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Abstract Due to the hallucination of the underlying large language model(LLMs) or the unclear description of the task’s ultimate goal, the agents have become somewhat confused. Despite having completed tasks, they have not ceased working, leading to a waste of resource. We propose similarity-based task timely termination method for image-based intelligent agents, This method involves recording the scenario state after the completion of each sub-task and comparing it with the fully completed task scenario state using a structural similarity method. The result is quantified and standardized into a structural similarity index, which is used to judge whether the task has been completed. Moreover, we categorize the types of agents based on model and created an image-based agent task dataset. In experimental results, the image-based agents using this method showed an average reduction of 1.94 steps in the number of steps to complete 20 task tests, a $$44.1\%$$ reduction in time costs, and a $$47.3\%$$ reduction in token costs. This method can effectively reduce the negative actions of image-based agents when they experience hallucinations, ensuring their tasks are completed excellently, and it can effectively reduce the waste of resources such as time, tokens, and hardware. Our project can be found at GitHub .

Abstract Acute lung injury (ALI) is a common critical respiratory disease in clinical practice, especially in the ICU, with a high mortality rate. The pathogenesis of ALI is relatively complex, mainly involving inflammatory response imbalance, oxidative stress, cell apoptosis, and other aspects. However, currently, the treatment measures taken based on the above mechanisms have not had significant effects. Recent research shows that mitochondrial dysfunction and pyroptosis play an important role in ALI, but there is not much analysis on the relationship between mitochondrial dysfunction and pyroptosis at present. This article reviews the situation of mitochondrial dysfunction in ALI, pyroptosis in ALI, whether mitochondrial dysfunction is related to pyroptosis in ALI, and how to do so, and further analyzes the relationship between them in ALI. This review describes how to alleviate mitochondrial dysfunction, and then suppress the associated immunological pyroptosis, providing new ideas for the clinical treatment of ALI.

Abstract Interferon Regulatory Factors (IRFs), a family of transcription factors, profoundly influence the immune system, impacting both physiological and pathological processes. This review explores the diverse functions of nine mammalian IRF members, each featuring conserved domains essential for interactions with other transcription factors and cofactors. These interactions allow IRFs to modulate a broad spectrum of physiological processes, encompassing host defense, immune response, and cell development. Conversely, their pivotal role in immune regulation implicates them in the pathophysiology of various diseases, such as infectious diseases, autoimmune disorders, metabolic diseases, and cancers. In this context, IRFs display a dichotomous nature, functioning as both tumor suppressors and promoters, contingent upon the specific disease milieu. Post-translational modifications of IRFs, including phosphorylation and ubiquitination, play a crucial role in modulating their function, stability, and activation. As prospective biomarkers and therapeutic targets, IRFs present promising opportunities for disease intervention. Further research is needed to elucidate the precise mechanisms governing IRF regulation, potentially pioneering innovative therapeutic strategies, particularly in cancer treatment, where the equilibrium of IRF activities is of paramount importance.

Klippel-Trenaunay Syndrome is a rare congenital disorder characterized by a triad of symptoms-capillary malformations, venous abnormalities, and hypertrophy of bones and soft tissues. The syndrome often presents with port wine stains, varicose veins, and limb hypertrophy, which can lead to significant complications such as venous thromboembolism and bleeding. We present a case of a 13 ` year female, with erythema in left upper limb and shoulder since birth.. An effective treatment method was employed, which incorporated a multidisciplinary team of experts specialized in various fields of dermatology and vascular surgery, all working collaboratively with the patient's well-being at the core of their efforts. This approach emphasized a personalized strategy based on the patient's preferences.

Hemoporfin mediated photodynamic therapy(HMME-PDT) has been proved safe and effective for treating PWS in both adults and children in previous articles, especially for lager segment lesions. However, crusts and scars associated with HMME-PDT cannot be ignored. The article briefly summarized several post-treatment reactions after HMME-PDT treatment relative to prognosis, and emphasized that early identification and intervention the post-treatment reactions after HMME-PDT, which has very important significance to prognosis.

Abstract Circular RNA (circRNA) is thought to mediate the occurrence and development of human cancer and usually acts as a tiny RNA (miRNA) sponge to regulate downstream gene expression. However, it is not clear whether and how circACVR2A (hsa_circ_0001073) is involved in the progression of HCC. The purpose of this study is to clarify the potential role and molecular mechanism of circACVR2A in regulating the progression of hepatocellular carcinoma cells (HCC). The abundance of related proteins in circACVR2A, microRNA (miR511-5p) and PI3K-Akt signaling pathway was determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) or Western blotting. Cell viability, invasion and apoptosis were analyzed by CCK-8, Transwell analysis and Tunel staining, respectively. The interaction between circACVR2A and microRNA was evaluated by double luciferase reporter gene assay. The results showed that circACVR2A was highly expressed in hepatocellular carcinoma cell lines. Our in vivo and in vitro data showed that circACVR2A promoted the proliferation, migration and invasion of HCC. In terms of mechanism, we found that circACVR2A can directly interact with miR511-5p and act as a miRNA sponge to regulate the expression of related proteins in PI3K-Akt signaling pathway. In HCC, circACVR2A can mediate miR-511-5p/mRNA network to activate PI3K signal pathway. This shows that the molecular regulatory network with circACVR2A as the core is a new potential target for diagnosis and treatment of hepatocellular carcinoma.

Abstract. Background:. Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection. Methods:. A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2. Results:. Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P

Abstract Introduction Recent advancements in androgenetic alopecia (AGA) treatment have highlighted the efficacy of botulinum toxin (BoNT). However, inconsistencies in injection sites and depths warrant attention. It remains unclear which injection strategy is most beneficial for patients. Methods This split-scalp randomized controlled trial divided each enrolled participant’s scalp along the midline: one side was randomized to receive intramuscular BoNT injections in the surrounding muscles, while the other side received intradermal BoNT injections directly into the balding areas. This study evaluated the impact of treatment on hair density and diameter through trichoscopic examinations conducted at baseline and 12 weeks post treatment. Additionally, assessments of pain and overall safety were integrated into the study protocol. Results Twenty-nine patients completed the study, with significant improvements in hair density observed in the intramuscular injection group compared to the intradermal group (p

Dermatopathology training is a crucial aspect of the education and training of residents in dermatology and venereology, while interpretation of pathological sections is essential for this training. We employ the general pattern teaching method to enhance teaching quality, focusing on initial observation of sections with the naked eye and low-power lens to deduce biopsy sites and diagnose diseases based on image outline and color contrast. Diseases which can be diagnosed by general pattern analysis can be categorized into six groups: changes in the epidermis, mass-like hyperplasia and band-like changes in the dermis, changes in the fat layer, unique shape, and vascular proliferation. Some of these major categories can be further divided into subgroups. There are a total 18 common pathological patterns, including 53 prevalent skin diseases, 26 of which are required to be mastered according to the training guideline. The general pattern teaching method in combination with informative content and an engaging approach can effectively stimulate residents' enthusiasm for learning skin pathology and enhance their educational experience, leading to the improvement of outcome of dermatopathology training programs for residents in dermatology and venereology.

