Interfacial-engineered living drugs with "ON/OFF" switching for oral delivery.

Living drugs offer a new frontier in medicine, paving the way for personalized and potentially curative treatments. A customized living drug generally requires specialized technologies for highly effective and selective delivery to lesion locations. In this study, we explored an interfacial engineering method for living drugs by wrapping them with a "stealth coating", achieving "ON/OFF" switching of the communications between probiotics and the gastrointesinal (GI) tract. This maximized the bioactivity of living drugs following oral administration to exempt acidic insults and then significantly improved the retention through the gastrointestinal tract. With the notable ability to improve oral availability, the interfacial-engineered living drugs represent remarkable effects for enhanced oral delivery and treatment efficacy in the dextran sulfate sodium (DSS)-induced acute colitis model. We believe that this work has the potential to revolutionize medicine by precisely targeting and increasing curative activity in the future of disease treatment.

Rash caused by lurasidone in old chinese patient with bipolar disorder: case-based review.

BACKGROUND: Rash is one of common adverse drug reaction and which have been reported in typical and atypical antipsychotics. Reports of lurasidone induced skin reactions are sparse. In this study, we report a case of rash caused by lurasidone. CASE PRESENTATION: A 63-year-old man with bipolar disorder (BD) who is treated by lurasidone. However, the patient presents a rash all over after lurasidone dose increasing from 40 mg/day to 60 mg/day. With the diagnosis of drug induced rash, lurasidone was discontinued, and the rash complete disappears within 2 weeks. In addition, all case reports about antipsychotics associated rash were reviewed by searching English and Chinese database including Pubmed, Embase, Cochrane Library, CNKI and Wanfang database. A total of 139 articles contained 172 patients were included in our study. The literature review and our case suggest that the cutaneous adverse events caused by antipsychotic drugs should not be ignored, particularly for the patient who was first use or at dose increasing of antipsychotic. CONCLUSIONS: In conclusion, we report a case of lurasidone related rash and review rash caused by antipsychotics. Psychiatrists should be alert to the possibility of the rash caused by antipsychotics, especially the patient was first use of antipsychotics or the antipsychotic dose was increasing.

Bioinspired aligned wrinkling dressings for monitoring joint motion and promoting joint wound healing.

Joint skin wounds are difficult to treat because of the frequent large motion of these active wounds; thus, dressings capable of simultaneous real-time monitoring of joint motion and promoting joint wound healing are highly needed. Herein, inspired by the aligned wrinkling microstructure and sensing functions of normal joint skins, we combine the electrospinning technique with a water-induced self-assembly approach to prepare bioinspired conductive dressings with aligned wrinkles for achieving the above-mentioned bifunctions. The results indicate that both the wavelength and height of the bioinspired aligned wrinkles can be facilely tuned by adjusting the thickness ratio of the two layers and the loading amount of conductive microparticles. Owing to the unique aligned wrinkling structure and good conductivity, the bioinspired dressing can monitor the donor student's diverse joint motions. Interestingly, the dressing can also accurately monitor different types of mouse neck motion, including up/down and left/right movements. The in vivo wound repairing results confirm that the bioinspired dressing can accelerate the healing of active wounds on the mouse neck by promoting collagen deposition, hair follicle regeneration, and epithelialization. The bioinspired dressing with the integration of real-time motion monitoring features and wound repairing functions will open a new avenue to improve the management of joint wounds.

Clinical effectiveness of orthodontic miniscrew implantation guided by a novel cone beam CT image-based computer aided design and computer aided manufacturing (CAD-CAM) template.

