Granuloma Annulare Exhibits Mixed Immune and Macrophage Polarization Profiles with Spatial Transcriptomics.

Granuloma annulare (GA) is an idiopathic condition characterized by granulomatous inflammation in the skin. Prior studies have suggested that GA develops from various triggers, leading to a complex interplay involving innate and adaptive immunity, tissue remodeling, and fibrosis. Macrophages are the major immune cells comprising GA granulomas, however, the molecular drivers and inflammatory signaling cascade behind macrophage activation is poorly understood. Histologically, GA exhibits both palisaded and interstitial patterns on histology, however the molecular composition of GA at the spatial level remains unexplored. GA is a condition without FDA-approved therapies despite the significant impact of GA on quality of life. Spatial transcriptomics is a valuable tool for profiling localized, genome-wide gene expression changes across tissue with emerging applications in clinical medicine. To improve our understanding of the spatially localized gene expression patterns underlying GA, we profiled the spatial gene expression landscape from six patients with GA. Our findings revealed mixed Th1 and Th2 signals comprising the GA microenvironment and spatially distinct M1 and M2 macrophage polarization characteristics. IFN-γ and TNF signals emerged as important regulators of GA granulomatous inflammation and interleukin-32 emerged as a key driver of granulomatous inflammation. Overall, our spatial transcriptomics data indicate that GA exhibits mixed immune and macrophage polarization.

Molecular Mechanisms of Chlorophyll Deficiency in Ilex × attenuata 'Sunny Foster' Mutant.

Ilex × attenuata 'Sunny Foster' represents a yellow leaf mutant originating from I. × attenuata 'Foster#2', a popular ornamental woody cultivar. However, the molecular mechanisms underlying this leaf color mutation remain unclear. Using a comprehensive approach encompassing cytological, physiological, and transcriptomic methodologies, notable distinctions were discerned between the mutant specimen and its wild type. The mutant phenotype displayed aberrant chloroplast morphology, diminished chlorophyll content, heightened carotenoid/chlorophyll ratios, and a decelerated rate of plant development. Transcriptome analysis identified differentially expressed genes (DEGs) related to chlorophyll metabolism, carotenoid biosynthesis and photosynthesis. The up-regulation of CHLD and CHLI subunits leads to decreased magnesium chelatase activity, while the up-regulation of COX10 increases heme biosynthesis-both impair chlorophyll synthesis. Conversely, the down-regulation of HEMD hindered chlorophyll synthesis, and the up-regulation of SGR enhanced chlorophyll degradation, resulting in reduced chlorophyll content. Additionally, genes linked to carotenoid biosynthesis, flavonoid metabolism, and photosynthesis were significantly down-regulated. We also identified 311 putative differentially expressed transcription factors, including bHLHs and GLKs. These findings shed light on the molecular mechanisms underlying leaf color mutation in I. × attenuata 'Sunny Foster' and provide a substantial gene reservoir for enhancing leaf color through breeding techniques.

Perioperative management and clinical outcomes of peristomal pyoderma gangrenosum.

Peristomal pyoderma gangrenosum is an uncommon subtype of pyoderma gangrenosum mainly affecting stoma sites of patients with inflammatory bowel disease. While surgical treatments are often used to assist healing, little is known about the relationship between surgical interventions and the rate of recurrence of peristomal pyoderma gangrenosum. The aim of this study was to identify patient and clinical factors associated with peristomal pyoderma gangrenosum recurrence following surgical intervention. A multi-institutional retrospective case series and literature review was conducted to evaluate patient characteristics and perioperative treatment. Patients of any age with peristomal pyoderma gangrenosum undergoing surgical operations related to their pyoderma gangrenosum or due to another comorbidity were included. Descriptive statistics were used to characterize demographic information. Associations were evaluated using Wilcoxon's rank-sum test for continuous variables and Fisher's exact test for categorical data. Thirty-seven cases were included, 78.3% of which had a history of inflammatory bowel disease. Overall, 13 (35.1%) cases experienced recurrence at 30 days. There was no significant association identified between patient demographics, stoma location, surgical intervention, or perioperative treatment with rate of recurrence at 30 days post-operation. While no clinical risk factors or treatments were associated with recurrence, our work underscores the importance of a multidisciplinary approach to this disease to address gastrointestinal, dermatologic, and surgical components of treatment.

