VR23 and Bisdemethoxycurcumin Enhanced Nanofiber Niche with Durable Bidirectional Functions for Promoting Wound Repair and Inhibiting Scar Formation.

Chronic wounds pose a significant clinical challenge worldwide, which is characterized by impaired tissue regeneration and excessive scar formation due to over-repair. Most studies have focused on developing wound repair materials that either facilitate the healing process or control hyperplastic scars caused by over-repair, respectively. However, there are limited reports on wound materials that can both promote wound healing and prevent scar hyperplasia at the same time. In this study, VR23-loaded dendritic mesoporous bioglass nanoparticles (dMBG) are synthesized and electrospun in poly(ester-curcumin-urethane)urea (PECUU) random composite nanofibers (PCVM) through the synergistic effects of physical adsorption, hydrogen bond, and electrospinning. The physicochemical characterization reveals that PCVM presented matched mechanical properties, suitable porosity, and wettability, and enabled sustained and temporal release of VR23 and BDC with the degradation of PCVM. In vitro experiments demonstrated that PCVM can modulate the functions and polarization of macrophages under an inflammatory environment, and possess effective anti-scarring potential and reliable cytocompatibility. Animal studies further confirmed that PCVM can efficiently promote re-epithelialization and angiogenesis and reduce excessive inflammation, thereby remarkably accelerating wound healing while preventing potential scarring. These findings suggest that the prepared PCVM holds promise as a bidirectional regulatory dressing for effectively promoting scar-free healing of chronic wounds.

Effect of Microwave Treatment on Protease Activity, Dough Properties and Protein Quality in Sprouted Wheat.

In this study, the effects of microwave treatment on protease activity, dough properties and protein quality in sprouted wheat were investigated. Microwave treatment led to a significant (p < 0.05) reduction in protease activity in sprouted wheat. Proteases with a pH optimum of 4.4 (cysteine proteinases) were more susceptible to microwave heating, which contributed mostly to protease inactivation. Significant improvements (p < 0.05) in the dough properties and gluten quality of sprouted wheat were observed, which are probably attributable to the synergistic effectiveness of protease inactivation and heat-induced gluten cross-linking. After microwave treatment, the decrease in the solubility and extractability of protein in sprouted wheat indicated protein polymerization, which was induced by intermolecular disulfide bond cross-linking. The changes in gliadin were less pronounced due to the relatively low temperature of the microwave treatment. The cross-linking in sprouted wheat that occurred after microwave treatment seemed to mainly involve glutenin, especially B/C low-molecular-weight glutenin subunits (B/C-LMW-GSs) in the range of 30-50 kD.

Whole-Exome Sequencing Reveals the Genomic Profile and IL6ST Variants as a Prognostic Biomarker of Paraneoplastic Pemphigus-Associated Unicentric Castleman Disease.

Unicentric Castleman disease (UCD) is a rare lymphoproliferative disorder. Paraneoplastic pemphigus (PNP) is a major complication associated with poor UCD prognosis. However, the genomic profiles and prognostic biomarkers of PNP-associated UCD remain unclear. In this study, we performed whole-exome sequencing analysis for 28 matched tumor-normal pairs and 9 tumor-only samples to define the genomic landscape of Chinese patients with PNP-associated UCD. An integrative analysis was performed to identify somatic variants, the mutational signatures, and key pathways in tumors. Besides, we analyzed the relationship among mutated genes, clinical characteristics, and prognosis. Sixty-one somatic mutant genes were identified in >1 patient with PNP-associated UCD. Specifically, IL6ST and PDGFRB were the most frequently mutated genes (32%), followed by DPP6 (18%) and MUC4 (18%). Signaling molecules and interactions, cellular processes, and signal transduction pathways were enriched. Furthermore, we found that poor overall survival was related to IL6ST variants (P = .02). Finally, we classified PNP-associated UCD into 4 genomic subgroups: IL6ST, PDGFRB, IL6ST-PDGFRB, and an unknown subgroup. In summary, we defined the molecular profile of PNP-associated UCD and identified a potential molecular biomarker for predicting prognosis, which may provide therapeutic targets for treating this severe disorder.

