MTHFR Gene Polymorphism Association With Psoriatic Arthritis Risk and the Efficacy and Hepatotoxicity of Methotrexate in Psoriasis.

Aims To assess whether MTHFR rs1801131 and rs1801133 SNPs are associated with concomitant psoriatic arthritis (PsA) and investigate the efficacy and hepatotoxicity of MTX in patients with psoriasis in the Han Chinese population. Methods This prospective, single-arm, interventional study recruited a total of 309 patients with psoriasis, 163 with psoriatic arthritis and 146 without psoriatic arthritis, who completed a 12-week MTX treatment and 1,031 healthy controls. Patients' characteristics including age, gender, disease duration, height, weight, smoking status, alcohol consumption, medical history, disease severity and liver function test results were accessed and recorded. Single nucleotide polymorphism (SNP) genotyping of rs1801131 and rs1801133 in the MTHFR gene was performed. Results The rs1801133 CC genotype was more frequent in patients with PsA than those with PsO and healthy controls (42.3% vs. 28.8% vs. 33.1%, p < 0.05). The 90% reduction from baseline PASI score (PASI 90) response rates to MTX were significantly higher in patients with the rs1801133 TT genotype than those with the CT and CC genotype (33.96% vs. 19.31% vs. 14.41%, OR = 2.76, p = 0.006). The rs1801133 CT+TT genotype was more frequent in PsA patients with abnormal liver function than in those with normal liver function (p < 0.05). In addition, patients with the rs1801131 CT genotype had lower PASI 75 response rates to MTX (OR = 0.49, p = 0.01), and lower risk of ALT elevation (OR = 0.46, p = 0.04). Conclusions This study provided some evidence for MTHFR polymorphism association with the risk of PsA and the efficacy and hepatotoxicity of the low-dose MTX in the Chinese population. Given the relatively small sample size and potentially missed diagnosis of PsA, the results from this study warrant further investigation

Dynamic changes in fecal microbiota in donkey foals during weaning: From pre-weaning to post-weaning

IntroductionA better understanding of the microbiota community in donkey foals during the weaning transition is a prerequisite to optimize gut function and improve feed efficiency. The objective of the present study was to investigate the dynamic changes in fecal microbiota in donkey foals from pre-to post-weaning period.MethodsA total of 27 fecal samples of donkey foals were collected in the rectum before morning feeding at pre-weaning (30 days of age, PreW group, n = 9), dur-weaning (100 days of age, DurW group, n = 9) and post-weaning (170 days of age, PostW group, n = 9) period. The 16S rRNA amplicon sequencing were employed to indicate the microbial changes during the weaning period.ResultsIn the present study, the cessation of breastfeeding gradually and weaning onto plant-based feeds increased the microbial diversity and richness, with a higher Shannon, Ace, Chao and Sobs index in DurW and PostW than in PreW (p &lt; 0.05). The predominant bacterial phyla in donkey foal feces were Firmicutes (&gt;50.5%) and Bacteroidota (&gt;29.5%), and the predominant anaerobic fungi and archaea were Neocallimastigomycota and Euryarchaeota. The cellulolytic related bacteria including phylum Firmicutes, Spirochaetota and Fibrobacterota and genus norank_f_F082, Treponema, NK4A214_group, Lachnospiraceae_AC2044_group and Streptococcus were increased from pre-to post-weaning donkey foals (p &lt; 0.05). Meanwhile, the functions related to the fatty acid biosynthesis, carbohydrate metabolism and amino acid biosynthesis were significantly enriched in the fecal microbiome in the DurW and PostW donkeys. Furthermore, the present study provided the first direct evidence that the initial colonization and establishment of anaerobic fungi and archaea in donkey foals began prior to weaning. The relative abundance of Orpinomyces were the highest in DurW donkey foals among the three groups (p &lt; 0.01). In terms of archaea, the abundance of Methanobrevibacter were higher in PreW than in DurW and PostW (p &lt; 0.01), but the abundance of Methanocorpusculum were significantly increased in DurW and PostW compared to PreW donkey foals (p &lt; 0.01).DiscussionAltogether, the current study contributes to a comprehensive understanding of the development of the microbiota community in donkey foals from pre-to post-weaning period, which may eventually result in an improvement of the digestion and feed efficiency in donkeys