Culprits of Medication-Induced Telogen Effluvium, Part 2.

Telogen effluvium (TE) is a common mechanism underlying medication-related alopecia. The inciting cause of TE may be difficult to identify due to delays in clinically apparent hair loss. Because medication-induced TE is a nonscarring alopecia that typically is reversible, appropriate management requires identification of the underlying trigger and cessation of potential culprit medications. In part 2 of this 2-part series on medication-induced TE, we focus on anticoagulant and antihypertensive medications.

Pro-Inflammatory Diet as a Risk Factor for Stomach Cancer: Findings from a Multicenter Study in Central and Western China.

Purpose: We conducted a multicenter cross-sectional study in central and western China to explore the association between inflammatory diet and stomach cancer odds. Patients and Methods: Participants from five hospitals in the central and western regions were collected. All participants completed the questionnaire we provided before the gastroscopy examination, which includes inquiries about risk factors for stomach cancer and food frequency. All participants underwent gastroscopy, and a mucosal biopsy was confirmed pathologically. Pathological findings were classified as chronic gastritis group, precancerous lesions group and stomach cancer group. Dietary Inflammatory Index (DII) scores were calculated based on the frequency of food occurrences in the questionnaire, and finally SPSS was used to calculate the correlation between variables. Results: A total of 1162 patients were included in this study, including 668 cases of chronic gastritis, 411 cases of precancerous lesions, and 83 cases of cancer. A single factor analysis was conducted to examine the risk factors of stomach cancer, revealing a significant association between a pro-inflammatory diet and the stomach cancer odds (p value < 0.05). The results of binary classification analysis further confirmed that a pro-inflammatory diet is a risk factor for stomach cancer 【odds ratio (OR) =7.400)】. Moreover, correlation analysis demonstrated a positive correlation between the severity of gastric mucosal diseases and an inflammatory diet (including anti-inflammatory and pro-inflammatory diets) (rs=0.274, p-value < 0.001). Conclusion: Pro-Inflammatory diet is a risk factor for stomach cancer, and may accelerate the progression of stomach mucosal disease.

More than just methylisothiazolinone: Retrospective analysis of patients with isothiazolinone allergy in North America, 2017-2020.

BACKGROUND: Isothiazolinones are a common cause of allergic contact dermatitis. OBJECTIVE: To examine the prevalence of positive patch test reactions to isothiazolinones from 2017-2020 and characterize isothiazolinone-allergic (Is+) patients compared with isothiazolinone nonallergic (Is-) patients. METHODS: Retrospective cross-sectional analysis of 9028 patients patch tested to methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI) 0.02% aqueous, MI 0.2% aqueous, benzisothiazolinone (BIT) 0.1% petrolatum, and/or octylisothiazolinone (OIT) 0.025% petrolatum. Prevalence, reaction strength, concurrent reactions, clinical relevance, and source of allergens were tabulated. RESULTS: In total, 21.9% (1976/9028) of patients had a positive reaction to 1 or more isothiazolinones. Positivity to MI was 14.4% (1296/9012), MCI/MI was 10.0% (903/9017), BIT was 8.6% (777/9018), and OIT was 05% (49/9028). Compared with Is-, Is+ patients were more likely to have occupational skin disease (16.5% vs 10.3%, P <.001), primary hand dermatitis (30.2% vs 19.7%, P <.001), and be >40 years (73.1% vs 61.9%, P <.001). Positive patch test reactions to >1 isothiazolinone occurred in 44.1% (871/1976) of Is+ patients. Testing solely to MCI/MI would miss 47.3% (611/1292) of MI and 60.1% (466/776) of BIT allergic reactions. LIMITATIONS: Retrospective cross-sectional study design and lack of follow-up data. CONCLUSION: Sensitization to isothiazolinones is high and concurrent sensitization to multiple isothiazolinone allergens is common.

