Heating conversion of indole-3-carbinol into N-substituted oligomers with anti-melanoma effect.

Cruciferous vegetables (CVs) are globally consumed with some health benefits believed to arise from indole-3-carbinol (I3C), a labile phytochemical liberated from indole glucosinolates, but few reports describe the effect of cooking on I3C reactions. Here, we present heat-promoted direct conversions of I3C in broccoli florets into indole derivatives, which are unique in the N-indolylmethylation and -hydroxymethylation of indole nuclei by 3-methyleneindole and formaldehyde formed in situ from the I3C dehydration and the dimerization of I3C to 3,3'-diindolylmethane (DIM), respectively. Such N-substituted indoles were found in a range of 0.4-4.6 µg per gram of steamed broccoli florets, with a novel compound N-(indol-3-ylmethyl)-3,3'-diindolylmethane (DIM-1) bio-evaluated to inhibit A375 cells with an IC50 value of 1.87 µM. In aggregation, the investigation discloses the promoting effect of heating on the I3C transformation in CVs and identifies DIM-1 as an anti-cancer drug candidate, and thus updates the knowledge of I3C and bioactive derivatives thereof.

Neuroimaging features of cognitive impairments in schizophrenia and major depressive disorder.

Cognitive dysfunctions are one of the key symptoms of schizophrenia (SZ) and major depressive disorder (MDD), which exist not only during the onset of diseases but also before the onset, even after the remission of psychiatric symptoms. With the development of neuroimaging techniques, these non-invasive approaches provide valuable insights into the underlying pathogenesis of psychiatric disorders and information of cognitive remediation interventions. This review synthesizes existing neuroimaging studies to examine domains of cognitive impairment, particularly processing speed, memory, attention, and executive function in SZ and MDD patients. First, white matter (WM) abnormalities are observed in processing speed deficits in both SZ and MDD, with distinct neuroimaging findings highlighting WM connectivity abnormalities in SZ and WM hyperintensity caused by small vessel disease in MDD. Additionally, the abnormal functions of prefrontal cortex and medial temporal lobe are found in both SZ and MDD patients during various memory tasks, while aberrant amygdala activity potentially contributes to a preference to negative memories in MDD. Furthermore, impaired large-scale networks including frontoparietal network, dorsal attention network, and ventral attention network are related to attention deficits, both in SZ and MDD patients. Finally, abnormal activity and volume of the dorsolateral prefrontal cortex (DLPFC) and abnormal functional connections between the DLPFC and the cerebellum are associated with executive dysfunction in both SZ and MDD. Despite these insights, longitudinal neuroimaging studies are lacking, impeding a comprehensive understanding of cognitive changes and the development of early intervention strategies for SZ and MDD. Addressing this gap is critical for advancing our knowledge and improving patient prognosis.

Puerarin alleviates atherosclerosis via the inhibition of Prevotella copri and its trimethylamine production.

OBJECTIVE: Puerarin (PU) is a natural compound that exhibits limited oral bioavailability but has shown promise in the treatment of atherosclerosis (AS). However, the precise mechanisms underlying its therapeutic effects remain incompletely understood. This study aimed to investigate the effects of PU and its mechanisms in mitigating AS in both mice and humans. DESIGN: The impact of PU on AS was examined in ApoE -/- mice fed a high-fat diet (HFD) and in human patients with carotid artery plaque. To explore the causal link between PU-associated gut microbiota and AS, faecal microbiota transplantation (FMT) and mono-colonisation of mice with Prevotella copri (P. copri) were employed. RESULTS: PU alleviated AS by modulating the gut microbiota, as evidenced by alterations in gut microbiota composition and the amelioration of AS following FMT from PU-treated mice into ApoE-/- mice fed HFD. Specifically, PU reduced the abundance of P. copri, which exacerbated AS by producing trimethylamine (TMA). Prolonged mono-colonisation of P. copri undermines the beneficial effects of PU on AS. In clinical, the plaque scores of AS patients were positively correlated with the abundance of P. copri and plasma trimethylamine-N-oxide (TMAO) levels. A 1-week oral intervention with PU effectively decreased P. copri levels and reduced TMAO concentrations in patients with carotid artery plaque. CONCLUSION: PU may provide therapeutic benefits in combating AS by targeting P. copri and its production of TMA. TRIAL REGISTRATION NUMBER: ChiCTR1900022488.

Copper-Catalyzed [4+1+1] Annulation of Ammonium Salts and Anthranils: Synthesis of 2,3-Diaroylquinolines.

