Evolution of the Correlated Genomic Variation Landscape Across a Divergence Continuum in the Genus Castanopsis.

The heterogeneous landscape of genomic variation has been well documented in population genomic studies. However, disentangling the intricate interplay of evolutionary forces influencing the genetic variation landscape over time remains challenging. In this study, we assembled a chromosome-level genome for Castanopsis eyrei and sequenced the whole genomes of 276 individuals from 12 Castanopsis species, spanning a broad divergence continuum. We found highly correlated genomic variation landscapes across these species. Furthermore, variations in genetic diversity and differentiation along the genome were strongly associated with recombination rates and gene density. These results suggest that long-term linked selection and conserved genomic features have contributed to the formation of a common genomic variation landscape. By examining how correlations between population summary statistics change throughout the species divergence continuum, we determined that background selection alone does not fully explain the observed patterns of genomic variation; the effects of recurrent selective sweeps must be considered. We further revealed that extensive gene flow has significantly influenced patterns of genomic variation in Castanopsis species. The estimated admixture proportion correlated positively with recombination rate and negatively with gene density, supporting a scenario of selection against gene flow. Additionally, putative introgression regions exhibited strong signals of positive selection, an enrichment of functional genes, and reduced genetic burdens, indicating that adaptive introgression has played a role in shaping the genomes of hybridizing species. This study provides insights into how different evolutionary forces have interacted in driving the evolution of the genomic variation landscape.

Genomic vulnerability to climate change in Quercus acutissima, a dominant tree species in East Asian deciduous forests.

Understanding the evolutionary processes that shape the landscape of genetic variation and influence the response of species to future climate change is critical for biodiversity conservation. Here, we sampled 27 populations across the distribution range of a dominant forest tree, Quercus acutissima, in East Asia, and applied genome-wide analyses to track the evolutionary history and predict the fate of populations under future climate. We found two genetic groups (East and West) in Q. acutissima that diverged during Pliocene. We also found a heterogeneous landscape of genomic variation in this species, which may have been shaped by population demography and linked selections. Using genotype-environment association analyses, we identified climate-associated SNPs in a diverse set of genes and functional categories, indicating a model of polygenic adaptation in Q. acutissima. We further estimated three genetic offset metrics to quantify genomic vulnerability of this species to climate change due to the complex interplay between local adaptation and migration. We found that marginal populations are under higher risk of local extinction because of future climate change, and may not be able to track suitable habitats to maintain the gene-environment relationships observed under the current climate. We also detected higher reverse genetic offsets in northern China, indicating that genetic variation currently present in the whole range of Q. acutissima may not adapt to future climate conditions in this area. Overall, this study illustrates how evolutionary processes have shaped the landscape of genomic variation, and provides a comprehensive genome-wide view of climate maladaptation in Q. acutissima.

Cutaneous nerve fibers participate in the progression of psoriasis by linking epidermal keratinocytes and immunocytes.

Recent studies have illustrated that psoriatic lesions are innervated by dense sensory nerve fibers. Psoriatic plaques appeared to improve after central or peripheral nerve injury. Therefore, the nervous system may play a vital role in psoriasis. We aimed to clarify the expression of nerve fibers in psoriasis and their relationship with immune cells and keratinocytes, and to explore the effect of skin nerve impairment. Our results illustrated that nerve fibers in psoriatic lesions increased and were closely innervated around immune cells and keratinocytes. RNA-seq analysis showed that peripheral sensory nerve-related genes were disrupted in psoriasis. In spinal cord hemi-section mice, sensory impairment improved psoriasiform dermatitis and inhibited the abnormal proliferation of keratinocytes. Botulinum toxin A alleviated psoriasiform dermatitis by inhibiting the secretion of calcitonin gene-related peptide. Collectively, cutaneous nerve fibers participate in the progression of psoriasis by linking epidermal keratinocytes and immunocytes. Neurological intervention may be a new treatment strategy for psoriasis.

Linked selection shapes the landscape of genomic variation in three oak species.

