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Xiangjin Gao,1,2,&ast; Xiuqi Zhang,1,&ast; Le Kuai,3,&ast; Qing Yang,4 Huan Li,4 Rui Zhang,1 Bin Li,1 Ruiping Wang1,2 1Clinical Research Center, Shanghai Skin Diseases Hospital, Medical School of Tongji University, Shanghai, People’s Republic of China; 2School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Yueyang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Obstetrics and Gynecology Department, Songjiang Maternal and Child Health-Care Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruiping Wang, Clinical Research Center, Shanghai Skin Diseases Hospital, Medical School of Tongji University, 1278 Baode Road, Jing’an District, Shanghai, 200443, People’s Republic of China, Tel +86-189 1879 1651, Fax +86-21-3680 3000, Email w19830901@126.comObjective: This study was based on a gestational diabetes mellitus (GDM) cohort in Shanghai to examine the association between physical exercise and plasma glucose control among GDM women with and determine what the effects of pre-pregnancy body mass index (BMI).Methods: In this study, GDM was diagnosed if the plasma glucose values at any of the following time points reached the diagnostic threshold: fasting blood glucose (5.1 mmol/L), 1-hour blood glucose (10.0 mmol/L), and 2-hour blood glucose (8.5 mmol/L) by 75 g oral glucose tolerance test (OGTT). Information on GDM women was extracted from the hospital’s health records and prenatal examination forms and was obtained through face-to-face interviews after delivery. A restricted cubic spline curve with four knots was used to flexibly model the relationship between the duration of moderate-intensity physical exercise and the percentage of abnormal plasma glucose among GDM patients with different BMI values. In this study, a P-value less than 0.05 (two-tailed) was considered as statistical significance.Results: Among 1139 GDM women with GDM, the median percentage of abnormal plasma glucose (PG) was 40.0% (interquartile range (IQR): 20.0– 66.7%), and the difference between overweight-obese group and underweight-normal group was statistically significant (50.0% vs 40.0%, P < 0.001). In this study, engaging in more physical exercise during pregnancy contributed to a higher prevalence of satisfactory glycemic control, and women with BMI < 25 kg/m2 should engage in no less than 90 minutes of moderate-intensity physical activity per day to achieve satisfactory glycemic control (prevalence of abnormal PG < 35%). However, over 120 minutes of daily moderate-intensity physical activity is required for GDM women with a BMI ≥ 25 kg/m2 to achieve satisfactory glycemic control.Conclusion: Overweight or obese women with GDM have a higher risk of poor glycemic control and require a longer duration of physical exercise to achieve the same level of blood glucose control.Keywords: gestational diabetes mellitus, plasma glucose control, physical exercise, overweight and obesity

Qi Zheng,1,&ast; Le Kuai,2,&ast; Wencheng Jiang,1,&ast; Yan Qiang,3 Lei Wei,2 Siting Chen,2 Bin Li,1 Ruiping Wang3,4 1Department of Traditional Chinese Medicine, Shanghai Skin Diseases Hospital, Tongji University, Shanghai, People’s Republic of China; 2Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Clinical Research and Innovation Transformation Center, Shanghai Skin Diseases Hospital, Tongji University, Shanghai, People’s Republic of China; 4School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Li; Ruiping Wang, Email 18930568129@163.com; w19830901@126.comBackground: Gender difference is prevalent in clinical feature, disease severity for noncommunicable diseases (NCD), but studies on gender disparity in clinical feature, disease severity and NCD comorbidity among psoriasis patients are limited. This cross-sectional study explores gender differences in clinical feature, lifestyle behavior and NCD comorbidity among psoriasis patients.Methods: Psoriasis patients were recruited through cluster survey method in two hospitals, and questionnaire interviews were applied to collect the demographic feature, lifestyle habits, clinical feature and NCD among patients.Results: A total of 2102 psoriasis patients included 1332 males (63.4%), 70% were over 35 years old and approximately 50% of them were overweight or obesity. The median value for psoriasis initiation age and disease duration was 33 years old (34 for male and 32 for female) and 9 years (10 for male and 7 for female), respectively. The psoriasis recurrence was mainly in winter (73.4%) and autumn (34.2%) both for patients. The prevalence of tobacco smoking and alcohol drinking was 31.2% and 12.6%. Male patients had higher prevalence of tobacco smoking (odds ratio (OR) = 13.26, 95% confidence interval (CI): 9.54– 18.44) and alcohol drinking (OR = 14.44, 95% CI: 7.90– 26.40). The prevalence of diabetes, hypertension, hyperlipidemia, and metabolic syndrome were 13.2%, 28.5%, 23.4% and 21.5%, respectively. Male patients had higher prevalence of diabetes (OR = 1.53, 95% CI: 1.16– 2.02), hypertension (OR = 1.87, 95% CI: 1.52– 2.30), hyperlipidemia (OR = 2.34, 95% CI: 1.85– 2.95) and metabolic syndrome (OR = 2.06, 95% CI: 1.63– 2.62) than female patients. The proportions for 4 types of NCDs diagnosed after psoriasis onset were over 58%, which were also higher in males than females.Conclusion: Female patients had shorter disease duration and with less NCD, and male patients had more body weight issue, with fewer sleep time and higher prevalence of tobacco smoking and alcohol drinking and NCDs. We recommend that dermatologist should notice the gender disparity in psoriasis patients, which is helpful for the disease diagnosis and treatment.Keywords: psoriasis, gender disparity, tobacco smoking, alcohol drinking, overweight, metabolic diseases, comorbidity