BACKGROUND: Although miniscrews are widely used in orthodontic treatment as temporary anchorage devices, their correct and safe placement has attracted little attention. This study aimed to introduce a novel cone beam CT (CBCT) image-based computer aided design and computer aided manufacturing (CAD-CAM) template for orthodontic miniscrew implantation and to evaluate the effectiveness of miniscrews implanted under the guidance of this template. METHODS: The CBCT scans of ten patients requiring miniscrews as anchorage were analyzed in NNT software to predetermine the insertion sites of miniscrew implants. The DICOM data of the scans, along with virtual miniscrews acquired in Solidworks software, were imported into Mimics software to construct three-dimensional (3D) images of teeth and bone and to determine the virtual position of miniscrews and 3D virtual templates were designed following consideration of the virtual implantation plans. A STL (Stereolithography) file of the virtual template was output, and the resin template was then fabricated with a stereolithographic appliance (SLA). 24 Miniscrews were then implanted guided by the template and clinical evaluation of their safety and stability, as well as their placement deviations, were made. A dental casts model and cephalometric analysis before and after orthodontic treatment were made to assess the dentomaxillofacial changes. RESULTS: All 24 miniscrews had no contact with adjacent roots. 18 miniscrews had a grade I safety score and six had a grade II. The miniscrews were stable at 1, 3, 6, and 9 months after implantation, although there was mild inflammation around two miniscrews. Implantation deviation of miniscrew in the crown was (1.03±0.65) and (1.26±0.72) mm in the apex, on average. Satisfactory dentomaxillofacial changes in 10 patients with these 24 miniscrews as anchorage were acquired. CONCLUSIONS: Miniscrews could be implanted in the targeted position safely and precisely when guided by the novel templates, and remained stable during orthodontic treatment. Patients treated with these miniscrews as anchorage in orthodontic treatment acquired satisfactory dentomaxillofacial changes.

Light-Responsive Nanofibrous Motor with Simultaneously Precise Locomotion and Reversible Deformation.

Light-powered micromotors have drawn enormous attention because of their potential applications in cargo delivery, environmental monitoring, and noninvasive surgery. However, the existing micromotors still suffer from some challenges, including slow speed, poor controllability, single locomotion mode, and no deformation during movement. Herein, we employ a combined electrospinning with brushing of Chinese ink to simply fabricate a light-responsive gradient-structured poly(vinyl alcohol)/carbon (PVA/carbon) composite motor. Because of the surface deposition and ultrahigh loading amount of carbon nanoparticles (ca. 43%), the motor exhibits rapid (39 mm/s), direction-controlled, and multimodal locomotion (vertical movement, horizontal motion, rotation) under light irradiation. Simultaneously, gradient alignment structure of the PVA nanofibrous matrix endows the motor with controllable and reversible deformation during locomotion. We finally demonstrate the potential applications of the motors in leakage monitoring, object salvage, smart access, and intelligent assembly. The present work will inspire the design of novel photosensitive motors for applications in various fields, such as microrobots, environmental monitoring, and biomedicine.

Nanofibrous Actuator with an Alignment Gradient for Millisecond-Responsive, Multidirectional, Multimodal, and Multidimensional Large Deformation.

Although progress has been made in the construction of stimulus-responsive actuators, the performance of these smart materials is still unsatisfactory, owing to their slow response, small deformation amplitude, uncontrollable bending direction, and unidirectional (2D to 3D) transformation. Herein, we employ a structural bionic strategy to design and fabricate a novel water/moisture responsive nanofibrous actuator with an alignment degree gradient. Owing to its different contraction gradient amplitudes along the thickness direction and the unique physical property of the nanofibrous material, the prepared actuator exhibits excellent shape deformation performance, including superfast response (less than 150 ms), controllable deformation directions, multiple actuation models, multiple dimensional deformation (0D-3D, 1D-3D, 2D-3D, and 3D-3D), large bending curvature (25.3 cm-1), and a repeatability rate of at least 1000. The actuation performance of the nanofibrous actuator is superior to the currently reported actuators. The nanofibers are integrated into layer-by-layer and side-by-side structures to achieve competitive and independent actuation, respectively. The outstanding shape-changing properties of the nanofibrous actuator result in the construction of practical intelligent devices for applications such as amphibious movement, intelligent protection, and cargo transportation. The nanofibrous actuator designed herein exhibits tremendous potential in soft robotics, sensors, and biomedicine.

