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C32H48CoMo2N16O7, triclinic, P1‾ $P\overline{1}$ (no. 2), a = 10.425(2) Å, b = 10.517(2) Å, c = 11.187(2) Å, α = 94.671(7)°, β = 112.270(6)°, γ = 104.108(7)°, V = 1080.0(3) Å3, Z = 1, Rgt (F) = 0.0407, wRref (F 2) = 0.1015, T = 273 K.

Abstract Background The purpose of this study was to investigate the photoprotection effect of peroxiredoxin 1 (PRDX1) protein in ultraviolet B (UVB) irradiation-induced damage of retinal pigment epithelium (RPE) and its possible molecular mechanism. Methods ARPE-19 cell viability and apoptosis were assessed by MTT assay and flow cytometry, respectively. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the PRDX1 expression. The corresponding kits were employed to measure the levels or activities of lactate dehydrogenase (LDH), 8-hydroxy-2-deoxyguanosine (8-OHdG), reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD). Western blotting was applied to examine PRDX1 expression and mitogen-activated protein kinase (MAPK) signaling pathway-related proteins. Results After exposure to 20 mJ/cm2 intensity of UVB irradiation for 24 h, ARPE-19 cells viability was decreased, the leakage degree of LDH and 8-OHdG were increased, and cell apoptosis was elevated. The expression of PRDX1 was significantly down-regulated in UVB-induced ARPE-19 cells. The low expression of PRDX1 was involved in high irradiation intensity. Overexpression of PRDX1 increased cell activity, decreased cell apoptosis, and LDH as well as 8-OHdG leakage in UVB-induced ARPE-19 cells. In addition to alleviating UVB-induced cell damage, PRDX1 overexpression also inhibited UVB-induced oxidative stress (down-regulation of ROS and MDA levels, up-regulation of GSH-Px and SOD activities) and the activation of MAPK signaling pathway in ARPE-19 cells. Conclusion PRDX1 exerts a photoprotection effect on RPE by attenuating UVB-induced cell damage and inhibiting oxidative stress, which can be attributed to the inhibition of MAPK signaling pathway activation.

IntroductionImmunotherapies targeting T cells in solid cancers are revolutionizing clinical treatment. Novel immunotherapies have had extremely limited benefit for acute myeloid leukemia (AML). Here, we characterized the immune microenvironment of t(8;21) AML patients to determine how immune cell infiltration status influenced prognosis.MethodsThrough multi-omics studies of primary and longitudinal t(8;21) AML samples, we characterized the heterogeneous immune cell infiltration in the tumor microenvironment and their immune checkpoint gene expression. Further external cohorts were also included in this research.ResultsCD8+ T cells were enriched and HAVCR2 and TIGIT were upregulated in the CD34+CD117dim%-High group; these features are known to be associated with immune exhaustion. Data integration analysis of single-cell dynamics revealed that a subset of T cells (cluster_2) (highly expressing GZMB, NKG7, PRF1 and GNLY) evolved and expanded markedly in the drug-resistant stage after relapse. External cohort analysis confirmed that the cluster_2 T-cell signature could be utilized to stratify patients by overall survival outcome.DiscussionIn conclusion, we discovered a distinct T-cell signature by scRNA-seq that was correlated with disease progression and drug resistance. Our research provides a novel system for classifying patients based on their immune microenvironment.

It is challenging to reveal the catalytic mechanism of Cu/ZnO catalysts with multivalent copper and improve the performance of CO2 hydrogenation to methanol. We synthesized Cu/ZnO catalysts with different Cu:Zn ratios using acetylacetone salts as the precursors, in which Cu, Cu2O, CuO coexist. The catalytic activity was significantly associated with the abundance of Cu+ active sites on the surface and the formation of more Cu+-ZnO interfaces. When the ratio of Cu:Zn = 5:4, the catalyst without reduction pretreatment showed good performance, with a CO2 conversion rate of 12.9%, methanol selectivity of 85.1%, and the space-time yield of 0.238 gMeOH gcat−1 h−1. It was suggested that Cu+ tends to closely bind with ZnO, and the preparation method leads to more Cu+-ZnO interfaces. The synergistic interaction between Cu+ and ZnO promoted the adsorption and dissociation of CO2 and H2, verifying its dual effect on CO2 and H2 and promoting CO2 hydrogenation to methanol.

