AIM Neurodevelopmental and clinical problems in childhood often precede adult Schizophrenia Spectrum Disorders. We investigated if children attending a psychiatric clinic presented more cognitive and motor alterations if there was a family history of Schizophrenia Spectrum Disorder (FHR-SZ) diagnosis. We also searched if there was a relationship between clinical scores in CBCL Thought Problems and increased problems in motor and cognitive performance. METHODS Seventy-five children (aged 7 to 16; mean 12 y/o; 53% males) were recruited (45 reported FHR-SZ -seven of them first degree-). They completed the Wechsler Intelligence Scale for Children (WISC-V), Movement Assessment Battery for Children (MABC-2), social cognition from the Developmental NEuroPSYchological Assessment (NEPSY-II) and Conners Continuous Performance Test (CPT-3). Parents completed the Child Behaviour Checklist (CBCL) and Behaviour Rating Inventory of Executive Function (BRIEF-2). RESULTS A neurodevelopmental disorder was the primary diagnosis in 65% (mainly ADHD). Motor performance and emotion recognition were below expected by age, and IQ was average. No relevant differences in relation to family history were found. Patients with high scores in the CBCL Thought Problems subscale (n=38) were older, more often presented a diagnosis of combined ADHD, performed worse in Emotion Recognition, had Executive Function problems and clinical symptoms in subscales Anxious/Depressed, Withdrawal/Depressed and Attention problems. CONCLUSIONS In children attending a psychiatric clinic, CBCL Thought Problems subscale associates with more internalizing clinical problems, executive function, and social cognition difficulties. Larger samples and first-degree FHR-SZ probands are needed to delineate risk profiles.

Solanum species of the Leptostemonum clade were mapped, and predictions made on the distribution and possible habitats using a set of environmental variables. The variables were temperature, rainfall, slope, soil and land use/cover. During field surveys, location presence data (geocoded with Germin S90 GPS) was collected. Additional data were obtained from herbarium specimens kept at Makerere University Herbarium and others obtained from the Global Biodiversity Information Facility. Distribution maps were generated in ArcMap software. Using MaxEnt software (version 3.3.3), spatial distribution models were generated. Model evaluation was based on the generated Area Under Curve (AUC) of both the testing and training gain data. The Jackknife test was used to assess the importance of each environmental variable in predicting species occurrence. Eighteen species were analyzed out of the 20 known to occur in the country. Solanum chrysotrichum was recorded as a new species to Uganda, thus, a new total of 21 species known for the country. Presence of S. forskalii in Uganda was confirmed. Most of the species occur in disturbed habitats in the land use/cover areas defined as croplands, tree cover and grasslands. The highest species richness was recorded in south western Uganda with a total of 11 species. Karamoja had unique diversity with species restricted to the region and these included S. forskalii, S. lanzae, S. coagulans and S. hastifolium. The environmental parameters selected for the study when used in combination had a good fit in predicting the occurrence of species as revealed by the high AUC values. Temperature and rainfall were the most useful variables in predicting occurrence of Solanum species. Karamoja region and south western Uganda are hotspots for conservation of the spiny Solanum. Periodic field surveys should be carried out to assess the effect of climate change and anthropogenic disturbance on the occurrence of the species.