A copper(I)-catalyzed protocol is developed for the synthesis of various 2,3-diaroylquinolines starting from achiral ammonium salts and anthranils through [4+1+1] annulation. Using copper(I) chloride as the sole catalyst, this reaction is featured with easily available starting materials, broad substrate scope, good yields and simple reaction conditions.

AP-1 and SP1 trans-activate the expression of hepatic CYP1A1 and CYP2A6 in the bioactivation of AFB1 in chicken.

Dietary exposure to aflatoxin B1 (AFB1) is harmful to the health and performance of domestic animals. The hepatic cytochrome P450s (CYPs), CYP1A1 and CYP2A6, are the primary enzymes responsible for the bioactivation of AFB1 to the highly toxic exo-AFB1-8,9-epoxide (AFBO) in chicks. However, the transcriptional regulation mechanism of these CYP genes in the liver of chicks in AFB1 metabolism remains unknown. Dual-luciferase reporter assay, bioinformatics and site-directed mutation results indicated that specificity protein 1 (SP1) and activator protein-1 (AP-1) motifs were located in the core region -1,063/-948, -606/-541 of the CYP1A1 promoter as well as -636/-595, -503/-462, -147/-1 of the CYP2A6 promoter. Furthermore, overexpression and decoy oligodeoxynucleotide technologies demonstrated that SP1 and AP-1 were pivotal transcriptional activators regulating the promoter activity of CYP1A1 and CYP2A6. Moreover, bioactivation of AFB1 to AFBO could be increased by upregulation of CYP1A1 and CYP2A6 expression, which was trans-activated owing to the upregulalion of AP-1, rather than SP1, stimulated by AFB1-induced reactive oxygen species. Additionally, nano-selenium could reduce ROS, downregulate AP-1 expression and then decrease the expression of CYP1A1 and CYP2A6, thus alleviating the toxicity of AFB1. In conclusion, AP-1 and SP1 played important roles in the transactivation of CYP1A1 and CYP2A6 expression and further bioactivated AFB1 to AFBO in chicken liver, which could provide novel targets for the remediation of aflatoxicosis in chicks.

Per- and polyfluoroalkyl substances and human health outcomes: An umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Although evidence on the association between per- and polyfluoroalkyl substances (PFASs) and human health outcomes has grown exponentially, specific health outcomes and their potential associations with PFASs have not been conclusively evaluated. METHODS: We conducted a comprehensive search through the databases of PubMed, Embase, and Web of Science from inception to February 29, 2024, to identify systematic reviews with meta-analyses of observational studies examining the associations between the PFASs and multiple health outcomes. The quality of included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and credibility of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The protocol of this umbrella review (UR) had been registered in PROSPERO (CRD 42023480817). RESULTS: The UR identified 157 meta-analyses from 29 articles. Using the AMSTAR measurement tool, all articles were categorized as of moderate-to-high quality. Based on the GRADE assessment, significant associations between specific types of PFASs and low birth weight, tetanus vaccine response, and triglyceride levels showed high certainty of evidence. Moreover, moderate certainty of evidence with statistical significance was observed between PFASs and health outcomes including lower BMI z-score in infancy, poor sperm progressive motility, and decreased risk of preterm birth as well as preeclampsia. Fifty-two (33%) associations (e.g., PFASs and gestational hypertension, cardiovascular disease, etc) presented low certainty evidence. Additionally, eighty-five (55%) associations (e.g., PFASs with infertility, lipid metabolism, etc) presented very low certainty evidence. CONCLUSION: High certainty of evidence supported that certain PFASs were associated with the incidence of low birth weight, low efficiency of the tetanus vaccine, and low triglyceride levels.

A reference-grade genome of the xerophyte Ammopiptanthus mongolicus sheds light on its evolution history in legumes and drought-tolerance mechanisms.

