Systemic Amyloidosis Secondary to Psoriasis: A Rare, Autoimmune and Genetically-Determined Disorder That Is Amenable to Treatment with Cyclosporin A—Cyclosporin A for Psoriasis-Induced Amyloidosis

Background: Systemic secondary amyloidosis (SSA) is associated with chronic inflammatory disorders and/or chronic infections. Patients and Methods: Over the past 10 years;a total of 21 patients, with long-term (17 months) and extensive psoriasis (P) with psoriasis area severity index (PASI) >29, were evaluated. Results: Two patients had nephrotic syndrome (proteinuria 3.9 and 3.6 g/day) and decrease creatinine clearance (46 and 62 ml/minute). Their renal biopsy revealed Congo-red (+) nodular glomerulosclerosis that lacked immune-deposits and resisted wash with K-permanganate wash indicating SSA. Three months subsequent to Cyclosporin A (CyA) therapy with 100 mg twice daily;psoriasis improved in all patients with decrease in (PASI) from 29.5 to 3.5 1. In the 2 patients with SSA;proteinuria decreased to 2.1 and 1.8 g/day and creatinine clearance improved to 51 and 69 ml/minute. Such improvement persisted up to 2 years of follow up and up to 78 months in patients with SSA. Conclusion: psoriasis-induced SSA is an autoimmune disease, with genetic predisposition that is amenable to CyA therapy.

COVID-19 exacerbates psoriasis progression through inducing IFN-αexpression

As a global public health issue that can cause systemic diseases,COVID-19 inflicts various harms on patients and impacts those with comorbidities.Psoriasis is primarily driven by a subset of T helper cells and the cytokines[1],and microbial infection is a predisposing factor in up to 45%of patients[2].Infection with SARS-CoV-2 may trigger the aggravation of psoriasis.Thus,we conducted a survey to explore the proportion of psoriasis patients who experienced exacerbation and relapse after SARS-CoV-2 infection and also performed a preliminary investigation into the mechanisms involved.One hundred and twenty-four psoriasis patients(79 males and 45 females)who contracted COVID-19 were followed up and provided detailed information.

Genetic pathways in cerebral palsy:a review of the implications for precision diagnosis and understanding disease mechanisms

Ce rebral palsy is a diagnostic term utilized to describe a group of permanent disorders affecting movement and posture.Patients with cerebral palsy are often only capable of limited activity,resulting from non-progressive disturbances in the fetal or neonatal brain.These disturbances severely impact the child’s daily life and impose a substantial economic burden on the family.Although cerebral palsy encompasses various brain injuries leading to similar clinical outcomes,the unde rstanding of its etiological pathways remains incomplete owing to its complexity and heterogeneity.This review aims to summarize the current knowledge on the genetic factors influencing cerebral palsy development.It is now widely acknowledged that genetic mutations and alterations play a pivotal role in cerebral palsy development,which can be further influenced by environmental fa ctors.Des pite continuous research endeavors,the underlying fa ctors contributing to cerebral palsy remain are still elusive.However,significant progress has been made in genetic research that has markedly enhanced our comprehension of the genetic factors underlying cerebral palsy development.Moreove r,these genetic factors have been categorized based on the identified gene mutations in patients through clinical genotyping,including thrombosis,angiogenesis,mitochondrial and oxidative phosphorylation function,neuronal migration,and cellular autophagy.Furthermore,exploring targeted genotypes holds potential for precision treatment.In conclusion,advancements in genetic research have substantially improved our understanding of the genetic causes underlying cerebral palsy.These breakthroughs have the potential to pave the way for new treatments and therapies,consequently shaping the future of cerebral palsy research and its clinical management.The investigation of cerebral palsy genetics holds the potential to significantly advance treatments and management strategies.By elucidating the underlying cellular mechanisms,we can develop to rgeted interventions to optimize outcomes.A continued collaboration between researchers and clinicians is imperative to comprehensively unravel the intricate genetic etiology of cerebral palsy.

Genetic screening of liver cancer:State of the art

Liver cancer,primarily hepatocellular carcinoma,remains a global health challenge with rising incidence and limited therapeutic options.Genetic factors play a pivotal role in the development and progression of liver cancer.This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer.We discuss the genetic underpinnings of liver cancer,emphasizing the critical role of risk-associated genetic variants,somatic mutations,and epigenetic alterations.We also explore the intricate interplay between environmental factors and genetics,highlighting how genetic screening can aid in risk stratification and early detection via using liquid biopsy,and advancements in high-throughput sequencing technologies.By synthesizing the latest research findings,we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer,shedding light on their potential to revolutionize early detection,risk assessment,and targeted therapies in the fight against this devastating disease.

