Pseudomonas aeruginosa two-component system CprRS regulates HigBA expression and bacterial cytotoxicity in response to LL-37 stress.

Pseudomonas aeruginosa is a highly pathogenic bacterium known for its ability to sense and coordinate the production of virulence factors in response to host immune responses. However, the regulatory mechanisms underlying this process have remained largely elusive. In this study, we investigate the two-component system CprRS in P. aeruginosa and unveil the crucial role of the sensor protein CprS in sensing the human host defense peptide LL-37, thereby modulating bacterial virulence. We demonstrate that CprS acts as a phosphatase in the presence of LL-37, leading to the phosphorylation and activation of the response regulator CprR. The results prove that CprR directly recognizes a specific sequence within the promoter region of the HigBA toxin-antitoxin system, resulting in enhanced expression of the toxin HigB. Importantly, LL-37-induced HigB expression promotes the production of type III secretion system effectors, leading to reduced expression of proinflammatory cytokines and increased cytotoxicity towards macrophages. Moreover, mutations in cprS or cprR significantly impair bacterial survival in both macrophage and insect infection models. This study uncovers the regulatory mechanism of the CprRS system, enabling P. aeruginosa to detect and respond to human innate immune responses while maintaining a balanced virulence gene expression profile. Additionally, this study provides new evidence and insights into the complex regulatory system of T3SS in P. aeruginosa within the host environment, contributing to a better understanding of host-microbe communication and the development of novel strategies to combat bacterial infections.

IL-6 Up-Regulates Expression of LIM-Domain Only Protein 4 in Psoriatic Keratinocytes through Activation of the MEK/ERK/NF-κB Pathway.

Psoriasis is a chronic inflammatory skin disease characterized by the activation of keratinocytes and the infiltration of immune cells. Overexpression of the transcription factor LIM-domain only protein 4 (LMO4) promoted by IL-23 has critical roles in regulating the proliferation and differentiation of psoriatic keratinocytes. IL-6, an autocrine cytokine in psoriatic epidermis, is a key mediator of IL-23/T helper 17-driven cutaneous inflammation. However, little is known about how IL-6 regulates the up-regulation of LMO4 expression in psoriatic lesions. In this study, human immortalized keratinocyte cells, clinical biopsy specimens, and an animal model of psoriasis induced by imiquimod cream were used to investigate the role of IL-6 in the regulation of keratinocyte proliferation and differentiation. Psoriatic epidermis showed abnormal expression of IL-6 and LMO4. IL-6 up-regulated the expression of LMO4 and promoted keratinocyte proliferation and differentiation. Furthermore, in vitro and in vivo studies showed that IL-6 up-regulates LMO4 expression by activating the mitogen-activated extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK)/NF-κB signaling pathway. These results suggest that IL-6 can activate the NF-κB signaling pathway, up-regulate the expression of LMO4, lead to abnormal proliferation and differentiation of keratinocytes, and promote the occurrence and development of psoriasis.

The novel type II toxin-antitoxin PacTA modulates Pseudomonas aeruginosa iron homeostasis by obstructing the DNA-binding activity of Fur.

Type II toxin-antitoxin (TA) systems are widely distributed in bacterial and archaeal genomes and are involved in diverse critical cellular functions such as defense against phages, biofilm formation, persistence, and virulence. GCN5-related N-acetyltransferase (GNAT) toxin, with an acetyltransferase activity-dependent mechanism of translation inhibition, represents a relatively new and expanding family of type II TA toxins. We here describe a group of GNAT-Xre TA modules widely distributed among Pseudomonas species. We investigated PacTA (one of its members encoded by PA3270/PA3269) from Pseudomonas aeruginosa and demonstrated that the PacT toxin positively regulates iron acquisition in P. aeruginosa. Notably, other than arresting translation through acetylating aminoacyl-tRNAs, PacT can directly bind to Fur, a key ferric uptake regulator, to attenuate its DNA-binding affinity and thus permit the expression of downstream iron-acquisition-related genes. We further showed that the expression of the pacTA locus is upregulated in response to iron starvation and the absence of PacT causes biofilm formation defect, thereby attenuating pathogenesis. Overall, these findings reveal a novel regulatory mechanism of GNAT toxin that controls iron-uptake-related genes and contributes to bacterial virulence.

