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Interleukin-27 is constitutively secreted by microglia in the retina or brain, and upregulation of IL-27 during neuroinflammation suppresses encephalomyelitis and autoimmune uveitis. However, while IL-35 is structurally and functionally similar to IL-27, the intrinsic roles of IL-35 in CNS tissues are unknown. Thus, we generated IL-35/YFP-knock-in reporter mice (p35-KI) and demonstrated that photoreceptor neurons constitutively secrete IL-35, which might protect the retina from persistent low-grade inflammation that can impair photoreceptor functions. Furthermore, the p35-KI mouse, which is hemizygous at the il12a locus, develops more severe uveitis because of reduced IL-35 expression. Interestingly, onset and exacerbation of uveitis in p35-KI mice caused by extravasation of proinflammatory Th1/Th17 lymphocytes into the retina were preceded by a dramatic decrease of IL-35, attributable to massive death of photoreceptor cells. Thus, while inflammation-induced death of photoreceptors and loss of protective effects of IL-35 exacerbated uveitis, our data also suggest that constitutive production of IL-35 in the retina might have housekeeping functions that promote sterilization immunity in the neuroretina and maintain ocular immune privilege. [ABSTRACT FROM AUTHOR]

Grating interferometers that use large two-dimensional grating splice modules for performing wide-range measurements have significant advantages for identifying the position of the wafer stage. However, the manufacturing process of large two-dimensional grating splice modules is very difficult. In contrast to existing redundant designs in the grating line dimension, we propose a novel interferometric reading head with a redundant design for obtaining wide-range displacement measurements. This interferometric reading head uses a one-dimensional grating splice module, and it was observed to be compatible with two orthogonal gratings. We designed a grating interferometer system composed of four reading heads to achieve a wide range of measurements and verified it using ZEMAX simulation. By conducting experiments, we were able to verify the compatibility of the reading head with gratings possessing different grating line directions; the measurement noise was found to be less than 0.3 nm. [ABSTRACT FROM AUTHOR]

Volatile organic compounds (VOCs) in indoor air are considered a major threat to human health and environmental safety. The development of applicable technologies for the removal of VOCs is urgently needed. Nowadays, photocatalytic oxidation (PCO) based on metal-containing photocatalysts has been regarded as a promising method. However, unmodified photocatalysts are generally limited in applications because of the narrow light response range and high recombination rate of photo-generated carriers. As a result, nano metal-containing photocatalysts doped with elements or other materials have attracted much attention from researchers and has developed over the past few decades. In addition, different doping types cause different levels of catalyst performance, and the mechanism for performance improving is also different. However, there are few reviews focusing on this aspect, which is really important for catalyst design and application. This work aims to give a comprehensive overview of nano metal-containing photocatalysts with different doping types for the removal of VOCs in an indoor environment. First, the undoped photocatalysts and the basic mechanism of PCO is introduced. Then, the application of metal doping, non-metal doping, co-doping, and other material doping in synthetic metal-containing photocatalysts are discussed and compared, respectively, and the synthesis methods, removal efficiency, and mechanisms are further investigated. Finally, a development trend for using nano metal-containing photocatalysts for the removal of VOCs in the future is proposed. This work provides a meaningful reference for selecting effective strategies to develop novel photocatalysts for the removal of VOCs in the future. [ABSTRACT FROM AUTHOR]

Proinflammatory T-lymphocytes recruited into the brain and spinal cord mediate multiple sclerosis (MS) and currently there is no cure for MS. IFN-γ-producing Th1 cells induce ascending paralysis in the spinal cord while IL-17-producing Th17 cells mediate cerebellar ataxia. STAT1 and STAT3 are required for Th1 and Th17 development, respectively, and the simultaneous targeting of STAT1 and STAT3 pathways is therefore a potential therapeutic strategy for suppressing disease in the spinal cord and brain. However, the pharmacological targeting of STAT1 and STAT3 presents significant challenges because of their intracellular localization. We have developed a STAT-specific single-domain nanobody (SBT-100) derived from camelids that targets conserved residues in Src homolog 2 (SH2) domains of STAT1 and STAT3. This study investigated whether SBT-100 could suppress experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We show that SBT-100 ameliorates encephalomyelitis through suppressing the expansion of Th17 and Th1 cells in the brain and spinal cord. Adoptive transfer experiments revealed that lymphocytes from SBT-100-treated EAE mice have reduced capacity to induce EAE, indicating that the immunosuppressive effects derived from the direct suppression of encephalitogenic T-cells. The small size of SBT-100 makes this STAT-specific nanobody a promising immunotherapy for CNS autoimmune diseases, including multiple sclerosis. [ABSTRACT FROM AUTHOR]

E0703, a new steroidal compound optimized from estradiol, significantly increased cell proliferation and the survival rate of KM mice and beagles after ionizing radiation. In this study, we characterize its preclinical pharmacokinetics (PK) and predict its human PK using a physiologically based pharmacokinetic (PBPK) model. The preclinical PK of E0703 was studied in mice and Rhesus monkeys. Asian human clearance (CL) values for E0703 were predicted from various allometric methods. The human PK profiles of E0703 (30 mg) were predicted by the PBPK model in Gastro Plus software 9.8 (SimulationsPlus, Lancaster, CA, USA). Furthermore, tissue distribution and the human PK profiles of different administration dosages and forms were predicted. The 0.002 L/h of CL and 0.005 L of Vss in mice were calculated and optimized from observed PK data. The plasma exposure of E0703 was availably predicted by the CL using the simple allometry (SA) method. The plasma concentration–time profiles of other dosages (20 and 40 mg) and two oral administrations (30 mg) were well-fitted to the observed values. In addition, the PK profile of target organs for E0703 exhibited a higher peak concentration (Cmax) and AUC than plasma. The developed E0703-PBPK model, which is precisely applicable to multiple species, benefits from further clinical development to predict PK in humans. [ABSTRACT FROM AUTHOR]