The impact of psoriasis on idiopathic pulmonary fibrosis: a two-sample Mendelian randomization study.

BACKGROUND: The association between psoriasis and pulmonary fibrosis has been reported in observational studies. However, the association is vulnerable to bias from using immunosuppressants such as methotrexate, which can cause fibrosis in multiple organs. The present study is to investigate whether psoriasis could independently increase the risk of idiopathic pulmonary fibrosis (IPF). METHODS: We conducted a two-sample Mendelian randomization (MR) study using summary statistics from genome-wide association studies. The random-effects inverse variance weighted analysis was used as the primary method. Some secondary analyses were further performed, including a sensitivity analysis using a genetic instrument that excluded extended single nucleotide polymorphisms (SNPs) in the major histocompatibility complex (MHC) gene region. RESULTS: Our study included 9267 cases and 364,071 controls for psoriasis, 2018 cases, and 373,064 controls for IPF of European ancestry, respectively. Genetically predicted psoriasis was associated with a higher risk of IPF (odds ratio (OR), 1.14; 95% confidence interval (CI), 1.08-1.22; P < 0.001). Sensitivity analyses did not uncover any statistically significant evidence of bias resulting from pleiotropy or the genetic instruments, including SNPs in the MHC gene region. CONCLUSIONS: These MR analyses support that genetically predicted psoriasis was associated with the risk of IPF, implying that pulmonary fibrosis in patients with psoriasis should not be neglected, even if they are not receiving immunosuppressant therapy.

General Defluoroalkylation of Trifluoromethylarenes with Both Electron-Donating and -Withdrawing Alkenes.

The incorporation of gem-difluoromethylene units into organic molecules remains a formidable challenge. Conventional methodologies for constructing aryldifluoromethyl derivatives relied on the use of high-functional fluorinating regents under harsh conditions. Herein, we report general and efficient photoredox catalytic systems for defluoroalkylation of readily available trifluoromethylarenes through selective C-F cleavage to deliver gem-difluoromethyl radicals which proceed through reductive addition to both electron-donating and withdrawing alkenes under transition-metal free conditions. Mechanistic studies reveal that thiol serves as both photocatalyst and HAT reagent under visible light irradiation. This synergistic photocatalysis and HAT catalysis protocol exhibits ample and salient features such as high chemo- and regioselectivity, broad substrate scope, amenable gram-scale synthesis and late-stage modification of bioactive molecules.

Contribution of gut-derived T cells to extraintestinal autoimmune diseases.

The mammalian intestine harbors abundant T cells with high motility, where these cells can affect both intestinal and extraintestinal disorders. Growing evidence shows that gut-derived T cells migrate to extraintestinal organs, contributing to the pathogenesis of certain autoimmune diseases, including type 1 diabetes (T1D) and multiple sclerosis (MS). However, three key questions require further elucidation. First, how do intestinal T cells egress from the intestine? Second, how do gut-derived T cells enter organs outside the gut? Third, what is the pathogenicity of gut-derived T cells and their correlation with the gut microenvironment? In this Opinion, we propose answers to these questions. Understanding the migration and functional regulation of gut-derived T cells might inform precise targeting for achieving safe and effective approaches to treat certain extraintestinal autoimmune diseases.

Electrocatalytic Cascade Selenylation/Cyclization/Deamination of 2-Hydroxyaryl Enaminones: Synthesis of 3-Selenylated Chromones under Mild Conditions.

Herein, we disclosed a highly efficient pathway toward 3-selenylated chromone derivatives via electrocatalytic cascade selenylation/cyclization/deamination of 2-hydroxyaryl enaminones with diselenides. This method showed mild conditions, easy operation, wide substrate scope, and good functional group tolerance. Furthermore, this electrosynthesis strategy was amendable to scale-up the reaction. Additionally, the preliminary experiments revealed that this reaction probably proceeded via a cation pathway instead of a radical pathway.

Photoionization cross sections measurements of the excited states of lutetium and ytterbium in the near threshold region.

In this work, the threshold photoionization cross sections from the excited states of lutetium and ytterbium atoms were investigated by the laser pump-probe scheme under the condition of saturated resonant excitation. We obtained the resonance enhanced multiphoton ionization spectra of the lutetium and ytterbium atoms of the lanthanide metals in the range of 307.50-312.50 nm and 265.00-269.00 nm, respectively; the photoionization cross sections of the 5d6s(1D)6p(2D05/2) and 5d6s(3D)6p(2P01/2) states of lutetium and the 4f13(2F0)5d6s2(J = 1) states of ytterbium above threshold regions (0.4-1.6 eV) were measured, and measured values ranged from 2.3 ± 0.2 to 17.7 ± 1.5 Mb.