Xiaoying Sun,1,2 Liu Liu,1,2 Siting Chen,1,2 Jiao Wang,1,2 Xiaoce Cai,1,2 Jiankun Song,3 Mi Zhou,1,2 Dongjie Guo,1,2 Le Kuai,1,2 Xiaojie Ding,1,2 Bin Li,2,4 Xin Li1,2 1Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Dermatology of TCM, Shanghai Skin Diseases Hospital, Shanghai, People’s Republic of China; 4Department of Dermatology, Shanghai Skin Diseases Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Xin Li, Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437, People’s Republic of China, Tel +8613661956326, Email 13661956326@163.com Bin Li, Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437, People’s Republic of China, Tel +8618930568129, Email 18930568129@163.comBackground: Psoriasis is an immune-mediated chronic systemic inflammatory skin disease whose diagnosis and severity assessment pose challenges for clinicians worldwide. The use of serum biomarkers facilitates the early diagnosis and treatment of psoriasis.Methods: This case–control study compared tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-17, IL-10, and fibrinogen-like protein 1 (FGL1) levels of 139 untreated psoriasis patients and 140 healthy controls. Serum samples were collected, and enzyme-linked immunosorbent assays were performed to quantify their levels. Subgroups were analyzed according to abnormal lipid metabolism status.Results: Compared to controls, patients with psoriasis exhibited lower concentrations of serum TNF-α, IL-17, and FGL1 (P < 0.05). A correlation analysis showed that FGL1 was inversely correlated with high-density lipoprotein cholesterol and IL-17 in the psoriatic state. Stepwise multiple regression analysis revealed that FGL1 and total cholesterol were the independent determinants of Psoriasis Area and Severity Index (PASI) score in psoriasis patients. The area under the receiver operating characteristic curve of FGL1 assessing moderate-to-severe psoriasis and mild psoriasis was 0.70, while the area under the curve (AUC) assessing severe psoriasis and mild-to-moderate psoriasis was 0.67, better than that of IL-17. In addition, FGL1, but not IL-17, was able to identify psoriasis with abnormal lipid metabolism to a certain extent (AUC = 0.60).Conclusion: In conclusion, serum FGL1 may be a promising biomarker for diagnosing and staging psoriasis. It may also be involved in its progression and comorbid abnormal lipid metabolism.Keywords: psoriasis, disease severity, biomarker, fibrinogen-like protein 1, lipid metabolism

For the past decade, observations of carbonyl sulfide (OCS or COS) have been investigated as a proxy for carbon uptake by plants. OCS is destroyed by enzymes that interact with CO2 during photosynthesis, namely carbonic anhydrase (CA) and RuBisCO, where CA is the more important one. The majority of sources of OCS to the atmosphere are geographically separated from this large plant sink, whereas the sources and sinks of CO2 are co-located in ecosystems. The drawdown of OCS can therefore be related to the uptake of CO2 without the added complication of co-located emissions comparable in magnitude. Here we review the state of our understanding of the global OCS cycle and its applications to ecosystem carbon cycle science. OCS uptake is correlated well to plant carbon uptake, especially at the regional scale. OCS can be used in conjunction with other independent measures of ecosystem function, like solar-induced fluorescence and carbon and water isotope studies. More work needs to be done to generate global coverage for OCS observations and to link this powerful atmospheric tracer to systems where fundamental questions concerning the carbon and water cycle remain.

