Adenosine A2A receptor activation regulates the M1 macrophages activation to initiate innate and adaptive immunity in psoriasis.

Psoriasis is a common inflammatory systemic disease characterized by pro-inflammatory macrophages activation (M1 macrophage) infiltrated in the dermal layer. How M1 macrophage contributes to psoriasis remains unknown. In this study, we found that adenosine A2A receptor (A2AR) agonist CGS 21680 HCl alleviated the imiquimod (IMQ) and mouse IL-23 Protein (rmIL-23)-induced psoriasis inflammation through reducing infiltration of M1. Conversely, Adora2a deletion in mice exacerbated psoriasis-like phenotype. Mechanistically, A2AR activation inhibited M1 macrophage activation via the NF-κB-KRT16 pathway to reduce the secretion of CXCL10/11 and inhibit Th1/17 differentiation. Notably, the KRT16 expression was first found in M1 macrophage in our study, not only in keratinocytes (KCs). CXCL10/11 are first identified as primarily derived from macrophages and dendritic cells (DCs) rather than KCs in psoriasis using single cell RNA sequencing (scRNA-Seq). In total, the study emphasizes the importance of M1 as an innate immune cell in pathogenesis of psoriasis.

Design and Preliminary Ground Experiment for Deployable Sunshade Structures of a Modular Space Telescope.

On-orbit assembling space telescope (OAST) is one of the most feasible methods to implement a large-scale space telescope. Unlike a monolithic space telescope (such as Hubble Space Telescope, HST) or a deployable space telescope (such as James Webb Space Telescope, JWST), OAST can be assembled in the spatial environment. To ensure proper telescope performance, OAST must be equipped with a large deployable sunshade. In order to verify the technology of the OAST, the authors propose a modular space telescope on the China Space Station (CSS) and design a deployable sunshade. The deployable mechanism of the sunshade is made up of a radial deployable mechanism and an axial deployable mechanism. The paper describes the overall design approach, the key component technologies, and the design and preliminary testing of a part of the deployable sunshade assembly.

Multi-omic analyses of m5C readers reveal their characteristics and immunotherapeutic proficiency.

5-methylcytosine (m5C) is a post-transcriptional RNA modification identified, m5C readers can specifically identify and bind to m5C. ALYREF and YBX1 as members of m5C readers that have garnered increasing attention in cancer research. However, comprehensive analysis of their molecular functions across pancancer are lacking. Using the TCGA and GTEx databases, we investigated the expression levels and prognostic values of ALYREF and YBX1. Additionally, we assessed the tumor microenvironment, immune checkpoint-related genes, immunomodulators, Tumor Immune Dysfunction and Exclusion (TIDE) score and drug resistance of ALYREF and YBX1. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) analyses were performed to investigate the potential functions associated with m5C readers and coexpressed genes. Aberrant expression of ALYREF and YBX1 was observed and positively associated with prognosis in KIRP, LGG and LIHC. Furthermore, the expression levels of ALYREF and YBX1 were significantly correlated with immune infiltration of the tumor microenvironment and immune-related modulators. Last, our analysis revealed significant correlations between ALYREF, YBX1 and eIFs. Our study provides a substantial understanding of m5C readers and the intricate relationship between ALYREF, YBX1, eIFs, and mRNA dynamics. Through multidimensional analysis of immune infiltration and drug sensitivity/resistance in ALYREF and YBX1, we propose a possibility for combined modality therapy utilizing m5C readers.

Evaluation of the inflammatory parameters as potential biomarkers of systemic inflammation extent and the disease severity in psoriasis patients.

The disease severity of psoriasis is mainly assessed subjectively via  psoriasis area and severity index (PASI) and body surface area (BSA), while an optimal measure of cutaneous response, may overlook systemic inflammation in psoriasis patients. The neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), monocyte to high density lipoprotein ratio (MHR), and systemic immune-inflammation index (SII) exhibit notable associations with the inflammation severity in multiple diseases. The aim of this retrospective study was to explore the associations between inflammatory parameters and the skin lesions' severity of psoriasis. After analysis, we found that patients with psoriasis had higher NLR, MLR, PLR, MHR, and SII levels compared to the control group. At baseline, the parameters of NLR (r = 0.124, P = 0.003), MLR (r = 0.153, P < 0.001), MHR (r = 0.217, P < 0.001) and SII (r = 0.141, P = 0.001) had a positive correlation with PASI in psoriasis patients. At the same time, we analyzed the patients who received different systemic therapy. We observed a significant decrease in NLR, PLR, MLR, and SII in psoriasis patients after treatment. Notably, TNF-α inhibitors and IL-17A inhibitors subgroups showed a more significant reduction than IL-23/IL-12/23 inhibitors and MTX medication. Additionally, we found the change of NLR (r = 0.194, P < 0.001), PLR (r = 0.104, P = 0.014), MLR (r = 0.191, P < 0.001), MHR (r = 0.106, P = 0.012), and SII (r = 0.228, P < 0.001) had a positive correlation with the change of PASI in psoriasis patients. In conclusion, this study suggests that NLR, MLR, and SII may serve as useful biomarkers for assessing systemic inflammation extent and disease severity in psoriasis patients.