Diabetic peripheral neuropathic pain (DPNP) is a major complication of diabetes that markedly affects the quality of life and health status of patients. Recent studies have investigated the potential regulatory influence of gut flora and bile acids on DPNP via the TGR5/TRPV1 signaling pathway. Dysbiosis of the gut flora not only directly affects bile acid metabolism but also significantly correlates with diabetes-associated neuropathy through interactions with the bile acid receptor TGR5 and the ion channel TRPV1. This review describes how alterations in the gut flora and bile acid metabolism contribute to the pathogenesis of DPNP through the TGR5/TRPV1 signaling pathway, revealing potential applications for this pathway in DPNP management. Furthermore, experimental and clinical studies have demonstrated the modulation of gut flora and bile acid metabolism as well as targeting the TGR5/TRPV1 signaling pathway as an innovative therapeutic approach. Further studies are warranted to elucidate the underlying mechanism and develop treatment modalities based on gut flora regulation and signaling pathway interventions, thus providing novel insights and approaches for DPNP therapy.

Rosacea is a chronic skin inflammatory disease with a global prevalence ranging from 1% to 20%. It is characterized by facial erythema, telangiectasia, papules, pustules, and ocular manifestations. Its pathogenesis involves a complex interplay of genetic, environmental, immune, microbial, and neurovascular factors. Recent studies have advanced our understanding of its molecular basis, focusing on toll-like receptor (TLR) 2 pathways, LL37 expression, mammalian target of rapamycin (mTOR) activation, interleukin (IL)-17 signaling, transient receptor potential vanilloid (TRPV) functions, and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways. LL37-associated signaling pathways, particularly involving TLR2 and mTORC1, are critical in the pathogenesis of rosacea. LL37 interacts with signaling molecules such as extracellular signal-regulated kinases 1 and 2 (ERK1/2), nuclear factor kappa B (NF-κB), inflammasomes, C-X-C motif chemokine ligand 8 (CXCL8), mas-related G-protein-coupled receptor X2 (MRGPRX2)-TRPV4, and vascular endothelial growth factor (VEGF). This interaction activates macrophages, neutrophils, mast cells, and vascular endothelial cells, leading to cytokine release including tumor necrosis factor-alpha (TNF-α), IL-6, IL-1β, C motif chemokine ligand (CCL) 5, CXCL9, and CXCL10. These processes contribute to immune response modulation, inflammation, and angiogenesis in rosacea pathophysiology. The IL-17 signaling pathway also plays a crucial role in rosacea, affecting angiogenesis and the production of inflammatory cytokines. In addition, recent insights into the JAK/STAT pathways have revealed their integral role in inflammatory and angiogenic mechanisms associated with rosacea. Rosacea treatment currently focuses on symptom management, with emerging insights into these molecular pathways providing more targeted and effective therapies. Biological agents targeting specific cytokines, IL-17 inhibitors, JAK inhibitors, and VEGF antagonists are promising for future rosacea therapy, aiming for enhanced efficacy and fewer side effects. This review provides a comprehensive overview of the current knowledge regarding signaling pathways in rosacea and potential targeted therapeutic strategies.

Abstract Introduction The aim of this study was to assess the efficacy and safety of 15% azelaic acid (AzA) gel in treating acne-induced post-inflammatory erythema (PIE) and post-inflammatory hyperpigmentation (PIH). The effects of 15% AzA gel on acne, skin barrier function, and quality of life were also evaluated. Methods A total of 72 patients with mild to moderate acne were enrolled in a randomized, double-blind, placebo-controlled trial. Patients were divided into two groups: patients in the AzA group applied 15% AzA gel twice daily for 12 weeks, and those in the placebo group applied AzA-free gel. Clinical evaluations using non-invasive skin detection technologies, including VISIA skin analysis, dermoscopy, and skin physiological function tests, were performed at 0, 4, 8, and 12 weeks. Main outcome measures included the post-acne hyperpigmentation index (PAHPI), melanin, hemoglobin, individual typology angle, water content, transepidermal water loss, and sebum. Investigator Global Assessment) and Dermatology Life Quality Index (DLQI) assessments were conducted at weeks 0 and 12. Adverse reactions were recorded. Results Of the 72 patients at study initiation, 60 completed the trial. At 8 and 12 weeks, patients in the AzA group showed significantly reduced PAHPI for PIE lesions compared to baseline and patients receiving placebo (P

BackgroundRecent advancements in artificial intelligence (AI) and large language models (LLMs) have shown potential in medical fields, including dermatology. With the introduction of image analysis capabilities in LLMs, their application in dermatological diagnostics has garnered significant interest. These capabilities are enabled by the integration of computer vision techniques into the underlying architecture of LLMs. ObjectiveThis study aimed to compare the diagnostic performance of Claude 3 Opus and ChatGPT with GPT-4 in analyzing dermoscopic images for melanoma detection, providing insights into their strengths and limitations. MethodsWe randomly selected 100 histopathology-confirmed dermoscopic images (50 malignant, 50 benign) from the International Skin Imaging Collaboration (ISIC) archive using a computer-generated randomization process. The ISIC archive was chosen due to its comprehensive and well-annotated collection of dermoscopic images, ensuring a diverse and representative sample. Images were included if they were dermoscopic images of melanocytic lesions with histopathologically confirmed diagnoses. Each model was given the same prompt, instructing it to provide the top 3 differential diagnoses for each image, ranked by likelihood. Primary diagnosis accuracy, accuracy of the top 3 differential diagnoses, and malignancy discrimination ability were assessed. The McNemar test was chosen to compare the diagnostic performance of the 2 models, as it is suitable for analyzing paired nominal data. ResultsIn the primary diagnosis, Claude 3 Opus achieved 54.9% sensitivity (95% CI 44.08%-65.37%), 57.14% specificity (95% CI 46.31%-67.46%), and 56% accuracy (95% CI 46.22%-65.42%), while ChatGPT demonstrated 56.86% sensitivity (95% CI 45.99%-67.21%), 38.78% specificity (95% CI 28.77%-49.59%), and 48% accuracy (95% CI 38.37%-57.75%). The McNemar test showed no significant difference between the 2 models (P=.17). For the top 3 differential diagnoses, Claude 3 Opus and ChatGPT included the correct diagnosis in 76% (95% CI 66.33%-83.77%) and 78% (95% CI 68.46%-85.45%) of cases, respectively. The McNemar test showed no significant difference (P=.56). In malignancy discrimination, Claude 3 Opus outperformed ChatGPT with 47.06% sensitivity, 81.63% specificity, and 64% accuracy, compared to 45.1%, 42.86%, and 44%, respectively. The McNemar test showed a significant difference (P

BackgroundPathological scars, including keloids and hypertrophic scars, represent a significant dermatological challenge, and emerging evidence suggests a potential role for the gut microbiota in this process.MethodsUtilizing a two-sample Mendelian randomization (MR) methodology, this study meticulously analyzed data from genome-wide association studies (GWASs) relevant to the gut microbiota, keloids, and hypertrophic scars. The integrity and reliability of the results were rigorously evaluated through sensitivity, heterogeneity, pleiotropy, and directionality analyses.ResultsBy employing inverse variance weighted (IVW) method, our findings revealed a causal influence of five bacterial taxa on keloid formation: class Melainabacteria, class Negativicutes, order Selenomonadales, family XIII, and genus Coprococcus2. Seven gut microbiota have been identified as having causal relationships with hypertrophic scars: class Alphaproteobacteria, family Clostridiaceae1, family Desulfovibrionaceae, genus Eubacterium coprostanoligenes group, genus Eubacterium fissicatena group, genus Erysipelotrichaceae UCG003 and genus Subdoligranulum. Additional sensitivity analyses further validated the robustness of the associations above.ConclusionOverall, our MR analysis supports the hypothesis that gut microbiota is causally linked to pathological scar formation, providing pivotal insights for future mechanistic and clinical research in this domain.