Primary Cutaneous Cryptococcosis in an Elderly Patient: A Case Report and Review of Literature.

ABSTRACT: This article reports an elderly male patient with nodules and ulcers on the face and behind the left ear after trauma. Primary cutaneous cryptococcosis was confirmed using pathological biopsy, special staining, tissue culture, and fungal sequencing. The patient received a therapeutic intervention involving the administration of the antifungal agent itraconazole. Substantial amelioration of cutaneous manifestations was observed after a 3-month course of treatment. After an elapsed interval, the patient was diagnosed with esophageal tumor. Moreover, the literature on 33 patients with primary cutaneous cryptococcosis published in the past 10 years was also reviewed.

Molecular basis for coordinating secondary metabolite production by bacterial and plant signaling molecules.

The production of secondary metabolites is a major mechanism used by beneficial rhizobacteria to antagonize plant pathogens. These bacteria have evolved to coordinate the production of different secondary metabolites due to the heavy metabolic burden imposed by secondary metabolism. However, for most secondary metabolites produced by bacteria, it is not known how their biosynthesis is coordinated. Here, we showed that PhlH from the rhizobacterium Pseudomonas fluorescens is a TetR-family regulator coordinating the expression of enzymes related to the biosynthesis of several secondary metabolites, including 2,4-diacetylphloroglucinol (2,4-DAPG), mupirocin, and pyoverdine. We present structures of PhlH in both its apo form and 2,4-DAPG-bound form and elucidate its ligand-recognizing and allosteric switching mechanisms. Moreover, we found that dissociation of 2,4-DAPG from the ligand-binding domain of PhlH was sufficient to allosterically trigger a pendulum-like movement of the DNA-binding domains within the PhlH dimer, leading to a closed-to-open conformational transition. Finally, molecular dynamics simulations confirmed that two distinct conformational states were stabilized by specific hydrogen bonding interactions and that disruption of these hydrogen bonds had profound effects on the conformational transition. Our findings not only reveal a well-conserved route of allosteric signal transduction in TetR-family regulators but also provide novel mechanistic insights into bacterial metabolic coregulation.

Antitoxin MqsA decreases antibiotic susceptibility through the global regulator AgtR in Pseudomonas fluorescens.

Type II toxin-antitoxin systems are highly prevalent in bacterial genomes and play crucial roles in the general stress response. Previously, we demonstrated that the type II antitoxin PfMqsA regulates biofilm formation through the global regulator AgtR in Pseudomonas fluorescens. Here, we found that both the C-terminal DNA-binding domain of PfMqsA and AgtR are involved in bacterial antibiotic susceptibility. Electrophoretic mobility shift assay (EMSA) analyses revealed that AgtR, rather than PfMqsA, binds to the intergenic region of emhABC-emhR, in which emhABC encodes an resistance-nodulation-cell division efflux pump and emhR encodes a repressor. Through quantitative real-time reverse-transcription PCR and EMSA analysis, we showed that AgtR directly activates the expression of the emhR by binding to the DNA motif [5´-CTAAGAAATATACTTAC-3´], leading to repression of the emhABC. Furthermore, we demonstrated that PfMqsA modulates the expression of EmhABC and EmhR. These findings enhance our understanding of the mechanism by which antitoxin PfMqsA contributes to antibiotic susceptibility.

Genome-wide association study identifies GhSAL1 affects cold tolerance at the seedling emergence stage in upland cotton (Gossypium hirsutum L.).

