Immunosuppressive microvesicles-mimetic derived from tolerant dendritic cells to target T-lymphocytes for inflammation diseases therapy.

The utilization of extracellular vesicles (EV) in immunotherapy, aiming at suppressing peripheral immune cells responsible for inflammation, has demonstrated significant efficacy in treating various inflammatory diseases. However, the clinical application of EV has faced challenges due to their inadequate targeting ability. In addition, most of the circulating EV would be cleared by the liver, resulting in a short biological half-life after systemic administration. Inspired by the natural microvesicles (MV, as a subset of large size EV) are originated and shed from the plasma membrane, we developed the immunosuppressive MV-mimetic (MVM) from endotoxin tolerant dendritic cells (DC) by a straightforward and effective extrusion approach, in which DC surface proteins were inherited for providing the homing ability to the spleen, while αCD3 antibodies were conjugated to the MVM membranes for specific targeting of T cells. The engineered MVM carried a large number of bioactive cargos from the parental cells, which exhibited a remarkable ability to promote the induction of regulatory T cells (Treg) and polarization of anti-inflammatory M2 macrophages. Mechanistically, the elevated Treg level by MVM was mediated due to the upregulation of miR-155-3p. Furthermore, it was observed that systemic and local immunosuppression was induced by MVM in models of sepsis and rheumatoid arthritis through the improvement of Treg and M2 macrophages. These findings reveal a promising cell-free strategy for managing inflammatory responses to infections or tissue injury, thereby maintaining immune homeostasis.

Reduced radiation dose and volume of contrast medium in heart rate-based, one-stop computed tomography angiography of coronary, carotid and cerebrovascular arteries.

BACKGROUND: Computed tomography angiography (CTA) is a reliable, non-invasive screening method for diagnosing panvascular disease. By using low contrast agent volume, CTA imaging enables one-stop multi-organ scanning, thereby minimizing the potential risk of contrast-induced nephropathy in patients with impaired renal function. PURPOSE: To evaluate the feasibility of one-stop CTA following a heart rate (HR)-based protocol using a low volume of contrast medium (CM) for examination of the coronary, carotid and cerebrovascular arteries. MATERIAL AND METHODS: Sixty patients undergoing coronary carotid, and cerebrovascular CTA after a single injection of CM were recruited and randomly divided into two groups. Group A (n = 30) underwent CTA following a traditional protocol. The timing of the scans in Group B (n = 30) was determined according to the patient's HR. RESULTS: The CT values for the thoracic aorta (432.2 ± 104.28 HU), anterior cerebral artery (303.96 ± 99.29 HU), and right coronary artery (366.70 ± 85.10 HU) in Group A did not differ significantly from those in Group B (445.80 ± 106.13, 293.73 ± 75.25 and 344.13 ± 111.04 HU, respectively). The qualities of most of the scanned images for both groups were scored as 3 or 4 (on a five-point scale). The radiation dose and the volume of CM were significantly higher in Group A (303.05 ± 110.95 mGy) (100 mL) than in Group B (239.46 ± 101.12 mGy) (50 mL). CONCLUSION: The radiation dose and volume of CM were significantly reduced in CTA following the HR-based protocol. The personalized administration of CM also simplified the scanning process.

Improved performance of UV-blue dual-band Bi2O3/TiO2 photodetectors and application of visible light communication with UV light encryption.

In this paper, self-powered photodetectors (PDs) with a dual-band photoresponse and excellent photodetection capabilities in complex environments can meet the needs of diverse detection targets, complex environments and diverse tasks. Herein, Bi2O3 nanosheets were deposited on the surface of TiO2 nanorod arrays (NRs) by chemical bath deposition (CBD) to construct self-powered heterojunction PDs with a UV-blue dual-band photoresponse. The nucleation and growth of Bi2O3 nanosheets on TiO2 NRs substrates were controlled by varying the concentration of the complexing agent triethanolamine (TEA) in the precursor solution, which regulated the morphology, crystalline quality and energy band structure as well as the photoelectronic properties of Bi2O3 films. The devices fabricated at a TEA concentration of 0.3 M exhibited excellent self-powered UV-blue dual-band photoresponse characteristics, achieving a photocurrent (Iph) of 144 nA, a responsivity of 1.79 mA W-1 and a detectivity of 5.94 × 1010 Jones under 405 nm illumination at 0 V, which can be attributed to the large built-in electric field (Eb) of Bi2O3/TiO2 heterojunctions, the low interfacial transfer resistance and suitable carrier transport path. In addition, Bi2O3/TiO2 heterojunction PDs with the UV-blue dual-band photoresponse characteristics can be applied in UV-encrypted visible light communication (VLC) with a light-controlled logic gate to improve the security of information transmission.