On-Demand Bacterial Reactivation by Restraining within a Triggerable Nanocoating.

Bacteria have been widely exploited as bioagents for applications in diagnosis and treatment, benefitting from their living characteristics including colonization, rapid proliferation, and facile genetic manipulation. As such, bacteria being tailored to perform precisely in the right place at the right time to avoid potential side effects would be of great importance but has proven to be difficult. Here, a strategy of on-demand bacterial reactivation is described by individually restraining within a triggerable nanocoating. Upon reaching at a location of interest, nanocoatings can be triggered to dissolution in situ and subsequently decoat the bacteria which are able to recover their bioactivities as needed. It is demonstrated that gut microbiota coated with an enteric nanocoating can respond to gastrointestinal environments and reactivate in the intestine by a pH-triggered decoating. In virtue of this unique, coated bacteria remain inactive following oral administration to exempt acidic insults, while revive to restore therapeutic effects after gastric emptying. Consequently, improved oral availability and treatment efficacy are achieved in two mouse models of intestinal infection. Bacteria restrained by a triggerable nanocoating represent a smart therapeutic that can take effect when necessary. On-demand bacterial reactivation suggests a robust platform for the development of precision bacterial-mediated bioagents.

Saikosaponin a attenuates hyperlipidemic pancreatitis in rats via the PPAR-γ/NF-κB signaling pathway.

The therapeutic effect of saikosaponin a (SSa) on hyperlipidemic pancreatitis (HP) is not completely understood. The aim of the present study was to investigate the therapeutic effect and the underlying mechanism of SSa using a rat model of HP. Following successful establishment of the HP rat model, different doses of SSa (low dose group, 10 mg/kg or high dose group, 20 mg/kg) were administrated. Histopathological examination, the wet/dry (W/D) ratio and myeloperoxidase (MPO) activity of the pancreatic tissues were assessed. The lipid, amylase (AMY), lipase and proinflammatory cytokine profiles in serum, as well as the expression of peroxisome proliferator-activated receptor (PPAR)-γ and the NF-κB signaling pathway-related proteins in pancreatic tissues were evaluated. The results showed that SSa effectively attenuated pancreatic pathological injury and reduced both the W/D ratio and MPO activity compared to the HP model rats. SSa also improved lipid metabolism by significantly decreasing the serum levels of total cholesterol and triglycerides (P<0.05). Following the administration of SSa, the activity of AMY and lipase, as well as the levels of the proinflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1ß and IL-6 were reduced, particularly in the high dosage group (P<0.05). Furthermore, SSa activated PPAR-γ expression and suppressed the NF-κB signaling pathway in pancreatic tissues. The present study suggested that SSa attenuated HP in rats by increasing lipid metabolism and inhibiting the release of proinflammatory cytokines via the NF-κB inflammatory pathway. The results from the present study indicated that SSa might be a promising therapeutic agent for the treatment of HP.

Unveiling femtosecond rogue-wave structures in noise-like pulses by a stable and synchronized time magnifier.

Mode-locked fiber lasers are an ideal platform for an ultrafast nonlinear physics study, and they have shown many intriguing, yet not fully understood, phenomena such as the optical rogue waves (ORWs) and noise-like pulses (NLPs). However, one of the major obstacles in the study of fiber laser dynamics is the lack of practical measurement techniques for round-trip tracking, and single-shot, real-time observation in the time domain at sub-picosecond (ps) resolution. Here we demonstrate an automatically synchronized characterization of NLPs using a parametric time magnifier. The round-trip evolution of ultrafast temporal structures in the noise-like pulses has been experimentally resolved at sub-ps resolution, to the best of our knowledge, for the first time, and ORWs have been identified.

Window screen inspired fibrous materials with anisotropic thickness gradients for improving light transmittance.