Natural selection shapes genome-wide patterns of diversity within species and divergence between species. However, quantifying the efficacy of selection and elucidating the relative importance of different types of selection in shaping genomic variation remain challenging. We sequenced whole genomes of 101 individuals of three closely related oak species to track the divergence history, and to dissect the impacts of selective sweeps and background selection on patterns of genomic variation. We estimated that the three species diverged around the late Neogene and experienced a bottleneck during the Pleistocene. We detected genomic regions with elevated relative differentiation ('FST -islands'). Population genetic inferences from the site frequency spectrum and ancestral recombination graph indicated that FST -islands were formed by selective sweeps. We also found extensive positive selection; the fixation of adaptive mutations and reduction neutral diversity around substitutions generated a signature of selective sweeps. Prevalent negative selection and background selection have reduced genetic diversity in both genic and intergenic regions, and contributed substantially to the baseline variation in genetic diversity. Our results demonstrate the importance of linked selection in shaping genomic variation, and illustrate how the extent and strength of different selection models vary across the genome.

Mupirocin blocks imiquimod-induced psoriasis-like skin lesion by inhibiting epidermal isoleucyl-tRNA synthetase.

BACKGROUND: The Isoleucyl-tRNA synthetase (IARS) catalyzes isoleucine to the corresponding tRNA, maintaining the accuracy of gene translation. Its role in psoriasis has been not investigated so far. In this study, we aimed to investigate the mechanisms underlying the efficacy of IARS inhibitor, mupirocin, treatment for psoriasis. METHODS: The expression of IARS was determined by immunofluorescence, Western blot and qRT-PCR in normal healthy control- and psoriatic human skin. An imiquimod (IMQ) -induced psoriasis-like skin disease model was used to study the phenotypes changed by an IARS inhibitor, mupirocin (MUP). Endotypes were analyzed by RNA-seq, R&D Luminex multi-factor technique, ELISA, immunofluorescence and flow cytometry. Additionally, the effect of MUP on epidermal keratinocytes (KCs) were conducted in-vitro in primary cultured human KCs. RESULTS: We found the expression of IARS was higher in psoriatic skin than in healthy controls. In IMQ-induced psoriasis-like C57BL/6 J mouse model, MUP reversed IMQ-induced keratinocytes proliferation, expression of inflammatory cytokines and infiltration of immune cells. Furthermore, in cultured human keratinocytes, MUP inhibited proliferation, but promoted apoptosis, which may be related with STAT3 signaling pathway. CONCLUSION: Our finding of blocking the infiltration of immune cells by inhibiting the formation of IARS, could be one mechanism to explain the effect of MUP in the treatment of psoriasis. Developing strategies targeting suppression IARS should open new perspectives for the treatment of psoriasis. Video Abstract.

Gradually increasing the dosing interval of Secukinumab for moderate to severe plaque psoriasis: A single-center, uncontrolled, prospective study in 36 weeks.

Secukinumab is a recombinant, fully human monoclonal anti-IL-17A antibody approved to treat moderate-to-severe psoriasis and psoriatic arthritis. Its effectiveness and safety have been confirmed, but a gradual increase in the secukinumab dosing interval has not been investigated. To assess the feasibility, efficacy, and safety of gradually increasing the secukinumab dosing interval; the interval duration was determined by changes in the Psoriasis Area and Severity Index scores. Patients with moderate-to-severe plaque psoriasis received secukinumab 300 mg subcutaneously at baseline and weeks 0, 1, 2, and 3. At week 4, the improvement from baseline PASI guided the next injection time until week 36. In total, 83 patients were recruited. PASI 75 was achieved by 80%, 96%, and 95% of patients at weeks 4, 12, and 36, respectively. PASI 90 was achieved by 54%, 95%, and 84% of patients at weeks 4, 12, and 36, respectively. PASI 100 was achieved by 28%, 89%, and 68% of patients at weeks 4, 12, and 36, respectively. The average PASI score (1.05 ± 1.83) was significantly lower at week 36 than at baseline. Most patients reached PASI 75 at week 36 in our modified study. This study may provide information for future biotherapies.

Inhibition of the INa/K and the activation of peak INa contribute to the arrhythmogenic effects of aconitine and mesaconitine in guinea pigs.