Cutaneous granulomas associated with rubella virus: A clinical review.

Since the initial identification of vaccine-derived rubella virus (RuV) in the cutaneous granulomas of pediatric patients with inborn errors of immunity in 2014, more than 80 cases of RuV granulomas have been reported implicating both vaccine-derived and wild type RuV. Previously thought to arise exclusively in patients with significant immunocompromise, the identification of RuV granulomas in clinically immunocompetent patients adds nuance to our understanding of the interplay between host environment, immune dysregulation, and RuV granuloma formation. This review summarizes the literature on RuV granulomas including clinical and histopathologic features, proposed pathomechanisms supporting granuloma development, and potential therapeutic options. There is no standardized algorithm to guide the workup and diagnosis of suspected RuV granulomas. We highlight the importance of contributing RuV granuloma cases to ongoing Centers for Disease Control and Prevention surveillance efforts to monitor wild type and vaccine-derived RuV transmission. Studies advancing our understanding of RuV granulomas may provide insights into the role of viral infectious agents in granulomatous disease pathogenesis and guide the development of improved therapeutic options.

Dynamic modeling and analysis of the rotor-stator coupling system of a coaxial contra-rotating gearbox.

In this paper, a main gearbox using an encased differential gear train to achieve coaxial contra-rotating is considered, and a dynamic modeling method of the rotor-stator coupling system of the gearbox based on box model updating is introduced. The transverse torsional dynamic model of the gear transmission subsystem is established based on the lumped parameter method. The finite element model of the box is updated according to the modal test data, and the reduced dynamic parameters of the box are obtained. According to the displacement coordination condition, the dynamic model of the rotor-stator system of the gearbox is established. The vibration response of the transmission components with or without the coupling box is calculated by numerical integration, and the response of the box caused by the dynamic support reaction force is analyzed by the finite element method. The results show that the vibration peak and fluctuation range of the transmission parts with coupling box are smaller than those without coupling box. The box response at the support of the input bevel gear pair is large, while that at the support of the output shaft is small.

Sociodemographic characteristics of healthy volunteers along with their experience, attitude and concerns of clinical trials in Wuhan, China.

China has became the world's second largest pharmaceutical market, and the number of her registered clinical trials exceeded 3000 in 2021. Although thousands of healthy volunteers are participating in a large number of clinical trials in this country, there is no report about the characteristics, recognition, attitude of Chinese healthy volunteers and their concerns of clinical trials. A questionnaire survey was designed and given to 324 healthy volunteers participating in clinical trials in Wuhan, China. Four important findings emerged from our data. First, young, single and less educated men constituted the majority of Chinese healthy volunteers. Second, differences between the male and female healthy volunteers were observed. Female healthy volunteers are supposed to face more challenges and pressure in life, be more cautious about the clinical trials and more concerned about their health and feelings than the male. Third, no sociodemographic characteristic was associated with poorly understanding of the protocol research content, which was subjectively evaluated. Fourth, more support from society/family and more positive media reports about the participation of healthy volunteers in clinical trials are badly needed. These findings would help us to get a better understanding of Chinese healthy volunteers as a group for protecting them and promoting drug development.

Serum Ferritin Levels: A Clinical Guide in Patients With Hair Loss.

Ferritin is a key regulator of iron homeostasis that serves as an important clinical indicator of body iron status. Low serum ferritin is a highly specific and sensitive marker for diagnosing iron deficiency. In patients presenting with diffuse hair loss, serum ferritin may be a clinically useful tool for ruling out underlying iron deficiency as a cause of alopecia. As an acute-phase reactant, ferritin may be nonspecifically elevated in a wide range of inflammatory conditions; however, the role of ferritin in disorders of the skin and hair is not well understood. In this article, we review the structure and function of ferritin, and we provide a guide for clinical use.