KEY MESSAGE: Genomic analysis of upland cotton revealed that cold tolerance was associated with ecological distribution. GhSAL1 on chromosome D09 negatively regulated cold tolerance of upland cotton. Cotton can undergo low-temperature stress at the seedling emergence stage, which adversely affects growth and yield; however, the regulatory mechanism underlying cold tolerance remains nebulous. Here, we analyze the phenotypic and physiological parameters in 200 accessions from 5 ecological distributions under constant chilling (CC) and diurnal variation of chilling (DVC) stresses at the seedling emergence stage. All accessions were clustered into four groups, of which Group IV, with most germplasms from the northwest inland region (NIR), had better phenotypes than Groups I-III under the two kinds of chilling stresses. A total of 575 significantly associated single-nucleotide polymorphism (SNP) were identified, and 35 stable genetic quantitative trait loci (QTL) were obtained, of which 5 were associated with traits under CC and DVC stress, respectively, while the remaining 25 were co-associated. The accumulation of dry weight (DW) of seedling was associated with the flavonoid biosynthesis process regulated by Gh_A10G0500. The emergence rate (ER), DW, and total length of seedling (TL) under CC stress were associated with the SNPs variation of Gh_D09G0189 (GhSAL1). GhSAL1HapB was the elite haplotype, which increased ER, DW, and TL by 19.04%, 11.26%, and 7.69%, respectively, compared with that of GhSAL1HapA. The results of virus-induced gene silencing (VIGS) experiment and determination of metabolic substrate content preliminarily illustrated that GhSAL1 negatively regulated cotton cold tolerance through IP3-Ca2+ signaling pathway. The elite haplotypes and candidate genes identified in this study could be used to improve cold tolerance at the seedling emergence stage in future upland cotton breeding.

Injections of platelet-rich plasma prepared by automatic blood cell separator combined with topical 5% minoxidil in the treatment of male androgenetic alopecia.

BACKGROUND: Platelet-rich plasma (PRP) has been increasingly accepted as a potential therapy in the treatment of androgenetic alopecia (AGA), However, there remains a dearth of data on the effectiveness of PRP prepared by automatic blood cell separator with a combination of topical minoxidil for the treatment of AGA. OBJECTIVE: To evaluate the efficacy and safety of PRP prepared by automatic blood cell separator combined with topical 5% minoxidil therapy in male AGA. METHODS: Thirty male patients with mild/moderate AGA were enrolled in a randomized double-blind controlled study. Patients were randomly divided into two treatment arms: (group A) PRP prepared by automatic blood cell separator combined with topical 5% minoxidil group; (group B) PRP prepared by automatic blood cell separator combined with a topical placebo group. Trichoscopic assessments regarding hair density/quantity and mean hair diameter were performed at baseline and follow-up. Clinical efficacy of global photography and patient satisfaction were conducted to verify the therapeutic efficacy of the treatment, and the occurrence of adverse reactions was recorded. RESULTS: We detected a significant increase in all patients in hair density and quantity after PRP treatment (p < 0.05), and there was no significant difference in mean hair diameter. Although hair density/quantity was more pronounced in group A than in group B, the difference between groups was not statistically significant (p > 0.05). In terms of clinical efficacy and patient satisfaction, group A was superior to group B, and no serious adverse reactions occurred. CONCLUSION: We hereby conclude that the injections of PRP prepared by an automated method are effective and safe in the treatment of mild-to-moderate male AGA patients, and its combination with topical 5% minoxidil therapy was superior to PRP monotherapy with better clinical efficacy and higher patient satisfaction.

Genome-wide association study identifies variants of GhSAD1 conferring cold tolerance in cotton.

