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Cedirogant is an inverse agonist of retinoic acid-related orphan receptor gamma thymus (RORγt) developed for the treatment of moderate to severe chronic plaque psoriasis. Here, we report the results from two phase I studies in which the pharmacokinetics (PK), safety, and efficacy of cedirogant in healthy participants and patients with moderate to severe chronic plaque psoriasis were evaluated. The studies consisted of single (20-750 mg) and multiple (75-375 mg once-daily [q.d.]) ascending dose designs, with effect of food and itraconazole on cedirogant exposure also evaluated. Safety and PK were evaluated for both healthy participants and psoriasis patients, and efficacy was assessed in psoriasis patients. Following single and multiple doses, cedirogant mean terminal half-life ranged from 16 to 28 h and median time to reach maximum plasma concentration ranged from 2 to 5 h across both populations. Cedirogant plasma exposures were dose-proportional after single doses and less than dose-proportional from 75 to 375 mg q.d. doses. Steady-state concentrations were achieved within 12 days. Accumulation ratios ranged from approximately 1.2 to 1.8 across tested doses. Food had minimal effect and itraconazole had limited impact on cedirogant exposure. No discontinuations or serious adverse events due to cedirogant were recorded. Psoriasis Area and Severity Index (PASI) and Self-Assessment of Psoriasis Symptoms (SAPS) assessments demonstrated numerical improvement with treatment of cedirogant 375 mg q.d. compared with placebo. The PK, safety, and efficacy profiles of cedirogant supported advancing it to phase II clinical trial in psoriasis patients.

Electron spin resonance spectroscopy(ESR) was used to investigate the effects of hydrogen ion concentration and hydroxide concentration in perchloric acid system and sodium hydroxide system on the state and behavior of free radicals generated by hydrazine bond breaking catalyzed by catalysts. The difference of free radicals generated by Pt/SiO2 catalyzed hydrazine decomposition in acid-base system was determined. The results show that in the alkaline system, with the increase of hydroxide concentration, the N-H bond breaking rate increases significantly, and the hydrolysis reaction is the main decomposition reaction. In acidic systems, with the increase of hydrogen ion concentration in the pH range from 6.9 to 1.1, the N-N bond breaking rate increases rapidly and is much higher than the N-H bond breaking rate. In the range of pH

Solar thermal storage ceramic materials use photothermal power generation technology to store heat energy, which is an important way to use clean energy and reduce carbon emissions. In this paper, MgAl2O4 ceramics were prepared by pressureless sintering with fused magnesia and α‐Al2O3 as the primary raw materials and TiO2 as the additive. The phase composition, microstructure, physical properties, thermal shock resistance, and thermal physical properties of MgAl2O4 thermal storage ceramics were studied. The results show that the main crystalline phase of B4 is MgAl2O4 and the secondary crystalline phase is MgTi2O5. Ti4+ is dissolved into MgAl2O4 lattice, which distorts the lattice, reduces activation energy, and promotes sintering. The sample B4 (69.73 wt% α‐Al2O3, 30.27 wt% fused magnesia, and 7 wt% TiO2) sintered at 1510°C had the best comprehensive physical properties, and its bending strength and bulk density were 89.41 MPa and 3.27 g/cm3, respectively. After 30 thermal shock cycles, the bending strength of the sample B4 is slightly lost. The thermal stress generated during the expansion and contraction of the grain volume led to the decrease of the bending strength. From room temperature to 1000°C, the specific heat capacity of sample B4 is.44–1.25 J/(g·K). The heat capacity increases with the increase of temperature, and the heat storage density increases. The heat storage density is 1218.75 kJ/kg (1000°C). Heat capacity increases with temperature due to intensified lattice vibration at high temperatures. Therefore, magnesia alumina spinel ceramics show great potential in solar thermal energy storage. [ABSTRACT FROM AUTHOR]