Methodology for Testing Key Parameters of Array-Level Small-Area Hafnium-Based Ferroelectric Capacitors Using Time-to-Digital Converter and Capacitance Calibration Circuits.

Hafnium-based ferroelectric memories are a promising approach to enhancing integrated circuit performance, offering advantages such as miniaturization, compatibility with CMOS technology, fast read and write speeds, non-volatility, and low power consumption. However, FeRAM (Ferroelectric Random Access Memory) still faces challenges related to endurance and retention susceptibility to process variations. Hence, testing and obtaining the core parameters of ferroelectric capacitors continuously is essential to investigate these phenomena and explore the potential solution. The traditional method for measuring ferroelectric capacitors has limitations in timing generation capability, introduces parasitic capacitance, and lacks accuracy for small-area capacitors. In this study, we analyzed the working principle of ferroelectric capacitors and designed a method to detect the remnant polarization, saturation polarization, and imprint offset of ferroelectric capacitors. Further, we further proposed a circuit implementation method. The proposed test circuit conquers these limitations and enables high-precision testing of ferroelectric capacitors, contributing to developing hafnium-based ferroelectric memories. The circuit includes a flip-readout circuit, a capacitance calibration circuit, and a voltage-to-time converter and time-to-digital converter (VTC&TDC) readout circuit. According to simulation results, the capacitance calibration circuit reduces the deviation of the capacitance by 84%, and the accuracy of the readout circuit is 5.91 bits, with a readout time of 150 ns and a power consumption of 1 mW. This circuit enables low-cost acquisition of array-level small-area ferroelectric capacitance data, which can guide subsequent device optimization and circuit design.

5-HT1A receptor in the central amygdala and 5-HT2A receptor in the basolateral amygdala are involved in social hierarchy in male mice.

Most social animals self-organize into dominance hierarchies that strongly influence their behavior and health. The serotonin (5-HT) system is believed to play an important role in the formation of social hierarchy. 5-HT receptors are abundantly expressed in the amygdala, which is considered as the central node for the perception and learning of social hierarchy. In this study, we assessed the functions of various 5-HT receptor subtypes related to social rank determination in different subregions of the amygdala using the confrontation tube test in mice. We revealed that most adult C57BL/6 J male mice exhibited a linear social rank after a few days of cohousing. The tube test ranks were slightly related to anxiety-like behavioral performance. After the tube test, the amygdala and 5-HT neurons in the dorsal raphe nucleus were activated in lower-rank individuals. Quantitative real-time polymerase chain reaction analysis revealed that despite the high expression of 5-HT1A receptor mRNA in the central amygdala (CeA), 5-HT2A receptor mRNA expression was downregulated in the basolateral amygdala (BLA) in higher-rank individuals. The dominant-subordinate relationship between mouse pairs could be switched via pharmacological modulation of these receptors in CeA and BLA, suggesting that these expression changes are essential for establishing social ranks. Our findings provide novel insights into the divergent functions of 5-HT receptors in the amygdala related to social hierarchy, which is closely related to our health and welfare.

Distribution pattern and change prediction of Phellodendron habitat in China under climate change.

Phellodendron has always been of great significance in promoting human health and ecological restoration. However, human activities and climate change have severely affected habitat, population dynamics and sustainable use of Phellodendron. Little is known about the geographical distribution pattern and their responses to climate change of Phellodendron. In order to reveal the impact of climate change on Phellodendron, we conducted a study based on natural distribution data of two species (297 occurrence points), 20 environmental factors, and an optimized MaxEnt model. Our results identified the main environmental factors influencing Phellodendron, predicted their potential geographical distribution, and assessed migration trends under climate change in China. Our analysis showed that Ph. amurense and Ph. chinense have potential suitable habitats of 62.89 × 104 and 70.71 × 104 km2, respectively. Temperature and precipitation were found to play an essential role in shaping the present geographical distribution of Phellodendron populations. Based on two future climate scenarios, we forecasted that the potential suitable habitat of Ph. amurense would decrease by 12.52% (SSP245) and increase by 25.28% (SSP585), while Ph. chinense would decline by 19.61% (SSP245) and 15.78% (SSP585) in the late-21st century. The potential suitable habitats of Ph. amurense and Ph. chinense would shift to northward and westward, respectively. Hydrothermal change was found to be the primary driver of the suitable habitat of Phellodendron populations in the future. We recommend establishing nature reserves for existing Phellodendron populations, especially Ph. chinense. Our study provided a practical framework for the impact of climate change on the suitable habitat of Phellodendron species and guided regional cultivation, long-term conservation, and sustainable use.