Cold stress is a major environmental factor affecting plant growth and development. Although some plants have developed resistance to cold stress, the molecular mechanisms underlying this process are poorly understood. Using genome-wide association mapping with 200 cotton accessions collected from different regions, we identified variations in the short chain alcohol dehydrogenase gene, GhSAD1, that responds to cold stress. Virus-induced gene silencing and overexpression in Arabidopsis revealed that GhSAD1 fulfils important roles in cold stress responses. Ectopic expression of a haploid genotype of GhSAD1 (GhSAD1HapB) in Arabidopsis increased cold tolerance. Silencing of GhSAD1HapB resulted in a decrease in abscisic acid (ABA) content. Conversely, overexpression of GhSAD1HapB increased ABA content. GhSAD1HapB regulates cold stress responses in cotton through modulation of C-repeat binding factor activity, which regulates ABA signalling. GhSAD1HapB induces the expression of COLD-REGULATED (COR) genes and increases the amount of metabolites associated with cold stress tolerance. Overexpression of GhSAD1HapB partially complements the phenotype of the Arabidopsis ABA2 mutant, aba2-1. Collectively, these findings increase our understanding of the mechanisms underlying GhSAD1-mediated cold stress responses in cotton.

Genome-wide association study reveals that GhTRL1 and GhPIN8 affect cotton root development.

KEY MESSAGE: Two regions located at chromosome A05 and D04 were found to be significantly associated with 0-0.5 mm and 0.5-2 mm diameter roots, respectively, and two candidate genes related to root development were identified. Roots absorb water and nutrients, and play an important role in plant growth. However, there are few genetic developmental studies on cotton root structural traits. In this study, we used 200 upland cotton (Gossypium hirsutum L.) varieties to analyze the phenotypic variation of 43 traits. A total of 2001 related single-nucleotide polymorphism (SNP) sites located within or near 1046 genes were detected through a genome-wide association study (GWAS). The 32 root traits were linked to SNPs that corresponded to 317 nonrepetitive genes. For SNPs associated with root length and 0-0.5 mm diameter root traits, a significant peak appeared on chromosome A05 (between 21.91 and 22.24 Mb). For SNPs associated with root surface area, root volume and 0.5-2 mm diameter root traits, a significant peak appeared on chromosome D04 (between 7.35 and 7.70 Mb). Within these two key regions, SNPs were detected in the promoter and coding regions of two candidate genes, GhTRL1-A05 and GhPIN8-D04. The expression levels of these two genes also changed significantly according to transcriptome sequencing and quantitative real-time PCR (qRT-PCR). After silencing the GhTRL1 and GhPIN8 genes via virus-induced gene silencing (VIGS), we found that the plants expressing TRV2::GhTRL1 and TRV2::GhPIN8 had a reduced root length, surface area. Moreover, the contents of cis-12-oxo-phytodienoic acid (cis-OPDA), isopentenyl adenosine (iPR) and cis-zeatin (cZ) in the roots of the plants expressing TRV2::GhTRL1 decreased. This study contributes to the cultivation and improvement of cotton varieties.

A novel four-gene signature predicts immunotherapy response of patients with different cancers.

BACKGROUND: Immune checkpoint blockade (ICB) therapy has demonstrated favorable clinical efficacy, particularly for advanced or difficult-to-treat cancer types. However, this therapy is ineffective for many patients displaying lack of immune response or resistance to ICB. This study aimed to establish a novel four-gene signature (CD8A, CD8B, TCF7, and LEF1) to provide a prognostic immunotherapy biomarker for different cancers. METHODS: Transcriptome profiles and clinical data were obtained from The Cancer Genome Atlas database. Multivariate Cox regression analysis was used to establish a four-gene signature. The R package estimate was used to obtain the immune score for every patient. RESULTS: Risk scores of the novel four-gene signature could effectively divided all patients into high- and low-risk groups, with distinct outcomes. The immune score calculated via the estimate package demonstrated that the four-gene signature was significantly associated with the immune infiltration level. Furthermore, the four-gene signature could predict the response to atezolizumab immunotherapy in patients with metastatic urothelial cancer. CONCLUSIONS: The novel four-gene signature developed in this study is a good prognostic biomarker, as it could identify many kinds of patients with cancer who are likely to respond to and benefit from immunotherapy.