IntroductionConventional rosacea treatments are not uniformly pervasive, and the adverse reactions can potentially constrain their utility. The clinical use of JAK1 inhibitors upadacitinib and abrocitinib in the treatment of refractory rosacea has rarely been explored.Case reportWe presented two cases of patients who received the JAK1 inhibitor upadacitinib and four cases of patients who received the JAK1 inhibitor abrocitinib for the treatment of refractory rosacea.DiscussionThe JAK1 inhibitors upadacitinib and abrocitinib may be promising medical options for patients with refractory rosacea. However, the long-term safety and efficacy of upadacitinib and abrocitinib require prospective controlled studies to assess them more comprehensively.

BackgroundRecent advancements in basic medicine and epidemiology suggest a potential influence of blood pressure on scar formation, yet the specifics of this relationship are not fully understood. This study aims to clarify the causal link between blood pressure and the development of pathological scars using Mendelian randomization (MR).MethodsThis study employed genetic variants closely linked to blood pressure as instrumental variables to explore the relationship between blood pressure and pathological scars. The inverse variance weighted (IVW) method was used for analysis.ResultsOur analysis identified a notable association where higher blood pressure was correlated with a lower risk of pathological scars. Specifically, an increase in diastolic blood pressure (odds ratio [OR] per standard deviation increase: 0.67 [95% Confidence Interval [CI], 0.49–0.99]), systolic blood pressure (OR per standard deviation increase: 0.66 [95% CI, 0.46–0.93]), and hypertension (pooled OR: 0.39 [95% CI, 0.18–0.85]) were significantly associated with a reduced risk of keloids. Similarly, a genetic predisposition to hypertension (pooled OR: 0.31 [95% CI, 0.11–0.89]) was significantly associated with a reduced risk of hypertrophic scars. Neither reverse MR analysis nor Steiger’s test indicated a significant reverse causal relationship between hypertension and either keloids or hypertrophic scars.ConclusionThe findings suggest a protective role of higher blood pressure against the development of pathological scars, including keloids and hypertrophic scars. However, the inconsistency observed across different MR methods warrants cautious interpretation and underscores the need for further investigation to confirm these findings.

Beclin-1 is the firstly-identified mammalian protein of the autophagy machinery, which functions as a molecular scaffold for the assembly of PI3KC3 (class III phosphatidylinositol 3 kinase) complex, thus controlling autophagy induction and other cellular trafficking events. Notably, there is mounting evidence establishing the implications of Beclin-1 in diverse tumorigenesis processes, including tumor suppression and progression as well as resistance to cancer therapeutics and CSC (cancer stem-like cell) maintenance. More importantly, Beclin-1 has been confirmed as a potential target for the treatment of multiple cancers. In this review, we provide a comprehensive survey of the structure, functions, and regulations of Beclin-1, and we discuss recent advances in understanding the controversial roles of Beclin-1 in oncology. Moreover, we focus on summarizing the targeted Beclin-1-regulating strategies in cancer therapy, providing novel insights into a promising strategy for regulating Beclin-1 to improve cancer therapeutics in the future.

Abstract Pyroptosis, apoptosis, and necroptosis are mainly programmed cell death (PCD) pathways for host defense and homeostasis. PANoptosis is a newly distinct inflammatory PCD pathway that is uniquely regulated by multifaceted PANoptosome complexes and highlights significant crosstalk and coordination among pyroptosis (P), apoptosis (A), and/or necroptosis(N). Although some studies have focused on the possible role of PANpoptosis in diseases, the pathogenesis of PANoptosis is complex and underestimated. Furthermore, the progress of PANoptosis and related agonists or inhibitors in disorders has not yet been thoroughly discussed. In this perspective, we provide perspectives on PANoptosome and PANoptosis in the context of diverse pathological conditions and human diseases. The treatment targeting on PANoptosis is also summarized. In conclusion, PANoptosis is involved in plenty of disorders including but not limited to microbial infections, cancers, acute lung injury/acute respiratory distress syndrome (ALI/ARDS), ischemia-reperfusion, and organic failure. PANoptosis seems to be a double-edged sword in diverse conditions, as PANoptosis induces a negative impact on treatment and prognosis in disorders like COVID-19 and ALI/ARDS, while PANoptosis provides host protection from HSV1 or Francisella novicida infection, and kills cancer cells and suppresses tumor growth in colorectal cancer, adrenocortical carcinoma, and other cancers. Compounds and endogenous molecules focused on PANoptosis are promising therapeutic strategies, which can act on PANoptosomes-associated members to regulate PANoptosis. More researches on PANoptosis are needed to better understand the pathology of human conditions and develop better treatment.

Abstract Natural evolution has nurtured a series of active molecules that play vital roles in physiological systems, but their further applications have been severely limited by rapid deactivation, short cycle time, and potential toxicity after isolation. For instance, the instability of structures and properties has greatly descended when sanshool is derived from Zanthoxylum xanthoxylum. Herein, natural polyphenols are employed to boost the key properties of sanshool by fabricating a series of nanoparticles (NPs). The intracellular evaluation and in vivo animal model are conducted to demonstrate the decreased photodamage score and skin‐fold thickness of prepared NPs, which can be attributed to the better biocompatibility, improved free radical scavenging, down‐regulated apoptosis ratios, and reduced DNA double‐strand breaks compared to naked sanshool. This work proposes a novel strategy to boost the key properties of naturally occurring active molecules with the assistance of natural polyphenol‐based platforms.

BackgroundRosacea, a chronic inflammatory skin condition affecting millions worldwide, is influenced by complex interactions between genetic and environmental factors. Although gut microbiota’s role in skin health is well-acknowledged, definitive causal links between gut microbiota and rosacea remain under-explored.MethodsUsing a two-sample Mendelian randomization (MR) design, this study examined potential causal relationships between gut microbiota and rosacea. Data was sourced from the largest Genome-Wide Association Study (GWAS) for gut microbiota and the FinnGen biobank for rosacea. A total of 2078 single nucleotide polymorphisms (SNPs) associated with gut microbiota were identified and analyzed using a suite of MR techniques to discern causal effects.ResultsThe study identified a protective role against rosacea for two bacterial genera: phylum Actinobacteria and genus Butyrivibrio. Furthermore, 14 gut microbiota taxa were discovered to exert significant causal effects on variant categories of rosacea. While none of these results met the strict False Discovery Rate correction threshold, they retained nominal significance. MR outcomes showed no pleiotropy, with homogeneity observed across selected SNPs. Directionality tests pointed toward a robust causative path from gut microbiota to rosacea.ConclusionThis study provides compelling evidence of the gut microbiota’s nominal causal influence on rosacea, shedding light on the gut-skin axis’s intricacies and offering potential avenues for therapeutic interventions in rosacea management. Further research is warranted to validate these findings and explore their clinical implications.