Gut-tropic T cells and extra-intestinal autoimmune diseases.

Gut-tropic T cells primarily originate from gut-associated lymphoid tissue (GALT), and gut-tropic integrins mediate the trafficking of the T cells to the gastrointestinal tract, where their interplay with local hormones dictates the residence of the immune cells in both normal and compromised gastrointestinal tissues. Targeting gut-tropic integrins is an effective therapy for inflammatory bowel disease (IBD). Gut-tropic T cells are further capable of entering the peripheral circulatory system and relocating to multiple organs. There is mounting evidence indicating a correlation between gut-tropic T cells and extra-intestinal autoimmune disorders. This review aims to systematically discuss the origin, migration, and residence of gut-tropic T cells and their association with extra-intestinal autoimmune-related diseases. These discoveries are expected to offer new understandings into the development of a range of autoimmune disorders, as well as innovative approaches for preventing and treating the diseases.

Keratinocyte-to-macrophage communication exacerbate psoriasiform dermatitis via LRG1-enriched extracellular vesicles.

Rationale: Macrophage-associated inflammation and keratinocytes excessive proliferation and inflammatory cytokines secretion induced by stimulation play an important role in the progression of psoriasiform dermatitis. However, how these two types of cells communicate remains obscure. Methods: We induced a mouse model with experimental psoriasiform dermatitis by Imiquimod (IMQ). To investigate whether damaged keratinocytes promote macrophage polarization and accelerate skin lesions by releasing extracellular vesicle (EV), purified EV were isolated from the primary epidermis of 5-day IMQ-induced psoriasiform dermatitis model mice, and then fluorescence-labeled the EV with PKH67. The EV was injected into the skin of mice treated with IMQ or vehicle 2 days in situ. In addition, we established a co-culture system of the human monocytic cell line (THP-1) and HaCaT, and THP-1/HaCaT conditioned media culture model in vitro respectively. Subsequently, we evaluated the effect of Leucine-rich α-2-glycoprotein 1 (LRG1)-enriched EV on macrophage activation. Results: We demonstrated macrophages can significantly promote keratinocyte inflammation and macrophage polarization may be mediated by intercellular communication with keratinocytes. Interestingly, IMQ-induced 5-day, keratinocyte-derived EV recruited macrophage and enhanced the progression of skin lesions. Similar to results in vivo, EV released from M5-treated HaCaT significantly promotes Interleukin 1ß (IL-1ß) and Tumor necrosis factor α (TNF-α) expression of THP-1 cells. Importantly, we found that LRG1-enriched EV regulates macrophages via TGF beta Receptor 1 (TGFßR1) dependent process. Conclusion: Our findings indicated a novel mechanism for promoting psoriasiform dermatitis, which could be a potential therapeutic target.

[Potential Ecological Risk Assessment and Source Analysis of Heavy Metals in Soil-crop System in Xiong'an New District].

In order to evaluate the distribution characteristics of fluorine geochemistry in the surface soil and human health risk in Xiong'an New District, GIS spatial analysis and correlation analysis were used to analyze the depleted and enriched features and influencing factors of soil fluoride and to carry out the soil fluoride health risk assessment. The uncertainty of the health risk assessment results was studied based on the Monte Carlo stochastic simulation. The results showed that the average content of fluorine was 641 mg·kg-1, which was 1.34 times the background value of the national A-layer soil. The excess fluorine and high-grade samples accounted for more than 85%, and the overall soil fluorine content was relatively high. The average content of fluoride of the irrigation water samples was 0.85 mg·L-1, the spatial distribution characteristics of which were affected by the hydrochemical type and flow direction of shallow groundwater. The vertical spatial variation of soil fluoride, mainly affected by the vertical distribution of soil physicochemical properties such as soil organic carbon and texture, was not obvious. The depletion and enrichment of topsoil fluorine was mainly controlled by the geological background, and its spatial distribution was affected by external inputs, such as human factors (agricultural irrigation water, fertilization, and atmospheric dry and wet deposition). The soil fluoride content was significantly correlated with the iconic indicators of the geomorphological environment, including the content of Al2O3, Fe2O3, MgO, K2O, soil organic carbon (Corg.), cation exchange capacity (CEC), clay, and silt (P<0.01). The results of human health risk assessment showed that oral intake was the main exposure risk route of soil fluoride. The non-carcinogenic health risk index HQ of adults was less than 1, and the harm could be ignored. The probability of non-carcinogenic health risk exceeding the threshold for adults and children was 34.3% and 27.6%, respectively, and daily soil intake was the most sensitive parameter.