Plants that grow in extreme environments represent unique sources of stress-resistance genes and mechanisms. Ammopiptanthus mongolicus (Leguminosae) is a xerophytic evergreen broadleaf shrub native to semi-arid and desert regions; however, its drought-tolerance mechanisms remain poorly understood. Here, we report the assembly of a reference-grade genome for A. mongolicus, describe its evolutionary history within the legume family, and examine its drought-tolerance mechanisms. The assembled genome is 843.07 Mb in length, with 98.7% of the sequences successfully anchored to the nine chromosomes of A. mongolicus. The genome is predicted to contain 47 611 protein-coding genes, and 70.71% of the genome is composed of repetitive sequences; these are dominated by transposable elements, particularly long-terminal-repeat retrotransposons. Evolutionary analyses revealed two whole-genome duplication (WGD) events at 130 and 58 million years ago (mya) that are shared by the genus Ammopiptanthus and other legumes, but no species-specific WGDs were found within this genus. Ancestral genome reconstruction revealed that the A. mongolicus genome has undergone fewer rearrangements than other genomes in the legume family, confirming its status as a "relict plant". Transcriptomic analyses demonstrated that genes involved in cuticular wax biosynthesis and transport are highly expressed, both under normal conditions and in response to polyethylene glycol-induced dehydration. Significant induction of genes related to ethylene biosynthesis and signaling was also observed in leaves under dehydration stress, suggesting that enhanced ethylene response and formation of thick waxy cuticles are two major mechanisms of drought tolerance in A. mongolicus. Ectopic expression of AmERF2, an ethylene response factor unique to A. mongolicus, can markedly increase the drought tolerance of transgenic Arabidopsis thaliana plants, demonstrating the potential for application of A. mongolicus genes in crop improvement.

Paired Electrolysis-Enabled Arylation of Quinoxalin-2(1H)-ones.

The first paired electrolysis-enabled arylation of quinoxalin-2(1H)-ones was achieved using cyanoarenes as the arylation reagents. A variety of 3-arylquinoxalin-2(1H)-ones with various important functional groups were obtained in moderate to good yields under metal- and chemical oxidant-free conditions. With a pair of reductive and oxidative processes occurring among the substrates and reaction intermediates, the power consumption can be dramatically reduced.

Terrirubrum flagellatum gen. nov., sp. nov. of Terrirubraceae fam. nov. and Lichenibacterium dinghuense sp. nov. from forest soil and proposal of Rhodoblastaceae fam. nov.

Two Gram-negative, aerobic, rod-shaped bacterial strains, 7MK25T and 6Y81T, were isolated from forest soil of Dinghushan Biosphere Reserve, Guangdong Province, PR China. Based on the results of 16S rRNA gene sequence analysis, strain 7MK25T showed the highest similarity (93.6 %) to Methyloferula stellata AR4T, followed by Bosea thiooxidans DSM 9653T (93.3 %). Strain 6Y81T had the highest similarity of 97.9 % to Lichenibacterium minor RmlP026T, followed by Lichenibacterium ramalinae RmlP001T (97.2 %). Phylogenomic analysis using the UBCG and PhyloPhlAn methods consistently showed that strain 7MK25T formed a sister clade to Boseaceae, while strain 6Y81T formed an independent clade within the genus Lichenibacterium, both in the order Hyphomicrobiales. The digital DNA-DNA hybridization and average nucleotide identity values between strains 7MK25T, 6Y81T and their close relatives were in the ranges of 19.1-29.9 % and 72.5-85.5 %, respectively. The major fatty acids of 7MK25T were summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c), C19 : 0 cyclo ω8c, C16 : 0 and C17 : 0 cyclo, while those of 6Y81T were summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c), C16 : 0 and C16 : 0 3-OH. Strains 7MK25T and 6Y81T took diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and phosphatidylcholine as their dominant polar lipids, and Q-10 as their major respiratory quinone. On the basis of phenotypic and phylogenetic data, strain 7MK25T is proposed to represent a novel species of a novel genus with name Terrirubrum flagellatum gen. nov., sp. nov., within a novel family Terrirubraceae fam. nov., with 7MK25T (=KCTC 62738T=GDMCC 1.1452T) as its type strain. Strain 6Y81T represents a novel species in the genus Lichenibacterium, for which the name Lichenibacterium dinghuense sp. nov. (type strain 6Y81T=KACC 21 727T=GDMCC 1.2176T) is proposed. Rhodoblastaceae fam. nov. with Rhodoblastus as the type genus is also proposed to solve the non-monophylectic problem of the family Roseiarcaceae.

Physiological and biochemical characteristics of the carbon ion beam irradiation-generated mutant strain Clostridium butyricum FZM 240 in vitro and in vivo.

