques offer all-optical wireless alternatives to modulate targeted neurons in behaving animals, but most existing upconversion-based optogenetic devices show prefixed emission that is used to excite just one channelrhodopsin at a restricted brain region. Here, a hierarchical upconversion device is reported to enable spatially selective and combinatory optogenetics in behaving rodent animals. The device assumes a multiarrayed optrode format containing engineered upconversion nanoparticles (UCNPs) to deliver dynamic light palettes as a function of excitation wavelength. Three primary emissions at 477, 540, and 654 nm are selected to match the absorption of different channelrhodopsins. The UCNPs are barcode assembled to multiple nanomachined optical pinholes in a microscale pipette device to allow remotely addressable, spectrum programmable, and spatially selective optical interrogation of complex brain circuits. Using the unique device, the basolateral amygdala and caudoputamen circuits are selectively modulated and the associated fear or anxiety behavior in freely behaving rodents is successfully differentiated. It is believed that the 3D barcode upconversion device would be a great supplement to current optogenetic toolsets and opens up new possibilities for sophisticated neural control.

Ultralarge anti-Stokes lasing through tandem upconversion.

Coherent ultraviolet light is important for applications in environmental and life sciences. However, direct ultraviolet lasing is constrained by the fabrication challenge and operation cost. Herein, we present a strategy for the indirect generation of deep-ultraviolet lasing through a tandem upconversion process. A core-shell-shell nanoparticle is developed to achieve deep-ultraviolet emission at 290 nm by excitation in the telecommunication wavelength range at 1550 nm. The ultralarge anti-Stokes shift of 1260 nm (~3.5 eV) stems from a tandem combination of distinct upconversion processes that are integrated into separate layers of the core-shell-shell structure. By incorporating the core-shell-shell nanoparticles as gain media into a toroid microcavity, single-mode lasing at 289.2 nm is realized by pumping at 1550 nm. As various optical components are readily available in the mature telecommunication industry, our findings provide a viable solution for constructing miniaturized short-wavelength lasers that are suitable for device applications.

Lanthanide-Based Luminescent Materials for Waveguide and Lasing.

Microlasers and waveguides have wide applications in the fields of photonics and optoelectronics. Lanthanide-doped luminescent materials featuring large Stokes/anti-Stokes shift, long excited-state lifetime as well as sharp emission bandwidth are excellent optical components for photonic applications. In the past few years, great progress has been made in the design and fabrication of lanthanide-based waveguides and lasers at the micrometer length scale. Waveguide structures and microcavities can be fabricated from lanthanide-doped amorphous materials through top-down process. Alternatively, lanthanide-doped organic compounds featuring large absorption cross-section can self-assemble into low-dimensional structures of well-defined size and morphology. In recent years, lanthanide-doped crystalline structures displaying highly tunable excitation and emission properties have emerged as promising waveguide and lasing materials, which substantially extends the range of lasing wavelength. In this minireview, we discuss recent advances in lanthanide-based luminescent materials that are designed for waveguide and lasing applications. We also attempt to highlight challenging problems of these materials that obstacle further development of this field.