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Neuromyelitis optica spectrum disorders (NMOSD) is a rare autoimmune disorder that causes severe inflammation in the central nervous system (CNS), primarily affecting the optic nerves, spinal cord, and brainstem. Aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) are a diagnostic marker of the disease and play a significant role in its pathogenesis, though the exact mechanism is not yet fully understood. To develop rodent models that best simulate the in vivo pathological and physiological processes of NMOSD, researchers have been continuously exploring how to establish the ideal model. In this process, two key issues arise: 1) how the AQP4 antibody crosses the blood-brain barrier, and 2) the source of the AQP4 antibody. These two factors are critical for the successful development of rodent models of NMOSD. This paper reviews the current state of research on these two aspects.

The ability to control the activity of CRISPR-dCas9 with precise spatiotemporal resolution will enable tight genome regulation of user-defined endogenous genes for studying the dynamics of transcriptional regulation. Optogenetic devices with minimal phototoxicity and the capacity for deep tissue penetration are extremely useful for precise spatiotemporal control of cellular behavior and for future clinic translational research. Therefore, capitalizing on synthetic biology and optogenetic design principles, we engineered a far-red light (FRL)-activated CRISPR-dCas9 effector (FACE) device that induces transcription of exogenous or endogenous genes in the presence of FRL stimulation. This versatile system provides a robust and convenient method for precise spatiotemporal control of endogenous gene expression and also has been demonstrated to mediate targeted epigenetic modulation, which can be utilized to efficiently promote differentiation of induced pluripotent stem cells into functional neurons by up-regulating a single neural transcription factor, NEUROG2. This FACE system might facilitate genetic/epigenetic reprogramming in basic biological research and regenerative medicine for future biomedical applications.

Silicon nitride was firstly used as anticorrosive pigment in organic coatings. An effective strategy by combining inorganic fillers and organosilanes was used to enhance the dispersibility of silicon nitride in epoxy resin. The formed nanocomposites were applied to protect Q235 carbon steel from corrosion. The anticorrosive performance of modified silicon nitride with silane (KH-570) was investigated by electrochemical impedance spectroscopy (EIS), water absorption and pull-off adhesion methods. With the increase of immersion time, the corrosion resistance as well as adhesion strength of epoxy resin coating and unmodified silicon nitride coating decreased significantly. However, for the modified silicon nitride coating, the corrosion resistance and adhesion strength still maintained 5.7×10 10 Ω cm 2 and 7.6 MPa after 2400-h and 1200-h immersion, respectively. The excellent corrosion resistance performance could be attributed to the chemical interactions between KH-570 functional groups and silicon nitride powders, which mainly came from the easy formation of Si-O-Si bonds. Furthermore, the modified silicon nitride coating formed a strong barrier to corrosive electrolyte due to the hydrophobic of modified silicon nitride powder and increased bonds.

Marine natural products (MNPs) are valuable resources for drug development. To date, 17 drugs from marine sources are in clinical use, and 33 pharmaceutical compounds are in clinical trials. Presently the success of drug development from the marine resources is higher than the industry average. It is a feasible strategy to conduct the discovery of drug-lead compounds based on marine chemical ecology by fully exploiting the pharmacological potential of marine chemical defense matters. In the search for bioactive MNPs, our group has constructed a biological resources library including more than 1500 strains of fungi. Focusing on the strategy of Blue Drug Library, we have discovered a series of novel MNPs with abundant biological functions. Highly efficient and scalable total synthesis of (+)-aniduquinolone A ( 44 ) and pesimquinolone I ( 48 ) have been completed, which will facilitate access to sufficient quantities of candidates for in vivo pharmacological and toxicological studies. As a nucleoprotein (NP) inhibitor, QLA ( 75 ) possesses significant anti-influenza A virus (IAV) activities both in vitro and in vivo . CHNQD-00803 ( 76 ) is a potent and selective AMP-activated kinase (AMPK) activator that can effectively inhibit metabolic disorders and metabolic dysfunction-associated steatohepatitis (MASH) progression. Moreover, we identified two new candidate molecules with potent anti-hepatocellular carcinoma effects. Particularly, as a natural guanine-nucleotide exchange factors for ADP-ribosylation factor GTPases (Arf-GEFs) inhibitor prodrug, CHNQD-01255 ( 78 ) is qualified to be developed as a targeted candidate anticancer drug, which may be promising to apply for cancer immunotherapy. Hence, it is evident that MNPs play an important role in drug development.