Spinal cord injury (SCI) leads to devastating physical consequences, such as severe sensorimotor dysfunction even lifetime disability, by damaging the corticospinal system. The conventional opinion that SCI is intractable due to the poor regeneration of neurons in the adult central nervous system (CNS) needs to be revisited as the CNS is capable of considerable plasticity, which underlie recovery from neural injury. Substantial spontaneous neuroplasticity has been demonstrated in the corticospinal motor circuitry following SCI. Some of these plastic changes appear to be beneficial while others are detrimental toward locomotor function recovery after SCI. The beneficial corticospinal plasticity in the spared corticospinal circuits can be harnessed therapeutically by multiple contemporary neuromodulatory approaches, especially the electrical stimulation-based modalities, in an activity-dependent manner to improve functional outcomes in post-SCI rehabilitation. Silent synapse generation and unsilencing contribute to profound neuroplasticity that is implicated in a variety of neurological disorders, thus they may be involved in the corticospinal motor circuit neuroplasticity following SCI. Exploring the underlying mechanisms of silent synapse-mediated neuroplasticity in the corticospinal motor circuitry that may be exploited by neuromodulation will inform a novel direction for optimizing therapeutic repair strategies and rehabilitative interventions in SCI patients.

Abstract Introduction To evaluate the efficacy and safety of lidocaine patches in Chinese patients with postherpetic neuralgia (PHN). Methods Patients were randomized to receive lidocaine patches or placebo every day for 4 weeks. Efficacy endpoints included the decrease of analogue scale score (VAS) value at week 4, 2 and 1 and the percentage of patients that achieved a 30% decrease of VAS value. Safety analyses were conducted as well. Results Two hundred forty Chinese patients were randomized. At week 1, lidocaine patch-treated patients had a higher clinical response versus placebo, and at week 4, the mean (SD) decreases of VAS value compared to the baseline were 14.01 (14.35) in the treatment group and 9.36 (12.03) in the placebo group (p = 0.0088). Overall, the safety profile in the treatment group was consistent with that observed in the placebo group [adverse event (AE) incidence rate: 33.33% versus 37.29%, p = 0.5857]. Conclusions Lidocaine patches resulted in improved clinical response versus placebo in the treatment of PHN patients and were well tolerated.

Simulating animal movement has long been a central focus of study in the area of wildlife behaviour studies. Conventional modelling methods have difficulties in accurately representing changes over time and space in the data, and they generally do not effectively use telemetry data. Thus, this paper introduces a new and innovative deep reinforcement learning technique known as AnimalEnvNet. This approach combines historical trajectory data and remote sensing images to create an animal agent using deep reinforcement learning techniques. It overcomes the constraints of conventional modelling approaches. We selected pandas as the subject of our research and carried out research using GPS trajectory data, Google Earth images, and Sentinel-2A remote sensing images. The experimental findings indicate that AnimalEnvNet reaches convergence during supervised learning training, attaining a minimal mean absolute error (MAE) of 28.4 m in single-step prediction when compared to actual trajectories. During reinforcement learning training, the agent has the capability to replicate animal locomotion for a maximum of 12 iterations, while maintaining an error margin of 1000 m. This offers a novel approach and viewpoint for mimicking animal behaviour.

Generalized pustular psoriasis (GPP) is a rare chronic inflammatory pustular dermatosis that presents as painful erythema with sterile pustules on nonacral skin. No unified standard and guideline for the treatment of GPP has been established. Several biologics have been tried for GPP, with varying success. Acrodermatitis continua of Hallopeau (ACH) is a very rare disabling variant of pustular psoriasis characterized by sterile pustules on the fingers and toes, including the nail bed. Comparatively, treating ACH is highly challenging due to its commonly therapy-resistant disease course. The pathogenic role of IL-36 signaling axis has been currently identified in GPP development. Spesolimab, the first anti-interleukin-36 receptor biologic, has been approved for treating GPP flares and shown promising results. In view of a shared pathogenesis between GPP and ACH, specolimab may be an effective treatment for ACH. Currently, there is no case and clinical trial data exist on this condition. Therefore, this case was aim to describe real-world experience of spesolimab use in ACH coexisting with GPP. We report an Asian patient with a 16-year-history of GPP and ACH with marked pustulosis on the nail bed and onychodystrophy. He received conventional systemic regimen acitretin, cyclosporine and biologics adalimumab and secukinumab, but experienced relapse for skin lesions and refractory for nail lesions. He was then treated with a single dose of spesolimab in combination with secukinumab, which resulted in skin clearance and nearly complete resolution of nail lesions over a 32-week period. Our observation suggests that spesolimab should be considered for the treatment of ACH, especially in the patients with intractable nail lesions and concomitant GPP.

Zanthoxylum bungeanum Maxim., commonly known as Chinese prickly ash, is a well-known spice and traditional Chinese medicine ingredient with a rich history of use in treating inflammatory conditions. This review provides a comprehensive overview of the botanical classification, traditional applications, and anti-inflammatory effects of Z. bungeanum, with a specific focus on its polyphenolic components. These polyphenols have exhibited considerable promise, as evidenced by preclinical studies in animal models, suggesting their therapeutic potential in human inflammatory diseases such as ulcerative colitis, arthritis, asthma, chronic obstructive pulmonary disease, cardiovascular disease, and neurodegenerative conditions. This positions them as a promising class of natural compounds with the potential to enhance human well-being. However, further research is necessary to fully elucidate their mechanisms of action and develop safe and effective therapeutic applications.

Malignant melanoma is the most lethal form of skin cancer, and its incidence rates are increasing in Europe, America, and Oceania countries. Despite immune checkpoint inhibitors, such as PD-1 inhibitors, have been shown to have significant therapeutic effects on malignant melanoma, many patients are unresponsive to these treatments, even emerged resistance. There is an urgent need to discover novel biomarkers that might distinguish resistant patients from responders. In this study, we used a series of bioinformatics analyses and experimental validation. The GSE65041 was used for differential expression analysis. Kaplan-Meier was used to assess the prognostic value. ESTIMATE, ssGSEA, EPIC, TIMER, quanTiseq and MCPcounter for estimation of immune infiltration in the tumor microenvironment. We eventually identified that CD3ζ was significantly down-regulated in IHC PD-L1(−) melanoma patients. Low level of CD3ζ expression possessed a poor prognosis. CD3ζ low expression population is significantly associated with lower immune infiltration. In vivo experiment, CD3ζ expression was significantly down-regulated in mice melanoma after intradermally injected with B16–F10R cells. Compared to their wildtype counterparts, melanoma resistant mice treated with nivolumab showed significant reductions in tumor volume and weight when adding CD3ζ. In vitro experiment, the addition of CD3ζ increased nivolumab effection on inhibiting B16–F10R cell viability. Our findings indicated that CD3ζ could be a novel predictive biomarker of PD-1 inhibitor resistance in melanoma.