Introduction:This study focused on investigating the effects of LncRNA DANCR regulation of Keap1-Nrf2/ARE pathway on inflammation and oxidative stress in RA. Methods:The levels of LncRNA DANCR/miR-486-3p/ Keap1 in peripheral blood of 30 RA groups and 30 normal subjects were examined, and the association of LncRNA DANCR with inflammatory indicators of rheumatoid arthritis was investigated. We construct overexpression plasmids and small interfering RNAs of LncRNA DANCR to investigate the relationship between LncRNA DANCR and FLSs viability and migration in rheumatoid arthritis, as well as the effects on cellular oxidative stress factors and Keap1-Nrf2/ARE pathway; molecular biology analysis was used to predict microRNAs that can bind LncRNA DANCR, and luciferase verified the binding sites of LncRNA DANCR with Keap1 and miR-486-3p; to further refine the gene and protein expression results, we used RT- qPCR and immunoblotting assays . Results: In both groups of PBMCs, the expression levels of LncRNA DANCR and Keap1 mRNA were higher in the rheumatoid arthritis group than in the normal control group, and the opposite was true for miR-486-3p; LncRNA DANCR was positively correlated with TAOC, IL6, RF, IL17, anti-CCP, MDA, and SOD, but not with ESR, DAS28, IL11, and SOD, DAS28, IL11, ROS, CRP were negatively correlated; overexpression of lncRNA DANCR stimulated the Keap1-Nrf2/ARE pathway, decreased the expression of IL10, SOD, TAOC, and increased the expression levels of MDA, IL11, IL-17, PD-L1, and silencing of lncRNA DANCR was the opposite, but knockdown of miR- 486-3p or overexpression of keap1 reversed the expression of the above-mentioned inflammatory and oxidative factors. In addition, pcDNA-DANCR clearly showed stronger cell invasion and migration ability and exacerbated its inflammatory response, we verified their targeting relationship using dual luciferase. Conclusion: The low-expressed lncRNA DANCR may regulate the Keap1-Nrf2/ARE pathway and suppress the inflammatory and oxidative responses in RA patients.

Background: Pulmonary thromboembolism (PTE) is a common complication of SARS-CoV-2, which raises the COVID-19 disease’s fatality rate from 3% to 45%. Nevertheless, due to fairly indistinguishable clinical symptoms and a lack of validated clinical prediction models, PTE diagnosis in COVID-19 patients is challenging. This study aims to investigate the applicability of hematological indices to predict PTE incidence and its severity in SARS-CoV-2 patients. Methods: A retrospective cohort study was conducted on hospitalized patients with a confirmed diagnosis of SARS-CoV-2 infection who underwent CT angiography to assess probable PTE in them. The correlation between CBC parameters one day prior to CT angiography and CT angiography outcomes, and simplified Pulmonary Embolism Severity Index (s-PESI) was investigated. Results: We discovered that among individuals with a probable PTE, males and those with higher platelet-to-lymphocyte (PLR) and neutrophil-to-lymphocyte (NLR) ratios had a greater likelihood of PTE incidence. PLR was a significant and independent predictor of PTE. Moreover, a higher neutrophil count was associated with a higher s-PESI score in COVID-19 patients developing PTE. Conclusions: Among haematological indices, NLR and more precisely PLR are cost-effective and simply calculable markers that can assist physicians in determining whether or not COVID-19 patients with clinically probable PTE require CT angiography and the higher neutrophil count can be employed as an indicator of PTE severity in COVID-19 patients. Further large multicenter and prospective studies are warranted to corroborate these observations.

In this study, we aimed to assess the interactions of mothers and fathers with their children diagnosed with Autism Spectrum Disorder (ASD), and compare the fathers and mothers in terms of emotional availability. Children, who applied to the Infant Mental Health Unit between January 2019-March 2021 and diagnosed with ASD, and their parents without any clinical diagnosis were included. The study was conducted with a total of 64 infants, 41 (64.1%) boys and 23 (35.9%) girls aged 7-60 months. According to the results obtained, it was determined that the mothers were more sensitive and better in structuring the content of play compared with the fathers. It was noted that the fathers were more hostile than the mothers. The results obtained were discussed in the literature.

Aliphatic alcohol hydroxyl or phenolic hydroxyl as a directing group has proved to be a versatile functional group and widely used in organic synthesis, however, ortho-benzyl alcohol used as a directing group has never been reported. We herein described an unprecedented multicomponent tandem reaction to assemble structurally diverse pyrroloquinolinediones (28 examples, 70-87% yields) starting from readily available raw materials under mild conditions. Significantly, this unique transformation involved an ortho-benzyl alcohol as directing group to promote a cascade reaction to the synthesis of functionalized aminomaleimides (29 examples, 71-91% yields), which then underwent I2-oxidized tandem annulations. This concise, environmentally friendly and practical protocol to the preparation of a series of potentially valuable N-fused heterocycles involved the formation of new multiple chemical bonds (C=N, 2C-N, C-C) in a one-pot fashion.

