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关键词： Lewis acid   rearrangement   regioselectivity  

摘要： Selective synthesis of 8- or 5-amino-substituted 1-naphthols through rearrangement is demonstrated using Lewis acids. A variety of tetrasubstituted 1-naphthols were selectively prepared from 2,4-disubstituted 5-amino-1,4-epoxy-1,4-dihydronaphthalenes in a Lewis-acid-dependent manner with AlCl3 or ZnCl2 serving as the activators. A unique reaction mechanism was proposed on the basis of NMR experiments.

关键词： action mechanism   biological control   microencapsulation   sclerotium rolfsii   Trichoderma afroharzianum  

摘要： BACKGROUND Sclerotium rolfsii is a devastating pathogen causing southern blight disease in many crops, including pepper. Currently, this disease is managed by laborious application of chemical fungicides, raising concerns regarding environmental and human health. Furthermore, the practical application of biological control agents is hindered by their instability. The objective of this study was to screen novel Trichoderma strains with potential as biological control agents and to develop formulations that enhance their persistence against pepper southern *** In this study, a Trichoderma afroharzianum strain YZ-1 exhibiting significant antifungal activity against S. rolfsii was identified. It had the ability to directly inhibit the growth of plant pathogens through mycoparasitism, and inhibit acid production and sclerotia germination. Additionally, YZ-1 demonstrated growth-promoting properties. Microencapsulation of YZ-1 using montmorillonite-sodium alginate produced spherical microcapsules that enhanced protection against UV radiation, enhanced storage stability, enabled controlled release and preserved inhibitory activity. Fourier transform infrared spectrophotometer analysis indicated interactions between YZ-1 and the microcapsules. The microencapsulated Trichoderma strain exhibited improved control of S. rolfsii, achieving a biocontrol efficacy of 84.90% after 21 days and prolonged persistence in pepper plant *** Our results revealed that the T. afroharzianum YZ-1 and its microcapsules represent a promising option for effective utilization as biopesticides against pepper southern blight. (c) 2025 Society of Chemical Industry.

关键词： amyotrophic lateral sclerosis   C9ORF72   neural organoid   microglia   phagocytosis   synapse  

摘要： Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease characterized by loss of upper and lower motor neurons and progressive muscle wasting. Accumulating evidence indicates a role for non-neuronal cells in ALS pathogenesis, but their exact role and mechanism-of-action remain incompletely understood. A hexanucleotide (GGGGCC) repeat expansion (HRE) in C9ORF72 is the most common genetic cause of ALS (C9-ALS) and a frequent cause of frontotemporal dementia (FTD).Several lines of experimental evidence support a role for the immune system and microglia in C9-ALS/FTD, and depending on experimental settings and species used, both reduced and increased microglial activity have been reported. To further study microglia in C9-ALS/FTD in the context of a complex, 3D disease environment, we developed cerebral organoids that innately develop microglia derived from induced pluripotent stem cells (iPSCs) of C9-ALS/FTD patients and ***, we show reduced cellular complexity and transcriptional changes in C9 neural organoid-derived microglia (C9-oMGs), involving phagocytic, lysosomal and immune response pathways. The release of inflammatory cues from C9-ALS/FTD organoids is decreased and LAMP1 expression in C9-oMGs is reduced. Functional analysis using live imaging reveals impaired phagocytosis by C9-oMGs and reduced engulfment of the post-synaptic protein PSD-95 by C9-oMGs in organoids. Finally, our transcriptomics analysis identifies a PU.1 (encoded by SPI1) regulon as the most strongly downregulated transcription factor network in C9-oMGs. Viral overexpression of PU.1 rescues phagocytosis and gene expression defects in ***, our data demonstrate reduced microglial functions in a complex cellular disease environment and identify PU.1 as a potential target for restoring microglia changes in C9-ALS/FTD. Accumulating evidence implicates non-neuronal cells in ALS pathogenesis. Using patient-derived cerebral organoids, Ljubikj et al. re

关键词： Polynomial identity   PI-algebra   matrix algebra   Grassmann algebra   Grassmann envelope   cocharacters   involution  