Fibrous materials with high light transmittance exhibit great potential in a wide range of applications; unfortunately, fabrication of such materials still remains a challenge due to the strong light scattering caused by the rough fibrous structure and the voids between fibers. Window screens are commonly used in our daily life, and their unique woven structure ensures excellent mechanical properties, while the voids between wires allow light to pass through. By learning from the architecture of window screens, we proposed a novel patterned electrospinning approach with window screen like wire meshes as collectors to deposit fibers with anisotropic thickness gradients and further to improve the optical properties. The results indicated that the obtained fibrous mats closely copied the structure of the wire meshes, and exhibited unique thickness anisotropy with most of the fibers densely packed on the wires in a small area, while very few fibers sparsely suspended in the voids over a large area. Owing to the large area of the thin region within fibrous mats, the overall light transmittance of such a well-organized mat was greatly improved as compared with that of an isotropous mat. Furthermore, by carefully investigating the microstructure of the fibrous mats and simulating the electric field distribution with the software Comsol Multiphysics, a novel needle array collector with an ultra large area of voids was designed to achieve optimal light transparency. Finally, as proof of concepts, we investigated the potential use of transparent fibrous mats as a visual wound dressing and a window dust filter, respectively.

Enhanced photoluminescence of LEuH nanosheets: 2D photonic crystals self-assembled by core-shell SiO2@LEuH spheres.

The enhancement in photoluminescence (PL) is a challenge for layered rare-earth hydroxides, which usually have weak PL due to the quenching effect of hydroxyls. In this work, we provide a strategy to enhance the PL behavior by constructing two-dimensional (2D) photonic crystals. The core-shell structured SiO2@LEuH spheres were prepared by attaching the positively charged layered europium hydroxide (LEuH) nanosheets onto the negatively charged surfaces of the SiO2 spheres; the core-shell spheres further formed a monolayered 2D colloidal crystal with the hexagonal lattice on a quartz substrate through an evaporation-induced assembly process. The 2D colloidal crystals exhibited a significantly enhanced photoluminescence at 611 nm related to the 5D0 → 7F2 transition of Eu3+ compared with the SiO2@LEuH spheres and the LEuH nanosheets dispersed in deionized water. The emission band of Eu3+ hardly changed in the three samples; therefore, the PL enhancement can be attributed to the emission band located at the short edge of the photonic band-gap of the 2D crystals.

Color-changing smart fibrous materials for naked eye real-time monitoring of wound pH.

Real-time monitoring of wound pH may provide information about the wound healing status and potential bacterial infection. Herein, we integrated the biocompatible color changing substance curcumin into a fibrous material, capable of in situ real-time visually monitoring the wound pH. The results indicate that the curcumin-loaded fibrous mat exhibits an obvious pH-dependent color change from yellow to red brown with a change in pH from 6.0 to 9.0, which can be easily detected by the human naked eye. Moreover, the wound pH conditions can be determined with the aid of a smart phone App after image analysis. Due to their flexibility, the fibrous materials have been further processed into various shapes from 1D to 3D for fitting the irregular wounds. It is believed that smart fibrous materials that can simultaneously real-time monitor the wound pH and repair the wound may change wound management to a convenient and comfortable way.

Video-rate centimeter-range optical coherence tomography based on dual optical frequency combs by electro-optic modulators.

Imaging speed and range are two important parameters for optical coherence tomography (OCT). A conventional video-rate centimeter-range OCT requires an optical source with hundreds of kHz repetition rate and needs the support of broadband detectors and electronics (>1 GHz). In this paper, a type of video-rate centimeter-range OCT system is proposed and demonstrated based on dual optical frequency combs by leveraging electro-optic modulators. The repetition rate difference between dual combs, i.e. the A-scan rate of dual-comb OCT, can be adjusted within 0~6 MHz. By down-converting the interference signal from optical domain to radio-frequency domain through dual comb beating, the down-converted bandwidth of the interference signal is less than 22.5 MHz which is at least two orders of magnitude lower than that in conventional OCT systems. A LabVIEW program is developed for video-rate operation, and the centimeter imaging depth is proved by using 10 pieces of 1-mm thick glass stacked as the sample. The effective beating bandwidth between two optical comb sources is 7 nm corresponding to ~108 comb lines, and the axial resolution of the dual-comb OCT is 158 µm. Dual optical frequency combs provide a promising solution to relax the detection bandwidth requirement in fast long-range OCT systems.