Evaluation of Dupilumab in Patients With Bullous Pemphigoid.

Importance: Dupilumab is a theoretically novel therapy for bullous pemphigoid (BP). However, its effectiveness and safety have yet to be confirmed in a large-scale study. Objective: To assess the efficacy and safety of dupilumab in patients with BP and evaluate factors that potentially affect short-term and long-term outcomes. Design, Setting, and Participants: A retrospective cohort study was conducted from January 1, 2021, to July 31, 2022. The median (IQR) follow-up period was 24.6 (11.5-38.4) weeks. This multicenter study was performed in 6 dermatology departments of the National Autoimmune Bullous Diseases Cooperative Group of China. Adult patients with BP that received 300 mg of dupilumab every 2 weeks following an initial dose of 600 mg were included. Patients were eligible if they had a clinical presentation of BP combined with immunological or pathological evidence. Patients with drug-induced BP, with less than 4 weeks of follow-up, and who received dupilumab or any other biologics within 6 months were excluded. Main Outcomes and Measures: The primary outcome was the proportion of patients who achieved disease control within 4 weeks. Disease control was defined as the absence of new lesions and pruritus, combined with the healing of existing lesions. Complete remission rates, relapse rates, changes in Bullous Pemphigoid Disease Area Index (BPDAI) scores, itching numerical rating scale (NRS) scores, laboratory results within 64 weeks, and adverse events (AEs) were also assessed. Results: Among 146 patients (median [IQR] age, 73 [64-85] years; 86 [58.9%] male patients) included in the study, 127 (87.0%) patients achieved disease control within 4 weeks, with a median (IQR) time of 14 (7-14) days. A total of 52 (35.6%) patients achieved complete remission, and 13 (8.9%) patients relapsed during the observation period. The complete remission rate and cumulative relapse rate at week 64 were 62.5% (5 of 8) and 30.9%, respectively. There was rapid and sustained improvement in clinical indicators and laboratory examination results after dupilumab treatment, including BPDAI scores, itching NRS scores, serum anti-BP180 and anti-BP230 antibodies, total IgE levels, and eosinophil count. Of these 146 patients, 107 (73.3%) did not report any AEs. The most common AEs were infections and eosinophilia. Serum anti-BP180 antibody levels of greater than 50 relative units (RU)/mL (OR, 3.63; 95% CI, 0.97-12.61; P = .045) were associated with 4-week disease control, and male patients were more likely to relapse (HR, 10.97; 95% CI, 1.42-84.92; P = .02). Conclusions and Relevance: In this retrospective cohort study, dupilumab treatment was associated with improved clinical symptoms in patients with BP. The safety profile was favorable, although concurrent infection and eosinophilia might pose potential concerns. This study suggests that patients with anti-BP180 antibody levels of at least 50 RU/mL and female sex may respond better.

Evaluation of clinical factors and outcome of systemic glucocorticoid therapy discontinuation in patients with pemphigus achieving complete remission.

Therapy discontinuation of systemic glucocorticoid treatment for pemphigus remains uncertain at the clinical end point of complete remission. The objective of this study was to identify the factors associated with achieving complete remission off therapy (CROT) and analyze the occurrence of relapse after therapy discontinuation. A retrospective cohort study was conducted at the Department of Dermatology of Peking University First Hospital. A total of 447 patients with pemphigus treated from 2005 to 2020 were identified. Univariate and multivariate analyses were conducted to analyze the associated factors of CROT and to evaluate the outcomes. The mean age was 48 years (±13.4 years), and 54.6% of the patients were women. During a median follow-up of 59 months (43-87.5 months), 160 of 447 (35.8%) patients achieved CROT after a median treatment duration of 51 months (38-66.2 months). Patients with a shorter therapy duration to complete remission on minimal therapy and negative desmoglein antibodies tested in remission were more likely to achieve early CROT. Thirty-five of 160 (21.9%) patients experienced relapse after CROT. Patients who discontinued therapy without guidance experienced significantly faster and higher occurrences of relapse than those withdrawing under guidance (log-rank p = 0.01). Minimal therapy maintenance ≤8 months from complete remission on minimal therapy and positive desmoglein antibodies tested at withdrawal increased the risk of early relapse after CROT.