Abstract Hepatocellular carcinoma (HCC) is a malignancy worldwide with one of the worst prognoses. Emerging studies have revealed that long noncoding RNAs (lncRNAs) contribute to HCC progression. This research probes the expression and regulatory effect of lncRNA SATB2-AS1 on HCC development. Reverse transcription-polymerase chain reaction (RT-PCR) was applied to measure the SATB2-AS1 profile in HCC tissues and adjacent non-tumor tissues. The impact of SATB2-AS1, miR-3678-3p, or GRIM-19 on HCC cell proliferation, growth, migration, invasion, and apoptosis was determined by gain- and loss-of-function experiments. The results revealed that SATB2-AS1 was downregulated in HCC tissues, and its lower levels were related to higher tumor staging and poorer prognosis of HCC patients. SATB2-AS1 overexpression repressed HCC cell proliferation, induced G1 arrest, and apoptosis, and inhibited migration, invasion, and epithelial-mesenchymal transition (EMT). Mechanistically, SATB2-AS1 inactivated STAT3/HIF-1α and strengthened GRIM-19 expression. After knocking down GRIM-19 with small interfering RNA (siRNA), the malignant phenotypes of HCC cells were enhanced. Further bioinformatics analysis showed that miR-3678-3p was targeted by SATB2-AS1. The dual-luciferase reporter assay, RNA immunoprecipitation (RIP) experiment, and Fluorescence in situ Hybridization (FISH) test confirmed that SATB2-AS1 sponged miR-3678-3p and the latter targeted GRIM-19. The rescue experiments showed that miR-3678-3p aggravated the malignant behaviors of HCC cells, whereas SATB2-AS1 overexpression reversed miR-3678-3p-mediated effects. Inhibition STAT3 promoted SATB2-AS1 and GRIM-19 expression, and reduced miR-3678-3p level. Activation STAT3 exerted opposite effects. Overall, this study confirmed that SATB2-AS1 is a potential prognostic biomarker for HCC and regulates HCC devolvement by regulating the miR-3678-3p/GRIM-19/STAT3/HIF-1α pathway.

In order to improve the life of software defined wireless sensor network (SDWSN) and reduce the energy consumption of data transmission, a hybrid optimization algorithm based on firefly algorithm (FA) and biogeography-based optimization (BBO) were designed, and based on the hybrid optimization algorithm, a distributed high-efficiency entropy energy-saving clustering routing algorithm (DHEEC) was designed, using energy entropy and hybrid optimization algorithm for cluster head selection.The simulation results show that the hybrid optimization algorithm outperforms other algorithms on standard functions.The number of death rounds of 10% nodes of DHEEC is about 13.89% higher than that of IFCEER, and about 41.05% higher than that of DEEC-FA, and the energy utilization is improved.

The purpose of triple extraction is to obtain relationships between entities from unstructured text and apply them to downstream tasks.The embedding mechanism has a great impact on the performance of the triple extraction model, and the embedding vector should contain rich semantic information that is closely related to the relationship extraction task.In Chinese datasets, the information contained between words is very different, and in order to avoid the loss of semantic information problems generated by word separation errors, a triple joint extraction method combining hybrid embedding and relational label embedding (HEPA) was designed, and a hybrid embedding means that combines letter embedding and word embedding was proposed to reduce the errors generated by word separation errors.A relational embedding mechanism that fuses text and relational labels was added, and an attention mechanism was used to distinguish the relevance of entities in a sentence with different relational labels, thus improving the matching accuracy.The method of matching entities with pointer annotation was used, which improved the extraction effect on relational overlapping triples.Comparative experiments are conducted on the publicly available DuIE dataset, and the F1 value of HEPA is improved by 2.8% compared to the best performing baseline model (CasRel).

Abstract Hair loss is a common skin disease that causes intense emotional suffering. Hair regeneration in a personalized area is highly desirable for patients with different balding conditions. However, the existing pharmaceutical treatments have difficulty precisely regenerating hair in a desired area. Here, we show a method to precisely control the hair regeneration using customized microneedle arrays (MNAs). The MNA with a customized shape is fast fabricated by a static optical projection lithography process in seconds, which is a 3D printing technology developed by our group. In the mouse model, MNA treatment could induce hair regrowth in a defined area corresponding to the customized shape of MNA. And the regenerated hair promoted by MNAs had improved quality. Cellular and molecular analysis indicated that MNA treatment could recruit macrophages in situ and then initiate the proliferation of hair follicle stem cells, thereby improving hair regeneration. Meanwhile, the activation of the Wnt/β-catenin signaling pathway was observed in hair follicles. The expressions of Hgf, Igf 1 and Tnf-α were also upregulated in the treated skin, which may also be beneficial for the MNA-induced hair regeneration. This study provides a strategy to precisely control hair regeneration using customized microneedle arrays by recruiting macrophages in situ, which holds the promise for the personalized treatment of hair loss.

Hydroxy- α-sanshool (HAS), an extract derived from Zanthoxylum plants, possesses anti-inflammatory and antioxidant effects. However, its potential effects on acne have not been reported. In this study, 2% absolute ethanol formulation of HAS was effective in inflammatory rashes in a rabbit ear model of acne, surpassing the performance of 0.1% adapalene and matching the effectiveness of 10% benzoyl peroxide, but with a faster onset of action. HAS effectively inhibited Cutibacterium acnes (C. acnes) growth with a minimum inhibitory concentration of 1.25 mg/mL. HAS could effectively inhibit the expression of reactive oxygen species (ROS), various inflammatory factors, and the activation of NF-κB and STAT3 pathways induced by C. acnes in HaCat and THP-1 cells. HAS's antioxidant and anti-inflammatory effects in acne may be mediated through TRPV1. Notably, 2% HAS lotion alone display efficacy in reducing inflammatory rashes in patients with mild to moderate acne, but studies with large samples are needed.

The risk of infection and malignancy may be a concern for patients with psoriasis receiving interleukin (IL)-17 and IL-23 inhibitors, particularly with long-term treatments. We aimed to estimate the short-term risks and long-term incidence rates of infection and malignancy with IL-17 or IL-23 antagonists in adult patients with psoriasis and psoriatic arthritis through this comprehensive meta-analysis (PROSPERO registration number: CRD42022363127). We searched PubMed, MEDLINE, Web of Science and ClinicalTrials.gov until May 17, 2023 for randomized placebo-controlled trials and long-term (≥ 52 weeks) open-label extension studies. The estimates of short-term risk ratios (RRs) and long-term exposure-adjusted incidence rates (EAIRs) were pooled using R software 4.1.1 and STATA 16.0. This review included 45 randomized placebo-controlled studies and 27 open-label extension studies. Short-term RRs of serious infection, overall infection and malignancy were 1.45 (95% confidence intervals, 95% CI: 0.81-2.59), 1.20 (95% CI: 1.06-1.35), 0.83 (95% CI: 0.41-1.71) with IL-17 inhibitors; and 0.68 (95% CI: 0.38-1.22), 1.13 (95% CI: 1.00-1.28), 0.87 (95% CI: 0.37-2.04) with IL-23 inhibitors. Increased short-term risks of nasopharyngitis and Candida infection with IL-17 inhibitors were found. Long-term EAIRs of serious infection, overall infection, nonmelanoma skin cancer (NMSC), malignancies excluding NMSC, nasopharyngitis and upper respiratory tract infection were 1.11/100 patient-years (PYs), 57.78/100PYs, 0.47/100PYs, 0.24/100PYs, 15.07/100PYs, 8.52/100PYs, 3.41/100PYs with IL-17 inhibitors; and 1.09/100PYs, 48.50/100PYs, 0.40/100PYs, 0.43/100PYs, 10.75/100PYs, 5.84/100PYs with IL-23 inhibitors. Long-term EAIR of Candida infection was 3.41/100PYs with IL-17 inhibitors. No active or reactivated tuberculosis was ever reported in all the trials, and only a few cases of latent tuberculosis, hepatitis, and herpes zoster were reported during the long-term extension periods. No evidence of increased EAIRs of infection and malignancy with longer durations was found. Our study suggested that short-term risk and long-term incidence of infections and malignancies in psoriasis patients receiving IL-17 inhibitors and IL-23 inhibitors are generally low. However, close monitoring is required for nasopharyngitis and Candida infection with IL-17 inhibitors.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022363127.