We present two new products from near-infrared Greenhouse Gases Observing Satellite (GOSAT) observations: Lowermost tropospheric (LMT, from 0 to 2.5km) and upper tropospheric-stratospheric (U, above 2.5km) carbon dioxide partial column mixing ratios. We compare these new products to aircraft profiles and remote surface flask measurements and find that the seasonal and year-to-year variations in the new partial column mixing ratios significantly improve upon the Atmospheric CO2 Observations from Space (ACOS) and GOSAT (ACOS-GOSAT) initial guess and/or a priori, with distinct patterns in the LMT and U seasonal cycles that match validation data. For land monthly averages, we find errors of 1.9, 0.7, and 0.8ppm for retrieved GOSAT LMT, U, and XCO2; for ocean monthly averages, we find errors of 0.7, 0.5, and 0.5ppm for retrieved GOSAT LMT, U, and XCO2. In the southern hemispheric biomass burning season, the new partial columns show similar patterns to MODIS fire maps and MOPITT multispectral CO for both vertical levels, despite a flat ACOS-GOSAT prior, and a CO-CO2 emission factor comparable to published values. The difference of LMT and U, useful for evaluation of model transport error, has also been validated with a monthly average error of 0.8 (1.4)ppm for ocean (land). LMT is more locally influenced than U, meaning that local fluxes can now be better separated from CO2 transported from far away.

We introduce a retrieval algorithm to estimate lower tropospheric methane (CH4) concentrations from the surface to 1 km with uncertainty estimates using Hyperspectral Thermal Emission Spectrometer (HyTES) airborne radiance measurements. After resampling, retrievals have a spatial resolution of 6 × 6 m2. The total error from a single retrieval is approximately 20 %, with the uncertainties determined primarily by noise and spectral interferences from air temperature, surface emissivity, and atmospheric water vapor. We demonstrate retrievals for a HyTES flight line over storage tanks near Kern River Oil Field (KROF), Kern County, California, and find an extended plume structure in the set of observations with elevated methane concentrations (3.0 ± 0.6 to 6.0 ± 1.2 ppm), well above mean concentrations (1.8 ± 0.4 ppm) observed for this scene. With typically a 20 % estimated uncertainty, plume enhancements with more than 1 ppm are distinguishable from the background values with its uncertainty. HyTES retrievals are consistent with simultaneous airborne and ground-based in situ CH4 mole fraction measurements within the reported accuracy of approximately 0.2 ppm (or ∼8 %), due to retrieval interferences related to air temperature, emissivity, and H2O.

Quantifying the carbonyl sulfide (OCS) land/ocean fluxes contributes to the understanding of both the sulfur and carbon cycles. The primary sources and sinks of OCS are very likely in a steady state because there is no significant observed trend or interannual variability in atmospheric OCS measurements. However, the magnitude and spatial distribution of the dominant ocean source are highly uncertain due to the lack of observations. In particular, estimates of the oceanic fluxes range from approximately 280 Gg S yr-1 to greater than 800 Gg S yr-1, with the larger flux needed to balance a similarly sized terrestrial sink that is inferred from NOAA continental sites. Here we estimate summer tropical oceanic fluxes of OCS in 2006 using a linear flux inversion algorithm and new OCS data acquired by the Aura Tropospheric Emissions Spectrometer (TES). Modeled OCS concentrations based on these updated fluxes are consistent with HIAPER Pole-to-Pole Observations during 4th airborne campaign and improve significantly over the a priori model concentrations. The TES tropical ocean estimate of 70±16GgS in June,when extrapolated over the whole year (about 840 ± 192 Gg S yr-1), supports the hypothesis proposed by Berry et al. (2013) that the ocean flux is in the higher range of approximately 800 Gg S yr-1.