Preparation and chromatographic performance of chiral peptide-based stationary phases for enantiomeric separation.

This study presents the development of three new chiral stationary phases. They are based on silica modified with peptides containing phenylalanine and proline. Successful analyses and characterizations were conducted using Fourier transform infrared spectra, elemental analysis, and thermogravimetric analysis. After this, the enantioselective performance of the three chiral peptide-based columns was evaluated. The evaluation used 11 racemic compounds under normal-phase high performance liquid chromatography mode. Optimized enantiomeric separation conditions were established. Under these conditions, the enantiomers of flurbiprofen and naproxen were successfully separated on CSP-1 column: the separation factor of these was 1.27 and 1.21, respectively. In addition, the reproducibility of the CSP-1 column was also investigated. The results of the investigation illustrated that the stationary phases have good reproducibility (RSD = 0.73%, n = 5).

Integrated Transcriptomic and Metabolomics Analysis of the Root Responses of Orchardgrass to Submergence Stress.

Submergence stress can severely affect plant growth. Orchardgrass (Dactylis glomerata L.) is an important forage grass, and the molecular mechanisms of orchardgrass to submergence stress are not well understood. The roots of the flood-tolerant cultivar "Dian Bei" were harvested at 0 h, 8 h and 24 h of submergence stress. The combined transcriptomic and metabolomic analyses showed that ß-alanine metabolism, flavonoid biosynthesis, and biosynthesis of amino acid pathways were significantly enriched at 8 h and 24 h of submergence stress and were more pronounced at 24 h. Most of the flavonoid biosynthesis-related genes were down-regulated for the synthesis of metabolites such as naringenin, apigenin, naringin, neohesperidin, naringenin chalcone, and liquiritigenin in response to submergence stress. Metabolites such as phenylalanine, tyrosine, and tryptophan were up-regulated under stress. The predominant response of flavonoid and amino acids biosynthesis to submergence stress suggests an important role of these pathways in the submergence tolerance of orchardgrass.

Mental health among healthcare workers during the prolonged COVID-19 pandemic: A cross-sectional survey in Jilin Province in China.

Background: The prolonged COVID-19 pandemic has seriously impacted the mental health of healthcare workers. This study aimed to explore the mental health status of healthcare workers, compare the differences in mental health between physicians and nurses, and verify the impact of risk perception on mental health in the long-term COVID-19 pandemic in Jilin Province, China. Methods: A stratified random sample was used to conduct an on-site questionnaire survey in December 2020 to measure the mental health status, risk perceptions, and demographic characteristics of healthcare workers in Jilin Province, China. A total of 3,383 participants completed the questionnaire survey, of which 3,373 were valid questionnaires. Results: A total of 23.6% (n = 795) of participants had symptoms of depression, 27.4% (n = 923) had symptoms of anxiety, and 16.3% (n = 551) had symptoms of stress. Physicians reported significantly higher rates of depression and anxiety than nurses (p = 0.023, p = 0.013, respectively). There was no significant difference in the proportion of participants with stress between physicians and nurses (p = 0.474). Multivariate logistic regression results showed that healthcare workers who had a high level of risk perception were more likely to have symptoms of depression (AOR = 4.12, p < 0.001), anxiety (AOR = 3.68, p < 0.001), and stress (AOR = 4.45, p < 0.001) after controlling for other variables. Conclusion: At least one in six healthcare workers experienced mental health problems, and physicians were more likely than nurses to suffer from depression during the prolonged COVID-19 epidemic. Risk perception was highly predictive of depression, anxiety, and stress symptoms in medical staff. Public health interventions are needed to mitigate the long-term psychological impact of the COVID-19 pandemic.

Ambient air pollution, temperature and hospital admissions due to respiratory diseases in a cold, industrial city.