Based on the hydrophilicity of carboxylated carbon nanotubes (CNTs) and the paramagnetism of ferroferric oxide (Fe3O4), a CNT‐Fe3O4 nanocomplex was produced by in situ liquid phase synthesis and a magnetically induced polysulfone amide (PSA) composited CNT‐Fe3O4 ultrafiltration membrane was prepared using an immersion precipitation phase transformation with an inexpensive PSA fiber as the matrix. Fe3O4 nanoparticles were distributed evenly on the CNTs, and the obtained CNT‐Fe3O4 complex exhibited good magnetic properties. For the magnetically induced PSA composited CNT‐Fe3O4 ultrafiltration membrane, the water flux and retention rate under the magnetic field of 1450 Gs were 421.26 L/m2 h and 96.70%, respectively; porosity and pore size were 38.75% and 58.52 nm; contact angle was 39.48°; average tensile strength was 4.61 N/mm2; and weight retention rate reached 29.00% under heat treatment at 900°C. The water flux decreased by 5.40% and 39.33% after 3 weeks of acid and alkaline immersions, respectively. The inhibition zone diameter of Escherichia coli was 11 ± 0.24 mm, and that of Staphylococcus aureus was 11 ± 0.35 mm. The magnetically induced PSA composited CNT‐Fe3O4 ultrafiltration membrane demonstrated stronger electronegativity, smaller average roughness, higher flux recovery rate value, and lower irreversible flux recovery rate value. [ABSTRACT FROM AUTHOR]

Nuclear factor-kappaB (NF-ĸB) plays a crucial role in both innate and adaptive immune systems, significantly influencing various physiological processes such as cell proliferation, migration, differentiation, survival, and stemness. The function of NF-ĸB in cancer progression and response to chemotherapy has gained increasing attention. This review highlights the role of NF-ĸB in inflammation control, biological mechanisms, and therapeutic implications in cancer treatment. NF-ĸB is instrumental in altering the release of inflammatory factors such as TNF-α, IL-6, and IL-1β, which are key in the regulation of carcinogenesis. Specifically, in conditions including colitis, NF-ĸB upregulation can intensify inflammation, potentially leading to the development of colorectal cancer. Its pivotal role extends to regulating the tumor microenvironment, impacting components such as macrophages, fibroblasts, T cells, and natural killer cells. This regulation influences tumorigenesis and can dampen anti-tumor immune responses. Additionally, NF-ĸB modulates cell death mechanisms, notably by inhibiting apoptosis and ferroptosis. It also has a dual role in stimulating or suppressing autophagy in various cancers. Beyond these functions, NF-ĸB plays a role in controlling cancer stem cells, fostering angiogenesis, increasing metastatic potential through EMT induction, and reducing tumor cell sensitivity to chemotherapy and radiotherapy. Given its oncogenic capabilities, research has focused on natural products and small molecule compounds that can suppress NF-ĸB, offering promising avenues for cancer therapy. [ABSTRACT FROM AUTHOR]

Cedirogant is an inverse agonist of retinoic acid‐related orphan receptor gamma, thymus (RORγt) developed for treatment of psoriasis. This study aimed to characterize pharmacokinetics, pharmacodynamics, safety, and tolerability of cedirogant following a single oral dose in Japanese participants and multiple oral doses in Japanese and Chinese participants. The single doses evaluated in healthy Japanese participants were 75, 225, and 395 mg. The multiple doses evaluated in both healthy Japanese and Chinese participants was 375 mg once daily for 14 days. Cedirogant plasma exposure increased dose proportionally with administration of single doses. Maximum cedirogant plasma concentration was reached within a median time of 4‐5 hours after dosing. The harmonic mean elimination half‐life ranged from 19 to 25 hours. Cedirogant pharmacokinetics were similar between Japanese and Chinese participants. Compared with healthy Western participants in a cross‐study analysis, steady‐state cedirogant plasma exposure was 38%‐73% higher in Japanese or Chinese participants. Ex vivo interleukin‐17 inhibition increased in a dose‐dependent manner and was maximized by 375 mg once‐daily doses. The cedirogant regimens tested were generally well tolerated, and no new safety issues were identified. The results supported enrollment of Japanese and Chinese subjects in subsequent clinical trials for cedirogant. [ABSTRACT FROM AUTHOR]