We present a description of the Tropospheric Emission Spectrometer (TES) carbonyl sulfide (OCS) retrieval algorithm, along with evaluation of the biases and uncertainties against aircraft profiles from the HIPPO campaign and data from the NOAA Mauna Loa site. In general, the OCS retrievals (1) have less than 1.0 degree of freedom for signals (DOFs), (2) are sensitive in the mid-troposphere with a peak sensitivity typically between 300 to 500 hPa, (3) but have much smaller systematic errors from temperature, CO2 and H2O calibrations relative to random errors from measurement noise. Here we estimate the monthly means from TES measurements averaged over multiple years so that random errors are reduced and useful information about OCS seasonala latitudinal variability can be derived. With this averaging, TES OCS data are found to be consistent (within the calculated uncertainties) with NOAA ground observations and HIPPO aircraft measurements. TES OCS data also captures the seasonal and latitudinal variations observed by these in situ data. [ABSTRACT FROM AUTHOR]

Monitoring the global distribution and long-term variations of CO2 sources and sinks is required for characterizing the global carbon budget. Total column measurements are useful for estimating regional-scale fluxes; however, model transport remains a significant error source, particularly for quantifying local sources and sinks. To improve the capability of estimating regional fluxes, we estimate lower tropospheric CO2 concentrations from groundbased near-infrared (NIR) measurements with space-based thermal infrared (TIR) measurements. The NIR measurements are obtained from the Total Carbon Column Observing Network (TCCON) of solar measurements, which provide an estimate of the total CO2 column amount. Estimates of tropospheric CO2 that are co-located with TCCON are obtained by assimilating Tropospheric Emission Spectrometer (TES) free tropospheric CO2 estimates into the GEOS-Chem model.We find that quantifying lower tropospheric CO2 by subtracting free tropospheric CO2 estimates from total column estimates is a linear problem, because the calculated random uncertainties in total column and lower tropospheric estimates are consistent with actual uncertainties as compared to aircraft data. For the total column estimates, the random uncertainty is about 0.55 ppm with a bias of -5.66 ppm, consistent with previously published results. After accounting for the total column bias, the bias in the lower tropospheric CO2 estimates is 0.26 ppm with a precision (one standard deviation) of 1.02 ppm. This precision is sufficient for capturing the winter to summer variability of approximately 12 ppm in the lower troposphere; double the variability of the total column. This work shows that a combination of NIR and TIR measurements can profile CO2 with the precision and accuracy needed to quantify lower tropospheric CO2 variability. [ABSTRACT FROM AUTHOR]

The article discusses a study on the use of Aura TES and TCCON instruments for profiling tropospheric carbon dioxide. The study aims to improve the capability of estimating regional fluxes and estimates near-surface carbon dioxide values from ground-based near infrared (NIR) measurements with space-based thermal infrared (TIR) measurements. It reveals the consistency of calculated random uncertainties in total column and boundary layer with actual uncertainties as compared to aircraft data.

An autotrophic denitrification process with elemental sulphur to achieve a high quality effluent with a low concentration of total N was tested at laboratory scale. Two types of wastewater were tested during a period of 10 months. One was a multiple household wastewater obtained from a municipal wastewater treatment plant and the other was a single household wastewater collected from a family. The wastewaters were first treated by primary sedimentation, followed by nitrifying trickling filtration. The nitrified effluents from the trickling filter were further denitrified in an autotrophic denitrification stage. The autotrophic denitrifying reactor was filled with a mixture of elemental sulphur powder and small pieces of limestone. Sulphur was used as an electron donor and CaCO3 in the limestone served as pH buffer. With a hydraulic retention time of 2-3 hours, up to 86% oftotal oxidizable nitrogen (TON) was removed from the multiple household wastewater and 75% from the single household wastewater. The total N concentration in the final effluents was 3 mg l-1 for the multiple household wastewater and 17 mg l-1 for the single household wastewater. Besides the high removal efficiency and the short hydraulic retention time, other advantages were also noted such as no specific need for inoculum, rapid start up, a wide temperature range for application and low technical labour requirement. Hence,autotrophic denitrification offers interesting potential for removing surplus nitrate from nitrified domestic wastewater particularly in small-scale wastewater treatment facilities. [ABSTRACT FROM AUTHOR]