Winter wheat yield improvement by genetic gain across different provinces in China

The replacement of winter wheat varieties has contributed significantly to yield improvement worldwide,with remarkable progress in China.Drawing on two sets of data,production yield from the National Bureau of Statistics of China and experimental yield from literature,this study aims to(1)illustrate the increasing patterns of production yield among different provinces from 1978 to 2018 in China,(2)explore the genetic gain in yield and yield relevant traits through the variety replacement based on experimental yield from 1937 to 2016 in China,and(3)compare the yield gap between experimental yield and production yield.The results show that both the production and experimental yields significantly increased along with the variety replacement.The national annual yield increase ratio for the production yield was 1.67%from 1978 to 2018,varying from 0.96%in Sichuan Province to 2.78%in Hebei Province;such ratio for the experimental yield was 1.13%from 1937 to 2016.The yield gap between experimental and production yields decreased from the 1970s to the 2010s.This study reveals significant increases in some yield components consequent to variety replacement,including thousand-grain weight,kernel number per spike,and grain number per square meter;however,no change is shown in spike number per square meter.The biomass and harvest index consistently and significantly increased,whereas the plant height decreased significantly.

Apigenin ameliorates imiquimod-induced psoriasis in C57BL/6J mice by inactivating STAT3 and NF-κB

Psoriasis is a chronic autoimmune disease featured by patches on the skin.It is caused by malfunction of immune cells and keratinocytes with inflammation as one of its key features.Apigenin(API)is a natural flavonoid with anti-inflammatory and immunoregulatory properties.Therefore,we speculated that API can ameliorate psoriasis,and determined its effect on the development of psoriasis by using imiquimod(IMQ)-induced psoriasis mouse model.Our results showed that API attenuated IMQ-induced phenotypic changes,such as erythema,scaling and epidermal thickening,and improved splenic hyperplasia.Abnormal differentiation of immune cells was restored in API-treated mice.Mechanistically,we revealed that API is a key regulator of signal transducer activator of transcription 3(STAT3).API regulated immune responses by reducing interleukin-23(IL-23)/STAT3/IL-17A axis.Moreover,it suppressed IMQ-caused cell hyperproliferation by inactivating STAT3 through regulation of extracellular signal-regulated kinase 1/2 and nuclear factor-κB(NF-κB)pathway.Furthermore,API reduced expression of inflammatory cytokines through inactivation of NF-κB.Taken together,our study demonstrates that API can ameliorate psoriasis and may be considered as a strategy for psoriasis treatment.

Cytokine release syndrome triggered by programmed death 1 blockade(sintilimab)therapy in a psoriasis patient:A case report

BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.

Genetic variants in C1GALT1 are associated with gastric cancer risk by influencing immune infiltration

Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer risk.By using the genome-wide association study data from the database of Genotype and Phenotype(dbGAP),we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk(odds ratio,0.83;95% confidence interval[CI],0.75-0.92;P=3.95×10^(-4)).C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues,and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates(hazards ratio,1.33;95%CI,1.05-1.68;P_(log-rank)=1.90×10^(-2)).Furthermore,we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4^(+)T cells and macrophages.These results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.

Genetically modified pigs:Emerging animal models for hereditary hearing loss

Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.

Conservation genomic investigation of an endangered conifer,Thuja sutchuenensis,reveals low genetic diversity but also low genetic load

Endangered species generally have small populations with low genetic diversity and a high genetic load.Thuja sutchuenensis is an endangered conifer endemic to southwestern China.It was once considered extinct in the wild,but in 1999 was rediscovered.However,little is known about its genetic load.We collected 67 individuals from five wild,isolated T.sutchuenensis populations,and used 636,151 SNPs to analyze the level of genetic diversity and genetic load in T.sutchuenensis to delineate the conservation units of T.sutchuenensis,based on whole transcriptome sequencing data,as well as target capture sequencing data.We found that populations of T.sutchuenensis could be divided into three groups.These groups had low levels genetic diversity and were moderately genetically differentiated.Our findings also indicate that T.sutchuenensis suffered two severe bottlenecks around the Last Glaciation Period and Last Glacial Maximum.Among Thuja species,T.sutchuenensis presented the lowest genetic load and hence might have purged deleterious mutations efficiently through purifying selection.However,distribution of fitness effects analysis indicated a high extinction risk for T.sutchuenensis.Multiple lines of evidence identified three management units for T.sutchuenensis.Although T.sutchuenensis possesses a low genetic load,low genetic diversity,suboptimal fitness,and anthropogenic pressures all present an extinction risk for this rare conifer.This might also hold true for many endangered plant species in the mountains all over the world.