How social connectedness contributes to life satisfaction among Chinese nurses: Testing potential moderated mediation pathways.

AIMS: The purpose of this study was to identify the mediating and moderating mechanisms by which social connectedness predicts life satisfaction among Chinese nurses. BACKGROUND: Previous researchers have primarily focused on sociodemographic and occupational domain risk factors for nurses' life satisfaction with relatively little insight into facilitative and protective factors and underlying psychological mechanisms. METHODS: We investigated 459 Chinese nurses' social connectedness, work-family enrichment, self-concept clarity, and life satisfaction via a cross-sectional design. We explored the underlying predictive mechanisms among these variables by creating a moderated mediation model. We followed STROBE checklist. RESULTS: Work-family enrichment played a mediating role in understanding the positive effects of social connectedness on nurses' life satisfaction. In addition, the moderating effect of self-concept clarity was manifested itself in the association between work-family enrichment and life satisfaction. DISCUSSION AND CONCLUSION: Interpersonal asset (social connectedness) and the positive aspect of the work-family interface (work-family enrichment) were significant contributors to nurses' life satisfaction. In particular, high self-concept clarity can enhance the beneficial effect of work-family enrichment on life satisfaction. IMPLICATIONS FOR NURSING POLICY AND PRACTICE: Strengthening social connectedness, promoting synergy in work-family roles, and maintaining a clarity of self-concept are important intervention pathways to enhance the health and well-being of nurses.

Recurrent Guillain-Barré syndrome presenting as pharyngeal-cervical-brachial variant with three species of ganglioside antibodies:case report.

BACKGROUND: Guillain-Barré syndrome (GBS) is generally considered to be monophasic, and recurrent GBS (RGBS) is very rare. Pharyngeal-cervical-brachial (PCB) is a less common variant of GBS. There have been no cases reported describing RGBS showing different phenotype presenting as PCB variant with three species of ganglioside antibodies. CASE PRESENTATION:  We report a case of a 77-year-old female patient with GT1a, GD1a and sulfatide-seropositive PCB-GBS after prior episode of AMAN-GBS 13 years ago. Our patient showed oropharyngeal and cervicobrachial weakness associated with areflexia in the upper limbs and partially improved after 5 days of IVIG and physiotherapy. CONCLUSION: This study reports a rare case characterized as recurrent GBS after a long period, showing different phenotypes in different episodes with three different species of ganglioside antibodies. Further studies are required to obtain better understanding of RGBS and PCB variant.

Different memory patterns of digits: a functional MRI study.

BACKGROUND: Psychological investigations and functional imaging technology have been used to describe neural correlations of different types of memory with various stimuli. Memory with limited storage capacity and a short retention time can be classified as short-term memory (STM) while long-term memory (LTM) can be life-long without defined capacity. METHODS: To identify brain activation pattern associated with different modes of memory for numerical figures, we detected brain activities from twenty-two healthy subjects when performing three types of memory tasks for numbers, namely STM, LTM and working memory (WM), by using functional magnetic resonance imaging (fMRI) technique. RESULTS: The result revealed variable patterns of activation in different brain regions responding to different types of memory tasks. The activation regions with primary processing and transient maintenance of STM for numerical figures are located in the visual cortex and mainly encoded by visual representations, while LTM was encoded by semantics and mainly recruiting left frontal cortex. We also found that subcortical structures, such as the caudate nucleus and the marginal division of the striatum, plays important roles in working memory. CONCLUSIONS: Activation of different brain regions in these three kinds of memories, indicating that different kinds of memories rely on different neural correlates and mental processes.

Generation of a dark spot beyond the diffraction limit with a radially polarized vortex beam.

We propose and demonstrate that a dark spot can be generated by a radially polarized beam with a first-order vortex after phase modulation by an optimal binary phase element. The distance between two mainlobe intensity peaks along the radial direction is 0.62λ on the focal plane. The proposed system is easy to implement in practice and has low energy loss, since it uses phase-only modulation. Then, the fluorescent spot is calculated for stimulated emission depletion microscopy when a radially polarized beam works as the pump beam. The FWHM of the fluorescent spot can achieve 0.008λ for a saturated case. This is much smaller than that achieved using a circular polarized vortex erase beam (0.0422λ) or an azimuthally polarized erase beam with optimizing amplitude-phase modulation (0.0279λ).

Self-powered SnSx/TiO2 photodetectors (PDs) with dual-band binary response and the applications in imaging and light-encrypted logic gates.