Research Progress on Ferroptosis-mediated Antitumor Immunotherapy

Ferroptosis is a form of programmed cell death driven by iron-dependent lipid peroxidation and is closely associated with a wide range of biological processes, such as aging, immunity, and cancer. Tumor multidrug resistance, especially resistance to apoptosis, has prompted the urgent search for a new antitumor treatment option. Remarkable progress has been made in the study of the role of ferroptosis in antitumor, especially the interaction with immune cells. Studying immunotherapy based on ferroptosis pathways has become a new direction in antitumor research. In this work, we review the role of ferroptosis in immune cells and antitumor immunotherapy to provide new ideas for ferroptosis-mediated antitumor immunotherapy

Transcriptomic, Proteomic, and Bioelectrochemical Characterization of an Exoelectrogen Geobacter soli Grown With Different Electron Acceptors

The ability of Geobacter species to transfer electrons outside cells enables them to play an important role in biogeochemical and bioenergy processes. Our knowledge of the extracellular electron transfer (EET) process in the genus Geobacter is mainly from the study of G. sulfurreducens, and in order to fully investigate the EET mechanisms in the genus Geobacter, other Geobacter species should also be considered. This study focused on the EET of Geobacter soli GSS01, which exhibited a capability of reducing insoluble Fe(III) oxides and generating electrical current comparable with G. sulfurreducens PCA. Electrochemical characterization, including cyclic voltammetry, differential pulse voltammetry, and electrochemical in situ FTIR spectra, revealed that different redox proteins contributed to the electrochemical behaviors of G. soli and G. sulfurreducens. Based on comparative transcriptomic and proteomic analyses, OmcS was the most upregulated protein in both G. soli and G. sulfurreducens cells grown with insoluble Fe(III) oxides vs. soluble electron acceptor. However, the proteins including OmcE and PilA that were previously reported as being important for EET in G. sulfurreducens were downregulated or unchanged in G. soli cells grown with insoluble electron acceptors vs. soluble electron acceptor, and many proteins that were upregulated in G. soli cells grown with insoluble electron acceptors vs. soluble electron acceptor, such as OmcN, are not important for EET in G. sulfurreducens. We also identified 30 differentially expressed small RNAs (sRNAs) in G. soli cells grown with different acceptors. Taken together, these findings help to understand the versatile EET mechanisms that exist in the genus Geobacter and point to the possibility of sRNA in modulating EET gene expression

Identification of proteins associated with development of psoriatic arthritis in peripheral blood mononuclear cells: a quantitative iTRAQ-based proteomics study.

BACKGROUND Biomarkers for distinguishing psoriatic arthritis (PsA) from psoriasis without arthritis (PsO) are still lacking. METHODS We applied isobaric tags for relative and absolute quantification (iTRAQ) and LC-MS/MS to analyze the proteome profile of peripheral blood mononuclear cells (PBMCs) collected from patients with PsO, patients with PsA, and healthy controls. Bioinformatics analysis and western blotting were performed to identify and validate differentially expressed proteins. RESULTS We identified 389, 199, 291, and 60 significantly differentially expressed proteins (adj.p < 0.05) in the comparison of all psoriatic patients versus healthy controls, PsO group versus healthy controls, PsA group versus healthy controls, and PsA group versus PsO group, respectively. Among these proteins, 14 proteins may represent promising biomarkers for PsA: SIRT2, NAA50, ARF6, ADPRHL2, SF3B6, SH3KBP1, UBA3, SCP2, RPS5, NUDT5, NCBP1, SYNE1, NDUFB7, HTATSF1. Furthermore, western blotting confirmed that SIRT2 expression was significantly higher in PBMCs from PsA patients than PsO and healthy controls, and was negatively correlated with the phosphorylation of p38 mitogen-activated protein kinase (p-p38MAPK; p = 0.006, r = - 0.582). CONCLUSIONS This pilot study provided a broad characterization of the proteome of PBMCs in PsA as compared to PsO and healthy controls, which may help to provide prospective strategies for PsA diagnosis

Genetic polymorphisms of rs9949644 in MAPK4 are associated with clinical response to methotrexate in patients with psoriasis.