P2X7 receptor antagonist BBG inhibits endoplasmic reticulum stress and pyroptosis to alleviate postherpetic neuralgia.

Postherpetic neuralgia (PHN) is the most common complication of acute herpes zoster. The treatment of PHN remains a challenge for clinical pain management. The present study investigated the P2X7 receptor antagonist brilliant blue G (BBG) whether inhibits endoplasmic reticulum stress and pyroptosis (a necrotic form of cell death) and alleviates PHN. Varicella zoster virus (VZV)-infected CV-1 cells were used to induce PHN model. Mechanical paw withdrawal thresholds were measured using an ascending series of von Frey filaments. Immunohistochemistry was used to detect the expression of P2X7R in nerve tissues. Western blot was used to determine the expression of endoplasmic reticulum (ER) stress and pyroptosis-related molecules. The expression of IL-1ß and IL-18 in tissue homogenate was detected by ELISA. The PHN rat has the lower paw withdrawal threshold, but higher expression of P2X7 in nerve tissues. And, endoplasmic reticulum stress was activated and pyroptosis was increased in PHN rats. BBG can decrease pain thresholds and reduce ER stress and pyroptosis in PHN rats. In addition, ER stress activator tunicamycin (TM) can reverse the effect of BBG on the paw withdrawal thresholds, endoplasmic reticulum stress, and pyroptosis. Therefore, P2X7 receptor antagonist BBG alleviates PHN by activating ER stress and reducing pyroptosis.

Comparative Transcriptome Analysis Provides Insights into the Seed Germination in Cotton in Response to Chilling Stress.

Gossypium hirsutum L., is a widely cultivated cotton species around the world, but its production is seriously threatened by its susceptibility to chilling stress. Low temperature affects its germination, and the underlying molecular mechanisms are rarely known, particularly from a transcriptional perspective. In this study, transcriptomic profiles were analyzed and compared between two cotton varieties, the cold-tolerant variety KN27-3 and susceptible variety XLZ38. A total of 7535 differentially expressed genes (DEGs) were identified. Among them, the transcripts involved in energy metabolism were significantly enriched during germination based on analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, such as glycolysis/gluconeogenesis, tricarboxylic acid cycle (TCA cycle), and glyoxylate cycle (GAC). Results from further GO enrichment analysis show the earlier appearance of DNA integration, meristem growth, cotyledon morphogenesis, and other biological processes in KN27-3 compared with XLZ38 under chilling conditions. The synthesis of asparagine, GDP-mannose, and trehalose and the catabolic process of raffinose were activated. DEGs encoding antioxidants (spermidine) and antioxidase (CAT1, GPX4, DHAR2, and APX1) were much more up-regulated in embryos of KN27-3. The content of auxin (IAA), cis-zeatin riboside (cZR), and trans-zeatin riboside (tZR) in KN27-3 are higher than that in XLZ38 at five stages (from 12 h to 54 h). GA3 was expressed at a higher level in KN27-3 from 18 h to 54 h post imbibition compared to that in XLZ38. And abscisic acid (ABA) content of KN27-3 is lower than that in XLZ38 at five stages. Results from hormone content measurements and the related gene expression analysis indicated that IAA, CTK, and GA3 may promote germination of the cold-tolerant variety, while ABA inhibits it. These results expand the understanding of cottonseed germination and physiological regulations under chilling conditions by multiple pathways.

The antitoxin MqsA homologue in Pseudomonas fluorescens 2P24 has a rewired regulatory circuit through evolution.