Background: The influences of air pollution exposure and temperature on respiratory diseases have become major global health concerns. This study investigated the relationship between ambient air pollutant concentrations and temperature in cold industrial cities that have the risk of hospitalization for respiratory diseases. Methods: A time-series study was conducted in Changchun, China, from 2015 to 2019 to analyse the number of daily admissions for respiratory diseases, air pollutant concentrations, and meteorological factors. Time-series decomposition was applied to analyse the trend and characteristics of the number of admissions. Generalized additive models and distributed lag nonlinear models were constructed to explore the effects of air pollutant concentrations and temperature on the number of admissions. Results: The number of daily admissions showed an increasing trend, and the seasonal fluctuation was obvious, with more daily admissions in winter and spring than in summer and autumn. There were positive and gradually decreasing lag effects of PM10, PM2.5, NO2, and CO concentrations on the number of admissions, whereas O3 showed a J-shaped trend. The results showed that within the 7-day lag period, 0.5°C was the temperature associated with the lowest relative risk of admission due to respiratory disease, and extremely low and high temperatures (<-18°C, >27°C, respectively) increased the risk of hospitalization for respiratory diseases by 8.3% and 12.1%, respectively. Conclusions: From 2015 to 2019, respiratory diseases in Changchun showed an increasing trend with obvious seasonality. The increased concentrations of SO2, NO2, CO, PM2.5, O3 and PM10 lead to an increased risk of hospitalization for respiratory diseases, with a significant lag effect. Both extreme heat and cold could lead to increases in the risk of admission due to respiratory disease.

Design, synthesis and evaluation of 2-(2-oxoethyl)pyrimidine-5-carboxamide derivatives as acetylcholinesterase inhibitors.

A novel series of 2-(2- oxoethyl)pyrimidine-5-carboxamide derivatives were designed, synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs) for the treatment of Alzheimer's disease (AD). Biological activity results demonstrated that compound 10q showed the best inhibitory activity against AChE (IC50 = 0.88 ± 0.78 µM), which was better than that of Huperzine-A, and its inhibitory effect on BuChE was weak (IC50 = 10.0 ± 1.30 µM), which indicated that compound 10q was a dominant AChE inhibitor. In addition, the result of molecular docking study displayed that 10q could simultaneously bind to CAS and PAS sites of AChE, which was consistent with the mixed inhibition mode shown by the enzymatic kinetics study of 10q. Furthermore, the molecular properties of the target compounds were predicted online using the molinspiration server and pkCSM, The results exhibited that compound 10q had drug-like properties that satisfied the Lipinski's rule of five. Based on the bioactivity and molecular properties, compound 10q for further development was valuable.

The relationship between public service motivation and turnover intention: the mediating role of work stress and task performance.

BACKGROUND: The shortage of health care workforce is a common problem all over the world and one of the main reasons for the shortage is the high turnover rate. Based on the characteristics of medical work, this study explored the relationship among public service motivation (PSM), work stress, task performance and turnover intention. METHODS: Medical personnel in public hospitals were selected by stratified random sampling in Jilin province of China and validated scales from previous studies were applied to measure the variables. Besides, a structural equation model of turnover intention was constructed to demonstrate the relationship. RESULTS: A total of 3191 valid questionnaires were collected. The results showed that the score of turnover intention was 2.02 ± 1.13. There are significant differences in turnover intention among medical staff of different genders and departments. At the same time, PSM had direct and negative effects on the turnover intention (ß = -0.292, P < 0.001), work stress had direct and positive effects on the turnover intention (ß = 0.479, P < 0.001), whereas task performance had no significant effect on turnover intention (ß = 0.044, P < 0.142). The results showed an acceptable fit model. CONCLUSION: The greater the PSM, the lower the turnover intention, and the higher the work stress, the higher the turnover intention. In addition, work stress and task performance play a mediating role between PSM and turnover intention. This paper provides theoretical support for the measures to reduce the turnover intention of medical staff.

Work Stress, Health Status and Presenteeism in Relation to Task Performance Among Chinese Medical Staff During COVID-19 Pandemic.