To treat household wastewater, a sequence of 'primary decantation-trickling filter percolation' was applied in a lab-scale designed treatment system. Poly-electrolyte was used as coagulant to enhance the primary treatment and charcoal was used as carrier material in the trickling filters. Oxygen was supplied to the trickling filters by means of natural ventilation. In the lab-scale system, the enhanced primarystage removed more than 91% of the suspended solids (SS), and 79% ofthe total chemical oxygen demand (CODt). The subsequent trickling filtration brought a complete nitrification to the wastewaters at a volumetric loading rate (Bv) of 0.7-1.0 g CODt L-1 d-1. On average, the concentrations of the CODt and SS in the final effluents were about 55 and 15 mg L-1 respectively. With respect to phosphate, physico-chemical removal was the dominant process. About 46-62% of total P was removed from the tested wastewaters. The integrated treatment system also achieved a fair degree of hygienisation. The numbers of total coliforms, fecal coliforms and fecal streptococci were decreased by 2-4 log units. The sludge production of the entire treatment system was about 1.7% (v/v) of the treated wastewater. Only primary sludge was produced; secondary sludge produced in the trickling filters was negligible. The cost savings in terms of minimization of sludge production and aeration energy are estimated to be substantial (i.e. some 50%) relative to a conventional activated sludge system. [ABSTRACT FROM AUTHOR]

A feasibility study was carried out in the laboratory for the sequential anaerobic/aerobic treatment of textile wastewater. The process units consisted of an anaerobic UASB (upflow anaerobic sludge blanket)reactor and a SCAS (semi-continuous activated sludge) reactor. A contact-sorption layer with GAC (granular activated carbon) was providedat the bottom of the conventional UASB reactor. The raw textile wastewater first passed through the GAC bed and then through the sludge bed. By means of the GAC bed, the top-layer granular sludge was protected from toxicants. Biological regeneration of GAC, which was enhanced via a recycle flow, was demonstrated. The combined GAC-UASB and SCAS treatments allowed a stable performance and a COD (chemical oxygen demand) and colour removal of 98 and 95%, respectively. [ABSTRACT FROM AUTHOR]

Background: Diabetic ulcers (DUs) is a common complication of diabetes, for which the morbidity and mortality increasing annually worldwide. The deficiency of PD-L1 in keratinocytes (KCs) may be linked to the diabetic wound healing impediments., Objective: Our study utilized transgenic mice to assess the functions of epidermal KCs-specific PD-L1 in DUs treatment., Methods and Results: Epidermal KCs-specific PD-L1 knockouted mice demonstrate deteriorated healing rates, concomitant with exacerbated inflammatory infiltration and excessive angiogenesis. The streptozotocin-induced murine diabetes model was used to imitate DUs in-vivo context, and the delayed healing was found under diabetic conditions. We then generated transgenic mice overexpressing PD-L1 in the epidermis. PD-L1 overexpression accelerate the DUs healing process accompanied by a reduction in inflammatory infiltration and a corresponding decreasion of angiogenesis. Therefore, overexpression of PD-L1 accelerates the healing process of DUs., Conclusion: In sum, epidermal KCs-specific PD-L1 plays vital roles in epidermis regeneration, inflammatory infiltration, and angiogenesis during DUs restoration, and would not be easily to format fibrous scar. Our study elucidated a new therapeutic idea for slow-healing wound care., (Copyright © 2024. Published by Elsevier B.V.)