The mqsRA operon encodes a toxin-antitoxin pair that was characterized to participate in biofilm and persister cell formation in Escherichia coli. Notably, the antitoxin MqsA possesses a C-terminal DNA-binding domain that recognizes the [5'-AACCT(N)2-4 AGGTT-3'] motif and acts as a transcriptional regulator controlling multiple genes including the general stress response regulator RpoS. However, it is unknown how the transcriptional circuits of MqsA homologues have changed in bacteria over evolutionary time. Here, we found mqsA in Pseudomonas fluorescens (PfmqsA) is acquired through horizontal gene transfer and binds to a slightly different motif [5'-TACCCT(N)3 AGGGTA-3'], which exists upstream of the PfmqsRA operon. Interestingly, an adjacent GntR-type transcriptional regulator, which was termed AgtR, is under negative control of PfMqsA. It was further demonstrated that PfMqsA reduces production of biofilm components through AgtR, which directly regulates the pga and fap operons involved in the synthesis of extracellular polymeric substances. Moreover, through quantitative proteomics analysis, we showed AgtR is a highly pleiotropic regulator that influences up to 252 genes related to diverse processes including chemotaxis, oxidative phosphorylation and carbon and nitrogen metabolism. Taken together, our findings suggest the rewired regulatory circuit of PfMqsA influences diverse physiological aspects of P. fluorescens 2P24 via the newly characterized AgtR.

Transcriptome analysis and identification of genes associated with fruiting branch internode elongation in upland cotton.

BACKGROUND: Appropriate plant architecture can improve the amount of cotton boll opening and allow increased planting density, thus increasing the level of cotton mechanical harvesting and cotton yields. The internodes of cotton fruiting branches are an important part of cotton plant architecture. Thus, studying the molecular mechanism of internode elongation in cotton fruiting branches is highly important. RESULTS: In this study, we selected internodes of cotton fruiting branches at three different stages from two cultivars whose internode lengths differed significantly. A total of 76,331 genes were detected by transcriptome sequencing. By KEGG pathway analysis, we found that DEGs were significantly enriched in the plant hormone signal transduction pathway. The transcriptional data and qRT-PCR results showed that members of the GH3 gene family, which are involved in auxin signal transduction, and CKX enzymes, which can reduce the level of CKs, were highly expressed in the cultivar XLZ77, which has relatively short internodes. Genes related to ethylene synthase (ACS), EIN2/3 and ERF in the ethylene signal transduction pathway and genes related to JAR1, COI1 and MYC2 in the JA signal transduction pathway were also highly expressed in XLZ77. Plant hormone determination results showed that the IAA and CK contents significantly decreased in cultivar XLZ77 compared with those in cultivar L28, while the ACC (the precursor of ethylene) and JA contents significantly increased. GO enrichment analysis revealed that the GO categories associated with promoting cell elongation, such as cell division, the cell cycle process and cell wall organization, were significantly enriched, and related genes were highly expressed in L28. However, genes related to the sphingolipid metabolic process and lignin biosynthetic process, whose expression can affect cell elongation, were highly expressed in XLZ77. In addition, 2067 TFs were differentially expressed. The WRKY, ERF and bHLH TF families were the top three largest families whose members were active in the two varieties, and the expression levels of most of the genes encoding these TFs were upregulated in XLZ77. CONCLUSIONS: Auxin and CK are positive regulators of internode elongation in cotton branches. In contrast, ethylene and JA may act as negative regulators of internode elongation in cotton branches. Furthermore, the WRKY, ERF and bHLH TFs were identified as important inhibitors of internode elongation in cotton. In XLZ77(a short-internode variety), the mass synthesis of ethylene and amino acid conjugation of auxin led to the inhibition of plant cell elongation, while an increase in JA content and degradation of CKs led to a slow rate of cell division, which eventually resulted in a phenotype that presented relatively short internodes on the fruiting branches. The results of this study not only provide gene resources for the genetic improvement of cotton plant architecture but also lay a foundation for improved understanding of the molecular mechanism of the internode elongation of cotton branches.

Analysis of Drought Tolerance and Associated Traits in Upland Cotton at the Seedling Stage.

