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This article discusses the development and validation of a prognostic model for predicting flares in generalized pustular psoriasis (GPP). GPP is a rare auto-inflammatory skin disease characterized by recurrent flares of neutrophil-filled sterile pustules. These flares can have a significant impact on the daily activities and overall well-being of patients and can lead to life-threatening complications if left untreated. The study aimed to identify risk factors for GPP flare and construct a predictive model based on clinical characteristics to forecast the occurrence of flares. The model incorporates four features: history of psoriasis vulgaris, risky alcohol use, temperature at fever, and albumin levels. The model achieved promising results in internal and external validation processes and may provide critical insights into GPP flare patterns and help prevent such episodes. [Extracted from the article]

Designing efficient and durable electrocatalysts for seawater splitting to avoid undesired chlorine evolution reaction and resist the corrosive seawater is crucial for seawater electrolysis technology. Herein, a functional bimetal (Co and Fe) is designed specifically to modify nickel phosphide (denoted as CoFe‐Ni2P) for boosting seawater splitting, where the Fe atom improves the conductivity of Ni2P for improving electron transfer, and the Co atom accelerates the self‐reconstruction process to favorably generate bimetal co‐incorporated NiOOH (CoFe‐NiOOH) species on the electrode surface. Additionally, these in situ‐generated CoFe‐NiOOH species remarkably inhibit the adsorption of Cl− ions but selectively adsorb OH− ions, which contributes to excellent performance of the CoFe‐Ni2P electrode for large‐current‐density seawater splitting. Therefore, the CoFe‐Ni2P electrode only requires low overpotentials of 266 and 304 mV to afford current densities of 100 and 500 mA cm−2 in a harsh 6 m KOH + seawater electrolyte, and can work stably for 600 h. Impressively, a flow‐type anion exchange membrane electrolyzer assembled by the CoFe‐Ni2P/Ni‐felt bifunctional electrode is demonstrated to run stably at an industrially large current density of 1.0 A cm−2 in 6 m KOH + seawater electrolyte for 350 h, which shows promising application prospects. [ABSTRACT FROM AUTHOR]

The infiltration of neutrophils in the epidermis and the release of neutrophil extracellular traps (NETs) are important events in the pathogenesis of psoriasis, but the regulatory roles and internal mechanism of NETs in psoriasis are largely unknown. Here, we demonstrate that NETs can activate the absent‐in‐melanoma‐2 (AIM2) inflammasome in keratinocytes through the p38‐MAPK signalling pathway, and targeting NETs with CI‐amidine in vivo reduces AIM2 expression and ameliorates imiquimod‐induced psoriasis‐like phenotype in mice. Notably, NETs‐activated AIM2 in keratinocytes not only promotes IL‐1β production through the classical inflammasome pathway but also promotes IFN‐γ production via X‐linked inhibitor of apoptosis protein (XIAP), thereby mediating the immune responses of keratinocytes. In conclusion, our study demonstrates that the NETs‐AIM2 axis exerts multiple pro‐inflammatory effects on keratinocytes and may serve as a potential target for psoriasis therapy. [ABSTRACT FROM AUTHOR]

As one of the primary therapeutic choices, chemotherapy is widely adopted for progressive gastric cancer (GC), but the development of chemoresistance has limited chemotherapy efficacy and partly contributes to poor prognosis. Immunotherapy is increasingly being applied in the clinical treatment of GC and is also benefitting patients. To ascertain whether ATXN2 affects chemotherapy efficacy in GC cells and its role in GC immune escape, we performed high-throughput sequencing to clarify genes differentially expressed between 5-FU-resistant and 5-FU-sensitive GC cells and then conducted qRT-PCR to assess ATXN2 expression in GC tissues. Furthermore, the influence of ATXN2 on resistance was studied in vitro and in vivo, ATXN2 and other protein expression levels were detected using Western blotting and immunohistochemistry (IHC), and the direct association of SP1 and ATXN2 was confirmed through luciferase reporter gene analysis. We found elevated ATXN2 in GC tumors and a negative correlation between ATXN2 levels and the prognosis of GC. Furthermore, by activating the PI3K/AKT pathway, ATXN2 was found to promote chemoresistance in GC, facilitating BCL2L1 expression. In GC cells, ATXN2 further stimulated PD-L1 expression and provided better immunotherapy efficacy. Finally, we demonstrated that SP1 transcriptionally regulated the expression of ATXN2 and prompted GC chemoresistance and immune escape. In conclusion, our study reveals the important roles of the SP1/ATXN2/PI3K-AKT/BCL2L1 signalling pathway in GC chemoresistance and of the SP1/ATXN2/PI3K-AKT/PD-L1 signalling pathway in GC immunotherapy. Our findings provide new theories and experimental references for overcoming chemotherapy resistance in GC and enhancing the efficacy of immunotherapy for GC. [ABSTRACT FROM AUTHOR]