Programmable Tetrahedral DNA-RNA Nanocages Woven with Stimuli-Responsive siRNA for Enhancing Therapeutic Efficacy of Multidrug-Resistant Tumors.

Multidrug resistance (MDR) is a major obstacle limiting the effectiveness of chemotherapy against cancer. The combination strategy of chemotherapeutic agents and siRNA targeting drug efflux has emerged as an effective cancer treatment to overcome MDR. Herein, stimuli-responsive programmable tetrahedral DNA-RNA nanocages (TDRN) have been rationally designed and developed for dynamic co-delivery of the chemotherapeutic drug doxorubicin and P-glycoprotein (P-gp) siRNA. Specifically, the sense and antisense strand sequences of the P-gp siRNA, which are programmable bricks with terminal disulfide bond conjugation, are precisely embedded in one edge of the DNA tetrahedron. TDRN provides a stimuli-responsive release element for dynamic control of functional cargo P-gp siRNA that is significantly more stable than the "tail-like" TDN nanostructures. The stable and highly rigid 3D nanostructure of the siRNA-organized TDRN nanocages demonstrated a notable improvement in the stability of RNase A and mouse serum, as well as long-term storage stability for up to 4 weeks, as evidenced by this study. These biocompatible and multifunctional TDRN nanocarriers with gold nanocluster-assisted delivery (TDRN@Dox@AuNCp) are successfully used to achieve synergistic RNAi/Chemo-therapy in vitro and in vivo. This programmable TDRN drug delivery system, which integrates RNAi therapy and chemotherapy, offers a promising approach for treating multidrug-resistant tumors.

The Impact of Agroecosystems on Nitrous Acid (HONO) Emissions during Spring and Autumn in the North China Plain.

Solar radiation triggers atmospheric nitrous acid (HONO) photolysis, producing OH radicals, thereby accelerating photochemical reactions, leading to severe secondary pollution formation. Missing daytime sources were detected in the extensive HONO budget studies carried out in the past. In the rural North China Plain, some studies attributed those to soil emissions and more recent studies to dew evaporation. To investigate the contributions of these two processes to HONO temporal variations and unknown production rates in rural areas, HONO and related field observations obtained at the Gucheng Agricultural and Ecological Meteorological Station during spring and autumn were thoroughly analyzed. Morning peaks in HONO frequently occurred simultaneously with those of ammonia (NH3) and water vapor both during spring and autumn, which were mostly caused by dew and guttation water evaporation. In spring, the unknown HONO production rate revealed pronounced afternoon peaks exceeding those in the morning. In autumn, however, the afternoon peak was barely detectable compared to the morning peak. The unknown afternoon HONO production rates were attributed to soil emissions due to their good relationship to soil temperatures, while NH3 soil emissions were not as distinctive as dew emissions. Overall, the relative daytime contribution of dew emissions was higher during autumn, while soil emissions dominated during spring. Nevertheless, dew emission remained the most dominant contributor to morning time HONO emissions in both seasons, thus being responsible for the initiation of daytime OH radical formation and activation of photochemical reactions, while soil emissions further maintained HONO and associated OH radial formation rates at a high level, especially during spring. Future studies need to thoroughly investigate the influencing factors of dew and soil emissions and establish their relationship to HONO emission rates, form reasonable parameterizations for regional and global models, and improve current underestimations in modeled atmospheric oxidation capacity.

Repression of the SUMO-conjugating enzyme UBC9 is associated with lowered double minutes and reduced tumor progression.

Double minutes (DMs), extrachromosomal gene fragments found within certain tumors, have been noted to carry onco- and drug resistance genes contributing to tumor pathogenesis and progression. After screening for SUMO-related molecule expression within various tumor sample and cell line databases, we found that SUMO-conjugating enzyme UBC9 has been associated with genome instability and tumor cell DM counts, which was confirmed both in vitro and in vivo. Karyotyping determined DM counts post-UBC9 knockdown or SUMOylation inhibitor 2-D08, while RT-qPCR and Western blot were used to measure DM-carried gene expression in vitro. In vivo, fluorescence in situ hybridization (FISH) identified micronucleus (MN) expulsion. Western blot and immunofluorescence staining were then used to determine DNA damage extent, and a reporter plasmid system was constructed to detect changes in homologous recombination (HR) and non-homologous end joining (NHEJ) pathways. Our research has shown that UBC9 inhibition is able to attenuate DM formation and lower DM-carried gene expression, in turn reducing tumor growth and malignant phenotype, via MN efflux of DMs and lowering NHEJ activity to increase DNA damage. These findings thus reveal a relationship between heightened UBC9 activity, increased DM counts, and tumor progression, providing a potential approach for targeted therapies, via UBC9 inhibition.