Sensitivity-enhanced ultrafast optical tomography by parametric- and Raman-amplified temporal imaging.

To overcome the speed limitation of conventional optical tomography, a temporal imaging technique has been integrated with optical time-domain reflectometry to realize ultrafast temporally magnified (TM) tomography. In this Letter, the sensitivity of TM tomography has been further enhanced using optical parametric amplification and distributed Raman amplification, and this technique is named temporally encoded amplified and magnified (TEAM) tomography. As a result, a 78-dB sensitivity has been realized, comparable to ultrafast optical coherence tomography systems. In addition, an 86.7-µm axial resolution can be realized across a 67.5-mm imaging range. To demonstrate the significance of sensitivity improvement, tomographic imaging of a centimeter-thick phantom is provided at an A-scan rate of 44 MHz.

102-nm, 44.5-MHz inertial-free swept source by mode-locked fiber laser and time stretch technique for optical coherence tomography.

A swept source with both high repetition-rate and broad bandwidth is indispensable to enable optical coherence tomography (OCT) with high imaging rate and high axial resolution. However, available swept sources are commonly either limited in speed (sub-MHz) by inertial or kinetic component, or limited in bandwidth (<100 nm) by the gain medium. Here we report an ultrafast broadband (over 100 nm centered at 1.55-µm) all-fiber inertial-free swept source built upon a high-power dispersion-managed fiber laser in conjunction with an optical time-stretch module which bypasses complex optical amplification scheme, which result in a portable and compact implementation of time-stretch OCT (TS-OCT) at A-scan rate of 44.5-MHz, axial resolution of 14 µm in air (or 10 µm in tissue), and flat sensitivity roll-off within 4.3 mm imaging range. Together with the demonstration of two- and three-dimensional OCT imaging of a mud-fish eye anterior segment, we also perform comprehensive studies on the imaging depth, receiver bandwidth, and group velocity dispersion condition. This all-fiber inertia-free swept source could provide a promising source solution for SS-OCT system to realize high-performance volumetric OCT imaging in real time.

Energy transfer between rare earths in layered rare-earth hydroxides.

Energy transfer between rare earths in layered rare-earth hydroxides (LRHs) is worth the intensive study because the hydroxyls that act as the bridge connecting the neighbouring rare earths would generate non-radiative transitions. This study focuses on the energy transfer in the intralayer and the adjacent layers of LRHs. A series of LEu x Tb1-x Hs (x = 0, 0.05, 0.2, 0.5, 0.8, and 0.95) was synthesized, the basal spacing (d basal) was adjusted from 8.3 to 46 Å through ion-exchange process, and unilamellar nanosheets were prepared through a delamination process. The luminescence behaviours of the samples demonstrated the following: (1) for the delaminated nanosheets, the quenching effect of both Eu3+ and Tb3+ was hardly observed. This implies that in the intralayer, the efficiency of energy transfer is extremely low, so that highly-concentrated co-doping does not influence the luminescence and by controlling the Eu/Tb molar ratio, white light can be obtained. (2) For small d basal, e.g., 27 Å, the fluorescence quenching of Tb3+ and Eu3+ was remarkable, while for large d basal, e.g., 46 Å, the emission of Tb3+ emerged and the self-quenching between Eu3+ ions weakened. (3) The energy transfer efficiency deceased with an increase in the distance between adjacent layers. In other words, either the energy transfer between Eu3+ and Tb3+ or the energy migration between Eu3+ ions was more efficient when they were located in adjacent layers than in intralayers even when they were the nearest neighbours.