(1) Background: Upland cotton (Gossypium hirsutum L.) is the most important natural fiber worldwide, and it is extensively planted and plentifully used in the textile industry. Major cotton planting regions are frequently affected by abiotic stress, especially drought stress. Drought resistance is a complex, quantitative trait. A genome-wide association study (GWAS) constitutes an efficient method for dissecting the genetic architecture of complex traits. In this study, the drought resistance of a population of 316 upland cotton accessions was studied via GWAS. (2) Methods: GWAS methodology was employed to identify relationships between molecular markers or candidate genes and phenotypes of interest. (3) Results: A total of 8, 3, and 6 SNPs were associated with the euphylla wilting score (EWS), cotyledon wilting score (CWS), and leaf temperature (LT), respectively, based on a general linear model and a factored spectrally transformed linear mixed model. For these traits, 7 QTLs were found, of which 2 each were located on chromosomes A05, A11, and D03, and of which 1 was located on chromosome A01. Importantly, in the candidate regions WRKY70, GhCIPK6, SnRK2.6, and NET1A, which are involved in the response to abscisic acid (ABA), the mitogen-activated protein kinase (MAPK) signaling pathway and the calcium transduction pathway were identified in upland cotton at the seedling stage under drought stress according to annotation information and linkage disequilibrium (LD) block analysis. Moreover, RNA sequencing analysis showed that WRKY70, GhCIPK6, SnRK2.6, and NET1A were induced by drought stress, and the expression of these genes was significantly different between normal and drought stress conditions. (4) Conclusions: The present study should provide some genomic resources for drought resistance in upland cotton. Moreover, the germplasm of the different phenotypes, the detected SNPs and, the potential candidate genes will be helpful for molecular marker-assisted breeding studies about increased drought resistance in upland cotton.

iTRAQ-Based Quantitative Proteomic Analysis Reveals Cold Responsive Proteins Involved in Leaf Senescence in Upland Cotton (Gossypium hirsutum L.).

Premature leaf senescence occurs in the ultimate phase of the plant, and it occurs through a complex series of actions regulated by stress, hormones and genes. In this study, a proteomic analysis was performed to analyze the factors that could induce premature leaf senescence in two cotton cultivars. We successfully identified 443 differential abundant proteins (DAPs) from 7388 high-confidence proteins at four stages between non-premature senescence (NS) and premature senescence (PS), among which 158 proteins were over-accumulated, 238 proteins were down-accumulated at four stages, and 47 proteins displayed overlapped accumulation. All the DAPs were mapped onto 21 different categories on the basis of a Clusters of Orthologous Groups (COG) analysis, and 9 clusters were based on accumulation. Gene Ontology (GO) enrichment results show that processes related to stress responses, including responses to cold temperatures and responses to hormones, are significantly differentially accumulated. More importantly, the enriched proteins were mapped in The Arabidopsis Information Resource (TAIR), showing that 58 proteins play an active role in abiotic stress, hormone signaling and leaf senescence. Among these proteins, 26 cold-responsive proteins (CRPs) are significantly differentially accumulated. The meteorological data showed that the median temperatures declined at approximately 15 days before the onset of aging, suggesting that a decrease in temperature is tightly linked to an onset of cotton leaf senescence. Because accumulations of H2O2 and increased jasmonic acid (JA) were detected during PS, we speculate that two pathways associated with JA and H2O2 are closely related to premature leaf senescence in cotton.

Modelling the structural response of cotton plants to mepiquat chloride and population density.