Laminar airflow ventilation systems in orthopaedic operating room do not prevent surgical site infections: a systematic review and meta-analysis.

BACKGROUND: Laminar airflow (LAF) technologies minimize infectious microorganisms to enhance air quality and surgical site infections (SSIs). LAF lowers SSIs in some clinical studies but not others. This study analyzes laminar airflow ventilation's capacity to reduce orthopaedic surgery-related SSIs. METHODS: The PRISMA-compliant keywords were utilized to conduct a search for pertinent articles in various databases including PubMed, MEDLINE, CENTRAL, Web of Sciences, and the Cochrane databases. Observational studies, including retrospective, prospective, and cohort designs, satisfy the PICOS criteria for research methodology. The assessment of quality was conducted utilizing the Robvis software, while the meta-analysis was performed using the RevMan application. The study's results were assessed based on effect sizes of odds ratio (OR) and risk ratio (RR). RESULTS: From 2000 to 2022, 10 randomized controlled clinical trials with 10,06,587 orthopaedic surgery patients met the inclusion criteria. The primary outcomes were: (1) Risk of SSI, (2) Bacterial count in sampled air and (3) Reduction in SSIs. The overall pooled OR of all included studies was 1.70 (95% CI 1.10-2.64), and the overall pooled RR was 1.27 (95% CI 1.02-1.59) with p < 0.05. LAF is ineffective at preventing SSIs in orthopaedic procedures due to its high-risk ratio and odds ratio. CONCLUSIONS: The present meta-analysis has determined that the implementation of LAF systems does not result in a significant reduction in the incidence of surgical site infections (SSIs), bacterial count in the air, or SSIs occurrence in orthopaedic operating rooms. Consequently, the installation of said equipment in operating rooms has been found to be both expensive and inefficient.

Systemic lupus erythematosus is associated with the risk of coeliac disease: a Mendelian randomisation study.

As an autoimmune disease, systemic lupus erythematosus (SLE) can affect multiple organs and systems. Whether SLE can increase the risk of coeliac disease (CeD) was not evaluated until now. We performed a two-sample Mendelian randomisation study to evaluate the relationship between SLE and CeD, and found that SLE can significantly increase the risk of CeD, suggesting the association between SLE and abnormal intestinal immune microenvironment.

Gut immune microenvironment and autoimmunity.

A variety of immune cells or tissues are present in the gut to form the gut immune microenvironment by interacting with gut microbiota, and to maintain the gut immune homeostasis. Accumulating evidence indicated that gut microbiota dysbiosis might break the homeostasis of the gut immune microenvironment, which was associated with many health problems including autoimmune diseases. Moreover, disturbance of the gut immune microenvironment can also induce extra-intestinal autoimmune disorders through the migration of intestinal pro-inflammatory effector cells from the intestine to peripheral inflamed sites. This review discussed the composition of the gut immune microenvironment and its association with autoimmunity. These findings are expected to provide new insights into the pathogenesis of various autoimmune disorders, as well as novel strategies for the prevention and treatment against related diseases.

Visible-Light-Induced Stoichiometric Coupling of Alkylarenes and Trifluoromethyl Ketones.

A visible-light induced direct C(sp3)-H functionalization of alkylarenes with trifluoromethyl ketones has been reported to access valuable benzyl-substituted trifluoromethyl alcohols in a stoichiometric manner. Readily available petroleum-derived alkylarenes are employed as latent benzylation reagents. With a bromine radical as the hydrogen atom transfer reagent, primary, secondary, and tertiary benzyl C-H bonds are suitable coupling partners. Additionally, the late-stage modification of bioactive molecules highlights the potential application of this approach.

Properties of Gaseous Deprotonated L-Cysteine S-Sulfate Anion [cysS-SO3]-: Intramolecular H-Bond Network, Electron Affinity, Chemically Active Site, and Vibrational Fingerprints.