摘要： Let K be a field of characteristic 0, and let E be the infinite-dimensional Grassmann algebra over K. We consider E as a & Zopf;(2)-graded algebra, where the grading is given by the vector subspaces E-0 and E-1, consisting of monomials of even and odd lengths, respectively. Thus, if A = A(0) circle plus A(1) is an associative & Zopf;(2)-graded algebra, we can consider the & Zopf;(2)-graded algebra A circle times E = (A(0) circle times E-0) circle plus (A(1) circle times E-1). In case both E and A are endowed with superinvolutions, we can define a & Zopf;(2)-graded involution on A circle times E induced by the respective superinvolutions. In this paper, we consider the & Zopf;(2)-graded matrix algebras M-1,M-1(K), UT1,1(K) and UT(0,1,0)(K) endowed with superinvolutions. We shall provide a description of the polynomial identities and the cocharacter sequences of M-1,M-1(K)circle times E, UT1,1(K)circle times E and UT(0,1,0)(K)circle times E, considering these resulting algebras as & Zopf;(2)-graded algebras with graded involution.

关键词： adult   heart failure   humans   inflammation   interleukin 1  

摘要： BACKGROUND: Decompensated heart failure with reduced ejection fraction (HFrEF) is associated with systemic inflammation that predicts unfavorable outcomes. We aimed to determine whether anakinra, an IL-1 (interleukin-1) blocker, favors inflammation resolution (CRP [C-reactive protein]) and improves peak oxygen consumption (VO2) in patients with recently decompensated HFrEF. METHODS: We randomized 102 adult patients recently hospitalized for HFrEF and CRP >= 2 mg/L (2:1) to receive anakinra 100 mg subcutaneously daily (n=68) or placebo for 24 weeks (n=34). The primary end point was the peak VO2 change at 24 weeks. Data are presented as median (Q1, Q3) or number (%). RESULTS: Of the 102 patients, 84 had primary end point data available (57 treated with anakinra and 27 with placebo). Peak VO2 increased from 13.0 (10.9, 17.0) to 14.9 (12.0, 18.0) mL & centerdot;kg(-)(1)& centerdot;min(-)(1) (P<0.001) in the entire cohort, without significant differences between anakinra and placebo (+1.5 [-0.2, +3.4] and +1.2 [+0.5, +3.9] mL & centerdot;kg(-)(1)& centerdot;min(-)(1), respectively;P=0.40;median difference +0.30 mL & centerdot;kg(-)(1)& centerdot;min(-)(1) [95% CI from -1.70 to +0.90]). A significant reduction in CRP levels was seen, with a -76% (-87%, -36%) in anakinra-treated patients and -48% (-77%, +14%) in the placebo group (P=0.050 between groups). There were no unexpected treatment-related serious adverse events, and no differences in HFrEF events between groups. CRP<2 mg/L was achieved in 47% and 37% of the anakinra and placebo groups, respectively (P=0.48). Patients achieving CRP<2 mg/L had a significantly greater increase in peak VO2 versus those with CRP >= 2 mg/L (+2.6 [+0.7, +4.6] and +1.0 [-0.3, +1.9] mL & centerdot;kg(-)(1)& centerdot;min(-)(1);P=0.007) and lower rates of HFrEF-related events (8% and 26%;P=0.045). CONCLUSIONS: Patients with recently decompensated HFrEF treated with maximally tolerated medical therapy had a significant improvement in CRP and

关键词： apoptosis   mitral valve prolapse   RNA binding protein   TGF-beta 1   ZFP36  