Current challenges in visible and infrared image fusion include color information distortion, texture detail loss, and target edge blur. To address these issues, a fusion algorithm based on double-domain transform filter and nonlinear contrast transform feature extraction (DDCTFuse) is proposed. First, for the problem of incomplete detail extraction that exists in the traditional transform domain image decomposition, an adaptive high-pass filter is proposed to decompose images into high-frequency and low-frequency portions. Second, in order to address the issue of fuzzy fusion target caused by contrast loss during the fusion process, a novel feature extraction algorithm is devised based on a novel nonlinear transform function. Finally, the fusion results are optimized and color-corrected by our proposed spatial-domain logical filter, in order to solve the color loss and edge blur generated in the fusion process. To validate the benefits of the proposed algorithm, nine classical algorithms are compared on the LLVIP, MSRS, INO, and Roadscene datasets. The results of these experiments indicate that the proposed fusion algorithm exhibits distinct targets, provides comprehensive scene information, and offers significant image contrast. [ABSTRACT FROM AUTHOR]

Biochar is widely used to improve soil physical properties and carbon sequestration. However, few studies focuse on the impact of maize stalk biochar on labile organic carbon (LOC) pool and the relationship between physical properties and LOC fractions. A field positioning experiment was performed in Mollisols region of Northeast China to evaluate the influence of maize stalk biochar on the spatial distribution and temporal changes of physical properties and LOC fractions. Maize stalk biochar treatments included C1 (1.5 kg ⋅ hm-2), C2 (3 kg ⋅ hm-2), C3 (15 kg ⋅ hm-2), C4 (30 kg ⋅ hm-2), and CK (0). The results showed that maize stalk biochar increased soil water contents (SWC) and soil porosity (SP), but reduced bulk density (BD). Maize stalk biochar reduced dissolved organic carbon (DOC) contents in the 0-20 cm soil layer, ranging from 0.25 g ⋅ kg-1 to 0.31 g ⋅ kg-1 in harvest period, while increased in the 20-40 cm soil layer. In addition, the application of biochar had a significant impact on the spatial distribution and temporal change of SWC, BD, SP, DOC, hot-water extractable carbon (HWC), acid hydrolyzed organic carbon (AHC I, II), and readily oxidized organic carbon (ROC). High amounts of maize stalk biochar up-regulated the contents of soil organic carbon SOC, HWC, AHC I, AHC II, and ROC. In addition, SWC and SP were the key physical factors to affect LOC fractions. In conclusions, maize stalk biochar could improve physical properties, and then influence LOC fractions, and maize stalk biochar could be used as an organic amendment for restoring degraded soils governed by their rates of addition. [ABSTRACT FROM AUTHOR]

Cedirogant is an inverse agonist of retinoic acid‐related orphan receptor gamma thymus (RORγt) developed for the treatment of moderate to severe chronic plaque psoriasis. Here, we report the results from two phase I studies in which the pharmacokinetics (PK), safety, and efficacy of cedirogant in healthy participants and patients with moderate to severe chronic plaque psoriasis were evaluated. The studies consisted of single (20–750 mg) and multiple (75–375 mg once‐daily [q.d.]) ascending dose designs, with effect of food and itraconazole on cedirogant exposure also evaluated. Safety and PK were evaluated for both healthy participants and psoriasis patients, and efficacy was assessed in psoriasis patients. Following single and multiple doses, cedirogant mean terminal half‐life ranged from 16 to 28 h and median time to reach maximum plasma concentration ranged from 2 to 5 h across both populations. Cedirogant plasma exposures were dose‐proportional after single doses and less than dose‐proportional from 75 to 375 mg q.d. doses. Steady‐state concentrations were achieved within 12 days. Accumulation ratios ranged from approximately 1.2 to 1.8 across tested doses. Food had minimal effect and itraconazole had limited impact on cedirogant exposure. No discontinuations or serious adverse events due to cedirogant were recorded. Psoriasis Area and Severity Index (PASI) and Self‐Assessment of Psoriasis Symptoms (SAPS) assessments demonstrated numerical improvement with treatment of cedirogant 375 mg q.d. compared with placebo. The PK, safety, and efficacy profiles of cedirogant supported advancing it to phase II clinical trial in psoriasis patients. [ABSTRACT FROM AUTHOR]