Syneilesis aconitifolia, with medicinal value and salt-alkali tolerance, is a potential ground cover and decorative material in gardens. To investigate the influence of arbuscular mycorrhiza (AM) fungi on the colonization and salt-alkali tolerance of S. aconitifolia, a pot experiment was conducted and the AM fungi community existing in Songnen salt-alkali grassland was selected as the inoculation. After 90 days of cultivation, NaCl and NaHCO3 solutions (50 mmol/L, 100 mmol/L, and 200 mmol/L) were applied for 10 days, subsequently, the mycorrhizal colonization, biomass, relative water content, chlorophyll content, malondialdehyde content, antioxidant enzyme activities and the level of osmotic regulation were measured. The results showed that the colonization rate and intensity decreased under saline-alkali stress, and the adaptability of AM fungi in low-concentration alkali stress was higher than that of salt stress. AM fungi could increase the biomass, relative water content, and chlorophyll content, and decrease the malondialdehyde content of S. aconitifolia to some extent. With the increase of salt or alkali solution concentration, AM fungi not only upregulated the activity of the antioxidant system, but also increased the content of osmotic regulatory substances, which indicated that AM fungi could improve the saline-alkali tolerance of S. aconitifolia. Multivariate analysis of variance (ANOVA) and radar map analysis showed that the mechanisms of resistance to salt stress and alkali stress were not the same in S. aconitifolia. In addition, the regulation of AM fungi on salt-alkali resistance of S. aconitifolia was also different. The results provided a scientific basis for the symbiosis between the local AM fungal community and S. aconitifolia, as well as data support for the restoration of saline habitat using S. aconitifolia with high medicinal value.

The objective of this study was to examine the effect of Prdm1 inhibition or overexpression on levels of CD4+T cells, and islet and skin transplantation, in mice. Mice CD4+T cells (from the spleen) were cultured, purified and enriched, and then transfected with shRNA lentiviral vector Prdm1-RNAi-GFP and overexpression lentiviral vector LV-Prdm1-puro. Murine cytokine levels were then measures. Murine islet transplantation and skin transplantation model were established, and the mice were injected with CD4+T cells transfected with lentivirus Prdm1-RNAi-GFP or LV-Prdm1-puro. Levels of IFN-γ and IL-10 were measured, and the survival times of the grafts were measured and compared. The expressions of IL-4 and IL-10 were up-regulated after overexpression of Prdm1, and the expression of IFN-γ was up-regulated in CD4+T cells after inhibition of Prdm1 (P<0.05). Overexpression of Prdm1 resulted in longer islet and skin graft survival and better graft function, while inhibition of Prdm1 shortened islet and skin graft survival. Microscopic examination showed evidence of mild rejection of islet and skin grafts in the LV-Prdm1-puro, but severe rejection in the Prdm1-RNAi group. Taken together, the results indicate that overexpression of Prdm1 can prolong graft survival and induce the formation of transplant immune tolerance via secretion of Th2 cytokines by CD4+T cells. Inhibition of Prdm1 can promote transplant rejection and shorten graft survival via secretion of Th1 cytokines.

Open Dialogue Approach is a collaborative intervention and framework for using with service users with complex mental health challenges such as psychosis. The aim of the study was to explore nurses’ experiences when using the approach through an interpretative phenomenological analysis, using semi structured interviews conducted with five mental health nurses. Data were thematically analysed and organised within three themes: • Experiential learning vs formalised training. • Efficacy of the approach: o Therapeutic relationship, o Service user empowerment o Openness/ transparency. • Tolerance of uncertainty principle; perceived as a barrier to implementing in UK. A key finding from the study was that participants (mental health nurses) disclosed that they felt conflicted when using the approach, because of the principle of tolerating uncertainty, that advocates minimal patient record keeping; which is at odds with current legislation (UK and Wales) that stipulates clinicians must keep full and accurate patient records. However, the study also indicates a mechanism for overcoming this and highlights the approach’s effectiveness by increasing service user control and empowerment of the service user and openness/ transparency from clinicians. If this is employed, then it appears that the principle of tolerance of uncertainty can be ameliorated to fit with UK legislation. Open Dialogue Approach is also reported as being effective by all of the participants within this study, but it will require further research to demonstrate this effectiveness within the UK to the wider clinical body and policy developers.