BackgroundThe management of acne requires the consideration of its severity; however, a universally adopted evaluation system for clinical practice is lacking. Artificial intelligence (AI) evaluation systems hold the promise of enhancing the efficiency and reproducibility of assessments. Artificial intelligence (AI) evaluation systems offer the potential to enhance the efficiency and reproducibility of assessments in this domain. While the identification of skin lesions represents a crucial component of acne evaluation, existing AI systems often overlook lesion identification or fail to integrate it with severity assessment. This study aimed to develop an AI-powered acne grading system and compare its performance with physician image-based scoring.MethodsA total of 1,501 acne patients were included in the study, and standardized pictures were obtained using the VISIA system. The initial evaluation involved 40 stratified sampled frontal photos assessed by seven dermatologists. Subsequently, the three doctors with the highest inter-rater agreement annotated the remaining 1,461 images, which served as the dataset for the development of the AI system. The dataset was randomly divided into two groups: 276 images were allocated for training the acne lesion identification platform, and 1,185 images were used to assess the severity of acne.ResultsThe average precision of our model for skin lesion identification was 0.507 and the average recall was 0.775. The AI severity grading system achieved good agreement with the true label (linear weighted kappa = 0.652). After integrating the lesion identification results into the severity assessment with fixed weights and learnable weights, the kappa rose to 0.737 and 0.696, respectively, and the entire evaluation on a Linux workstation with a Tesla K40m GPU took less than 0.1s per picture.ConclusionThis study developed a system that detects various types of acne lesions and correlates them well with acne severity grading, and the good accuracy and efficiency make this approach potentially an effective clinical decision support tool.

BackgroundThe surge in the number of publications on psoriasis has posed significant challenges for researchers in effectively managing the vast amount of information. However, due to the lack of tools to process metadata, no comprehensive bibliometric analysis has been conducted.ObjectivesThis study is to evaluate the trends and current hotspots of psoriatic research from a macroscopic perspective through a bibliometric analysis assisted by machine learning based semantic analysis.MethodsPublications indexed under the Medical Subject Headings (MeSH) term “Psoriasis” from 2003 to 2022 were extracted from PubMed. The generative statistical algorithm latent Dirichlet allocation (LDA) was applied to identify specific topics and trends based on abstracts. The unsupervised Louvain algorithm was used to establish a network identifying relationships between topics.ResultsA total of 28,178 publications were identified. The publications were derived from 176 countries, with United States, China, and Italy being the top three countries. For the term “psoriasis”, 9,183 MeSH terms appeared 337,545 times. Among them, MeSH term “Severity of illness index”, “Treatment outcome”, “Dermatologic agents” occur most frequently. A total of 21,928 publications were included in LDA algorithm, which identified three main areas and 50 branched topics, with “Molecular pathogenesis”, “Clinical trials”, and “Skin inflammation” being the most increased topics. LDA networks identified “Skin inflammation” was tightly associated with “Molecular pathogenesis” and “Biological agents”. “Nail psoriasis” and “Epidemiological study” have presented as new research hotspots, and attention on topics of comorbidities, including “Cardiovascular comorbidities”, “Psoriatic arthritis”, “Obesity” and “Psychological disorders” have increased gradually.ConclusionsResearch on psoriasis is flourishing, with molecular pathogenesis, skin inflammation, and clinical trials being the current hotspots. The strong association between skin inflammation and biologic agents indicated the effective translation between basic research and clinical application in psoriasis. Besides, nail psoriasis, epidemiological study and comorbidities of psoriasis also draw increased attention.

Antimicrobial photodynamic therapy (aPDT) has become a potent contender in the fight against microbial infections, especially in the context of the rising antibiotic resistance crisis. Recently, there has been significant interest in polyphenolic natural products as potential photosensitizers (PSs) in aPDT, given their unique chemical structures and inherent antimicrobial properties. Polyphenolic natural products, abundant and readily obtainable from natural sources, are generally regarded as safe and highly compatible with the human body. This comprehensive review focuses on the latest developments and future implications of using natural polyphenols as PSs in aPDT. Paramount polyphenolic compounds, including curcumin, hypericin, quercetin, hypocrellin, celastrol, riboflavin, resveratrol, gallic acid, and aloe emodin, are elaborated upon with respect to their structural characteristics, absorption properties, and antimicrobial effects. Furthermore, the aPDT mechanism, specifically its targeted action on microbial cells and biofilms, is also discussed. Polyphenolic natural products demonstrate immense potential as PSs in aPDT, representing a promising alternate approach to counteract antibiotic-resistant bacteria and biofilm-related infections.

Abstract Peripheral myelin protein 22 (PMP22) and epithelial membrane proteins (EMP-1, -2, and -3) belong to a small hydrophobic membrane protein subfamily, with four transmembrane structures. PMP22 and EMPs are widely expressed in various tissues and play important roles in cell growth, differentiation, programmed cell death, and metastasis. PMP22 presents its highest expression in the peripheral nerve and participates in normal physiological and pathological processes of the peripheral nervous system. The progress of molecular genetics has shown that the genetic changes of the PMP22 gene, including duplication, deletion, and point mutation, are behind various hereditary peripheral neuropathies. EMPs have different expression patterns in diverse tissues and are closely related to the risk of malignant tumor progression. In this review, we focus on the four members in this protein family which are related to disease pathogenesis and discuss gene mutations and post-translational modification of them. Further research into the interactions between structural alterations and function of PMP22 and EMPs will help understand their normal physiological function and role in diseases and might contribute to developing novel therapeutic tools.

Seeking for extremely active and durable bifunctional electrocatalysts towards the overall water splitting possesses a strategic significance on the development of sustainable and clean energy for the replacement of fossil fuels. Ir-based nanomaterials are deemed as one of the most high-efficiency oxygen evolution reaction electrocatalysts while the hydrogen evolution reaction performance is unfavorable. In this work, we report a one-pot hydrothermal synthesis of N-doped graphene anchored Ir nanoparticles (Ir/N-rGO) with ultrasmall particle size (∼2.0 nm). Apart from the predictably superior OER performance, the resultant Ir/N-rGO also displays excellent hydrogen evolution reaction (HER) performance, requiring merely 76 and 260 mV overpotentials to achieve the current density of 10 mA cm−2 towards HER and OER, respectively. When applied as the bifunctional electrodes for overall water splitting, Ir/N-rGO needs a lower overpotential (1.74 V) to achieve a current density of 50 mA cm−2 in alkaline solution, exceeding that of Pt/C and RuO2 couple (1.85 V). Thus, the as-fabricated Ir/N-rGO has a commendable prospect in the practical application of alkaline water electrocatalysis.