Clostridium butyricum (C. butyricum) represents a new generation of probiotics, which is beneficial because of its good tolerance and ability to produce beneficial metabolites, such as short-chain fatty acids and enzymes; however, its low enzyme activity limits its probiotic efficacy. In this study, a mutant strain, C. butyricum FZM 240 was obtained using carbon ion beam irradiation, which exhibited greatly improved enzyme production and tolerance. The highest filter paper, endoglucanase, and amylase activities produced by C. butyricum FZM 240 were 125.69 U/mL, 225.82 U/ mL, and 252.28 U/mL, which were 2.58, 1.95, and 2.21-fold higher, respectively, than those of the original strain. The survival rate of the strain increased by 11.40 % and 5.60 % after incubation at 90 °C for 5 min and with simulated gastric fluid at pH 2.5 for 2 h, respectively, compared with that of the original strain. Whole-genome resequencing and quantitative real-time PCR(qRT-PCR) analysis showed that the expression of genes related to enzyme synthesis (GE000348, GE001963 and GE003123) and tolerance (GE001114) was significantly up-regulated, while that of genes related to acid metabolism (GE003450) was significantly down-regulated. On this basis, homology modeling and functional prediction of the proteins encoded by the mutated genes were performed. According to the results, the properties related to the efficacy of C. butyricum as a probiotic were significantly enhanced by carbon ion beam irradiation, which is a novel strategy for the application of Clostridium spp. as feed additives.

The application value of deep learning-based nomograms in benign-malignant discrimination of TI-RADS category 4 thyroid nodules.

Thyroid nodules are a common occurrence, and although most are non-cancerous, some can be malignant. The American College of Radiology has developed the Thyroid Imaging Reporting and Data System (TI-RADS) to standardize the interpretation and reporting of thyroid ultrasound results. Within TI-RADS, a category 4 designation signifies a thyroid nodule with an intermediate level of suspicion for malignancy. Accurate classification of these nodules is crucial for proper management, as it can potentially reduce unnecessary surgeries and improve patient outcomes. This study utilized deep learning techniques to effectively classify TI-RADS category 4 thyroid nodules as either benign or malignant. A total of 500 patients were included in the study and randomly divided into a training group (350 patients) and a test group (150 patients). The YOLOv3 model was constructed and evaluated using various metrics, achieving an 84% accuracy in the classification of TI-RADS category 4 thyroid nodules. Based on the predictions of the model, along with clinical and ultrasound data, a nomogram was developed. The performance of the nomogram was superior in both the training and testing groups. Furthermore, the calibration curve demonstrated good agreement between predicted probabilities and actual outcomes. Decision curve analysis further confirmed that the nomogram provided greater net benefits. Ultimately, the YOLOv3 model and nomogram successfully improved the accuracy of distinguishing between benign and malignant TI-RADS category 4 thyroid nodules, which is crucial for proper management and improved patient outcomes.

Effect of total flavonoids of Dracocephalum moldavica L. On neuroinflammation in Alzheimer's disease model amyloid-ß (Aß1-42)-peptide-induced astrocyte activation.

One of the main pathological features noted in Alzheimer's disease (AD) is the presence of plagues of aggregated ß-amyloid (Aß1-42)-peptides. Excess deposition of amyloid-ß oligomers (AßO) are known to promote neuroinflammation. Sequentially, following neuroinflammation astrocytes become activated with cellular characteristics to initiate activated astrocytes. The purpose of this study was to determine whether total flavonoids derived from Dracocephalum moldavica L. (TFDM) inhibited Aß1-42-induced damage attributed to activated C8-D1A astrocytes. Western blotting and ELISA were used to determine the expression of glial fibrillary acidic protein (GFAP), and complement C3 to establish the activation status of astrocytes following induction from exposure to Aß1-42. Data demonstrated that stimulation of C8-D1A astrocytes by treatment with 40 µM Aß1-42 for 24 hr produced significant elevation in protein expression and protein levels of acidic protein (GFAP) and complement C3 accompanied by increased expression and levels of inflammatory cytokines. Treatment with TFDM or the clinically employed drug donepezil in AD therapy reduced production of inflammatory cytokines, and toxicity initiated following activation of C8-D1A astrocytes following exposure to Aß1-42. Therefore, TFDM similar to donepezil inhibited inflammatory secretion in reactive astrocytes, suggesting that TFDM may be considered as a potential compound to be utilized in AD therapy.

A Review: Cytochrome P450 in Alcoholic and Non-Alcoholic Fatty Liver Disease.

Alcoholic fatty liver disease (FALD) and non-alcoholic fatty liver disease (NAFLD) have similar pathological spectra, both of which are associated with a series of symptoms, including steatosis, inflammation, and fibrosis. These clinical manifestations are caused by hepatic lipid synthesis and metabolism dysregulation and affect human health. Despite having been studied extensively, targeted therapies remain elusive. The Cytochrome P450 (CYP450) family is the most important drug-metabolising enzyme in the body, primarily in the liver. It is responsible for the metabolism of endogenous and exogenous compounds, completing biological transformation. This process is relevant to the occurrence and development of AFLD and NAFLD. In this review, the correlation between CYP450 and liver lipid metabolic diseases is summarised, providing new insights for the treatment of AFLD and NAFLD.