Aconitine (ACO), a main active ingredient of Aconitum, is well-known for its cardiotoxicity. However, the mechanisms of toxic action of ACO remain unclear. In the current study, we investigated the cardiac effects of ACO and mesaconitine (MACO), a structurally related analog of ACO identified in Aconitum with undocumented cardiotoxicity in guinea pigs. We showed that intravenous administration of ACO or MACO (25 µg/kg) to guinea pigs caused various types of arrhythmias in electrocardiogram (ECG) recording, including ventricular premature beats (VPB), atrioventricular blockade (AVB), ventricular tachycardia (VT), and ventricular fibrillation (VF). MACO displayed more potent arrhythmogenic effect than ACO. We conducted whole-cell patch-clamp recording in isolated guinea pig ventricular myocytes, and observed that treatment with ACO (0.3, 3 µM) or MACO (0.1, 0.3 µM) depolarized the resting membrane potential (RMP) and reduced the action potential amplitude (APA) and durations (APDs) in a concentration-dependent manner. The ACO- and MACO-induced AP remodeling was largely abolished by an INa blocker tetrodotoxin (2 µM) and partly abolished by a specific Na+/K+ pump (NKP) blocker ouabain (0.1 µM). Furthermore, we observed that treatment with ACO or MACO attenuated NKP current (INa/K) and increased peak INa by accelerating the sodium channel activation with the EC50 of 8.36 ± 1.89 and 1.33 ± 0.16 µM, respectively. Incubation of ventricular myocytes with ACO or MACO concentration-dependently increased intracellular Na+ and Ca2+ concentrations. In conclusion, the current study demonstrates strong arrhythmogenic effects of ACO and MACO resulted from increasing the peak INa via accelerating sodium channel activation and inhibiting the INa/K. These results may help to improve our understanding of cardiotoxic mechanisms of ACO and MACO, and identify potential novel therapeutic targets for Aconitum poisoning.

[Famous veteran traditional Chinese medicine doctors' medication rules in treating spermatorrhea].

To explore famous veteran traditional Chinese medicine( TCM) doctors' medication rules in treating spermatorrhea based on the medical cases about spermatorrhea collected from Hundred TCM Clinical Doctors of Hundred Years in China and Proven Cases and National Medical Master Test Case. Researchers extracted such data as medicinal and therapies from these cases according to the inclusion and exclusion criteria. Then,Excle 2010,SPSS Clementine 12. 0 and SPSS 22. 0 were adopted respectively for frequency analysis,association rules analysis,cluster analysis and factor analysis. Cluster analysis was carried out by Ochiai algorithm of binary variable data,one of the systematic clustering methods. And principal component analysis was used for factor analysis. Finally,27 medical cases and 41 prescriptions were included in total. The frequency analysis showed that the most common therapy was the astringent therapy( n = 28),which was followed by the tonifying method,tranquilizing method,heat-clearing method,damp-dispelling method and Qiregulating method. The top three kinds of high-frequency traditional Chinese medicines were Poria,Ostreae Concha and Dioscoreae Rhizoma. The association rules analysis found out 11 association rules of medicine pairs,23 association rules of medicine combinations of the three kinds of herbs and 6 association rules of medicine combinations of five kinds of herbs. Among them,the representatives were Rubi Fructus→Fossilia Ossis Mastodi,Rehmanniae Radix Praeparata + Corni Fructus→Dioscoreae Rhizoma,and Pinelliae Rhizoma→Citri Reticulatae Pericarpium,which showed the therapeutic characteristics of astringing,tonifying the kidney and replenishing essence,fortifying the spleen and dispelling dampness. Moreover,7 medicine groups with relevance were extracted from the tree map generated by cluster analysis,including " Phellodendri Chinensis Cortex and Anemarrhenae Rhizoma" and " Angelicae Sinensis Radix,Rehmanniae Radix,Bupleuri Radix and Glycyrrhizae Radix et Rhizoma",which demonstrated the effects of nourishing Yin and purging fire,tonifying and soothing the liver. Besides,totally 12 common factors were obtained according to factor analysis,including 14 drug combinations,like " Amomi Fructus,Anemarrhenae Rhizoma and Phellodendri Chinensis Cortex" and " Nelumbinis Stamen,Moutan Cortex,Poria and Scrophulariae Radix",which indicated the compatibility characteristics of tonifying the spleen and purging fire,dispelling dampness and clearing heat. In conclusion,data mining techniques( including frequency analysis,association rules analysis,cluster analysis and factor analysis) were used to comprehensively analyze the famous veteran TCM doctors' medication rules in treating spermatorrhea,which was helpful for guiding the clinical practice of treating spermatorrhea in TCM.