To date, RNA-targeted chemical matter is under explored due to a lack of robust screening assays. In this study, we present a novel RNA-targeted small molecule screening approach using a specialized DNA-encoded library (DEL). Our findings reveal that the specialized DEL library, called "DEL Zipper", can significantly reduce single-stranded DNA-RNA region interaction signals during various kinds of RNA selection. By performing the selection against both G-quadruplex, we have identified novel hits that interact with RNA targets and the results are validated through binding. This study demonstrates that the "DEL Zipper" method is a robust screening assay that has potential for discovering small molecule ligands for diverse RNA targets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Acne patients increasingly face mental health challenges such as anxiety, depression, and suicidal thoughts. However, no global systematic analysis exists on this topic., Objective: To examine the prevalence of mental disorders-specifically, anxiety, depression, and suicidal thoughts-among acne patients., Methods: An exhaustive search of six databases was conducted up to May 2023. Data analysis was performed using Python and STATA MP 17, including subgroup evaluations, meta-regression, and sensitivity analyses., Results: Forty-three studies were analyzed. Findings indicate depression, anxiety, and suicidal thoughts in acne patients are prevalent at 22%, 30%, and 12% respectively. Depression rates peaked in Asia at 42%, led by India (53%) and Saudi Arabia (51%). Anxiety was also most common in Asia, at 45%, notably in Singapore (60%) and Iran (58%). Suicidal thoughts were highest in Oceania, specifically New Zealand, at 24%., Limitations: The study is limited by the inclusion of only Chinese and English-language research, potentially introducing selection bias., Conclusion: The results of this study highlight the incidence of mental health disorders coexisting with acne, which may help to foster greater understanding and awareness among both medical professionals and patients regarding the psychological complexities tied to acne., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Adenanthin is a structurally unique ent-kaurane diterpenoid isolated from Rabdosia adenantha, a traditional Chinese medicinal plant with potent anti-cancer and anti-inflammatory activities. However, its anti-inflammatory molecular mechanism remains largely elusive to date. Here, we developed an affinity-based label-free protein profiling (ALFPP) to identify potential covalent targets of electrophilic natural products with ketone or aldehyde groups. Using ALFPP, we identified 27 potential covalent targets of adenanthin, among which p65 (RelA) has been associated with its anti-inflammatory activities. Through a series of experiments, including LC-MS/MS, molecular docking, electrophoretic mobility shift assays (EMSA), and genome editing, we demonstrated that adenanthin could covalently modify the Cys38 residue of p65 to affect the binding of DNA to p65, thereby inhibiting the NF-κB signaling pathway. ALFPP will facilitate the target identification of electrophilic carbonylated natural products, especially those containing α, β-unsaturated keto groups. Furthermore, the elucidation of the molecular mechanism of adenanthin will contribute to new drug development of adenanthin to treat inflammations and cancers, enhancing the possibility for its clinical application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management., Competing Interests: Compliance with ethics guidelines. Keke Huang, Qingkai Liu, Ruoxi Zhang, Hua Nian, Ying Luo, Yue Luo, Xiaoya Fei, Le Kuai, Bin Li, Yimei Tan, Su Li, and Xin Ma declare that they have no conflicts of interest. The study was approved by the Institutional Review Board of Yueyang Hospital and the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Informed consent was obtained from all patients for being included in the study. All institutional and national guidelines for the care and use of laboratory animals were followed., (© 2024. Higher Education Press.)

Atopic dermatitis (AD) is one of the most common allergic skin disorders affecting over 230 million people worldwide, while safe and efficient therapeutic options for AD are currently rarely available. Reactive oxygen species (ROS) accumulation plays a key role in AD's disease progression. Therefore, a novel single-atom catalyst is designed with isolated Cu 1 -N 4 sites anchored on carbon support (Cu 1 -N 4 ISAC), featuring triple antioxidant enzyme-mimicking activities, for efficient AD cascade catalytic therapy (CCT). The excellent superoxide dismutase (SOD)-, glutathione peroxidase (GPx)-, and ascorbate peroxidase (APx)-like activities of Cu 1 -N 4 ISACs enable the sequential conversion of O 2 • - to H 2 O 2 and then to harmless H 2 O, thereby protecting keratinocytes from oxidative stress damage. Notably, two novel experimental methods are developed to directly prove the SOD-GPx and SOD-APx cascade catalytic activities for the first time. In vivo experiments show that Cu 1 -N 4 ISACs are more potent than a recommended typical medicine (halcinonide solution). Additionally, RNA sequencing and bioinformatic analysis reveal that Cu 1 -N 4 ISACs reduce inflammation and inhibit ROS production by activating PPAR signaling, which is aberrantly reduced in AD. Therefore, the synthesized catalytic medicine offers an alternative to alleviate AD and has the potential to serve as PPAR agonists for treating similar diseases., (© 2024 Wiley‐VCH GmbH.)