Genetic variation of circHIBADH enhances prostate cancer risk through regulating HNRNPA1-related RNA splicing

The current study aimed to investigate associations of circRNAs and related genetic variants with the risk of prostate cancer(PCa)as well as to elucidate biological mechanisms underlying the associations.We first compared expression levels of circRNAs between 25 paired PCa and adjacent normal tissues to identify riskassociated circRNAs by using the MiOncoCirc database.We then used logistic regression models to evaluate associations between genetic variants in candidate circRNAs and PCa risk among 4662 prostate cancer patients and 3114 healthy controls,and identified circHIBADH rs11973492 T>C as a significant risk-associated variant(odds ratio=1.20,95%confidence interval:1.08-1.34,P=7.06×10^(-4))in a dominant genetic model,which altered the secondary structure of the corresponding RNA chain.In the in silico analysis,we found that circHIBADH sponged and silenced 21 RNA-binding proteins(RBPs)enriched in the RNA splicing pathway,among which HNRNPA1 was identified and validated as a hub RBP using an external RNA-sequencing data as well as the in-house(four tissue samples)and publicly available single-cell transcriptomes.Additionally,we demonstrated that HNRNPA1 influenced hallmarks including MYC target,DNA repair,and E2F target signaling pathways,thereby promoting carcinogenesis.In conclusion,genetic variants in circHIBADH may act as sponges and inhibitors of RNA splicing-associated RBPs including HNRNPA1,playing an oncogenic role in PCa.

Genetic algorithm assisted meta-atom design for high-performance metasurface optics

Metasurfaces,composed of planar arrays of intricately designed meta-atom structures,possess remarkable capabilities in controlling electromagnetic waves in various ways.A critical aspect of metasurface design involves selecting suitable meta-atoms to achieve target functionalities such as phase retardation,amplitude modulation,and polarization conversion.Conventional design processes often involve extensive parameter sweeping,a laborious and computationally intensive task heavily reliant on designer expertise and judgement.Here,we present an efficient genetic algorithm assisted meta-atom optimization method for high-performance metasurface optics,which is compatible to both single-and multiobjective device design tasks.We first employ the method for a single-objective design task and implement a high-efficiency Pancharatnam-Berry phase based metalens with an average focusing efficiency exceeding 80%in the visible spectrum.We then employ the method for a dual-objective metasurface design task and construct an efficient spin-multiplexed structural beam generator.The device is capable of generating zeroth-order and first-order Bessel beams respectively under right-handed and left-handed circular polarized illumination,with associated generation efficiencies surpassing 88%.Finally,we implement a wavelength and spin co-multiplexed four-channel metahologram capable of projecting two spin-multiplexed holographic images under each operational wavelength,with efficiencies over 50%.Our work offers a streamlined and easy-to-implement approach to meta-atom design and optimization,empowering designers to create diverse high-performance and multifunctional metasurface optics.

A dual-RPA based lateral flow strip for sensitive,on-site detection of CP4-EPSPS and Cry1Ab/Ac genes in genetically modified crops

Traditional transgenic detection methods require high test conditions and struggle to be both sensitive and efficient.In this study,a one-tube dual recombinase polymerase amplification(RPA)reaction system for CP4-EPSPS and Cry1Ab/Ac was proposed and combined with a lateral flow immunochromatographic assay,named“Dual-RPA-LFD”,to visualize the dual detection of genetically modified(GM)crops.In which,the herbicide tolerance gene CP4-EPSPS and the insect resistance gene Cry1Ab/Ac were selected as targets taking into account the current status of the most widespread application of insect resistance and herbicide tolerance traits and their stacked traits.Gradient diluted plasmids,transgenic standards,and actual samples were used as templates to conduct sensitivity,specificity,and practicality assays,respectively.The constructed method achieved the visual detection of plasmid at levels as low as 100 copies,demonstrating its high sensitivity.In addition,good applicability to transgenic samples was observed,with no cross-interference between two test lines and no influence from other genes.In conclusion,this strategy achieved the expected purpose of simultaneous detection of the two popular targets in GM crops within 20 min at 37°C in a rapid,equipmentfree field manner,providing a new alternative for rapid screening for transgenic assays in the field.