Personalized exercise recommendation was an important topic in the era of education informatization, the forgetting laws of students in the learning process were ignored by the traditional problem recommendation algorithm, which failed to fully tap the students’ knowledge mastery level and the common characteristics of similar students, insufficient, could not reasonably promote students’ learning of new knowledge or help students find and fill omissions.In view of the above defects, a multi-index exercise recommendation method based on student knowledge tracking was proposed, which was divided into two modules: preliminary screening and re-filtering of exercises, focusing on the novelty, difficulty and diversity of exercise recommendation.Firstly, a knowledge probability prediction (SF-KCCP) model combined with students’ forgetting law was constructed to ensure the novelty of the recommended exercises.Then, students’ knowledge and concept mastery level was accurately excavated based on the dynamic key-value knowledge tracking (DKVMN) model to ensure that exercises of appropriate difficulty were recommended.Finally, the user-based collaborative filtering (UserCF) algorithm was integrated into the re-filtering module, and the similarity between student groups was used to achieve the diversity of recommendation results.The proposed method is demonstrated by extensive experiments to achieve better performance than some existing baseline models.

IntroductionRosacea, a widespread chronic skin condition, may be influenced by macrophages, key immune cells in the skin, although their exact role is not yet fully understood. This review delves into the function of macrophages, their potential contribution to rosacea pathogenesis, current treatments, and promising macrophage-targeted therapies. It concludes by identifying knowledge gaps and potential areas for future rosacea research.MethodLeveraging systematic and narrative literature review techniques, we conducted a comprehensive search of databases such as PubMed, Embase, and Web of Science. Utilizing keywords like “rosacea” and “macrophages”, we targeted English articles from the last 5 years (2018-2023). We manually checked reference lists of relevant articles for additional studies. We included only articles emphasizing macrophages’ role in rosacea and/or the development of related therapies and published within the specified timeframe.ResultsThe systematic search of electronic databases yielded a total of 4,263 articles. After applying the inclusion and exclusion criteria, 156 articles were selected for inclusion in this review. These articles included original research studies, review articles, and clinical trials that focused on the role of macrophages in rosacea and/or the development of macrophage-targeted therapies for the disease. The selected articles provided a comprehensive and up-to-date overview of the current state of research on macrophages in rosacea, including their function in the skin, the potential mechanisms through which they may contribute to rosacea pathogenesis, and the current treatments and therapies available for the disease. Additionally, the articles identified gaps in knowledge regarding the role of macrophages in rosacea and suggested potential areas for future research.ConclusionThis literature review emphasizes the important role that macrophages, vital immune cells in the skin, may play in the pathogenesis of rosacea, a common chronic inflammatory skin disorder. The selected studies suggest potential mechanisms by which these cells might contribute to rosacea progression, although these mechanisms are not yet fully understood. The studies also spotlight current rosacea treatments and illuminate the promising potential of new macrophage-focused therapies. Despite these insights, significant gaps persist in our understanding of the precise role of macrophages in rosacea. Future research in this area could provide further insights into the pathogenesis of rosacea and contribute to the development of more effective, targeted therapeutic strategies.

BackgroundOrally administered small-molecule drugs including tyrosine kinase 2 (TYK2) inhibitors and phosphodiesterase 4 (PDE4) inhibitors are new candidates for systemic therapy in plaque psoriasis. However, no previous articles evaluated the benefit and risk profile of TYK2 and PDE4 inhibitors in psoriasis.ObjectivesThe objective of this study was to compare the efficacy and safety of oral small-molecule drugs, including TYK2 and PDE4 inhibitors, in treating moderate-to-severe plaque psoriasis.MethodsPubMed, Embase, and Cochrane library were searched for eligible randomized clinical trials (RCTs). Response rates for a 75% reduction from baseline in Psoriasis Area and Severity Index (PASI-75) and Physician’s Global Assessment score of 0 or 1 (PGA 0/1) were used for efficacy assessment. Safety was evaluated with the incidence of adverse events (AEs). A Bayesian multiple treatment network meta-analysis (NMA) was performed.ResultsIn total, 13 RCTs (five for TYK2 inhibitors and eight for PDE4 inhibitors) involving 5274 patients were included. The study found that deucravacitinib at any dose (except for 3 mg QOD), ropsacitinib (200 and 400 mg QD), and apremilast (20 and 30 mg BID) had higher PASI and PGA response rates than placebo. In addition, deucravacitinib (3 mg BID, 6 mg QD, 6 mg BID, and 12 mg QD), and ropsacitinib (400 mg QD) showed superior efficacy than apremilast (30 mg BID). In terms of safety, deucravacitinib or ropsacitinib at any dose did not lead to a higher incidence of AEs than apremilast (30 mg BID). The ranking analysis of efficacy revealed that deucravacitinib 12 mg QD and deucravacitinib 3 mg BID had the highest chance of being the most effective oral treatment, followed by deucravacitinib 6 mg BID and ropsacitinib 400 mg QD.ConclusionsOral TYK2 inhibitors demonstrated satisfactory performance in treating psoriasis, surpassing apremilast at certain doses. More large-scale, long-term studies focusing on novel TYK2 inhibitors are needed.Systematic review registrationPROSPERO (ID: CRD42022384859), available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022384859, identifier CRD42022384859.

With the continuous development and evolution of network technology in recent years, the user’s demand for network resources is becoming larger and larger, and the content is becoming more and more complex.The traditional network architecture is difficult to meet the current flexible network needs.The revolutionary technology of SDN endows the network with programm ability and evolvability, and realizes more flexible management of network resources.In order to improve the utilization of network resources, a traffic prediction agent based on LSTM model was proposed, which provides a theoretical basis for routing planning.By predicting the network traffic in advance, we can take defensive measures before the traffic surge to ensure the security and stability of the network.The function of route planning and lossless path switching based on traffic prediction was realized.

This study aims to explore the correlation between the activity trajectory of Crested Ibis and meteorological changes. The trajectory data of Crested Ibis were obtained using the HQBG3621L backpack-style tracker, and the spatiotemporal characteristics of the trajectory data were analyzed to obtain information on the activity range and habitat of Crested Ibis. The Scheirer–Ray–Hare test and Kruskal–Wallis test were used to investigate the impact of meteorological factors on the activity of Crested Ibis. The study found that meteorological factors have a certain influence on the habitat selection and activity patterns of Crested Ibis. Through this research, a better understanding of the interaction between Crested Ibis and the meteorological environment can be achieved, providing a scientific basis for the conservation and ecological management of Crested Ibis.

Background: Endogenous gasotransmitters are small gaseous mediators that can be generated endogenously by mammalian organisms. The dysregulation of the gasotransmitter system is associated with numerous disorders ranging from inflammatory diseases to cancers. However, the relevance of these endogenous gasotransmitters, prodrug donors and inhibitors in inflammatory dermatological disorders has not yet been thoroughly reviewed and discussed. Aim of review: This review discusses the recent progress and will provide perspectives on endogenous gasotransmitters in the context of inflammatory dermatological disorders. Key scientific concepts of review: Endogenous gasotransmitters nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) are signaling molecules that regulate several physiological and pathological processes. In addition, sulfur dioxide (SO₂), methane (CH4), hydrogen gas (H2), ammonia (NH3), and carbon dioxide (CO2) can also be generated endogenously and may take part in physiological and pathological processes. These signaling molecules regulate inflammation, vasodilation, and oxidative stress, offering therapeutic potential and attracting interest in the field of inflammatory dermatological disorders including psoriasis, atopic dermatitis, acne, rosacea, and chronic skin ulcers. The development of effective gas donors and inhibitors is a promising alternative to treat inflammatory dermatological disorders with controllable and precise delivery in the future.