Impact of copy neutral loss of heterozygosity and total genome aberrations on survival in myelodysplastic syndrome.

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases with varying genetic aberrations. Half of MDS patients have normal karyotype, obscuring the underlying condition indicating a need for new markers for improved diagnostics and prognosis. We performed a retrospective review of sequential MDS patients who underwent chromosomal genetic array testing (CGAT) between November 2008 and March 2014. Total Genomic Aberration (TGA) scores, with and without copy-neutral loss of heterozygosity (cnLOH), were compared to pathology and clinical data. Of 68 MDS participants, 50 patients (73%) had abnormal CGAT results. 32% showedcnLOH, 41% had no cnLOH but displayed copy number aberration (CNAs). Of 26 patients with normal cytogenetics, 46% had clonal abnormalities by CGAT. Abnormal CGAT results were associated with lower overall survival (P=0.04). Overall survival in patients with TGA above the median (68.6 Mb) was significantly inferior to those below the median (HR=2.9, 95% CI=1.3-6.8, P=0.01). Furthermore, there was an observed association between increased TGA and increased dysplastic lineages (Ptrend=0.003). CGAT studies provide important findings that extend beyond current standard testing. Clinical utility of CGAT includes improved diagnostic yield, correlation of extent of TGA and increased dysplastic features, and survival.

[A real-time fluorescence quantitative PCR method for source identification of Crocus sativus and Carthamus tinctorius].

The specific PCR primer was designed base on ITS2 sequence in GenBank, and we developed a SYBRGreen real-time fluorescence quantitative PCR system for identification of Crocus sativus and Carthamus tinctorius source. Compared with Chinese herbal medicine DNA barcode technique, this method showed characteristics of shorter time, higher specificity and sensitivity. Using this method to detect 15 samples, 4 were C. sativus, 8 were C. tinctorius, and the other 3 samples were none of them. The result was in accordance with Chinese herbal medicine DNA barcode. This study lays the foundation for identification of related Chinese medical materials.

Genetic Variants in the ELOVL5 but not ELOVL2 Gene Associated with Polyunsaturated Fatty Acids in Han Chinese Breast Milk.

The present study was designed to examine the contributions of the fatty acid elongase (ELOVL) gene polymorphisms to the levels of polyunsaturated fatty acids (PUFAs) in breast milk. Two hundred and nine healthy Han Chinese mothers were included in the study. Carriers of minor alleles of SNPs (rs2397142 and rs9357760) in ELOVL5 were associated with higher levels of linoleic acid (LA), dihomo-γ-linolenic acid (DGLA), arachidonic acid (AA), docosatetraenoic acid (DTA), docosahexenoic acid (DHA), while in rs209512 of ELOVL5 the carriers of minor alleles had lower levels of DTA compared to major homozygote alleles (P ranged from 0.004-0.046), and genetically explained variability ranged from 3.2% for eicosapentaenoic acid (EPA) to 6.0% for LA. Our findings demonstrated that common variation in ELOVL5 gene encoding rate-limiting enzymes in the metabolism of PUFAs contribute to the PUFAs in breast milk.

Exogenous melatonin for sleep disorders in neurodegenerative diseases: a meta-analysis of randomized clinical trials.

The purpose of this work is to investigate the efficacy of exogenous melatonin in the treatment of sleep disorders in patients with neurodegenerative disease. We searched Pubmed, the Cochrane Library, and ClinicalTrials.gov, from inception to July 2015. We included randomized clinical trials (RCTs) that compared melatonin with placebo and that had the primary aim of improving sleep in people with neurodegenerative diseases, particularly Alzheimer's disease (AD) and Parkinson's disease (PD). We pooled data with the weighted mean difference in sleep outcomes. To assess heterogeneity in results of individual studies, we used Cochran's Q statistic and the I (2) statistic. 9 RCTs were included in this research. We found that the treatment with exogenous melatonin has positive effects on sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI) in PD patients (MD: 4.20, 95 % CI: 0.92-7.48; P = 0.01), and by changes in PSQI component 4 in AD patients (MD: 0.67, 95 % CI: 0.04-1.30; P = 0.04), but not on objective sleep outcomes in both AD and PD patients. Treatment with melatonin effectively improved the clinical and neurophysiological aspects of rapid eye movement (REM) sleep behavior disorder (RBD), especially elderly individuals with underlying neurodegenerative disorders. This meta-analysis provided some evidence that melatonin improves sleep quality in patients with AD and PD, and melatonin can be considered as a possible sole or add-on therapy in neurodegenerative disorders patients with RBD.