Causal effect of psoriasis on aortic valve stenosis:a two-sample Mendelian randomization study

Background Epidemiological studies have suggested a potential connection between psoriasis and an increased risk of aortic valve stenosis(AS),though the impact of psoriasis on AS progression remains uncertain.The study aims to investigate the causal relationship between psoriasis and AS using Mendelian randomization(MR)analysis,as well as to uncover potential mechanisms underlying this association.Methods A two-sample MR analysis was conducted using publicly available summary statistics from genome-wide association studies(GWAS)of psoriasis and AS.Cis-eQTL and significant genes were identified for each causal single-nucleotide polymorphisms(SNPs),followed by pathway enrichment and protein-protein interaction(PPI)analysis for functional evaluation.Hub genes were pinpointed by Cytospace.The transcriptional profile of AS population was acquired,and interconnected genes networks were clustered using Molecular Complex Detection(MCODE).Results Our results demonstrate a significant causal relationship between psoriasis and AS,with a genetic predisposition to psoriasis associated with a higher AS risk(odds ratio:1.46).Pathway and PPI analyses unveiled 15 hub genes,including HLA-C,HLA-B,ISG15,IFIT3,and MX2,along with immune-related pathways linking psoriasis and AS.Moreover,the transcriptional profiling of the AS database highlighted the significant involvement of adaptive immune cells in AS development.Notably,among the 15 hub genes,ISG15,MX2,OAS3,OASL,IFI6,and EPSTI1 exhibited higher expression in the AS population.Conclusion Our study provides compelling evidence supporting a causal relationship between psoriasis and AS.Furthermore,the identified hub genes and immune-related pathways may play an important role in the development of both diseases.

Coleus forskohlii shows anti-psoriatic activity in imiquimod-induced psoriasis rats

Objective:To evaluate anti-psoriatic activity of Coleus forskohlii in rats with imiquimod-induced psoriasis.Methods:Imiquimod was used to induce psoriasis in rats.Body weight,skin thickness,erythema,scaling,spleen weight,and histological alternations were measured to assess the effect of Coleus forskohlii.Furthermore,an emulgel formulation containing Coleus forskohlii 10%was prepared and characterized along with its ex vivo permeation studies.Results:The emulgel formulation containing Coleus forskohlii 10%had a pH of 5.40±0.36,with optimum spreadability of(31.67±2.08)g/(cm·s)and viscosity of(15966.67±1274.10)cps,and enhanced both the rate and the extent of drug permeation through psoriatic skin.In an ex vivo study,the quantity of drug permeated(19.18%),deposited(52.38%),and drug remaining in the donor compartments(28.31%)was satisfactory.Coleus forskohlii significantly alleviated imiquimod-induced psoriasis by increasing glutathione and superoxide dismutase activity,decreasing malondialdehyde and nitric oxide levels,and alleviating histological alternations in rat skin.Conclusions:Coleus forskohlii can alleviate imiquimod-induced psoriasis,which may be used as a therapeutic candidate for the treatment of psoriasis.

The Application Progress of Skin Imaging Technology in Psoriasis

Skin imaging technologies such as dermoscopy, high-frequency ultrasound, reflective confocal microscopy and optical coherence tomography are developing rapidly in clinical application. Skin imaging technology can improve clinical diagnosis rate, and its non-invasiveness and repeatability make it occupy an irreplaceable position in clinical diagnosis. With the “booming development” of medical technology, skin imaging technology can improve clinical diagnosis rate. Researchers have made significant advances in assisting clinical diagnosis, prediction, and treatment of disease. This article reviews the application and progress of skin imaging in the diagnosis of psoriasis.

An efficient method for constructing a random insertional mutant library for forward genetics in Nannochloropsis oceanica

Insertional mutation,phenotypic evaluation,and mutated gene cloning are widely used to clone genes from scratch.Exogenous genes can be integrated into the genome during non-homologous end joining(NHEJ)of the double-strand breaks of DNA,causing insertional mutation.The random insertional mutant library constructed using this method has become a method of forward genetics for gene cloning.However,the establishment of a random insertional mutant library requires a high transformation efficiency of exogenous genes.Many microalgal species show a low transformation efficiency,making constructing random insertional mutant libraries difficult.In this study,we established a highly efficient transformation method for constructing a random insertional mutant library of Nannochloropsis oceanica,and tentatively tried to isolate its genes to prove the feasibility of the method.A gene that may control the growth rate and cell size was identified.This method will facilitate the genetic studies of N.oceanica,which should also be a reference for other microalgal species.