Severe photochemical pollution formation associated with strong HONO emissions from dew and guttation evaporation.

The unknown daytime source of HONO has been extensively investigated due to unexplained atmospheric oxidation capacity and current modelling bias, especially during cold seasons. In this study, abrupt morning increases in atmospheric HONO at a rural site in the North China Plain (NCP) were observed almost on daily basis, which were closely linked to simultaneous rises in atmospheric water vapor content and NH3 concentrations. Dew and guttation water formation was frequently observed on wheat leaves, from which water samples were taken and chemically analyzed for the first time. Results confirmed that such natural processes likely governed the daily nighttime deposition and daytime release of HONO and NH3, which have not been considered in the numerous HONO budget studies investigating its large missing daytime source in the NCP. The dissolved HONO and NH3 in leaf surface water droplets reached 1.4 and 23 mg L-1 during the morning on average, resulting in averaged atmospheric HONO and NH3 increases of 0.89 ± 0.61 and 43.7 ± 29.3 ppb during morning hours, with relative increases of 186 ± 212 % and 233 ± 252 %, respectively. The high atmospheric oxidation capacity contained within HONO was stored in near surface liquid water (such as dew, guttation and soil surface water) during nighttime, which prevented its atmospheric dispersion after sunset and protected it from photodissociation during early morning hours. HONO was released in a blast during later hours with stronger solar radiation, which triggered and then accelerated daytime photochemistry through the rapid photolysis of HONO and subsequent OH production, especially under high RH conditions, forming severe secondary gaseous and particulate pollution. Results of this study demonstrate that global ecosystems might play significant roles in atmospheric photochemistry through nighttime dew formation and guttation processes.

Characterization of organic vapors by a Vocus proton-transfer-reaction mass spectrometry at a mountain site in southeastern China.

Biogenic and anthropogenic organic vapors are crucial precursors of ozone and secondary organic aerosol (SOA) in the atmosphere. Here we conducted real-time measurements of gaseous organic compounds using a Vocus proton-transfer-reaction mass spectrometer (Vocus PTR-MS) at the Shanghuang mountain site (1128 m a.s.l.) in southeastern China during November 2022. Our results revealed a substantial impact of mixed biogenic and anthropogenic compounds at the mountain site, with oxygenated volatile organic compounds (OVOCs) comprising 74 % of the organic vapors. Two distinct periods, characterized by sunny days (P1) and persistent cloud events (P2), were observed. P1 exhibited higher concentrations of biogenic-related emissions compared to P2. For instance, isoprene, monoterpenes, and sesquiterpenes during P1 were 2.4-2.9 times higher than those during P2. OVOCs such as acetaldehyde, MVK + MACR, acetone, and MEK also showed higher concentrations during P1, indicating a dominant source from the photochemical oxidation of biogenic VOCs. Anthropogenic-related VOCs like benzene and toluene had higher concentrations during P2, displaying different diurnal cycles compared to P1. Our analysis identified four biogenic-related factors dominated by isoprene and sesquiterpene oxidation products, and two anthropogenic-related factors. During P1, biogenic sources contributed approximately 80 % to total organic compounds, while during P2, anthropogenic sources, particularly the aromatic-related factor, increased from 16 % to 35 %. Furthermore, a unique factor characterized by C2 amines and C3 amides and periodic plumes indicated the influence of industrial emissions from regional transport. The study highlights the significant variations in sources and compositions of gaseous organic compounds at regional mountain sites due to changes in meteorology and photochemical processing, potentially impacting regional ozone and SOA formation.

Expert Consensus on the Application of Stem Cells in Psoriasis Research and Clinical Trials.

Psoriasis is an immune-mediated, chronic, relapsing, inflammatory, systemic disease induced by individual-environmental interactions, and is often lifelong because of the difficulty of treatment. In recent years, a variety of targeted therapies, including biologics, have improved the lesions and quality of life of most psoriasis patients, but they still do not address the problem of relapse and may be associated with decreased efficacy or adverse events such as infections over time. Therefore, there is an urgent need for breakthroughs in psoriasis treatment and in relapse-delaying and non-pharmacologic strategies, and stem cell therapy for psoriasis has emerged. In recent years, research on stem cell therapy for psoriasis has received a lot of attention, however, there is no reference standard as well as consensus in this field of research. Therefore, according to the latest consensus and guidelines, combined with relevant literature reports, clinical practice experience and the results of discussions with experts, this consensus specifies the types of stem cells commonly used in the treatment of psoriasis, the methods, dosages, and routes of stem cell therapy for psoriasis, as well as the clinical evaluations (efficacy and safety) of stem cell therapy for psoriasis. In addition, this consensus also provides normative standards for the processes of collection, preparation, preservation and quality control of stem cells and their related products, as well as recommendations for the management of stem cells during infusion for the treatment of psoriasis. This consensus provides the latest specific reference standards and practice guidelines for the field of stem cell therapy for psoriasis.