Objectives: This study aims to evaluate the direct effects of work stress, health status and presenteeism on task performance, and further explore the mediating effects of health status and presenteeism, hoping to provide theoretical basis for improving the performance of medical staff. Methods: A cross-sectional study was conducted among medical staff in Jilin Province, Northeast China. The Challenge and Hindrance-Related Self-Reported Stress scale, Short Form-8 Health Survey scale, Stanford Presenteeism Scale and Task Performance Scale were adopted to assess the work stress, health status, presenteeism and task performance of medical staff. Results: A total of 4,347 questionnaires were distributed among medical staff, and 4261 were valid, for an effective rate of 98.02%. The mean scores for work stress, health status, presenteeism and task performance were 2.05 ± 0.84, 4.18 ± 0.68, 2.15 ± 0.79 and 4.49 ± 0.64, respectively. The ANOVA results showed that there were significant differences in the task performance scores between different genders, ages, marital statuses, professional titles, departments and work years (P < 0.05). Work stress (ß = -0.136, P < 0.001) and presenteeism (ß = -0.171, P < 0.001) were negative predictors of task performance. Health status (ß = 0.10; P < 0.001) was positive predictor of task performance. Health status (ß = -0.070; P < -0.001) and presenteeism (ß = -0.064; P < 0.001) mediated the relationship between work stress and task performance (P < 0.001). Presenteeism mediated the relationship between health status and task performance (ß = 0.07; P < 0.001). Conclusion: Work stress and presenteeism had significant negative impact on the task performance of medical staff; health status had a significant positive effect on task performance. Meanwhile, health status and presenteeism played a mediating role in the relationship between work stress and task performance, and presenteeism played a mediating role in the relationship between health status and task performance. Reasonable assignment of tasks can reduce the work stress, but to improve the performance of medical staff, we should pay more attention on improving health, such as making health-related safeguard measures, raising awareness, building a platform, etc.

Inhibitory Effect of S100A11 on Airway Smooth Muscle Contraction and Airway Hyperresponsiveness.

OBJECTIVE: S100A11 is a member of the S100 calcium-binding protein family and has intracellular and extracellular regulatory activities. We previously reported that S100A11 was differentially expressed in the respiratory tracts of asthmatic rats as compared with normal controls. Here, we aimed to analyze the potential of S100A11 to regulate both allergen-induced airway hyperresponsiveness (AHR) as well as acetylcholine (ACh)-induced hypercontractility of airway smooth muscle (ASM) and contraction of ASM cells (ASMCs). METHODS: Purified recombinant rat S100A11 protein (rS100A11) was administered to OVA-sensitized and challenged rats and then the AHR of animals was measured. The relaxation effects of rS100A11 on ASM were detected using isolated tracheal rings and primary ASMCs. The expression levels of un-phosphorylated myosin light chain (MLC) and phosphorylated MLC in ASMCs were analyzed using Western blotting. RESULTS: Treatment with rS100A11 attenuated AHR in the rats. ASM contraction assays showed that rS100A11 reduced the contractile responses of isolated tracheal rings and primary ASMCs treated with ACh. In addition, rS100A11 markedly decreased the ACh-induced phosphorylation of the myosin light chain in ASMCs. Moreover, rS100A11 also suppressed the contractile response of tracheal rings in calcium-free buffer medium. CONCLUSION: These results indicate that S100A11 protein can relieve AHR by relaxing ASM independently of extracellular calcium. Our data support the idea that S100A11 is a potential therapeutic target for reducing airway resistance in asthma patients.

Analysis of factors affecting medical personnel seeking employment at primary health care institutions: developing human resources for primary health care.

BACKGROUND: The serious shortage of human resources for primary health care (PHC) is a common issue in health reforms worldwide. China has proposed that it is an effective way to encourage and guide qualified medical personnel to work in primary health care institutions (PHCIs). However, few studies have been conducted on the willingness and influencing factors of medical personnel to seek employment at PHCIs. METHODS: Based on implicit theory and lexical approach, pre-investigation was conducted to collect the items that influence the medical personnel to seek employment at PHCIs from the perspective of guided objects. Through a three-phase investigation of 1160 doctors in 29 public hospitals in 9 cities, the items were categorized, and a structural equation model was established and verified to explore the interrelationship of influencing factors. RESULTS: A total of 6 factors were rotated, including Sense of Gain (SG), Internal Organization Development (IOD), Remuneration and Development (RD), Condition of the City Where the PHCI Is Located (CCPL), Job Responsibilities (JR) and Family Support (FS). The results of the model showed that IOD, RD, JR and FS had a significantly positive effect on the SG. In addition, the FS, RD and JR significantly mediated the relationship between the internal and external environment of PHCIs and SG. The values of the fit index indicated an acceptable-fitting model. CONCLUSION: Family, remuneration, individual development, and job responsibility are closely related to the willingness of medical personnel to seek employment at PHCIs, and the internal and external environment of PHCIs is also an important factor. Therefore, the development of PHC providers can be promoted by paying attention to the family members of medical personnel, establishing a reasonable remuneration system, providing suitable development opportunities, arranging work rationally and improving the internal construction of PHCIs.