Genetic variability and trait association analysis in linseed(Linum usitatissimum L.)for yield and related traits

Diversity information mining about a crop for different attributes is an essential step for effective breeding programs.The present investigation evaluates the quantum of genetic variability and determines the relationship among the important agro-economic traits based on two years of phenotypic data of 210 accessions of linseed.The traits,capsule weight per plant,capsule per plant,husk weight per plant,and seed weight per plant exhibited comparatively higher genetic coefficient of variation(GCV)and phenotypic coefficient of variation(PCV).In contrast,oil content and seed per capsule exhibited a lower value.The high magnitude of broad sense heritability was observed for all traits except seeds per capsule and husk weight per plant.The trait,capsules per plant,plant height,and days to 50%flowering showed high genetic advance coupled with high heritability.Hierarchical cluster analysis grouped 210 accessions into six distinct clusters.Out of 210,144(68.57%)accessions were grouped into three clusters(I,II,and III),in which cluster-III was the largest,containing 64 accessions followed by cluster II and cluster-I.The highest inter-cluster distance was observed between clusters-I and V(127.85),while the lowest was between clusters-II and IV(27.09).The positive correlation of capsule weight per plant with the seed weight per plant and a negative correlation with the days to 50%flowering indicates that high yielding linseed varieties with early flowering/maturity could be developed through direct and indirect selection.Further,seed yield and oil content could be enhanced together as indicated by ghe positive association among these two important traits.In this study,high yielding accessions with moderate to high oil content such as GP36,GP31,GP14,GP54,GP26,GP24,GP34,GP21,GP37 and GP27 and early flowering(less than 70 days)accessions such as GP2,GP26,GP27,CG33,CG44,CG42,CG132,and CG31 identified as potential genetic materials that could be exploited for developing early maturing varieties with high yield.In addition,information’s on various genetic parameters will help breeders to devise suitable breeding methodology for linseed genetic improvement for targeted traits.

Genetic Variations and Nonalcoholic Fatty Liver Disease:Field Synopsis,Systematic Meta-Analysis,and Epidemiological Evidence

Objective To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease(NAFLD).Methods Literature from Web of Science,PubMed,and Embase between January 1980 and September 2022 was systematically searched.Meta-analyses of the genetic variants were conducted using at least five data sources.The epidemiologic credibility of the significant associations was graded using the Venice criteria.Results Based on literature screening,399 eligible studies were included,comprising 381 candidate gene association,16 genome-wide association,and 2 whole-exome sequencing studies.We identified 465 genetic variants in 173 genes in candidate gene association studies,and 25 genetic variants in 17 genes were included in the meta-analysis.The meta-analysis identified 11 variants in 10 genes that were significantly associated with NAFLD,with cumulative epidemiological evidence of an association graded as strong for two variants in two genes(HFE,TNF),moderate for four variants in three genes(TM6SF2,GCKR,and ADIPOQ),and weak for five variants in five genes(MBOAT7,PEMT,PNPLA3,LEPR,and MTHFR).Conclusion This study identified six variants in five genes that had moderate to strong evidence of an association with NAFLD,which may help understand the genetic architecture of NAFLD risk.

Genetic Diversity of Jute Mallow (Corchorus spp.) Accessions Based on ISSR Markers

Jute mallow is a nutritious leafy vegetable. The leaves are rich in proteins, vitamins and essential amino acids. Molecular characterization of Jute mallow with focus on improvement of leaf yield is scarcely reported. In the present study, inter sequence simple repeats (ISSR) molecular markers were employed to assess genetic diversity and relationships of 83 accessions of Jute mallow from different parts of Africa and Asia conserved at the World Vegetable Center East and Southern Africa. A total of 89 bands were amplified by 8 ISSR primers. Number of polymorphic bands per primer ranged from 2 to 6 with an average of 2.75 bands per primer. Polymorphic information content (PIC) values ranged from 0.390 to 0.760 with average of 0.53. Average Nei’s gene diversity (h) and Shannon’s information index (I) were 0.335 and 0.494 respectively. The highest pairwise genetic distance was 0.431 observed in a population from East Africa accessions. PC1 and PC2 axis explained 21.69% and 11.66% of the total variation respectively. UPGMA cluster analysis grouped the accessions into six main clusters at genetic similarity coefficient of 0.53 as standard value for classification. These results have important implications for jute mallow breeding and conservation.