Background: To investigate the distribution of bacterial pathogens of lower respiratory tract infection (LRTI) in hospitalized elderly patients during the COVID-19 epidemic and to explore the influence of COVID-19 on the distribution of bacterial pathogens, in order to provide guidance for clinical diagnosis. Methods: Specimens of sputum from elderly LRTIs patients at Fuding Hospital of China were collected from October 2022 to January 2023. Cultures and identification were done, and RT-PCR was employed to detect SARS-Cov-2 nucleic acid. Results: A total of 195 isolates were characterized in 163 sputum samples of consecutive hospitalized elderly patients, of which 11.3% were Gram-positive bacteria and 88.7% Gram-negative. The top of frequently isolated pathogens were Klebsiella pneumonia (30.3%), Pseudomonas aeruginosa (19.0%), Acinetobacter baumannii (12.8%), Stenotrophomonas maltophili, (7.7%), Escherichia coli (7.2%). According to the results of novel coronavirus nucleic acid detection, the 163 patients were divided into COVID-19 group and non-COVID control (CNT) group. The comparison of bacterial distribution between the groups revealed that Stenotrophomonas maltophilia was lower in the COVID-19 than in the CNT group, while Acinetobacter baumannii was higher in the COVID-19 group, and the difference was statistically significant (P < 0.05). Conclusion: The major bacteria identified in sputum culture of hospitalized elderly patients were Klebsiella pneumonia, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, and Escherichia coli. Furthermore, the distribution of Stenotrophomonas maltophilia and Acinetobacter baumannii between the COVID-19 and CNT groups was found to be significantly different (P< 0.05), while there were no significant differences in the distribution of other bacteria.

Aims: This study aimed to assess the relationship between CCI and 90-day mortality among AKI patients with CRRT. Methods: CCI is a scoring system predicting short- and long-term mortality risk. A secondary analysis of the Dyrad database from 2009 to 2016 was carried out. Demographic and clinical data were collected at baseline, while mortality was calculated 90 days after CRRT. Statistical analyses were performed using R and SPSS. This study enrolled 826 patients including 496 (60%) males and 330 (40%) females with an overall median age of 63.42 years. They were divided into low-, medium-low-, medium- and high-risk groups according to different CCI scores (0, 1-2, 3-4, >4) at baseline. Results: Univariate and multivariate analyses both showed positive correlation between CCI and mortality risk (p<0.05). Kaplan-Meier analysis showed increased mortality over groups with increased levels of mortality risk. For each point increase in CCI, the 90-day mortality risk would increase by 13.3% if CCI is less than 4.037 (p<0.001) and increase by 1.3% if CCI went beyond 4.037 (p=0.7855). Conclusions: CCI is significantly associated with 90-day mortality in AKI patients with CRRT. Further studies may focus on more recent data from various data repositories and compare CCI against other scoring systems to ensure its validity in predicting prognosis among AKI patients with CRRT in clinic.

A document by Yisma Tsige Yeshanew. Click on the document to view its contents.

Background Extracellular matrix (ECM) degradation, chondrocyte inflammation, and cellular senescence contribute to the pathology of osteoarthritis (OA). Empagliflozin, a selective inhibitor of sodium-glucose cotransporter-2 (SGLT2), has been reported to show the anti-inflammatory properties in several conditions. However, whether empagliflozin can be used to improve OA is still unknown. Methods The protective effects and underlying mechanism of empagliflozin in OA were investigated in vitro and in vivo. Cell viability, catabolic markers, inflammatory mediators, cellular senescence level, cartilage degeneration were evaluated by CCK-8 assay, safranine O staining, ELISA, real-time PCR, western blot, β-galactosidase Staining, and histological analysis. Results We found that empagliflozin significantly downregulated the expression of catabolic enzymes (MMP9 and MMP13), and decreased the expression of inflammatory mediators (NO, PGE2, IL-6, COX2, and INOS), and reduced the cellular senescence level in IL-1β-treated chondrocytes by inhibiting the nuclear factor kappa-B (NF-κB) signaling pathway. What’s more, empagliflozin prevented cartilage degeneration in DMM-induced OA mice model with significant lower OARSI grade. Conclusion Our findings reveal that empagliflozin inhibited chondrocytes ECM degradation, inflammation and cellular senescence in vitro and prevented cartilage degeneration in vivo by suppressing NF-κB signal pathway, indicating a therapeutic potential in OA treatment.