Recent works on fine-grained visual categorization rely on detecting discriminative regions that correspond to specific visual patterns. Promising progress has been obtained by constructing complicated network architecture, which either involves explicitly or implicitly capturing subtle differences to learn part-level representations. Instead of sophisticated model designs, we consider the learning paradigm of data augmentation to utilize subtle cues through a single vanilla neural network (e.g., ResNet). However, the powerful regional dropout strategy, Cutout , which randomly overlays a square patch of inputs in training, may produce inefficient images for fine-grained classification. This is because constant and causal block extent is potentially inflexible for the variety of object position and size. To generate more reasonable samples, we propose an enhanced image synthesis strategy called Attentive Cutout , which purposefully conceals informative details by performing attention-guided content sampling on the high responses from channels. As the feature channels generally represent the multitude of different clues for specified categories, our method is capable of selecting distinct parts to occlude in every iteration. Compare with previous synthesizing training data approaches, Attentive Cutout ensures more diversity and attends to part-level features among generated images. Extensive experiments and analysis studies demonstrate the effectiveness of our approach, which is efficient but easy to implement and achieves competitive performance with structure-based methods.

Bronchopulmonary dysplasia (BPD) is a major complication in preterm infants, particularly those born before 33 weeks of gestation. Inhaled nitric oxide (iNO) is widely used to manage pulmonary hypertension (PH) and improve oxygenation, but its role in reducing BPD incidence in preterm infants with PH during the early postnatal period remains unclear. This study aimed to evaluate the impact of early iNO administration, both alone and in combination with pulmonary surfactant (PS), on the incidence of BPD in preterm infants diagnosed with PH within the first three days of life. A retrospective cohort study was conducted on 56 preterm infants (< 33 weeks gestation) with confirmed PH and hypoxemia (PaO₂ < 50 mmHg at FiO₂ ≥ 30%). Clinical outcomes, including BPD incidence, were compared between infants receiving iNO and/or PS and those who did not. Multivariate logistic regression was used to identify independent predictors of BPD. The incidence of BPD was significantly lower in the iNO group (15%) compared to the non-iNO group (63.9%) ( P  = 0.012). Infants receiving both iNO and PS demonstrated the best outcomes, with a marked reduction in BPD risk. Male gender and lack of PS therapy were associated with increased BPD risk. Multivariate analysis confirmed iNO (OR = 0.097, 95% CI: 0.014–0.682; P  = 0.019) and PS (OR = 0.125, 95% CI: 0.021–0.728; P  = 0.021) as independent protective factors against BPD. Early administration of iNO, particularly in combination with PS, significantly reduces the incidence of BPD in preterm infants with PH. These findings highlight the potential benefits of iNO and PS as preventive therapies in this high-risk population. Further prospective studies are needed to validate these results and guide clinical practice.