N-[4-(4,6-Dimethyl-2-pyrimidinyloxy)-3-methylphenyl]-N'-[2-(dimethylamino)] benzoylurea induces cell-cycle arrest and apoptosis in human cancer cells.

N-[4-(4,6-Dimethyl-2-pyrimidinyloxy)-3-methylphenyl]-N'-[2-(dimethylamino)]benzoylurea (SUD) is a novel synthesized benzoylurea derivative. We selected several human cancer cell lines to investigate whether SUD can inhibit the growth of cancer cells. We selected the liver cell line L-02 to investigate the effect of SUD on the normal cells. Flow cytometric analysis was used to detect the effect of SUD on cell cycle, Hoechst 33258 staining was used to evaluate the apoptosis induced by SUD, real-time fluorescence quantitative PCR was used to investigate the expression of the cell cycle-relevant and apoptosis-relevant genes, a reactive oxygen species (ROS) assay was used to observe the production of ROS, and western blotting was used to determine the level of cell cycle-relevant and apoptosis-relevant proteins. According to the results of the MTT assay, the growth of human cancer cell lines was significantly inhibited by SUD treatment in a time-dependent and concentration-dependent manner; however, the growth of human normal cells was not significantly inhibited by SUD treatment. The results of flow cytometric analyses showed that SUD induced cell-cycle arrest at the G2-phase in MCF-7 cells and at the G1-phase in BGC-823 cells. The results of Hoechst 33258 staining showed that SUD induced apoptosis in MCF-7 and BGC-823 cells. The results of the ROS assay showed that the production of ROS was increased by SUD in MCF-7 and BGC-823 cells. Our research suggests that the growth-inhibitory effect of SUD on MCF-7 cells was related to G2-phase arrest, which was associated with the upregulated expression of p53 and Chk1 proteins, and downregulation of the cyclin B1 gene, cdc25a, and cyclin-dependent kinase 1 (CDK1) proteins; the growth-inhibitory effect of SUD on BGC-823 cells was related to G1-phase arrest, which was associated with upregulation of the p53 gene and Chk1 protein and downregulation of cdc25a protein and the CDK4 gene. SUD also induced apoptosis in MCF-7 and BGC-823 cell lines through the mitochondrial pathway in a p53-dependent manner.

[m-Nisodipine inhibited 5-HT-induced proliferation of rat PASMCs through Rho/ROCK signal pathway].

This paper is to report the exploration of the activation of Rho/ROCK signal pathway in 5-HT-induced proliferation of rat pulmonary artery smooth muscle cells (PASMCs) and the inhibitory effect of m-Nis on this pathway. PASMCs were cultured with the explant technique. MTT assay was used to explore the proliferation of PASMCs after 5-HT treated for different time and the intervening effect of m-Nis. RT-PCR and Western blot were used respectively to explore the mRNA expression of RhoA, ROCK1 and the protein expression of p-MYPT1 in 5-HT-treated PASMCs and intervening effect of m-Nis. The results of MTT assay suggested that 5-HT (1 µmol · L(-1)) treatment for 12-72 h significantly induced the proliferation of rat PASMCs (P<0.05 or P < 0.01), which were inhibited by m-Nis (1 x 10(-5), 1 x 10(-6), l x 10(-7), 1 x10(-8) mol · L(-1)) in dose-dependent manners (P < 0.05 or P < 0.01). Similarly, the mRNA expression of RhoA, ROCK1 and the protein expression of p-MYPT1 were also inhibited by m-Nis in different degrees (P < 0.05 or P < 0.01). Thus, the results of this study suggested that Rho/ROCK pathway played an important role in 5-HT-induced proliferation of rat PASMCs, m-Nis inhibited 5-HT-induced proliferation obviously, which may be related to the blockage of Rho/ROCK signal pathway.

Glycyl-tRNA Synthetase Induces Psoriasis-Like Skin by Facilitating Skin Inflammation and Vascular Endothelial Cell Angiogenesis.