In this work, we report the design and fabrication of self-powered binary response PDs based on II-type heterostructures consisting of SnSx nanoflakes (NFs) and rutile TiO2 nanorod arrays (NRs). The TiO2 NRs effectively block light with wavelengths below 400 nm from reaching SnSx. Under 385 nm light, the photoelectrons in TiO2 recombine with holes in SnSx at the interface due to the energy band bending, resulting in a positive photocurrent. Under 410 nm light, the photoelectrons in SnSx and the photogenerated holes in TiO2 accumulate at the interface, overcoming the interfacial potential barriers induced by the higher Fermi levels of SnSx and inducing a negative photocurrent. Based on the bipolar response, the dual-band imaging capability without external filters and the light-encrypted OR, AND, and NOT logic gates using a single device are demonstrated. This work provides a blueprint for the development of multifunctional self-powered PDs that can simplify system architecture, reduce the energy consumption, and improve accuracy for applications, such as visual systems, light-controlled logic circuits, and encrypted optical communications.

Engineering Efferocytosis-Mimicking Nanovesicles to Regulate Joint Anti-Inflammation and Peripheral Immunosuppression for Rheumatoid Arthritis Therapy.

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation of the synovial joints and the dysfunction of regulatory T cells (Tregs) in the peripheral blood. Therefore, an optimal treatment strategy should aim to eliminate the inflammatory response in the joints and simultaneously restore the immune tolerance of Tregs in peripheral blood. Accordingly, we developed an efferocytosis-mimicking nanovesicle that contains three functional factors for immunomodulating of efferocytosis, including "find me" and "eat me" signals for professional (macrophage) or non-professional phagocytes (T lymphocyte), and "apoptotic metabolite" for metabolite digestion. We showed that efferocytosis-mimicking nanovesicles targeted the inflamed joints and spleen of mice with collagen-induced arthritis, further recruiting and selectively binding to macrophages and T lymphocytes to induce M2 macrophage polarization and Treg differentiation and T helper cell 17 (Th17) recession. Under systemic administration, the efferocytosis-mimicking nanovesicles effectively maintained the pro-inflammatory M1/anti-inflammatory M2 macrophage balance in joints and the Treg/Th17 imbalance in peripheral blood to prevent RA progression. This study demonstrates the potential of efferocytosis-mimicking nanovesicles for RA immunotherapy.

Self-Powered UV Photodetector of TiO2 with BaTiO3 Surface Modification and Light-Controlled Logic Circuits Application.

One-dimensional (1D) metal oxides with excellent carrier transport and light absorption properties can be applied to photodetectors (PDs), facilitating device miniaturization, portability, and integration. Surface modification of 1D semiconductors can reduce carrier recombination in PDs as a way to increase photocurrent and decrease dark current of PDs. Herein, ultrathin BaTiO3 (BTO) shell layers are grown on the surface of TiO2 nanorod arrays (NRs) by in situ conversion using hydrothermal reaction, and the self-powered TiO2-BTO NRs PDs are constructed. The effect of the thickness of BTO shell layers on the photoresponse characteristics of self-powered TiO2-BTO NRs PDs is investigated by controlling the Ba2+ conversion concentration. The results show that the BTO shell layer reduces the dark current of the PDs because of the decreased interfacial transfer resistance and improved transfer of photogenerated carriers for building a "bridge" of carrier transport between BTO and TiO2 due to the formation of Ti-O-Ti bonds. Moreover, the presence of the spontaneous polarization electric field in BTO enhances the photocurrent and response speed of PDs. The self-powered TiO2-BTO NRs PDs are integrated in series and parallel to realize the functions of "and" and "or" gates of light-controlled logic gates. The ability to convert light signals into electrical signals for the self-powered PDs in real time demonstrates its great potential for optoelectronic interconnection circuits, which has important application prospects in the field of optical communication.

Polyethylene-Glycol-Modified Halide Perovskite for Enhancing the Switching Ratio and Cycling Stability of Resistive Random Access Memory.

As a result of the apparent hysteresis caused by ion migration, halide perovskites (HPs) are used as the active layer of resistive devices. Here, polyethylene glycol (PEG) is used to form an organic network in the Cs3Bi2Br9 precursor solution to influence the nucleation growth rate of the substrate and, thus, control the perovskite surface morphology, crystallization process, and halide ion migration activation energy. Furthermore, the organic network consisting of non-conducting polymer PEG rests on the boundaries between perovskite crystals to cross-link perovskite particles. As a result, the particle size of perovskite increased from 64.6 to 76.2 nm as the nucleation rate of perovskite gradually decreased with the increase of the PEG concentration and the activation energy of the ion increases from 0.15 to 0.25 eV. Meanwhile, as the concentration of PEG increases, the switching ratio and cycle stability of the devices is improved.