In order to study the impact of gas released from coal fire combustion on the spatial–temporal distribution of CO 2 and CH 4 and other greenhouse gas emissions, the impact of regional coal fire on CO 2 and CH 4 emission flux was comprehensively evaluated using Landsat 8 and GOSAT satellite data in Xinjiang. In addition, typical fire areas are selected, a single-channel algorithm is used to invert the surface temperature of the coal field, the spatial distribution of the coal fire area is extracted by setting the threshold, and the influence law of CO 2 and CH 4 emissions in the typical fire area is accurately analyzed. The results show that during 2017–2018, CO 2 and CH 4 emissions in Xinjiang were generally dispersed and locally concentrated, while CO 2 -O and CH 4 -O were at low levels in most regions, fluctuating in the ranges of 0.01 ~ 0.14 g·m −2 ·day −1 and 0.001 ~ 0.003 g·m −2 ·day −1 , respectively. However, the emission intensity of CO 2 -O and CH 4 -O in coal fire concentrated areas is higher, which are 1.6 ~ 3.8 g·m −2  day −1 and 0.013 ~ 0.026 g·m −2 ·day −1 , respectively. CO 2 -F and CH 4 -ag have similar laws. The fire area of Daquan Lake is scattered, and there are four areas with the surface temperature over 35 °C: A, B, C, and D, respectively. The Sandaoba fire area is more concentrated, and only two areas are E and F when the surface temperature exceeds 35 °C. CO 2 and CH 4 released by burning in Daquan Lake and Sandaoba fire areas increased CO 2 -F and CH 4 -ag by 2.08 and 0.89 times, respectively. The results provide a reference for coal fire control and carbon emission reduction.

The combination of ASC22, an anti-PD-L1 antibody potentially enhancing HIV-specific immunity and chidamide, a HIV latency reversal agent, may serve as a strategy for antiretroviral therapy-free virological control for HIV. People living with HIV, having achieved virological suppression, were enrolled to receive ASC22 and chidamide treatment in addition to their antiretroviral therapy. Participants were monitored over 24 weeks to measure changes in viral dynamics and the function of HIV-specific CD8 + T cells (NCT05129189). 15 participants completed the study. At week 8, CA HIV RNA levels showed a significant increase from baseline, and the values returned to baseline after discontinuing ASC22 and chidamide. The total HIV DNA was only transiently increased at week 4 ( P  = 0.014). In contrast, integrated HIV DNA did not significantly differ from baseline. Increases in the proportions of effector memory CD4 + and CD8 + T cells (T EM ) were observed from baseline to week 24 ( P  = 0.034 and P  = 0.002, respectively). The combination treatment did not succeed in enhancing the function of HIV Gag/Pol- specific CD8 + T cells. Nevertheless, at week 8, a negative correlation was identified between the proportions of HIV Gag-specific T EM cells and alterations in integrated DNA in the T cell function improved group ( P  = 0.042 and P  = 0.034, respectively). Nine adverse events were solicited, all of which were graded 1 and resolved spontaneously. The combined treatment of ASC22 and chidamide was demonstrated to be well-tolerated and effective in activating latent HIV reservoirs. Further investigations are warranted in the context of analytic treatment interruption.

The purpose of this study was to identify fecal bacterial microbiome changes in patients with chronic human immunodeficiency virus (HIV) infection in China. Bacterial 16S rRNA genes were amplified, sequenced (454 pyrosequencing), and clustered into operational taxonomic units using the QIIME software. Relative abundance at the phylum and genus levels were calculated. Alpha diversity was determined by Chao 1 and observed-species indices, and beta diversity was determined by double principal component analysis using the estimated phylogeny-based unweighted Unifrac distance matrices. Fecal samples of the patients with chronic HIV-infection tended to be enriched with bacteria of the phyla Firmicutes (47.20% ± 0.43 relative abundance) and Proteobacteria (37.21% ± 0.36) compared with those of the non-HIV infected controls (17.95% ± 0.06 and 3.81% ± 0.02, respectively). Members of the genus Bilophila were exclusively detected in samples of the non-HIV infected controls. Bacteroides and arabacteroides were more abundant in the chronic HIV-infected patients. Our study indicated that chronic HIV-infected patients in China have a fecal bacterial microbiome composition that is largely different from that found in non-HIV infected controls, and further study is needed to evaluate whether microbiome changes play a role in disease complications in the distal gut, including opportunistic infections.