BACKGROUND AND AIMS: Cotton (Gossypium hirsutum) has indeterminate growth. The growth regulator mepiquat chloride (MC) is used worldwide to restrict vegetative growth and promote boll formation and yield. The effects of MC are modulated by complex interactions with growing conditions (nutrients, weather) and plant population density, and as a result the effects on plant form are not fully understood and are difficult to predict. The use of MC is thus hard to optimize. METHODS: To explore crop responses to plant density and MC, a functional-structural plant model (FSPM) for cotton (named CottonXL) was designed. The model was calibrated using 1 year's field data, and validated by using two additional years of detailed experimental data on the effects of MC and plant density in stands of pure cotton and in intercrops of cotton with wheat. CottonXL simulates development of leaf and fruits (square, flower and boll), plant height and branching. Crop development is driven by thermal time, population density, MC application, and topping of the main stem and branches. KEY RESULTS: Validation of the model showed good correspondence between simulated and observed values for leaf area index with an overall root-mean-square error of 0·50 m(2) m(-2), and with an overall prediction error of less than 10% for number of bolls, plant height, number of fruit branches and number of phytomers. Canopy structure became more compact with the decrease of leaf area index and internode length due to the application of MC. Moreover, MC did not have a substantial effect on boll density but increased lint yield at higher densities. CONCLUSIONS: The model satisfactorily represents the effects of agronomic measures on cotton plant structure. It can be used to identify optimal agronomic management of cotton to achieve optimal plant structure for maximum yield under varying environmental conditions.

A novel MVK missense mutation in one Chinese family with disseminated superficial actinic porokeratosis.

Disseminated superficial actinic porokeratosis (DSAP) is a severe chronic autosomal dominant cutaneous disorder with high genetic heterogeneity. mevalonate kinase, (MVK) a gene know to play an important role in regulation of calcium-induced keratinocyte differentiation and proliferation, has recently been suggested as the disease-causing gene for DSAP. Here we report a direct sequencing analysis of this gene in 3 DSAP families, 6 sporadic cases, and 100 unrelated healthy controls. We detected a heterozygous T to A transition at nucleotide 205 in exon 3 of MVK gene in one familial case. This mutation will result in an amino acid change at codon 69 (P.Ser69Thr), which is from a serine codon (TCA) to a threonine codon (ACA). No such mutation was detected in the unaffected family members or the 100 unrelated healthy controls. Our results demonstrated a novel missense mutation in MVK gene. This will be valuable for the diagnosis of DSAP as well as for genetic counseling and prenatal diagnosis of affected families.

Risk Factors of Onset Time and Persistence of Atopic Dermatitis in Children Under Age 5 Years: A Cross-Sectional Study.

Background: The prevalence of atopic dermatitis (AD) is high among children, with development of AD occurring during early childhood in most affected children and some having a chronic disease course. Risk factors for AD in this group remain undefined. Objectives: We analyzed the medical records of children with AD under 5 years of age. We summarized characteristics of the natural course of AD in these children and explored relevant risk factors of AD in infancy and early childhood. Methods: Using a self-developed questionnaire, we investigated 716 children under 5 years of age who were treated for AD at the Dermatology Department of the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China. We conducted the study from October 2021 to September 2022 using telephone and on-site interviews with the children's parents. In parental interviews, data were gathered on neonatal diseases, comorbidities, parental allergy history, maternal history of tobacco and alcohol use, and basic infant information at birth. Some children were tested for serum total immunoglobulin E (IgE) before this study. Results: Neonatal hyperbilirubinemia, neonatal respiratory distress syndrome (NRDS), neonatal infection, and infection during childhood had a significant impact on persistent symptoms and the onset of first symptoms in children with AD (P < 0.05). Allergic diseases as common comorbidities with AD, which had earlier onset of AD related to more obvious disease activity (P < 0.05). Parental history of allergy was also significant in AD (P < 0.05). Serum total iIgE levels in children with AD showed an impact on the clinical course of AD; neonatal hyperbilirubinemia and NRDS may affect IgE levels (P < 0.05). Persistent AD had a significant effect on the physical growth of children with height/length for age Z score ≤3 and weight for height/length Z score ≤3 (P < 0.05). Conclusions: Early adverse events in infants, infection before onset, and susceptibility to infection may affect the onset and clinical course of childhood AD. Serum total IgE levels affect the progression of AD. Persistent AD in childhood may have a slight impact on children's physical growth.