Design and Simulation Analysis of a 3TnC MLC FeRAM Using a Nondestructive Readout and Offset-Canceled Sense Amplifier for High-Density Storage Applications.

Hf0.5Zr0.5O2-based multi-level cell (MLC) ferroelectric random-access memory (FeRAM) has great potential for high-density storage applications. However, it is usually limited by the issues of a small operation margin and a large input offset. The study of circuit design and optimization for MLC FeRAM is necessary to solve these problems. In this work, we propose and simulate a configuration for a Hf0.5Zr0.5O2-based 3TnC MLC FeRAM macro circuit, which also presents a high area efficiency of 12F2 for each bit. Eight polarization states can be distinguished in a single fabricated Hf0.5Zr0.5O2-based memory device for potential MLC application, which is also simulated by a SPICE model for the subsequent circuit design. Therein, a nondestructive readout approach is adopted to expand the reading margin to 450 mV between adjacent storage levels, while a capacitorless offset-canceled sense amplifier (SA) is designed to reduce the offset voltage to 20 mV, which improves the readout reliability of multi-level states. Finally, a 4 Mb MLC FeRAM macro is simulated and verified using a GSMC 130 nm CMOS process. This study provides the foundation of circuit design for the practical fabrication of a Hf0.5Zr0.5O2-based MLC FeRAM chip in the future, which also suggests its potential for high-density storage applications.

Factors associated with increased risk of lurasidone-induced somnolence: Two case-control studies based on one bioequivalence trial in healthy volunteers.

Somnolence is a common adverse effect of antipsychotic drugs used to treat psychotic disorders. It causes problems in many areas of life, such as gainful employment, driving, childcare, and social interactions. Somnolence is a major problem for a relatively new antipsychotic drug, lurasidone, whose dose-effect relationship remains unclear. Based on data from a bioequivalence study of two 40 mg lurasidone hydrochloride tablets, we designed two case-control studies to explore the correlation between somnolence and exposure to lurasidone and determine the factors associated with lurasidone-induced somnolence. In the first case-control study, lurasidone was administered to healthy volunteers; 30 experienced somnolence (as pre-defined) but 29 did not. Moreover, plasma concentration at 1 h was significantly associated with somnolence (OR = 1.124; p = 0.001). In the second case-control study, 48 volunteers administered lurasidone were classified into somnolence and no-somnolence groups based on different time-related criteria. We observed a positive association between plasma concentration at 0.75 h and somnolence (OR = 1.024; p = 0.002). Receiver operating characteristic analysis revealed that a plasma lurasidone concentration >21.65 ng/mL 1 h after administration strongly predicted somnolence. Our findings in healthy volunteers need to be further validated in patients in clinical settings to determine the optimal dose and duration of lurasidone administration.

COVID-19 associated severe mucocutaneous blistering eruptions: A case series.