Meningitis, a disease that commonly manifests in African meningitis belt, continues to be a public health problem as it is a fatal disease that leave survivors with long-term effects. Most cases of meningitis are due to bacterial and viral infection, although parasites, fungus, cancer, drugs, and immune disorders can rarely cause meningitis. Stiff neck, high temperature, light sensitivity, disorientation, headaches, and vomiting are the most typical symptoms of meningitis. Niger being in African meningitis belt, has been impacted by many meningitis outbreaks. Since 2015, a total of 20 789 cases and 1369 fatalities (CFR 6.6%) have been documented in Niger. In contrast to earlier seasons, the current outbreak of meningitis in Niger exhibits both an increase in the number of cases and a rise in the growth rate. A total of 559 instances of meningitis, including 18 fatalities (overall CFR 3.2%), were reported in the Zinder Region, southeast of Niger, from 1 November 2022 to 27 January 2023, compared to 231 cases reported from 1 November 2021 to 31 January 2022. In the current outbreak, the Neisseria meningitidis serogroup C (NmC) is responsible for the majority of laboratory confirmed cases (104/111; 93.7%). To organize the response to the pandemic, a global team from the WHO and other partners, including MSF and UNICEF, has been sent out in Niger. Even though there are many challenges in battle against meningitis in Niger, immunization, antibiotics administration and strong disease surveillance are recommended techniques to cope with the current meningitis outbreak in Niger.

More than 250 million children will not meet their developmental potential due to poverty and malnutrition. Psychosocial stimulation (PS) has shown promising effects for improving development in children exposed to severe acute malnutrition (SAM) but programs are rarely implemented. In this study, we used qualitative methods to inform the development of a PS programme to be integrated with SAM treatment in Mwanza, Tanzania. We conducted in-depth interviews with seven caregivers of children recently treated for SAM and nine professionals in early child development. We used thematic content analysis and group feedback sessions and organised our results within the Nurturing Care Framework. Common barriers to stimulate child development included financial and food insecurity, competing time demands, low awareness about importance of responsive caregiving and stimulating environment, poor father involvement, and gender inequality. Caregivers and professionals suggested that community-based support after SAM treatment and counselling on PS would be helpful, e.g. how to create homemade toys and stimulate through involvement in everyday chores. Based on the findings of this study we developed a context-relevant PS programme. Some issues identified were structural highlighting the need for programmes to be linked with broader supportive initiatives.

Using medicinal plants for healthcare practices in indigenous communities presents a chance to discover natural remedies. This study aims to provide a detailed account of the ethnoveterinary knowledge of medicinal plants utilized for therapeutic purposes. From December 2020 to December 2021, a field investigation was carried out within the Oulad Heriz tribes. Two hundred local farmers were interviewed using open-ended, semi-structured discussions, free listing and focus groups. A total of one hundred medicinal plants belonging to 87 genera and 33 families were discovered to be employed for ethnoveterinary purposes. Rosmarinus officinalis L. was the most frequently utilized ethnoveterinary plant species in the study area (70 citations). Leaves are shown to be the most commonly employed plant parts (55%). However, digestive disorders were the most often mentioned ailment (33 medicinal plants, 599 citations), and most herbal medicines were made by infusion (46.2%). According to the current investigation findings, local farmers in Oulad Heriz have continuous knowledge of ethnoveterinary plants. This ethnoveterinary medicinal heritage needs to be incorporated with contemporary medicine to use plants and their products as potentially viable medications for various cattle illnesses.