Background The study aimed to investigate the relationship of MAPK4 genetic variants with the efficacy of MTX in psoriasis patients. Methods Patients treated with MTX were classified as responders or nonresponders if the Psoriasis Area and Severity Index (PASI) at week 12 was reduced to greater than 75% or lower than 75%, respectively. The genotypes of 14 MAPK4 single nucleotide polymorphisms (SNPs) in 310 patients were analyzed. The expression levels of MAPK4 protein were detected by western blot. Results Only rs9949644 polymorphisms were associated with the efficacy after adjusting for the confounding factors. Patients with the rs9949644 AG or GG genotype had a better clinical response compared to patients with the AA genotype. Rs9949644 polymorphisms were significantly associated with the PASI improvement rate. Besides, the protein level of MAPK4, positively associated with the psoriasis severity, was higher in patients. There were no significant differences of MAPK4 protein levels among three groups. While after treatment, MAPK4 levels in the AG or GG group showed a significantly down-regulated trend. Conclusions By demonstrating the significant association of MAPK4 with the efficacy of MTX, this study indicates that MAPK4 may be involved in the psoriasis progression and act as a predictor of therapeutic response

Marine Carbonate Component in the Mantle Beneath the Southeastern Tibetan Plateau: Evidence From Magnesium and Calcium Isotopes

Tracing and identifying recycled carbonates is a key issue to reconstruct the deep carbon cycle. To better understand carbonate subduction and recycling beneath the southeastern Tibetan Plateau, high-K cal-alkaline volcanic rocks including trachy-basalts and trachy-andesites from Tengchong were studied using Mg and Ca isotopes. The low Mg-26 (-0.310.03 to -0.380.03) and Ca-44/40 (0.67 +/- 0.07 parts per thousand to 0.80 +/- 0.04 parts per thousand) values of these volcanic rocks compared to those of the mantle (-0.25 +/- 0.07 parts per thousand and 0.94 +/- 0.05 parts per thousand, respectively) indicate the incorporation of isotopically light materials into the mantle source, which may be carbonate-bearing sediments with low Mg-26 and Ca-44/40 values. In addition, no correlations of Mg-26 and Ca-44/40 with either SiO2 contents or trace element abundance ratios (e.g., Sm/Yb and Ba/Y) were observed, suggesting that limited Mg and Ca isotopic fractionation occurred during cal-alkaline magmatic differentiation. A binary mixing model using Mg-Ca isotopes shows that 5-8% carbonates dominated primarily by dolostone were recycled back into the mantle. Since Tengchong volcanism is still active and probably related to ongoing plate tectonic movement, we propose that the recycled carbonates are derived from oceanic crust related to the ongoing subduction of the Indian plate

Table_1_Transcriptomic, Proteomic, and Bioelectrochemical Characterization of an Exoelectrogen Geobacter soli Grown With Different Electron Acceptors.xlsx

<p>The ability of Geobacter species to transfer electrons outside cells enables them to play an important role in biogeochemical and bioenergy processes. Our knowledge of the extracellular electron transfer (EET) process in the genus Geobacter is mainly from the study of G. sulfurreducens, and in order to fully investigate the EET mechanisms in the genus Geobacter, other Geobacter species should also be considered. This study focused on the EET of Geobacter soli GSS01, which exhibited a capability of reducing insoluble Fe(III) oxides and generating electrical current comparable with G. sulfurreducens PCA. Electrochemical characterization, including cyclic voltammetry, differential pulse voltammetry, and electrochemical in situ FTIR spectra, revealed that different redox proteins contributed to the electrochemical behaviors of G. soli and G. sulfurreducens. Based on comparative transcriptomic and proteomic analyses, OmcS was the most upregulated protein in both G. soli and G. sulfurreducens cells grown with insoluble Fe(III) oxides vs. soluble electron acceptor. However, the proteins including OmcE and PilA that were previously reported as being important for EET in G. sulfurreducens were downregulated or unchanged in G. soli cells grown with insoluble electron acceptors vs. soluble electron acceptor, and many proteins that were upregulated in G. soli cells grown with insoluble electron acceptors vs. soluble electron acceptor, such as OmcN, are not important for EET in G. sulfurreducens. We also identified 30 differentially expressed small RNAs (sRNAs) in G. soli cells grown with different acceptors. Taken together, these findings help to understand the versatile EET mechanisms that exist in the genus Geobacter and point to the possibility of sRNA in modulating EET gene expression.</p