摘要： The objective of this work was to investigate the role of ZFP36 in mitral valve prolapse (MVP). Mitral valve and plasma were collected to assess the expression of ZFP36, transforming growth factor beta (TGF-beta), collagen and elastin and apoptosis rates. Mitral valve interstitial cells (MICs) were transfected with ZFP36 plasmids to observe changes in the secretion of collagen, elastin and matrix metalloproteinases (MMPs) and apoptosis rates. MICs were exposed to TGF-beta 1 to evaluate the changes in expression of collagen, elastin, MMPs and ZFP36 and apoptosis. Subsequently, after transfection with ZFP36 plasmid, exogenous TGF-beta 1 was added to the MICs, and the secretion of collagen, elastin and MMPs and apoptosis rate were re-evaluated. Finally, transcriptome and RNA immunoprecipitation (RIP) sequencing was conducted to identify downstream genes of TGF-beta 1 that could bind to ZFP36. Patients with MVP showed elevated levels of TGF-beta 1 in plasma and increased rates of apoptosis, along with higher expression of ZFP36, TGF-beta 1, collagen and elastin in the prolapsed valve. Overexpression of ZFP36 in MICs did not significantly alter the secretion of collagen or elastin or apoptosis rates. TGF-beta 1 promoted apoptosis of MICs, increased the secretion of collagen, elastin, MMP-3,9, ZFP36 and reduced the expression of MMP-1,2,13. Moreover, overexpression of ZFP36 inhibited the effects of TGF-beta 1 on MICs. Co-analysis of transcriptome and RIP sequencing identified three genes: CFAP184, GTP binding protein 6 (GBP6) and HERC6. Knockdown of GBP6 reduced the pro-apoptotic effects of TGF-beta 1 on MICs. ZFP36 exerts a protective role in MVP by inhibiting the effects of TGF-beta 1 on MICs. Notably, ZFP36 can mitigate the pro-apoptotic effects of TGF-beta 1 on MICs through the GBP6 pathway.

关键词： identity   type 1 diabetes mellitus   T1DM   qualitative research  

摘要： Despite literature acknowledging the significance of identity, thorough understanding of how Type 1 Diabetes Mellitus (T1DM) impacts identity, and individuals' responses to this, is absent. This systematic literature review gathers, organises and evaluates existing qualitative studies investigating or reporting on how diagnosis of T1DM has impacted an individual's identity, and the ongoing impact that diagnosis of T1DM has on an individual's identity. Thematic synthesis of evidence from 13 studies produced four overarching themes: Social Identity;Loss of Self;Rejecting T1DM from Identity;and Acceptance into Identity. Findings highlight that T1DM impacts various aspects of an individual's identity and individuals may respond to this in a range of ways, including struggling to adhere to T1DM management. It is of significant importance that healthcare teams expand the way they think about and work with T1DM, developing appropriate psychological interventions, including conversations about identity and a broader systemic focus on T1DM stigma.

关键词： Genetic polymorphism   Sudden sensorineural hearing loss   X-ray repair cross-complementing group 1  

摘要： Objective:Sudden sensorineural hearing loss (SSNHL) is a condition with largely unknown etiology, though both vascular and genetic components have been implicated. The X-ray repair cross-complementing group 1 (XRCC1) gene, involved in DNA repair and oxidative stress response, has been linked to ischemic stroke and noise-induced hearing loss. This study aimed to investigate the association between XRCC1 single nucleotide polymorphisms (SNPs) and SSNHL risk in ***:Prospective case-control ***:Tertiary academic medical *** and methods:A total of 276 patients with SSNHL and 293 healthy controls were enrolled. Three XRCC1 SNPs (rs1799782, rs25489, and rs25487) were genotyped using TaqMan assays. All SNPs were tested for Hardy-Weinberg equilibrium. Associations with SSNHL risk were analyzed under dominant and recessive models using multivariate logistic regression. Clinical predictors of recovery were also ***:The TT genotype of XRCC1 rs1799782 was significantly associated with increased SSNHL risk compared with the CC genotype [adjusted odds ratio (aOR)=2.005;95% CI=1.13-3.62;P=0.0164]. This association persisted under the recessive model (TT vs. CC+CT) (aOR=1.983;95% CI=1.15-3.49;P=0.0134). No significant associations were observed for rs25489 and rs25487. High-tone (aOR=6.42;P = 0.0043) and flat-type (aOR=4.12;P=0.0071) audiogram patterns and longer treatment delay were linked to unfavorable clinical outcomes. XRCC1 genotypes were not predictive of treatment ***:The TT genotype of XRCC1 rs1799782 is significantly associated with increased SSNHL susceptibility in the Taiwanese population.

