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A simple method for the synthesis of (Z)‐3‐benzylidene‐2‐(quinolin‐8‐yl)isoindolin‐1‐ones through C(sp2)−H bond activation, Sonogashira cross‐coupling and annulation tandem reactions using calcium carbide as a solid alkyne source, and benzamides as starting materials is described. The inexpensive and easy‐to‐handle calcium carbide is first employed as the coupling partner in non‐activated C(sp2)−H bond activation. The one‐pot three‐component reactions proceed efficiently with a broad range of substrates and good tolerance for a diversity of functional groups. The reaction routes can also be scaled up to gram scale. [ABSTRACT FROM AUTHOR]

Based on 491 farmers joining in cooperatives microscopic data in Jiangxi Province,the paper uses Ordinary Least Squares to test the influence mechanism of cooperative green production on green performance, and takes environmental regulation as a regulatory variable to explore the relationship between cooperative green production and cooperative green performance. The results have shown that: (1) The green production cooperatives have a significant positive impact on their green performance, and the impact of green production on economic performance, social performance and ecological performance gradually strengthens from weak to strong; (2) Environmental regulations have a positive regulatory effect on the relationship between cooperative green production and cooperative green performance, among which three types of environmental regulations, namely, incentive, restraint and guided, can strengthen the positive relationship between green production and green performance. [ABSTRACT FROM AUTHOR]

Safe and fast charging is important for graphite/lithium iron phosphate (Gr/LFP) batteries in the fast-growing electric vehicle industry. However, conventional carbonate-based electrolytes produce an obstructive solid-electrolyte interface (SEI), which hinders the fast charging of lithium-ion batteries (LIBs). In this study, a unique tri-methylsilyl-2-(fluorosulfonyl)difluoroacetate (TMSFS) additive was introduced to regulate the SEI of Gr/LFP batteries containing a lithium bis(fluorosulfonyl)imide-based electrolyte during fast charging. The addition of TMSFS significantly reduced the charge-transfer resistance of the anode, substantially extending the cycle life of commercial Gr/LFP batteries to over 1000 cycles at 2C rate, which was far superior to that of the baseline electrolyte (< 530 cycles). Further mechanistic studies showed that the inorganic fluorinated and sulfurized species formed on the SEI film stabilized the intermediate lithium carbonate from attack by the side-reaction products. TMSFS acts as a film-forming additive, curbing electrolyte decomposition, and fortifying the structural integrity of the electrode through the formation of a robust and low-impedance SEI film on the anode. These results provide a simple and effective strategy for combining F and S via electrolyte optimization to implement commercially safe fast-charging LIBs. [ABSTRACT FROM AUTHOR]

This letter introduces an efficient registration method for large-scale point clouds with low overlap, which adopts a two-stage transformation learning process. In the first stage, we integrate a point-voxel encoding structure with an attention mechanism to predict rotation and point-wise importance weight. In the second stage, we employ a PointNet-based structure to estimate translation using optimized data. By adopting this two-stage procedure, our model can effectively learn rotation and translation separately, thereby increasing flexibility. We conducted extensive experiments on two large-scale indoor datasets (3Dmatch and S3DIS) and an outdoor dataset (KITTI odometry). The results demonstrate that our method outperforms traditional and deep learning-based approaches, achieving state-of-the-art performance in registration. Furthermore, our method exhibits superior generalization capabilities, highlighting its effectiveness in various registration scenarios. [ABSTRACT FROM AUTHOR]

Background: The study aimed to investigate the relationship of MAPK4 genetic variants with the efficacy of methotrexate (MTX) in psoriasis patients. Methods: Patients treated with MTX were classified as responders or nonresponders if the Psoriasis Area and Severity Index (PASI) at week 12 was reduced to greater than 75% or lower than 75%, respectively. The genotypes of 14 MAPK4 single-nucleotide polymorphisms in 310 patients were analyzed. The expression levels of MAPK4 protein were detected by Western blot. Results: Only rs9949644 polymorphisms were associated with the efficacy after adjusting for the confounding factors. Patients with the rs9949644 AG or GG genotype had a better clinical response compared to patients with the AA genotype. Rs9949644 polymorphisms were significantly associated with the PASI improvement rate. Besides, the protein level of MAPK4, positively associated with the psoriasis severity, was higher in patients. There were no significant differences of MAPK4 protein levels among the three groups. While after treatment, MAPK4 levels in the AG or GG group showed a significantly down-regulated trend. Conclusion: By demonstrating the significant association of MAPK4 with the efficacy of MTX, this study indicates that MAPK4 may be involved in the psoriasis progression and act as a predictor of therapeutic response. [ABSTRACT FROM AUTHOR]