Mucocutaneous eruptions are associated with numerous infectious processes and can present as erythema multiforme (EM), reactive infectious mucocutaneous eruption (RIME), Stevens Johnson syndrome (SJS), or toxic epidermal necrolysis (TEN). Limited reports have detailed the association of these eruptions with SARS-CoV-2 infection. We present a series of eight cases of severe mucocutaneous blistering eruptions associated with SARS-CoV-2 infection. A retrospective case series was performed at six tertiary medical centers from March 1, 2020 to August 1, 2022. Inclusion criteria were met with a clinical diagnosis of EM, RIME, SJS, or TEN and a positive SARS-CoV-2 test (rapid antigen or polymerase chain reaction) less than 4 weeks prior to onset of dermatologic manifestation. Data was collected at time of each patient encounter. Eight patients met criteria with six pediatric patients (<18 years of age) having a median age of 15 years and two adult patients (>18 years of age) having a median age of 36 years. Patients were found to have a clinical diagnosis of RIME in 85.7% of cases. Oral mucosal involvement was the most common clinical finding (100%), followed by ocular (50.0%), urogenital (50.0%), and skin (37.5%) involvement. Evaluation did not reveal any additional infectious triggers in four patients. Evidence of possible concurrent or previous infectious triggers were identified in four patients. This case series highlights the development of severe mucocutaneous eruptions in association with COVID-19 infection, as well as the potential contributing role of concurrent or prior infections.

Cutaneous Signs of Malnutrition Secondary to Eating Disorders.

Patients with eating disorders (EDs) frequently experience malnutrition that may lead to nutritional dermatoses. Effects of malnutrition and starvation on the skin may include xerosis, lanugo, pruritus, acrocyanosis, carotenoderma, telogen effluvium, and other hair and mucosal findings. Although these dermatologic sequelae often are reported among patients with EDs, the pathomechanisms of these cutaneous symptoms are poorly understood. This article reviews the existing literature on nutritional dermatoses to clarify visible signs that should heighten clinical suspicion for an underlying ED. The skin may present the first visible signs of an otherwise occult ED diagnosis, offering the dermatologist a special opportunity for early diagnosis and coordination with a multidisciplinary team for ED treatment.

Genome-Wide Identification and Characterization of WRKY Transcription Factors and Their Expression Profile in Loropetalum chinense var. rubrum.

The WRKY gene family plays important roles in plant growth and development, as well as in the responses to biotic and abiotic stresses. Loropetalum chinense var. rubrum has high ornamental and medicinal value. However, few WRKY genes have been reported in this plant, and their functions remain unknown. To explore the roles that the WRKY genes play in L. chinense var. rubrum, we identified and characterized 79 LcWRKYs through BLAST homology analysis and renamed them (as LcWRKY1-79) based on their distribution on the chromosomes of L. chinense var. rubrum. In this way, according to their structural characteristics and phylogenetic analysis, they were divided into three groups containing 16 (Group I), 52 (Group II), and 11 (Group III) WRKYs, respectively. LcWRKYs in the same group have similar motifs and gene structures; for instance, Motifs 1, 2, 3, 4, and 10 constitute the WRKY domain and zinc-finger structure. The LcWRKY promoter region contains light response elements (ACE, G-box), stress response elements (TC-rich repeats), hormone response elements (TATC-box, TCA-element), and MYB binding sites (MBS, MBSI). Synteny analysis of LcWRKYs allowed us to establish orthologous relationships among the WRKY gene families of Arabidopsis thaliana, Oryza sativa, Solanum lycopersicum L., Vitis vinifera L., Oryza sativa L., and Zea mays L.; furthermore, analysis of the transcriptomes of mature leaves and flowers from different cultivars demonstrated the cultivar-specific LcWRKY gene expression. The expression levels of certain LcWRKY genes also presented responsive changes from young to mature leaves, based on an analysis of the transcriptome in leaves at different developmental stages. White light treatment led to a significant decrease in the expression of LcWRKY6, 18, 24, 34, 36, 44, 48, 61, 62, and 77 and a significant increase in the expression of LcWRKY41, blue light treatment led to a significant decrease in the expression of LcWRKY18, 34, 50, and 77 and a significant increase in the expression of LcWRKY36 and 48. These results enable a better understanding of LcWRKYs, facilitating the further exploration of their genetic functions and the molecular breeding of L. chinense var. rubrum.