L-cysteine S-sulfate, Cys-SSO3H, and their derivatives play essential roles in biological chemistry and pharmaceutical synthesis, yet their intrinsic molecular properties have not been studied to date. In this contribution, the deprotonated anion [cysS-SO3]- was introduced in the gas phase by electrospray and characterized by size-selected, cryogenic, negative ion photoelectron spectroscopy. The electron affinity of the [cysS-SO3]• radical was determined to be 4.95 ± 0.10 eV. In combination with theoretical calculations, it was found that the most stable structure of [cysS-SO3]- (S1) is stabilized via three intramolecular hydrogen bonds (HBs); i.e., one O-H⋯⋯N between the -COOH and -NH2 groups, and two N-H⋯⋯O HBs between -NH2 and -SO3, in which the amino group serves as both HB acceptor and donor. In addition, a nearly iso-energetic conformer (S2) with the formation of an O-H⋯⋯N-H⋯⋯O-S chain-type binding motif competes with S1 in the source. The most reactive site of the molecule susceptible for electrophilic attacks is the linkage S atom. Theoretically predicted infrared spectra indicate that O-H and N-H stretching modes are the fingerprint region (2800 to 3600 cm-1) to distinguish different isomers. The obtained information lays out a foundation to better understand the transformation and structure-reactivity correlation of Cys-SSO3H in biologic settings.

The length of stay and inpatient burden in inpatients with different psoriasis subtypes.

Background: Heavy disease burden of psoriasis has been indicated by previous studies. However, the cost of care and length of stay (LOS) in inpatients with different psoriasis subtypes were rarely addressed. This study aimed to investigate the cost of care and LOS in Chinese patients with different psoriasis types and to clarify the independent factors affecting LOS. Methods: We conducted a cross-sectional study by enrolling patients with psoriasis who were hospitalized between 13 Feb 2017 and 29 Mar 2021. Demographic and clinical characteristics of the patients were collected by reviewing their Electronic Medical Records. Multivariate linear regression was used to estimate the associations with adjustments. Results: A total of 310 adult patients with psoriasis were included (mean cost of care: 13.0±22.3 kCNY; mean LOS: 7.9±4.3 days). Statistically significant differences were found among patients with different psoriasis subtypes in LOS (P<0.001) but not in the cost of care (P=0.530). Relative to psoriasis vulgaris, pustular psoriasis (Adjusted coefficient: 2.37, 95% confidence interval (CI): 0.87-3.87) and erythrodermic psoriasis (Adjusted coefficient: 2.92, 95%CI: 1.38-4.47) were significantly associated with an increased LOS. Meanwhile, respiratory tract infections (Adjusted coefficient: 1.60, 95%CI: 0.11-3.10) also significantly increased the LOS. On the contrary, a decreased LOS was found in psoriatic arthritis patients treated with TNF-alpha inhibitors (Adjusted coefficient: -2.21, 95%CI: -4.37 to -0.05). Conclusions: LOS differed significantly among different psoriasis subtypes while the inpatient burden for a single hospitalization was alike. Infection is an important factor associated with a longer LOS. TNF-alpha inhibitors evidently reduced the total hospital stay period for patients with psoriatic arthritis.

Human umbilical cord mesenchymal stem cells for psoriasis: a phase 1/2a, single-arm study.

Psoriasis is a common, chronic immune-mediated systemic disease that had no effective and durable treatment. Mesenchymal stem cells (MSCs) have immunomodulatory properties. Therefore, we performed a phase 1/2a, single-arm clinical trial to evaluate the safety and efficacy of human umbilical cord-derived MSCs (UMSCs) in the treatment of psoriasis and to preliminarily explore the possible mechanisms. Seventeen patients with psoriasis were enrolled and received UMSC infusions. Adverse events, laboratory parameters, PASI, and PGA were analyzed. We did not observe obvious side effects during the treatment and 6-month follow-up. A total of 47.1% (8/17) of the psoriasis patients had at least 40% improvement in the PASI score, and 17.6% (3/17) had no sign of disease or minimal disease based on the PGA score. And the efficiency was 25% (2/8) for males and 66.7% (6/9) for females. After UMSC transplantation (UMSCT), the frequencies of Tregs and CD4+ memory T cells were significantly increased, and the frequencies of T helper (Th) 17 and CD4+ naive T cells were significantly decreased in peripheral blood (PB) of psoriasis patients. And all responders showed significant increases in Tregs and CD4+ memory T cells, and significant decreases in Th17 cells and serum IL-17 level after UMSCT. And baseline level of Tregs in responders were significantly lower than those in nonresponders. In conclusion, allogeneic UMSCT is safe and partially effective in psoriasis patients, and level of Tregs may be used as a potent biomarker to predict the clinical efficacy of UMSCT. Trial registration Clinical Trials NCT03765957.

Microbiota differences of skin and pharyngeal microbiota between patients with plaque and guttate psoriasis in China.