Factors Influencing Medical Personnel to Work in Primary Health Care Institutions: An Extended Theory of Planned Behavior.

In China, the primary health care institutions (PHCIs) have difficulty winning the trust of residents because of the shortage of medical personnel and the low level of skills. The government has advocated encouraging qualified doctors to work in PHCIs, but no obvious results are achieved. Based on the theory of planned behavior (TPB), this paper explores the factors affecting medical personnel seeking employment in PHCIs and then putting forward measures to improve the human resources construction of PHCIs. A three-stage survey was conducted to obtain the factors and a structural equation modeling (SEM) was applied to examine the relationship of the factors. We found that the factors affecting medical personnel to work in PHCIs include the specific conditions and work contents of PHCIs, as well as the family life and regional factors. Besides, there is a significant correlation and indirectness between these factors. Therefore, targeted measures can be proposed to improve the intention of medical personnel seeking employment in PHCIs. This study provides theoretical support for encouraging medical personnel to work in PHCIs and improving the primary health care system.

Role of IL-6 in dendritic cell functions.

Dendritic cells (DCs) are efficient antigen-presenting cells that serve as a link between the innate and adaptive immune systems. These cells are broadly involved in cellular and humoral immune responses by presenting antigens to initiate T cell reactions, cytokine and chemokine secretion, T cell differentiation and expansion, B cell activation and regulation, and the mediation of immune tolerance. The functions of DCs depend on their activation status, which is defined by the stages of maturation, phenotype differentiation, and migration ability, among other factors. IL-6 is a soluble mediator mainly produced by a variety of immune cells, including DCs, that exerts pleiotropic effects on immune and inflammatory responses through interaction with specific receptors expressed on the surface of target cells. Here, we review the role of IL-6, when generated in an inflammatory context or as derived from DCs, in modulating the biologic function and activation status of DCs and emphasize the importance of searching for novel strategies to target the IL-6/IL-6 signaling pathway as a means to diminish the inflammatory activity of DCs in immune response or to prime the immunogenic activity of DCs in immunosuppressive conditions.

Analysis of Acupoint Selection and Combinations in Acupuncture Treatment of Asthma Based on Data Mining.

OBJECTIVE: Asthma is a highly prevalent respiratory disease that remains difficult to control. Acupuncture, as an important alternative therapeutic modality in preventing and treating asthma, is widely used in the world due to its promising efficacy and safety. Although acupoint selection and combinations are critical to therapeutic effects of acupuncture, its fundamental rules for asthma have not been fully understood. Thus, using data mining, the present study aimed to discover the most effective acupoints and combinations in the acupuncture treatment of asthma. METHODS: Controlled clinical trials (CCTs) of acupuncture treatment for asthma were searched and retrieved from databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang, and PubMed. Data regarding the main acupoints prescribed in these clinical trials was collected and quantified. A network analysis was performed to uncover the interconnections between the acupoints. Additionally, hierarchical clustering analysis and association rule mining were conducted to discover the potential acupoint combinations. RESULTS: A total of 183 CCTs were retrieved. Feishu (BL13), Dingchuan (EX-B1), Dazhui (GV14), Shengshu (BL23), Pishu (BL20), and Fengmen (BL12) appeared to be the most frequently used acupoints for asthma. While the Bladder Meridian of Foot Taiyang, the Governor Vessel, and the Conception Vessel, compared to other meridians, were found to be the more commonly selected meridians. In the acupoint interconnection network, Feishu (BL13), Fengmen (BL12), Dingchuan (EX-B1), and Dazhui (GV14) were defined as key node acupoints. Moreover, acupoint clustering analysis revealed the treatment principle of "facilitating the flow of the lung Qi, tonifying spleen and kidney, and treating both the symptoms and root causes." Association rule mining analysis demonstrated that the combination of Pishu, Shenshu, Feishu, and Dingchuan, as well as that of Feishu, Dazhui, and Fengmen were potential acupoint combinations that should be selected with priority in asthma treatment. CONCLUSION: Based on a data mining analysis of published CCTs, this study provides valuable information regarding the selection of the most effective acupoints and combinations for clinical acupuncture practice and experimental study aimed at the prevention and treatment of asthma.

