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Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disease with a wide range of heterogeneity. Accurate biomarkers or predictors are the keys to instructing personalized tailored precise treatment. The development of technology such as transcriptomics, genomics, and proteomics provides novel insights into the possibility to find potential biomarkers. Meanwhile, emerging minimally invasive methods such as tape stripping were used to reveal different profiles of patients’ skin without biopsy. Several potential biomarkers or predictors have been found. In this review, we summarized the current development of potential biomarkers of AD. Nitric oxide synthase 2/inducible nitric oxide synthase (NOS2/iNOS), human beta-defensin-2 (hBD-2), and matrix metalloproteinases 8/9 (MMP8/9) may be the candidate biomarkers for AD diagnosis. Filaggrin (FLG) gene mutation increased the occurrence risk of AD. Fatty-acid-binding protein 5 (FABP5) may serve as an effective biomarker for the atopic march (AM). Squamous cell carcinoma antigen 2 (SCCA2), serum thymus and activation-regulated chemokine (TARC), cutaneous T-cell-attracting chemokine (CTACK), eosinophil-derived neurotoxin (EDN), macrophage-derived chemokine (MDC), lactate dehydrogenase (LDH), and interleukin (IL)-18 can be the candidate biomarkers for disease severity monitoring. IL-17, IL-23, IL-33, and indoleamine 2,3-dioxygenase (IDO1) can be used as predictive biomarkers for AD comorbidities. LDH, TARC, pulmonary and activation-regulated chemokine (PARC), periostin, IL-22, eotaxin-1/3, and IL-8 may be the candidate biomarkers for monitoring treatment effects. There are still unmet needs and a long way to go for more convenient, non-invasive, and effective predictors and biomarkers to better guide personalized precise treatment.

Vunakizumab is effective and safe for treating moderate-to-severe plaque psoriasis patients. This analysis was intended to assess the effects of vunakizumab in patients with different body mass index (BMI). In the phase III trial of vunakizumab (NCT04839016), 461 moderate-to-severe plaque psoriasis patients receiving vunakizumab were enrolled and categorized into baseline BMI<24 kg/m (N = 179), 24≤BMI<28 kg/m (N = 183), and BMI≥28 kg/m (N = 99) groups. At least 75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75), PASI 90, PASI 100, static physician's global assessment (sPGA) 0/1, patient-reported outcomes (PROs), serum concentration of vunakizumab, and adverse events from week 0 (W0)-W52 were recorded. A lower BMI was associated with higher W0--W12 accumulating PASI 75, PASI 90, PASI 100, and sPGA 0/1 response rates. From W0--W52, a lower BMI was associated with higher PASI 75, PASI 90, and PASI 100 scores at most time points and was related to sPGA 0/1 response rates from W4--W48. With respect to PROs, higher BMI was related to increased mean dermatology life quality index scores at several time points but was not associated with the mean worst itch numerical rating scale, EuroQoL-5D (EQ-5D) utility index, EQ-5D visual analog scale score, or short form-36 mental/physical component score. A lower BMI was related to a higher mean serum concentration of vunakizumab. The incidences of any adverse events and most specific adverse events did not differ among the groups. A lower BMI is associated with a greater treatment response and quality of life in moderate-to-severe plaque psoriasis patients receiving vunakizumab.

A bstract We systematically study how the integrality of the conformal characters shapes the space of fermionic rational conformal field theories in two dimensions. The integrality suggests that conformal characters on torus with a given choice of spin structures should be invariant under a principal congruence subgroup of PSL(2 , ℤ). The invariance strongly constrains the possible values of the central charge as well as the conformal weights in both Neveu-Schwarz and Ramond sectors, which improves the conventional holomorphic modular bootstrap method in a significant manner. This allows us to make much progress on the classification of fermionic rational conformal field theories with the number of independent characters less than five.

The conversion of carbon-based solids, like non-recyclable plastics, biomass, and coal, into small molecules appears attractive from different points of view. However, the strong carbon–carbon bonds in these substances pose a severe obstacle, and thus—if such reactions are possible at all—high temperatures are required 1 – 5 . The Bergius process for coal conversion to hydrocarbons requires temperatures above 450 °C 6 , pyrolysis of different polymers to pyrolysis oil is also typically carried out at similar temperatures 7 , 8 . We have now discovered that efficient hydrogenation of different solid substrates with the carbon-based backbone to light hydrocarbons can be achieved at room temperature by ball milling. This mechanocatalytic method is surprisingly effective for a broad range of different carbon substrates, including even diamond. The reaction is found to proceed via a radical mechanism, as demonstrated by reactions in the presence of radical scavengers. This finding also adds to the currently limited knowledge in understanding mechanisms of reactions induced by ball milling. The results, guided by the insight into the mechanism, could induce more extended exploration to broaden the application scope and help to address the problem of plastic waste by a mechanocatalytic approach. Conventional methods to gasify or liquefy carbon-based polymers use high temperatures because of carbon–carbon bond stability. Here, the authors describe a mechanochemical ball milling method to break carbon–carbon bonds without heating.