Background: Patients with COVID‐19 display a broad spectrum of manifestations from asymptomatic to life‐threatening disease with dysregulated immune responses. Mechanisms underlying the detrimental immune responses and disease severity remain elusive. Methods: We investigated a total of 137 APs infected with SARS‐CoV‐2. Patients were divided into mild and severe patient groups based on their requirement of oxygen supplementation. All blood samples from APs were collected within three weeks after symptom onset. Freshly isolated PBMCs were investigated for B cell subsets, their homing potential, activation state, mitochondrial functionality and proliferative response. Plasma samples were tested for cytokine concentration, and titer of Nabs, RBD‐, S1‐, SSA/Ro‐ and dsDNA‐specific IgG. Results: While critically ill patients displayed predominantly extrafollicular B cell activation with elevated inflammation, mild patients counteracted the disease through the timely induction of mitochondrial dysfunction in B cells within the first week post symptom onset. Rapidly increased mitochondrial dysfunction, which was caused by infection‐induced excessive intracellular calcium accumulation, suppressed excessive extrafollicular responses, leading to increased neutralizing potency index and decreased inflammatory cytokine production. Patients who received prior COVID‐19 vaccines before infection displayed significantly decreased extrafollicular B cell responses and mild disease. Conclusion: Our results reveal an immune mechanism that controls SARS‐CoV‐2‐induced detrimental B cell responses and COVID‐19 severity, which may have implications for viral pathogenesis, therapeutic interventions and vaccine development. [ABSTRACT FROM AUTHOR]

The current COVID-19 pandemic caused by SARS-Cov-2 is responsible for more than 6 million deaths globally. The development of broad-spectrum and cost-effective antivirals is urgently needed. Medicinal plants are renowned as a complementary approach in which antiviral natural products have been established as safe and effective drugs. Here, we report that the percolation extract of Spatholobus suberectus Dunn (SSP) is a broad-spectrum viral entry inhibitor against SARS-CoV-1/2 and other enveloped viruses. The viral inhibitory activities of the SSP were evaluated by using pseudotyped SARS-CoV-1 and 2, HIV-1ADA and HXB2 , and H5N1. SSP effectively inhibited viral entry and with EC50 values ranging from 3.6 to 5.1 μg/ml. Pre-treatment of pseudovirus or target cells with SSP showed consistent inhibitory activities with the respective EC50 value of 2.3 or 2.1 μg/ml. SSP blocked both SARS-CoV-2 spike glycoprotein and the host ACE2 receptor. In vivo studies indicated that there was no abnormal toxicity and behavior in long-term SSP treatment. Based on these findings, we concluded that SSP has the potential to be developed as a drug candidate for preventing and treating COVID-19 and other emerging enveloped viruses. [ABSTRACT FROM AUTHOR]