Rationale: Etomidate is a short-acting general anesthetic for clinical use and has been used as alternative to propofol or added to the powdered drug and e-cigarette cartridges recently, leading to an increase in abuse. But there have been no studies conducted on the abuse potential of etomidate., Objectives and Methods: This study aimed to evaluate the abuse potential of etomidate via conditioned place preference (CPP) and self-administration tests, reflecting its rewarding and reinforcing effects. In addition, righting reflex and open-field tests were conducted to evaluate the anesthetic and sedative effects of etomidate., Results: In male mice, the ED 50 after intraperitoneal (i.p.) injection of anesthetic effect for etomidate was 9.156 mg/kg and the ED 50 of the sedative effect 5 min after intraperitoneal injection was 2.389 mg/kg. Etomidate induced CPP in male mice at the minimum dose of 3 mg/kg i.p. and supported stable self-administration in male rats at the dose of 0.075 mg/kg/intravenous infusion. The dose-response curve of etomidate was an inverted U-shape, which showed significant self-administrations compared with the vehicle group at doses of 0.05-0.1 mg/kg/infusion etomidate and the highest intake of 21.1 ± 0.64 infusions per 4 h-session., Conclusions: These results clearly demonstrate that etomidate has rewarding and reinforcing effects in male rodents, as well as effects on anesthesia and motor inhibition. These findings indicate the possibility of abuse potential in humans using etomidate., Competing Interests: Declarations Ethics approval and consent to participate All procedures followed the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Conflict of interest The authors declare no conflict of interest related to this work., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Psoriasis (PSO) poses a global health threat. The current research challenge in PSO is relapse. Liquiritin (LIQ), a major active compound from Glycyrrhiza inflata Batalin, has multiple pharmacological properties, including anti-inflammatory and anti-proliferative. Nonetheless, the precise mechanisms underlying LIQ's therapeutic actions in PSO and prevention abilities remain elusive., Purpose: The present study aimed to delve into the potential to treat and prevent PSO and the mechanism of LIQ., Methods: The anti-inflammatory and anti-proliferative effects of LIQ were studied in vitro with the HaCaT cell line. Then, Transcriptional analysis and bioinformatic analysis were used to determine the internal associations of the target set. Subsequently, functional experiment, luciferase report assay, ChIP-PCR, and immunohistochemical validation of clinical samples were performed to investigate the mechanism of LIQ. Finally, the anti-psoriatic effects and prevention abilities of LIQ were verified in vivo with imiquimod (IMQ)-induced PSO-like mouse models., Results: Here, we identified differentially expressed genes in LIQ-stimulated HaCaT cells and Retinol-Binding Protein 3 (RBP3) as the core target, whereas YY1 was a predicted upstream transcription factor of RBP3. The YY1/RBP3 axis was obviously altered after administering LIQ at optimal doses of 20 μM in vitro and 100 µg/ml in vivo. LIQ can significantly inhibit the progression of PSO in vivo. Notably, LIQ also prevented the relapse of psoriatic lesions induced by the second round of low-dose IMQ. Mechanistically, we observed that LIQ could increase the promotion of YY1 for RBP3 by enhancing the binding affinity between them., Conclusion: These findings revealed that the YY1/RBP3 axis is a potential psoriatic target, and LIQ is a promising and innovative therapeutic candidate for the treatment and prevention of PSO., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Psoriasis is a skin disease that is inflammatory and persistent, causing a high rate of recurrence, poor quality of life, and significant socioeconomic burden. Its main pathological manifestations are abnormal activation and infiltration of T cells and excessive proliferation of keratinocytes (KCs). The great majority of patients with psoriasis will relapse after remission. It usually lasts a lifetime and necessitates long-term treatment strategies. During periods of activity and remission, one of the main cell types in psoriasis is memory T cells, which include tissue-resident memory T (TRM) cells, central memory T (TCM) cells, and effector memory T (TEM) cells. They work by releasing inflammatory factors, cytotoxic particles, or altering cell subpopulations, leading to increased inflammation or recurrence. This review summarizes the role of memory T cells in the pathology and treatment of psoriasis, with a view to potential novel therapies and therapeutic targets., (© 2024 John Wiley & Sons Ltd.)