Novel Self-Powered Photodetector with Binary Photoswitching Based on SnSx/TiO2 Heterojunctions.

Binary photoresponse characteristics can help realize optical signal processing and logic operations. UV photodetectors (PDs) with SnSx nanoflakes and TiO2 nanorod arrays (NRs) show a novel binary photoswitching behavior (change in current from positive to negative) by manipulating the light wavelength without an external power source, utilizing the interfacial recombination of the photogenerated carriers in the type-I SnSx/TiO2 heterojunctions. The enhanced responsivity (R*), detectivity (D*), and fast photoresponse time for self-powered SnSx/TiO2PDs can be achieved by adjusting the phase ratio of SnS and SnS2 nanoflakes. The binary photoswitching in the self-powered UV PDs can be applied in the encrypted optical signal processing and imaging in some special conditions without external bias.

Fasudil alleviates brain damage in rats after carbon monoxide poisoning through regulating neurite outgrowth inhibitor/oligodendrocytemyelin glycoprotein signalling pathway.

Carbon monoxide (CO) poisoning can lead to many serious neurological symptoms. Currently, there are no effective therapies for CO poisoning. In this study, rats exposed to CO received hyperbaric oxygen therapy, and those in the Fasudil group were given additional Fasudil injection once daily. We found that the escape latency in CO poisoning group (CO group) was significantly prolonged, the T1 /Ttotal was obviously decreased, and the mean escape time and the active escape latency were notably extended compared with those in normal control group (NC group, P < 0.05). After administration of Fasudil, the escape latency was significantly shortened, T1 /Ttotal was gradually increased as compared with CO group (>1 week, P < 0.05). Ultrastructural damage of neurons and blood-brain barrier of rats was serious in CO group, while the structural and functional integrity of neuron and mitochondria maintained relatively well in Fasudil group. Moreover, we also noted that the expressions of neurite outgrowth inhibitor (Nogo), oligodendrocyte-myelin glycoprotein (OMgp) and Rock in brain tissue were significantly increased in CO group, and the elevated levels of the three proteins were still observed at 2 months after CO poisoning. Fasudil markedly reduced their expressions compared with those of CO group (P < 0.05). In summary, the activation of Nogo-OMgp/Rho signalling pathway is associated with brain injury in rats with CO poisoning. Fasudil can efficiently down-regulate the expressions of Nogo, OMgp and Rock proteins, paving a way for the treatment of acute brain damage after CO poisoning.

Safety and efficacy of T-614 in the treatment of patients with active rheumatoid arthritis: a double blind, randomized, placebo-controlled and multicenter trial.

BACKGROUND: A novel anti-rheumatic drug, T-614, has been shown to have an anti-inflammatory effect and to improve abnormal immunological findings in rheumatoid arthritis (RA). To assess the safety and efficacy of T-614 versus placebo in patients with active RA we conducted a 24-week clinical study in 280 Chinese patients. METHODS: In a multicenter, randomized, double blind, placebo controlled study, 280 patients were randomly assigned to receive placebo (n = 95) or T-614 at 50 mg (n = 93) or 25 mg (n = 92) daily. Active disease was defined by 4 of the following 5 criteria: >or= 5 tender joints, >or= 3 swollen joints, morning stiffness lasting for >or= 60 minutes, and Westergren erythrocyte sedimentation rate (ESR) >or= 28 mm/h, the assessment of pain at the rest by patient as moderate or severe. Clinical and laboratory parameters were analyzed at baseline, 2, 4, 6, 12, 18 and 24 weeks. The primary efficacy variable at week 24 was the American College of Rheumatology (ACR) response rate using the intent-to-treat population. RESULTS: The ACR response rate was significantly higher in the T-614 treatment group compared with the placebo group within 8 weeks after the initiation of treatment. After 24 weeks, the 25 mg/d and 50 mg/d dosage groups and the placebo group showed 39.13%, 61.29% and 24.21% in ACR20 and 23.91%, 31.18% and 7.37% in ACR50, respectively. A time-response in ACR response was observed, with clear superiority for the 25 mg/d and 50 mg/d dosage groups compared to placebo (P < 0.0001), and the 50 mg/d dose compared to the 25 mg/d dose (P < 0.05) when using the ACR response analyses after 24 weeks. ESR and c-reactive protein (CRP) were significantly different in the treatment groups after 24 weeks. The incidence of adverse events (AEs) was not significantly higher with T-614 than with placebo, but upper abdominal discomfort, leucopenia, elevated serum alanine aminotransferase (sALT), skin rash and/or pruritus were more common in the 50 mg and 25 mg dosage groups. CONCLUSION: T-614, a new slow-acting drug, is effective in treatment of rheumatoid arthritis and is well tolerated.