Background: Inflammatory bowel disease (IBD; mainly ulcerative colitis and Crohn’s disease) is associated with the development of colorectal cancer (CRC) referred to as colitis-associated colorectal cancer (CAC). In inflammatory flares of IBD, the production of luminal nitric oxide (NO) increases due to the increased inducible nitric oxide synthase (iNOS) activity in inflamed tissue. It is believed that iNOS parallels pro-inflammatory interleukin-1β (IL-1β). How these biomarkers relate to CAC pathogenesis or survival is unknown. Aim: The primary aim of this study was to investigate iNOS and IL-1β immunoreactivity in CAC tumors in comparison with CRC and normal colonic mucosa, and the secondary aim was to determine if immunoreactivity correlates with 5-year survival of CAC. Methods: Immunohistochemistry was performed on tissue sections as follows: CAC (n = 59); sporadic CRC (sCRC) (n = 12); colonic mucosa >2 cm outside sCRC margin (normal mucosa) (n = 22); paracancerous IBD (pIBD) (n = 12). The expression of iNOS and IL-1β was quantified separately for epithelium and stroma. Data were evaluated using the Mann-Whitney U-test and the log-rank test for 5-year Kaplan-Meier survival curves. Results were compared with online mRNA databases. Results: Immunoreactivity occurred predominantly in epithelial cells and to lesser extent in stroma. Compared with normal mucosa, immunoreactivity for iNOS (P < 0.01) and IL-1β (P < 0.005) was higher in CAC epithelium. In CAC stroma, iNOS immunoreactivity was lower than normal mucosa (P < 0.001), whereas IL-1β was higher (P < 0.05). Immunoreactivity differences of iNOS or IL-1β among CAC patients failed to correlate with 5-year survival. These findings were supported by online mRNA databases. Conclusion: Consistent with high NO production in IBD, there is more iNOS in CAC epithelium, albeit not in stroma. This immunoreactivity difference exists for IL-1β in both epithelium and stroma. The intervention of arginine or iNOS activity for CAC chemotherapy is not straightforward.

The clinical applications of acrosin activity are limited. We analyzed 61 578 male partners in infertile couples who visited the outpatient department of the Reproductive and Genetic Hospital of CITIC-Xiangya (Changsha, China) between August 2014 and December 2019 to determine the reference ranges and thresholds for acrosin activity in infertile Chinese men; to determine whether correlations exist between acrosin activity and age, sperm concentration, sperm morphology, or sperm motility; and to evaluate whether acrosin activity could serve as an effective prognostic indicator for choosing between in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in the clinic. The cut-off value for the normal reference range of acrosin activity for male partners in infertile couples was 24.78 μIU per 10[6] sperm. There was no significant association between acrosin activity and age, sperm concentration, semen volume, total sperm count, progressive motility, or total motile spermatozoa. A weak positive correlation was found between acrosin activity and normal sperm morphology. There was a statistically significant difference in abnormal acrosome morphology between the group with high acrosin activity (>24.78 μIU per 10[6] sperm) and the group with low acrosin activity (

The crystallography of transformation products with different cooling rates has been investigated in a typical low-carbon alloy steel, and its effect on low-temperature impact toughness uniformity in the thickness direction of heavy steel plates has been elucidated. The results show that both the full lath martenite (LM) microstructure transformed at the cooling rate of 45 K s−1 and granular bainite (GB) + lath bainite (LB) + LM microstructure transformed at the cooling rates of 3∼6 K s−1 have higher density of high-angle grain boundaries (HAGBs). The density of HAGBs in the full GB microstructure transformed at the cooling rate of 0.5 K s−1 is the lowest, and that in the LB + LM microstructure transformed at the cooling rates of 15∼22 K s−1 is the middle. In the GB + LB + LM microstructure, the division of austenite by multi-stage transformation reduces the LB and LM transformation temperatures, contributing to a weakening of variant selection and a tendency to close-packed plane grouping. Therefore, the GB + LB + LM microstructure achieves the refinement degree similar to the full LM microstructure, but slightly higher than that of the LB + LM microstructure. For the 60 mm thick heavy steel plate with ultra-fast cooling, the cooling rate decreases from 41 K s−1 at the subsurface to 14 K s−1 at the 1/4-thickness and then to 4 K s−1 at the 1/2-thickness. The full LM microstructure, LB + LM microstructure, and GB + LB + LM microstructure are obtained in sequence, resulting in a more uniform density of HAGBs. Consequently, the relatively uniform impact toughness at 143 K in the thickness direction is achieved with a small difference of ∼30 J.

Dendritic cells (DCs) are crucial in initiating and shaping both innate and adaptive immune responses. Clinical studies and experimental models have highlighted their significant involvement in various autoimmune diseases, positioning them as promising therapeutic targets. Nicotinamide (NAM), a form of vitamin B3, with its anti-inflammatory properties, has been suggested, while the involvement of NAM in DCs regulation remains elusive. Here, through analyzing publicly available databases, we observe substantial alterations in NAM levels and NAM metabolic pathways during DCs activation. Furthermore, we discover that NAM, but not Nicotinamide Mononucleotide (NMN), significantly inhibits DCs over-activation in vitro and in vivo. The suppression of DCs hyperactivation effectively alleviates symptoms of psoriasis. Mechanistically, NAM impairs DCs activation through a Poly (ADP-ribose) polymerases (PARPs)-NF-κB dependent manner. Notably, phosphoribosyl transferase (NAMPT) and PARPs are significantly upregulated in lipopolysaccharide (LPS)-stimulated DCs and psoriasis patients; elevated NAMPT and PARPs expression in psoriasis patients correlates with higher psoriasis area and severity index (PASI) scores. In summary, our findings underscore the pivotal role of NAM in modulating DCs functions and autoimmune disorders. Targeting the NAMPT-PARP axis emerges as a promising therapeutic approach for DC-related diseases.