Genome transcription and replication of influenza A virus (FluA), catalyzed by viral RNA polymerase (FluAPol), are delicately controlled across the virus life cycle. A switch from transcription to replication occurring at later stage of an infection is critical for progeny virion production and viral non-structural protein NS2 has been implicated in regulating the switch. However, the underlying regulatory mechanisms and the structure of NS2 remained elusive for years. Here, we determine the cryo-EM structure of the FluAPol-NS2 complex at ~3.0 Å resolution. Surprisingly, three domain-swapped NS2 dimers arrange three symmetrical FluPol dimers into a highly ordered barrel-like hexamer. Further structural and functional analyses demonstrate that NS2 binding not only hampers the interaction between FluAPol and the Pol II CTD because of steric conflicts, but also impairs FluAPol transcriptase activity by stalling it in the replicase conformation. Moreover, this is the first visualization of the full-length NS2 structure. Our findings uncover key molecular mechanisms of the FluA transcription-replication switch and have implications for the development of antivirals., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Volatile oil is widely used in traditional Chinese medicine owing to its unique hydrophobic and lipophilic properties and rapid skin absorption. Artemisia annua L. (A.annua) essential oil (AAEO), a volatile oil extracted from A. annua, exhibits anti-inflammatory properties. However, few studies have investigated its effects on skin inflammation., Aim of the Study: To investigate and elucidate the mechanisms of action of AAEO in the treatment of atopic dermatitis (AD)., Materials and Methods: Network pharmacology was used to predict the targets and pathways of AAEO for the treatment of AD. The AD mouse model was established by topical application of 2,4-dintrochlorobenzene (DNCB), AAEO, and the positive control drug hydrocortisone butyrate cream (HBC). We evaluated the symptoms of AD, SCORAD scores, histological analysis, and serum IgE and TNF-α levels in mice. Immunofluorescence, western blotting, and qPCR were used to investigate the signaling pathways., Results: Network pharmacology analysis indicated that AAEO may exert its effects via the MAPK/NF-κB signaling pathway. Animal experiments demonstrated that topical application of AAEO and HBC significantly ameliorated skin lesions, reduced dermatitis score, and decreased spleen weight compared to DNCB treatment. AAEO reduced skin epidermal thickness and mast cell infiltration. DNCB markedly reduced the protein levels of filaggrin (FLG) and loricrin (LOR), whereas AAEO reversed these changes. Notably, the 5% concentration of AAEO demonstrated substantial improvement in skin barrier function. Compared to the DNCB group, the levels of FLG and LOR remained almost unchanged following HBC treatment. DNCB markedly elevated IgE and TNF-α levels, which were reversed by AAEO and HBC treatment. Among the inflammatory cytokines, DNCB increased mRNA expression of TNF-α, IL-1β, and IL-6, however, it reduced IL-10, with AAEO and HBC reversing these changes to various degrees. Additionally, DNCB-induced ERK, JNK, and P38 phosphorylation, associated with the upregulation of phosphorylation of NF-κB, whereas, AAEO and HBC exhibited potent inhibition of the MAPK/NF-κB signaling pathway., Conclusions: This study systematically demonstrated the possible therapeutic effects and mechanisms of AAEO in AD via network pharmacological analysis and experimental confirmation. These results revealed that topical application of AAEO can suppress skin inflammation and restore skin barrier function. These findings provide the potential application of AAEO in synthesizing external preparations for both pharmacological and cosmetic industries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Support modification is an important way to improve the activity of the Ru/MgO-based NH 3 synthesis catalyst. This work synthesized 24 composite MgO-based supports of MO x -MgO (M = La, Zn, etc.) via a microdrop-confined pyrolysis (MDCPy) method and then prepared the corresponding Cs-Ba-Ru/MO x -MgO catalysts using the impregnation method. Under the same NH 3 synthesis conditions, the activity of the Cs-Ba-Ru/MO x -MgO catalysts composed of 17 elements such as Pr was significantly lower than that of Cs-Ba-Ru/MgO, while the activity of the Cs-Ba-Ru/MO x -MgO catalysts composed of four elements such as Nd was comparable to that of Cs-Ba-Ru/MgO, and the activity of the Cs-Ba-Ru/MO x -MgO catalysts composed of three elements such as La was significantly higher than that of Cs-Ba-Ru/MgO. Among them, it is clear that La 2 O 3 -MgO composite supports have the most significant effect on the improvement of NH 3 synthesis performance. Through the optimization of the La/Mg ratio and loading of Ru, the optimal activities achieved ∼7 mol (NH3) /g (Ru) /h with corresponding Ru loading of 0.25-0.5 wt % under mild conditions as follows: H 2 /N 2 ratio of 3:1, temperature of 400 °C, pressure of 3 MPa and a weight hourly space velocity (WHSV) of 96.0 L/g cat /h. In addition, the CsBa-Ru/La 2 O 3 -MgO catalyst showed good stability.