BRAF mutation plays an important role in the pathogenesis and progression of melanoma and is correlated to the prognosis of melanoma patients. However, fewer studies have attempted to develop a BRAF mutation-associated gene risk model for predicting the prognosis of melanoma. The current research explores BRAF mutation-related biological features in melanoma and establishes a prognostic signature. First, we identified three significantly enriched KEGG pathways (glycosphingolipid biosynthesis - ganglio series, ether lipid metabolism, and glycosaminoglycan biosynthesis - keratan sulfate) and corresponding genes in the BRAF mutant group by gene set enrichment analysis. We then developed a prognostic signature based on 7 BRAF-associated genes (PLA2G2D, FUT8, PLA2G4E, PLA2G5, PLA2G1B, B3GNT2, and ST3GAL5) and assessed its prediction accuracy using ROC curve analysis. Finally, the nomogram was established according to the prognostic signature and independent clinical characteristics to predict the survival of melanoma patients. Furthermore, we found higher proportions of naive B cells, plasma cells, CD8 T cells, CD4 memory-activated T cells, and regulatory T cells in the low-risk group. Whereas lower proportions of M0, M1, and M2 macrophages and resting NK cells were observed in the high-risk group. The analysis also showed a significantly higher expression of immune checkpoint molecules (PD-1, PD-L1, CTLA4, BTLA, CD28, CD80, CD86, HAVCR2, ICOS, LAG3, and TIGIT) in the low-risk group. Our results provide novel insights into the effect of BRAF mutation on melanoma growth and indicate a promising direction toward immunotherapy and precision medicine in melanoma patients.

Abstract Linear canonical transform (LCT) is a powerful tool for improving the detection accuracy of the conventional Wigner distribution (WD). However, the LCT free parameters embedded increase computational complexity. Recently, the instantaneous cross-correlation function type of WD (ICFWD), a specific WD relevant to the LCT, has shown to be an outcome of the tradeoff between detection accuracy and computational complexity. In this paper, the ICFWD is applied to detect noisy single component and bi-component linear frequency-modulated (LFM) signals through the output signal-to-noise ratio (SNR) inequality modeling and solving with respect to the ICFWD and WD. The expectation-based output SNR inequality model between the ICFWD and WD on a pure deterministic signal added with a zero-mean random noise is proposed. The solutions of the inequality model in regard to single component and bi-component LFM signals corrupted with additive zero-mean stationary noise are obtained respectively. The detection accuracy of ICFWD with that of the closed-form ICFWD (CICFWD), the affine characteristic Wigner distribution (ACWD), the kernel function Wigner distribution (KFWD), the convolution representation Wigner distribution (CRWD) and the classical WD is compared. It also compares the computing speed of ICFWD with that of CICFWD, ACWD, KFWD and CRWD.

Abstract. Rosacea is a chronic inflammatory skin disease that primarily affects the centrofacial areas and mainly manifests as recurrent flushing and erythema. In recent years, there has been progress in the understanding of the diagnosis and treatment of rosacea. Therefore, a group of dermatological experts updated the guidelines based on the 2016 expert consensus statement on rosacea diagnosis and treatment in China. These new guidelines propose diagnostic criteria for rosacea at different sites to further standardize the diagnosis and treatment of rosacea in China.

Abstract Psoriasis is a complex chronic inflammatory skin disease with unclear molecular mechanisms. We found that the Src homology‐2 domain‐containing protein tyrosine phosphatase‐2 (SHP2) was highly expressed in both psoriatic patients and imiquimod (IMQ)‐induced psoriasis‐like mice. Also, the SHP2 allosteric inhibitor SHP099 reduced pro‐inflammatory cytokine expression in PBMCs taken from psoriatic patients. Consistently, SHP099 significantly ameliorated IMQ‐triggered skin inflammation in mice. Single‐cell RNA sequencing of murine skin demonstrated that SHP2 inhibition impaired skin inflammation in myeloid cells, especially macrophages. Furthermore, IMQ‐induced psoriasis‐like skin inflammation was significantly alleviated in myeloid cells (monocytes, mature macrophages, and granulocytes)—but not dendritic cells conditional SHP2 knockout mice. Mechanistically, SHP2 promoted the trafficking of toll‐like receptor 7 (TLR7) from the Golgi to the endosome in macrophages by dephosphorylating TLR7 at Tyr1024, boosting the ubiquitination of TLR7 and NF‐κB‐mediated skin inflammation. Importantly, Tlr7 point‐mutant knock‐in mice showed an attenuated psoriasis‐like phenotype compared to wild‐type littermates following IMQ treatment. Collectively, our findings identify SHP2 as a novel regulator of psoriasis and suggest that SHP2 inhibition may be a promising therapeutic approach for psoriatic patients.

Interleukin (IL)-18, an interferon-γ inducer, belongs to the IL-1 family of pleiotropic pro-inflammatory factors, and IL-18 binding protein (IL-18BP) is a native antagonist of IL-18 in vivo, regulating its activity. Moreover, IL-18 exerts an influential function in host innate and adaptive immunity, and IL-18BP has elevated levels of interferon-γ in diverse cells, suggesting that IL-18BP is a negative feedback inhibitor of IL-18-mediated immunity. Similar to IL-1β, the IL-18 cytokine is produced as an indolent precursor that requires further processing into an active cytokine by caspase-1 and mediating downstream signaling pathways through MyD88. IL-18 has been implicated to play a role in psoriasis, atopic dermatitis, rosacea, and bullous pemphigoid in human inflammatory skin diseases. Currently, IL-18BP is less explored in treating inflammatory skin diseases, while IL-18BP is being tested in clinical trials for other diseases. Thereby, IL-18BP is a prospective therapeutic target.

Existing researchers use threat modeling and security analysis system to evaluate and predict SDN (software defined network) security threats, but this method does not consider the vulnerability utilization of SDN controller and the location of devices in the network, so the security evaluation is not accurate.In order to solve the above problems, according to the probability of device vulnerability utilization and device criticality, combined with PageRank algorithm, a algorithm to calculate the importance of each device in SDN was designed; according to SDN attack graph and Bayesian theory, a method to measure the success probability of device being attacked was designed.On this basis, a SDN security prediction method based on Bayesian attack graph was proposed to predict the attacker's attack path.Experimental results show that this method can accurately predict the attacker's attack path and provide more accurate basis for security defense.

Frostbite in Southwestern China has been overlooked due to its low incidence, relatively mild temperature and lack of literature published before. However, it needs to be further studied for religious diversity and distinct geomorphology. In this article, we reported an 18-year-old Tibetan girl who suffered from blizzard attack during pilgrimage. Her feet and several fingers showed mummified gangrene upon physical examination with poor movement. She was diagnosed with 3rd to 4th degree of frostbite. The girl was given oral ibuprofen, debridement and other regular treatment daily, but she was eventually amputated due to insufficient thrombolytic management in primary hospital, delayed informing consent in the referral hospital and ethnic conflict between religion and guidelines. This case enriched the experience of managing complex frostbite in Tibetan population and alarms that efforts should be integrated to protect pilgrims and mountaineers in the Tibetan region.