Comparative transcriptomic analysis of the gene expression and underlying molecular mechanism of submergence stress response in orchardgrass roots.

Introduction: Submergence stress creates a hypoxic environment. Roots are the first plant organ to face these low-oxygen conditions, which causes damage and affects the plant growth and yield. Orchardgrass (Dactylis glomerata L.) is one of the most important cold-season forage grasses globally. However, their submergence stress-induced gene expression and the underlying molecular mechanisms of orchardgrass roots are still unknown. Methods: Using the submergence-tolerant 'Dianbei' and submergence-sensitive 'Anba', the transcriptomic analysis of orchardgrass roots at different time points of submergence stress (0 h, 8 h, and 24 h) was performed. Results: We obtained 118.82Gb clean data by RNA-Seq. As compared with the control, a total of 6663 and 9857 differentially expressed genes (DEGs) were detected in Dianbei, while 7894 and 11215 DEGs were detected in Anba at 8 h and 24 h post-submergence-stress, respectively. Gene Ontology (GO) enrichment analysis obtained 986 terms, while Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis obtained 123 pathways. Among them, the DEGs in plant hormones, mitogen-activated protein kinase (MAPK) and Ca2+ signal transduction were significantly differentially expressed in Dianbei, but not in Anba. Discussion: This study was the first to molecularly elucidate the submergence stress tolerance in the roots of two orchardgrass cultivars. These findings not only enhanced our understanding of the orchardgrass submergence tolerance, but also provided a theoretical basis 36 for the cultivation of submergence-tolerant forage varieties.

Case Report: Successful Treatment of Chromoblastomycosis Caused by Fonsecaea monophora in a Patient with Psoriasis Using Itraconazole and Acitretin.

Chromoblastomycosis is a worldwide chronic subcutaneous infection caused by dematiaceous fungi and clinically characterized by verrucous lesions. Herein, we report a rare case of chromoblastomycosis caused by Fonsecaea monophora in a 60-year-old male carpenter with a 40-year history of psoriasis from Shandong in northern China. A fungal infection coexisting with psoriasis presents a management dilemma. Our patient responded well to combined itraconazole and acitretin therapy and the lesions resolved completely after 1 month of treatment.

A large-scale genome-wide association and meta-analysis identified four novel susceptibility loci for leprosy.

Leprosy, a chronic infectious disease, results from the uncultivable pathogen Mycobacterium leprae (M. leprae), and usually progresses to peripheral neuropathy and permanent progressive deformity if not treated. Previously published genetic studies have identified 18 gene/loci significantly associated with leprosy at the genome-wide significant level. However as a complex disease, only a small proportion of leprosy risk could be explained by those gene/loci. To further identify more susceptibility gene/loci, we hereby performed a three-stage GWAS comprising 8,156 leprosy patients and 15,610 controls of Chinese ancestry. Four novel loci were identified including rs6807915 on 3p25.2 (P=1.94 × 10-8, OR=0.89), rs4720118 on 7p14.3 (P=3.85 × 10-10, OR=1.16), rs55894533 on 8p23.1 (P=5.07 × 10-11, OR=1.15) and rs10100465 on 8q24.11 (P=2.85 × 10-11, OR=0.85). Altogether, these findings have provided new insight and significantly expanded our understanding of the genetic basis of leprosy.