Biotic stress causes immense damage to agricultural products worldwide and raises the risk of hunger in many areas. Plants themselves tolerate biotic stresses via several pathways, including pathogen-associated molecular patterns (PAMPs), which trigger immunity and plant resistance (R) proteins. On the other hand, humans use several non-ecofriendly methods to control biotic stresses, such as chemical applications. Compared with chemical control, melatonin is an ecofriendly compound that is an economical alternative strategy which can be used to protect animals and plants from attacks via pathogens. In plants, the bactericidal capacity of melatonin was verified against Mycobacterium tuberculosis, as well as multidrug-resistant Gram-negative and -positive bacteria under in vitro conditions. Regarding plant–bacteria interaction, melatonin has presented effective antibacterial activities against phytobacterial pathogens. In plant–fungi interaction models, melatonin was found to play a key role in plant resistance to Botrytis cinerea, to increase fungicide susceptibility, and to reduce the stress tolerance of Phytophthora infestans. In plant–virus interaction models, melatonin not only efficiently eradicated apple stem grooving virus (ASGV) from apple shoots in vitro (making it useful for the production of virus-free plants) but also reduced tobacco mosaic virus (TMV) viral RNA and virus concentration in infected Nicotiana glutinosa and Solanum lycopersicum seedlings. Indeed, melatonin has unique advantages in plant growth regulation and increasing plant resistance effectiveness against different forms of biotic and abiotic stress. Although considerable work has been done regarding the role of melatonin in plant tolerance to abiotic stresses, its role in biotic stress remains unclear and requires clarification. In our review, we summarize the work that has been accomplished so far; highlight melatonin’s function in plant tolerance to pathogens such as bacteria, viruses, and fungi; and determine the direction required for future studies on this topic.

The fundamental technology behind bitcoin, known as blockchain, has been studied and used in a variety of industries especially in finance. The security of blockchain is extremely important as it will affects the assets of the clients as well as it is the lifeline feature of the entire system that needs to be guaranteed. Currently, there is a lack of a methodical approach to guarantee the security and dependability of the private key during its whole life. Furthermore, there is no quick, easy, or secure way to create the encryption key. A biometric-based private key encryption and management framework (BPKEM) for blockchain is proposed not only to solve the private key lifecycle manag- ement problem, but also it maintains compatibility with existing blockchain systems. For the problem of private key encryption, a biometric-based stable key generation method is proposed. By using the relative invariance between facial and fingerprint feature points, this measure can convert feature points into stable and distinguishable descriptors, then using a reusable fuzzy extractor to create a stable key. The correct- ness and efficiency of the newly proposed biometric-based blockchain encryption tech- nique in this paper has been validated in the experiments.

Autophagy is a complicated cellular mechanism that maintains cellular and tissue homeostasis and integrity degradation of senescent, defective subcellular organelles, infectious agents, and misfolded proteins. Accumulating evidence has shown that autophagy is involved in numerous immune processes, such as removal of intracellular bacteria, cytokine production, autoantigen presentation, and survival of lymphocytes, indicating an apparent and important role in innate and adaptive immune responses. Indeed, in genome-wide association studies, autophagy-related gene polymorphisms have been suggested to be associated with the pathogenesis of several autoimmune and inflammatory disorders, such as systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. In addition, conditional knockdown of autophagy-related genes in mice displayed therapeutic effects on several autoimmune disease models by reducing levels of inflammatory cytokines and autoreactive immune cells. However, the inhibition of autophagy accelerates the progress of some inflammatory and autoimmune diseases promotion of inflammatory cytokine production. Therefore, this review will summarize the current knowledge of autophagy in immune regulation and discuss the therapeutic and pathogenic role of autophagy in autoimmune diseases to broaden our understanding of the etiopathogenesis of autoimmune diseases and shed light on autophagy-mediated therapies.

Melatonin (MT) is a pleiotropic molecule with diverse and numerous actions both in plants and animals. In plants, MT acts as an excellent promotor of tolerance against abiotic stress situations such as drought, cold, heat, salinity, and chemical pollutants. In all these situations, MT has a stimulating effect on plants, fomenting many changes in biochemical processes and stress-related gene expression. Melatonin plays vital roles as an antioxidant and can work as a free radical scavenger to protect plants from oxidative stress by stabilization cell redox status; however, MT can alleviate the toxic oxygen and nitrogen species. Beyond this, MT stimulates the antioxidant enzymes and augments antioxidants, as well as activates the ascorbate–glutathione (AsA–GSH) cycle to scavenge excess reactive oxygen species (ROS). In this review, we examine the recent data on the capacity of MT to alleviate the effects of common abiotic soil stressors, such as salinity, alkalinity, acidity, and the presence of heavy metals, reinforcing the general metabolism of plants and counteracting harmful agents. An exhaustive analysis of the latest advances in this regard is presented, and possible future applications of MT are discussed.

Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD. This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied. At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs . placebo, 95% CI 31%-69%) and 45% (low vs . placebo, 95% CI 26%-64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator's Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.

In this paper, an adaptive and robust Kalman filter algorithm based on the maximum correntropy criterion (MCC) is proposed to solve the problem of integrated navigation accuracy reduction, which is caused by the non-Gaussian noise and time-varying noise of GPS measurement in complex environment. Firstly, the Grubbs criterion was used to remove outliers, which are contained in the GPS measurement. Then, a fixed-length sliding window was used to estimate the decay factor adaptively. Based on the fixed-length sliding window method, the time-varying noises, which are considered in integrated navigation system, are addressed. Moreover, a MCC method is used to suppress the non-Gaussian noises, which are generated with external corruption. Finally, the method, which is proposed in this paper, is verified by the designed simulation and field tests. The results show that the influence of the non-Gaussian noise and time-varying noise of the GPS measurement is detected and isolated by the proposed algorithm, effectively. The navigation accuracy and stability are improved.