Ni and Co Active Site Transition and Competition in Fluorine-Doped NiCo(OH)2 LDH Electrocatalysts for Oxygen Evolution Reaction.

The oxygen evolution reaction (OER) performance of NiCo LDH electrocatalysts can be improved through fluorine doping. The roles of Ni and Co active sites in such catalysts remain ambiguous and controversial. In addressing the issue, this study draws upon the molecular orbital theory and proposes the active center competitive mechanism between Ni and Co. The doped F-atoms can directly impact the valence state of metal atoms or exert an indirect influence through the dehydrogenation, thereby modulating the active center. As the F-atoms are progressively aggregate, the eg orbitals of Ni and Co transition from e2 g to e1 g , and subsequently to e0 g . The corresponding valence state elevates from +2 to +3, and then to +4, signifying an initial increase followed by a subsequent decrease in the electrocatalytic performance. Furthermore, a series of F-NiCo LDH catalysts are synthesized to verify the eg orbital occupancy analysis, and the catalytic OER overpotentials are 303, 243, 240, and 246 mV at the current density of 10 mA cm-2 , respectively, which coincides well with the theoretical prediction. This investigation not only provides novel mechanistic insights into the transition and competition of Ni and Co in F-NiCo LDH catalysts but also establishes a foundation for the design of high-performance catalysts.

Nanodrug delivery systems for regulating microglial polarization in ischemic stroke treatment: A review.

The incidence of ischemic stroke (IS) is rising in tandem with the global aging population. There is an urgent need to delve deeper into the pathological mechanisms and develop new neuroprotective strategies. In the present review, we discuss the latest advancements and research on various nanodrug delivery systems (NDDSs) for targeting microglial polarization in IS treatment. Furthermore, we critically discuss the different strategies. NDDSs have demonstrated exceptional qualities to effectively permeate the blood-brain barrier, aggregate at the site of ischemic injury, and target specific cell types within the brain when appropriately modified. Consequently, NDDSs have considerable potential for reshaping the polarization phenotype of microglia and could be a prospective therapeutic strategy for IS. The treatment of IS remains a challenge. However, this review provides a new perspective on neuro-nanomedicine for IS therapies centered on microglial polarization, thereby inspiring new research ideas and directions.

Identification and validation of UBE2B as a prognostic biomarker promoting the development of esophageal carcinomas.

Introduction: Ubiquitination is a crucial biological mechanism in humans, essential for regulating vital biological processes, and has been recognized as a promising focus for cancer therapy. Our objective in this research was to discover potential enzymes associated with ubiquitination that may serve as therapeutic targets for individuals with esophageal carcinoma (ESCA). Methods: To identify genes linked to the prognosis of ESCA, we examined mRNA sequencing data from patients with ESCA in the TCGA database. Further investigation into the role of the candidate gene in ESCA was conducted through bioinformatic analyses. Subsequently, we carried out biological assays to assess its impact on ESCA development. Results: Through univariate Cox regression analysis, we identified Ubiquitin Conjugating Enzyme E2 B (UBE2B) as a potential gene associated with the prognosis of ESCA. UBE2B exhibited significant upregulation and was found to be correlated with survival outcomes in ESCA as well as other cancer types. Additionally, UBE2B was observed to be involved in various biological pathways linked to the development of ESCA, including TNF-a signaling via NF-κB, epithelial-mesenchymal transition, inflammatory response, and hypoxia. Moreover, immune-related pathways like B cell activation (GO: 0042113), B cell receptor signaling pathway (GO: 0050853) and B cell mediated immunity (GO:0019724) were also involved. It was found that high expression of UBE2B was correlated with the increase of several kinds of T cells (CD8 T cells, Th1 cells) and macrophages, while effector memory T cell (Tem) and Th17 cells decreased. Furthermore, UBE2B showed potential as a prognostic biomarker for ESCA, displaying high sensitivity and specificity. Notably, proliferation and migration in ESCA cells were effectively suppressed when the expression of UBE2B was knocked down. Conclusions: To summarize, this study has made a discovery regarding the importance of gaining new insights into the role of UBE2B in ESCA. UBE2B might be an oncogene with good ability in predicting and diagnosing ESCA. Consequently, this discovery highlights the feasibility of targeting UBE2B as a viable approach for treating patients with ESCA.