Empathy plays an important role in children’s early social-emotional development. However, there are not many instruments available for measuring the different aspects/levels of empathy in preschool children. Moreover, few studies examined the validity of the existing measures for empathy in Chinese children. The present study tested the Chinese version of the Empathy Questionnaire (EmQue) upon a group of Chinese preschool children (N = 182) aged from 2 to 6 years. The Chinese EmQue is a parent-report translated from Dutch that assesses the behavioral manifestations of three distinct levels of empathy: emotion contagion, attention to others’ feelings, and prosocial behaviors among preschool children. Confirmatory factor analysis showed satisfactory goodness-of-fit indexes for a three-level structure with 19 loading items. The results of concurrent validity showed that the three levels of empathy were functioning differently in the early social-emotional development. We could conclude that the 19-item Chinese EmQue is a valid, reliable instrument for measuring empathy in 2- to 6-year-old children in the Chinese context.

Psammogeton canescens subsp. cabulicus Wagenitz (Apiaceae), a new distributional record for the Flora of India is investigated in this work from Jammu district Jammu and Kashmir. Some intriguing plants were collected from the district Jammu between 2010 and 2018 as part of a field survey in the south-west regions, district Jammu of the state of Jammu and Kashmir. The taxa differing from others subspecies of the species by having lateral branches far exceeding the main axis, bracts ±2 mm long, bracteoles ±1.3 mm long, fruit 1.4 to 2.0 mm long. For ease in identification, a brief description, a key to subspecies of Psammogeton canescens and photographs of the plant and its parts are provided.

This paper reviews the molecular classification of Sapindaceae, by collating the existing wood anatomical details of each tribe. The comparison is restricted to how much the wood anatomical distribution is supported or conflicts with the current subfamilial and tribal shifting of the genera, from their traditional placement in Radlkofer's classification. The presence of simple vessel perforations, alternate vessel wall pitting, and vessel-ray and vessel-parenchyma pits similar in size, shape, and arrangement to the inter vessel pits, and fibers of the libriform type with simple to minutely bordered pits in both Aceraceae and Hippocastanceae clades strongly support their embedding under Sapindaceae. The present analysis also confirms the placement of the Delavaya group as the basal clade under Sapindoideae, the retrieval of Conchopetalum to the Dodonaeoideae subfamily, and the definition of Hippocastanoideae as a temperate subfamily. The wood anatomical similarity of the Dodonaeoideae genera with the other three subfamilies points towards the polyphyly of the Dodonaeoideae subfamily and is comparable with the polyphyly concept of Radlkofer. The current circumscription of Tinopsis and Neotina under Tina is also agreed by their homogenous Cupania type wood anatomy. The systematic affinities of the traditional Schleichereae and Cupanieae tribe are also revealed in their Cupania type wood anatomy. Albeit the wood anatomy agrees with the wider circumscription of Sapindaceae, the wood anatomy details for the majority of the tribes go in line with that of the traditional Radlkofer's concept.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic with serious complications. After the coronavirus disease 2019 (COVID-19), several post-acute COVID-19 syndromes (PACSs) and long-COVID sequels were reported. PACSs involve many organs, including the nervous, gustatory, and immune systems. One of the PACSs after SARS-CoV-2 infection and vaccination is Guillain-Barré syndrome (GBS). There is a lower chance of getting GBS after a SARS-CoV-2 infection compared to other infections. However, the high prevalence of COVID-19 and severe complications of GBS, e.g., autonomic dysfunction and respiratory failure, highlight the importance of post-COVID-19 GBS. It is while patients with simultaneous COVID-19 and GBS seem to have higher admission rates to the intensive care unit, and demyelination is more aggressive in post-COVID-19 GBS patients. SARS-CoV-2 can trigger GBS via several pathways like direct neurotropism and neurovirulence, microvascular dysfunction and oxidative stress, immune system disruption, molecular mimicry, and autoantibody production. This review discusses the most recent evidence regarding the molecular and cellular mechanisms of GBS after SARS-CoV-2 infection and vaccination.

Ransomware is a menace to the vibrant digital ecosystem. The exponential growth in ransomware attacks, its detrimental impacts, and the ever-changing methods adopted by threat actor groups demands a focused understanding of the evolution of ransomware. This would help the organizations devise novel defensive frameworks and security controls against the modern ransomware. In this work, the impacts and evolution of ransomware through different phases up to its current form are detailed. Further, based on the study and analysis of the most prevalent modern ransomware variants, their most used tactics, techniques and procedures (TTPs) are identified as per the MITRE ATT&CK model. This acts as a platform to propose a generic attack model for ‘modern ransomware’. Building on the existing MITRE mitigation, D3FEND-based approaches and considering the resource and budget constraints of organizations, a simplified three-tier defensive model that is cost-effective and implementable is put forward. Thus, this work aims to open avenues for understanding the TTPs, and attack methodology of ‘modern ransomware’, thereby developing feasible and implementable defensive security controls.