Psoriasis can be provoked or exacerbated by environmental exposures such as certain microbiomes. The distinction between plaque psoriasis (PP) and guttate psoriasis (GP) in the skin or pharyngeal microbiota is not yet clear. High-throughput sequencing using Illumina MiSeq was used in this study to characterize skin and pharyngeal microbial composition in patients with PP [large PP (LPP, n = 62), small PP (SPP, n = 41)] and GP (n = 14). The alpha- and beta-diversity of skin microbiota LPP was similar to that of the SPP group, but different from the GP group. There were no differences in pharyngeal microbiota among the groups. According to linear discriminant analysis effect size (LEfSe) analysis, Staphylococcus, Stenotrophomonas, Enhydrobacter, Brevundimonas, and Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium were the dominant genera of skin microbiota in PP. Diversity of skin microbiota correlated with Psoriasis Area and Severity Index (PASI). Moderate-to-severe psoriasis and mild psoriasis have different microbiota compositions. The skin microbiota may be related to the pharyngeal microbiota. Furthermore, two microbiota-based models could distinguish psoriasis subtypes with area under the receiver-operating characteristic curve (AUC-ROC) of 0.935 and 0.836, respectively. In conclusion, the skin microbiota in patients with LPP is similar to that in patients with SPP, but displays variations compared to that of GP, no differences are noted between subtypes in pharyngeal microbiota. Skin microbiota diversity correlated with PASI.

Insights into a Low-Rank Naomaohu Coal Structural Information by Multistage Fractions Coupled with LIAD-VUVPI-TOFMS.

In-depth insights into the chemical composition and structural information of coal are an effective way to improve the efficiency of coal utilization. Laser-induced acoustic desorption coupling with vacuum ultraviolet photoionization time-of-flight mass spectrometry (LIAD-VUVPI-TOFMS) was applied to structural characterization of cyclohexane extracts of low-rank Naomaohu coal. The characterization of four types (12 model compounds) of mixed coal model compounds (three compounds per category)-saturated hydrocarbons, substitute aromatic hydrocarbons, aromatic hydrocarbons, and aromatic heteroatom rings-demonstrated that the approach can provide intact molecular weight information. The cyclohexanone extract (E CYC) was obtained by microwave-assisted extraction and separated into four group components (F1-4) by column chromatography to achieve component classification and simplify analysis. The molecular weight and structure were obtained by LIAD-VUVPI-TOFMS and synchronous fluorescence spectroscopy, combined with microwave-assisted extraction and column chromatography to separate product characteristics. Chemical components of a total of 248 species were observed, of which 46 are derived from aliphatic hydrocarbons embedded in the coal skeleton structure, 132 species are derived from aromatic hydrocarbons embedded in the coal skeleton structure, 61 are derived from possible coal skeleton units (compounds have obvious stacking and bonding effects), and 9 could not be determined (aromatic hydrocarbons or a possible coal skeleton structure unit).

Relationship between patient acceptable symptom state and disease scores in psoriasis.

Patient acceptable symptom state (PASS) is a patient-reported outcome that reflects patients' perspective well. The relationship between the PASS and disease scores in psoriasis has not been described. The aim of the present study was to investigate the association of PASS with Psoriasis Area and Severity Index (PASI) and body surface area (BSA) affected by lesions in patients with psoriasis. A sectional study was conducted. PASS was evaluated by a binary question on the patient's feeling that they have about their symptoms. Clinical data including PASI, BSA, and other patient characteristics were collected. Logistic regression was used to investigate the associations. Receiver-operator curve (ROC) analysis was utilized to determine the PASI/BSA thresholds for PASS. A total of 198 participants (27.8% female, mean age 41.9 ± 12.6 years, mean disease duration 10.2 ± 8.6 years) completed this study. Of patients with mild psoriasis, 71.4% based on PASI and 76.3% based on BSA considered their symptom state acceptable. Female sex (adjusted odds ratio [OR] = 0.47; 95% confidence interval [CI = 0.42-0.92) and patients with exposed skin involved (adjusted OR = 0.38; 95% CI = 0.19-0.76) were less likely to report acceptable symptom state. The threshold for differentiating psoriasis patients in PASS was 3.85 (area under the curve [AUC], 0.67; sensitivity, 0.67; specificity, 0.60) for PASI and 2.85% (AUC, 0.66; sensitivity, 0.79; specificity, 0.54) for BSA, respectively. These results showed that mild psoriasis based on PASI/BSA score align well with PASS status. Female and exposed skin involved are risk factors for acceptable status. Both PASI and BSA have limited capability in differentiating acceptable symptom state in psoriasis.