Amino acid surfactants have mild performance and are sourced from renewable biomass. Compared to classical surfactants, Gemini surfactants have superior properties. The amino acid Gemini surfactants are believed to be adopted more widely. The Gemini surfactant with tripeptide structure, sodium di(lauroyl glutamyl) lysine (DLGL), was prepared by amidation utilizing methyl laurate, glutamate and lysine and characterized by 1H NMR, 13C NMR and MS. Additionally, the pKa value, surface activities, aggregation, foaming properties and emulsifying attributes of the DLGL surfactant in aqueous solution with varied pH values were examined. The results indicate that the protonation‐deprotonation behavior of the DLGL surfactant is highly dependent on pH values. The surface tension, critical micelle concentration (cmc), foamability and foam stability exhibited superior performance at pH 6 and 7. Conversely, superior emulsifying ability was observed at pH 9 and 10. Moreover, the spherical vesicles were formed by the DLGL surfactant at pH 6, 7 or 8 while the micelles were generated at pH 9 or 10. [ABSTRACT FROM AUTHOR]

Both increased arterial stiffness and higher total homocysteine (tHcy) are associated with an elevated risk for cardiovascular disease. However, the relationship between tHcy and arterial stiffness is still inconclusive. The authors aimed to test the relationship of tHcy with carotid-femoral pulse wave velocity (cfPWV) and examine the possible effect modifiers in adults. A study was conducted from July to September 2016 in Jiangsu Province, China. A total of 16 644 participants were enrolled in the final analysis. Increased arterial stiffness is defined as a cfPWV ≥10 m/s. Overall, there was a positive association between tHcy and cfPWV levels (per 5-μmol/L tHcy increase: β = 0.10; 95% confidence interval [CI], 0.08-0.13) and increased arterial stiffness (per 5-μmol/L tHcy increase: odds ratio, 1.11; 95% CI, 1.07-1.14). Compared with participants with tHcy <10 μmol/L, the significantly higher cfPWV levels were observed in those with tHcy ≥15 μmol/L (β = 0.37; 95% CI, 0.28-0.47). Accordingly, a higher prevalence of increased arterial stiffness was found in patients with tHcy10 to <15 μmol/L (odds ratio, 1.18; 95% CI, 1.05-1.33) and tHcy ≥15 μmol/L (odds ratio, 1.50; 95% CI, 1.32-1.71) as compared with participants with tHcy <10 μmol/L. Furthermore, the stronger positive association was found in participants who were older (≥60 years, P for interaction = .008), had low body mass index (<25 kg/m2 , P for interaction = .026), high systolic blood pressure levels (≥145 mm Hg [median], P for interaction = .048), or diabetes mellitus (P for interaction = .045). The present study demonstrated that serum tHcy concentrations were positively associated with cfPWV and the prevalence of increased arterial stiffness. These results suggest that the cardiovascular effects of tHcy may partly be mediated through arterial stiffness. [ABSTRACT FROM AUTHOR]

Psoriasis is an autoimmune skin disease, in which keratinocytes play a crucial pathogenic role. High-mobility group protein B1 ( HMGB1) is an inflammatory factor that can be released from keratinocyte nuclei in psoriatic lesions. We aimed to investigate the proinflammatory effect of HMGB1 on keratinocytes and the contribution of HMGB1 to psoriasis development. Normal human keratinocytes were treated with recombinant human HMGB1, and the production of inflammatory factors and the intermediary signalling pathways were examined. Furthermore, the imiquimod-induced psoriasis-like mouse model was used to investigate the role of HMGB1 in psoriasis development in vivo. A total of 11 inflammatory factors were shown to be upregulated by HMGB1 in keratinocytes, among which interleukin ( IL)-18 showed the greatest change. We then found that activation of the nuclear factor- κB signalling pathway and inflammasomes accounted for HMGB1-induced IL-18 expression and secretion. Moreover, HMGB1 and downstream IL-18 contributed to the development of psoriasiform dermatitis in the imiquimod-treated mice. In addition, T-helper 17 immune response in the psoriasis-like mouse model could be inhibited by both HMGB1 and IL-18 blockade. Our findings indicate that HMGB1 secreted from keratinocytes can facilitate the production and secretion of inflammatory factors such as IL-18 in keratinocytes in an autocrine way, thus promoting the development of psoriasis. Blocking the proinflammatory function of the HMGB1-IL-18 axis may be useful for psoriasis treatment in the future. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]