Hemiramphus far (Forsskål, 1775) is a marine non-migratory fish, caracterised by a greatly prolonged, beak-like lower jaw, a short upper jaw, native in the Indo-West Pacific, but which has been observed in different places in the Mediterranean, due to the different climatic changes, as is the case of the present report in the east coast of Algeria .

NR4a1 has been demonstrated to exert a protective role in various chronic inflammatory disease. The underlying mechanism has yet to be clarified. This research aimed to explore the anti-inflammatory mechanism of NR4a1on macrophage through bioinformatics analysis and further verified by a series of experiments. In this study, The GSMs (GEO samples) that LPS(lipopolysaccharide) treated macrophage derived from wild type and NR4a1 knockout mice were extracted from GSE68167 gene expression profiles in Gene Expression Omnibus (GEO) database. DEGs (Differentially expressed genes) screened out. The gene ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes pathway) enrichment were conducted. PPI (Protein-protein interaction) network that comprised 49 nodes was mapped. The enrichment of biological process (BP) was principally and significantly revealed in signal transduction, inflammatory response and positive regulation of chemokine production. In terms of KEGG pathway, DEGs were primarily enriched in Cytokine-cytokine receptor interaction, JAK-STAT signaling pathway and cAMP signaling pathway. In the PPI network, IL10, IFNG, Fos, IL19, PDE4B NPY, Cnr1, MMP13, Rtn1, UCHL1 were selected as Hub gene. PDE4B and cAMP signaling pathway may associate with anti-inflammatory function of NR4a1. Our data showed that NR4a1 could promotes the protein level of cAMP, p-PKA and decreased p-p65, p-IκBα through down-regulating PDE4B. NR4a1-downregulated PDE4B expression notably decreased the LPS induced mRNA level of IL-6 and IL1β. This study also pointed the potential physiological processes regulated by NR4a1.Our findings supports that NR4a1 may be a considerable therapeutic target in inflammatory disease.

Background: Psoriasis is a recurrent chronic skin inflammatory disease. Its biomarkers are currently inaccurate and lack specificity. Hence, the immune infiltration mechanism of the key differential genes in psoriasis and related principles are discussed in this article. Methods: The GSE30999, GSE67853 and GSE78097 data sets were downloaded from the Gene Expression Omnibus(GEO) database, and the differentially expressed genes were screened with p＜0.05 & |Log2FC|＞1 by R language. Then, hub genes were picked out through LASSO and BORUTA analyses and verified in exterior dataset GSE83582. Further, we used ssGSEA to evaluate the effect of genes on immune infiltration. GSVA and GSEA algorithms were applied to assess associations between hub genes and different pathways for enrichment. Finally, the gene selection model of psoriasis-based immune infiltration will be examined by ROC. Results: The characteristic genes of psoriasis are determined to be TMPRSS11D, S100A12 and KYNU by the intersection of two algorithms. These three genes all have strong correlations with the content of immune cells and immune-related genes. Highly expressed TMPRSS11D, S100A12, and KYNU genes are involved in HEME_METABOLISM, XENOBIOTIC_METABOLISM, and MTORC1 pathways indicating that core genes affect the development and progression of psoriasis by regulating metabolism and T cell-related immunity. GESA showed that hub genes are linked to immune factors concerning enriched pathways. The AUC values of these three core genes are TMPRSS11D = AUC: 0.980 (0.959–1.000), S100A12= AUC: 0.982 (0.963–1.000), KYNU= AUC: 0.992 (0.982–1.000). Hub genes are actively associated with each other. Eventually, the differential gene expression of these key genes is validated by external datasets. Conclusion: Combining bioinformatics to analyze the immune infiltration mechanism of psoriasis provides a basis for discovering novel diagnostic biomarkers.