关键词： thyroid cancer   autoimmunity   thyroglobulin antibodies  

摘要： Introduction: Thyroglobulin antibodies (Tg-Abs) are often thought to be associated with thyroid autoimmunity, and as such, a link with thyroid cancer has been found in some, but not all, studies. Tg-Abs are also found in non-autoimmune thyroid-follicular destruction. Given these contradictory results, we designed the present study. Methods: We reviewed data from patients undergoing thyroidectomy for different indications in multiple centers across Greece and the US over 10 years. We compared the incidence of thyroid cancer and its features of tumor aggressiveness among patients with positive (>= 30 IU/mL) and negative (<30 IU/mL) Tg-Abs titers and the Tg-Abs titers among patients with cancer, benign disease, and those with and without features of tumor aggressiveness. Furthermore, we performed multivariate and multiple regression analyses to identify if these effects were independently statistically significant. Results: We reviewed n = 9463 consecutive thyroidectomies and included n = 2873 subjects in the present work: n = 1537 with thyroid cancer and n = 1336 with benign disease. The incidence of thyroid cancer was significantly higher in preoperative Tg-Abs+ subjects, n = 273/638 (57.2%), compared with Tg-Abs- subjects, n = 1063/2235 (52.4%), OR 1.21, p < 0.05. Tumor size was larger, and capsular invasion and lymph node involvement were significantly more common in Tg-Abs+ subjects. Mean Tg-Abs were higher in subjects with tumors with extrathyroidal extension, capsular invasion, and lymph node involvement. On regression, Tg-Abs positivity was not associated with thyroid cancer incidence or aggressiveness, though, with the important exception of lymph node involvement (p < 0.001). Conclusions: Elevated preoperative thyroglobulin-antibody titers do not seem to affect the likelihood of developing thyroid cancer, even though they seem to be a surrogate for lymph node metastasis (as opposed to thyroid peroxidase antibodies, TPO-Abs). Further work is needed to clarify

关键词： Programmed cell death protein 1/programmed death-ligand 1 inhibitors (PD-1/PD-L1 inhibitors)   triple-negative breast cancer (TNBC)   atezolizumab   pembrolizumab   chemotherapy (CT)  

摘要： Background: Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1)/ programmed death-ligand 1 (PD-L1), such as atezolizumab (Ate) and pembrolizumab (Pem), have expanded therapeutic options for breast cancer (BC). However, the comparative efficacy of ICI-chemotherapy (ICICT) combinations with different CT backbones [e.g., solvent-based paclitaxel vs. nab-paclitaxel (nP)] and the impact of steroid premedication (immunosuppressive, often required for solvent-based taxanes) on ICIs efficacy remain underexplored-gaps that hinder precise regimen selection. This meta-analysis evaluates the effectiveness of these regimens, focusing on triple-negative BC (TNBC) and PD-L1-positive populations. Methods: Searches were performed across PubMed, Embase, Cochrane and Web of Science to identify relevant studies comparing Ate- or Pem-based combinations (e.g., Ate + nP, Ate + CT, Pem + CT) with control regimens. Outcomes included overall survival (OS), progression-free survival (PFS), and subgroup analyses for TNBC. Meta-analyses were performed using random-effects models for pooled hazard ratios (HR) with corresponding 95% confidence intervals (CI). Heterogeneity was assessed using I2 statistics, and publication bias was evaluated using Cochran's Q. Results: A total of 12 studies involving 6,691 patients were included in the analysis. Ate combined with nP significantly improved OS (HR =0.75;95% CI: 0.65-0.86) and PFS (HR =0.69;95% CI: 0.62-0.78) compared to placebo + CT. Pem + CT also enhanced OS (HR =0.70;95% CI: 0.57-0.86;I2=4.9%) and PFS (HR =0.75;95% CI: 0.65-0.87;I2=44.6%). In TNBC, Ate-based regimens showed superior OS (HR =0.90;95% CI: 0.78-1.04;I2=24.2%) and PFS (HR =0.83;95% CI: 0.75-0.91;I2=49.0%), while Pem demonstrated Ate + CT in OS (HR =0.75 vs. 1.18) and PFS (HR =0.69 vs. 0.81), though CT combinations required further improving survival. These findings support prioritizing Ate + nP for this population in clinical practice and underscore th