B7‐H4 is a recently discovered member of B7 family that negatively regulates T‐cell immunity, specifically Th1 and Th17 cell responses. However, its role in the pathogenesis of psoriasis has yet to be determined. This study aims to investigate the effect of B7‐H4 polymorphism on the efficacy of methotrexate (MTX) and its mechanism in psoriasis. Four single nucleotide polymorphisms of B7‐H4 were genotyped in 310 psoriatic patients who received 12‐week MTX. The protein expression of B7‐H4 in platelets was characterized using immunofluorescence staining, confocal laser scanning microscopy, and flow cytometry techniques. We found that GG genotype carriers of B7‐H4 rs1935780 had a lower Psoriasis Area and Severity Index (PASI) 75 response rate and higher weight (p = 0.0245) and body mass index (p = 0.0185) than AA and AG genotype carriers. Multiple regression analysis showed that the PASI score at baseline (p = 0.01) and age at disease onset (p = 0.003) were positively correlated with PASI 75 response rate, while weight (p = 0.005) and the rs1935780 genotype (p = 0.003) were negatively associated with PASI 75 response rate. B7‐H4 was expressed in the platelet plasma membrane and cytoplasm. Furthermore, the expression of B7‐H4 protein in platelets was lower in good responders than in non‐responders and was upregulated considerably after 12‐week MTX or in vitro MTX stimulation in good responders. Collectively, these results demonstrate that psoriatic patients with GG genotype of B7‐H4 rs1935780 had a poorer response to MTX. Low expression of B7‐H4 protein in platelets correlated with better clinical outcomes of MTX in psoriasis. [ABSTRACT FROM AUTHOR]

Background: Vunakizumab, a novel anti-IL-17A antibody, has showed promising efficacy for moderate-to-severe plaque psoriasis in a phase 2 trial., Objective: We conducted a double-blind, randomized phase 3 trial (NCT04839016) to further evaluate vunakizumab in this population., Methods: 690 subjects were randomized (2:1) to receive vunakizumab 240 mg or placebo at weeks 0, 2, 4 and 8. At week 12, subjects on placebo were switched to vunakizumab 240 mg (weeks 12, 14, 16 and q4w thereafter). The co-primary endpoints were ≥90% improvement from baseline in the psoriasis area-and-severity index score (PASI 90) and a static Physicians Global Assessment score of 0/1 (sPGA 0/1) at week 12., Results: At week 12, the vunakizumab group showed higher PASI 90 (76.8% vs 0.9%) and sPGA 0/1 (71.8% vs 0.4%) response rates, as well as higher PASI 75 (93.6% vs 4.0%), PASI 100 (36.6% vs 0.0%) and sPGA 0 (38.2% vs 0.0%) response rates (all two-sided P<0.0001 vs placebo). Efficacy was maintained through week 52 with continuous vunakizumab. Possible treatment-related serious adverse events occurred in 0.9% of vunakizumab-treated subjects., Limitations: Chinese subjects only; no active comparator., Conclusion: Vunakizumab demonstrated robust clinical response at week 12 and through week 52, with good tolerability in moderate-to-severe plaque psoriasis., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: Conflicts of interest The authors have no potential conflicts of interest.

Introduction: Porokeratosis (PK) is an autoinflammatory keratinization disease (AIKD) characterized by circular or annular skin lesions with a hyperkeratotic rim, pathologically shown as the cornoid lamella. Four genes that cause PK are associated with the mevalonate (MV) pathway. In Chinese PK patients, mevalonate diphosphate decarboxylase (MVD) is the most common causative gene. The lack of an animal model has greatly limited research on PK pathogenesis., Materials and Methods: In this research, we constructed K14-CreER T2 -Mvd fl/fl mice using the Cre-LoxP system to create a mouse model for in-depth studies of PK. The Epidermal Mvd gene was knocked out by intraperitoneal injection of Tamoxifen (TAM). Pathology, immunohistochemistry, RNA-seq, and Western Blot analysis were performed., Results: Skin lesions appeared following Mvd deficiency, and pathological examination revealed the characteristic cornoid lamella, as well as cutaneous inflammation. Furthermore, we observed elevated levels of IL-17A and IL-1β, and a decreased Loricrin level in epidermal Mvd-deficient mice. Compared with the wild-type (WT) group, Mvd deficiency activated the expression of lipid metabolism-related proteins., Conclusion: We developed the first mouse model for PK research, enabling further studies on disease development and treatment approaches., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Cobalt-based materials are reported to be the most efficient catalysts in sulfate radical advanced oxidation processes (SR-AOPs). A green and facile method was developed in this work to prepare uniform Co(OH) 2 hexagonal nanosheets, which was void of any organic solvents via mere ambient temperature stirring. The obtained nanosheets were assembled into a catalytic gravity-driven membrane, through which the removal efficiency of a typical pharmaceutical contaminant, ranitidine (RNTD), could reach ∼100% within 20 min. Meanwhile, the catalytic membrane also demonstrated effective removal performance towards various pollutants. In order to augment the long-term stability of catalytic membranes, Co(OH) 2 /rGO composites were fabricated using the same strategy, and a Co(OH) 2 /rGO catalytic membrane was prepared correspondingly. The Co(OH) 2 /rGO membrane could maintain a ∼100% removal of RNTD over a constant reaction period lasting for up to 165 hours, which was approximately 11 times that of the sole Co(OH) 2 membrane (15 h). Analysis of element chemical states, metal ion concentration in filtrates, and quenching experiments suggested that the combination with rGO could promote the electron transfer to accelerate the Co(II) regeneration, restrain the cobalt dissolution to alleviate the active site loss, and contribute to the production of 1 O 2 via synergistic effects of oxygen-containing groups in rGO. Toxicity assessment was performed on RNTD and its degradation intermediates to confirm the reduction in ecotoxicity of the treated feed. Overall, this work not only offered guidance for the application of nanosheets in AOP membranes, but also had implications for the environmentally-friendly preparation protocol to obtain functional metal hydroxides.