Psoriasis is characterized by excessive keratinocyte proliferation and immunocyte infiltration, but the underlying pathogenesis remains unclear. Aminoacyl-tRNA synthetases are universally expressed enzymes that catalyze the first step of protein synthesis. Glycyl-tRNA synthetase (GARS) is a member of the aminoacyl-tRNA synthetase family. In addition to its canonical function, we found that GARS was overexpressed in the serum and skin lesions of patients with psoriasis. Moreover, GARS was highly expressed in human skin keratinocytes, and GARS knockdown in keratinocytes suppressed cell proliferation and promoted apoptosis through NF-κB/MAPK signaling pathway. Moreover, intradermal injection of recombinant GARS protein caused skin thickening, angiogenesis, and IFN/TNF-driven skin inflammation. Intriguingly, the reported functional receptor for GARS, cadherin 6 (CDH6), was specifically expressed in vascular endothelial cells, and we found that keratinocyte-derived GARS promotes inflammation and angiogenesis of vascular endothelial cells through CDH6. In addition, intradermal injection of GARS aggravated the phenotype and angiogenesis in imiquimod-induced psoriasiform dermatitis models, whereas the psoriatic phenotype and angiogenesis were relieved after knockdown of GARS by adeno-associated virus. Taken together, the results of this study identify the critical role of GARS in the pathogenesis of psoriasis and suggest that blocking GARS may be a therapeutic approach for alleviating psoriasis.

SPRY1 Deficiency in Keratinocytes Induces Follicular Melanocyte Stem Cell Migration to the Epidermis through p53/Stem Cell Factor/C-KIT Signaling.

The function and survival of melanocytes is regulated by an elaborate network of paracrine factors synthesized mainly by epidermal keratinocytes (KCs). KCs and melanocytes respond to UV exposure by eliciting a tanning response. However, how KCs and melanocytes interact in the absence of UV exposure is unknown. In this study, we demonstrate that after SPRY1 knockout in epidermal KCs, melanocyte stem cells in the hair follicle exit the niche without depleting the pool of these cells. We also found that melanocyte stem cells migrate to the epidermis in a p53/stem cell factor/C-KIT-dependent manner induced by a tanning-like response resulting from SPRY1 loss in epidermal KCs. Once there, these cells differentiate into functional melanocytes. These findings provide an example in which the migration of melanocyte stem cells to the epidermis is due to loss of SPRY1 in epidermal KCs and show the potential for developing therapies for skin pigmentation disorders by manipulating melanocyte stem cells.

Chromosome-scale genome assembly of sweet tea (Lithocarpus polystachyus Rehder).

Lithocarpus, with >320 species, is the second largest genus of Fagaceae. However, the lack of a reference genome limits the molecular biology and functional study of Lithocarpus species. Here, we report the chromosome-scale genome assembly of sweet tea (Lithocarpus polystachyus Rehder), the first Lithocarpus species to be sequenced to date. Sweet tea has a 952-Mb genome, with a 21.4-Mb contig N50 value and 98.6% complete BUSCO score. In addition, the per-base consensus accuracy and completeness of the genome were estimated at 60.6 and 81.4, respectively. Genome annotation predicted 37,396 protein-coding genes, with repetitive sequences accounting for 64.2% of the genome. The genome did not undergo whole-genome duplication after the gamma (γ) hexaploidy event. Phylogenetic analysis showed that sweet tea diverged from the genus Quercus approximately at 59 million years ago. The high-quality genome assembly and gene annotation resources enrich the genomics of sweet tea, and will facilitate functional genomic studies in sweet tea and other Fagaceae species.

Keratinoctye-neuro-immune-units (KNICUs): collaborative impact on the initiation and maintenance of psoriasis.

The skin is the outermost barrier that separates the human body from the external environment. In psoriasis, immune cells reside within or infiltrate the epidermis to form the epidermal (epithelial) immunological microenvironment (EIME) and engage in complex interactions with keratinocytes, nerves, and microbiota. The proposed hypothesis is that psoriasis is a chronic inflammatory disease mainly mediated by a specific inflammatory environment composed of keratinocyte-neuro-immune cell units (KNICUs). These KNICUs arise from the interaction between activated epidermal keratinocytes, nerves, immune cells, and the skin microbiota, forming a complex interaction framework. Multiple units gather to complete the circulatory and amplified loops, consequently serving as a group army to initiate and maintain psoriasis.