Comprehensive analysis of stearoyl-coenzyme A desaturase in prostate adenocarcinoma: insights into gene expression, immune microenvironment and tumor progression.

Prostate adenocarcinoma (PRAD) is a prevalent global malignancy which depends more on lipid metabolism for tumor progression compared to other cancer types. Although Stearoyl-coenzyme A desaturase (SCD) is documented to regulate lipid metabolism in multiple cancers, landscape analysis of its implications in PRAD are still missing at present. Here, we conducted an analysis of diverse cancer datasets revealing elevated SCD expression in the PRAD cohort at both mRNA and protein levels. Interestingly, the elevated expression was associated with SCD promoter hypermethylation and genetic alterations, notably the L134V mutation. Integration of comprehensive tumor immunological and genomic data revealed a robust positive correlation between SCD expression levels and the abundance of CD8+ T cells and macrophages. Further analyses identified significant associations between SCD expression and various immune markers in tumor microenvironment. Single-cell transcriptomic profiling unveiled differential SCD expression patterns across distinct cell types within the prostate tumor microenvironment. The Gene Ontology and Kyoto Encyclopedia of Genes and Genome analyses showed that SCD enriched pathways were primarily related to lipid biosynthesis, cholesterol biosynthesis, endoplasmic reticulum membrane functions, and various metabolic pathways. Gene Set Enrichment Analysis highlighted the involvement of elevated SCD expression in crucial cellular processes, including the cell cycle and biosynthesis of cofactors pathways. In functional studies, SCD overexpression promoted the proliferation, metastasis and invasion of prostate cancer cells, whereas downregulation inhibits these processes. This study provides comprehensive insights into the multifaceted roles of SCD in PRAD pathogenesis, underscoring its potential as both a therapeutic target and prognostic biomarker.

An atlas on risk factors for gastrointestinal cancers: A systematic review of Mendelian randomization studies.

OBJECTIVE: Gastrointestinal cancers are one of the most frequent cancer types and seriously threaten human life and health. Recent studies attribute the occurrence of gastrointestinal cancers to both genetic and environmental factors, yet the intrinsic etiology remains unclear. Mendelian randomization is a powerful well-established statistical method that is based on genome-wide association study (GWAS) to evaluate the causal relationship between exposures and outcomes. In the present study, we aimed to conduct a systematic review of Mendelian randomization studies investigating any causal risk factors for gastrointestinal cancers. METHODS: We systematically searched Mendelian randomization studies that addressed the associations of genetically predicted exposures with five main gastrointestinal cancers from September 2014 to March 2024, as well as testing the research quality and validity. RESULTS: Our findings suggested robust and consistent causal effects of body mass index (BMI), basal metabolic rate, fatty acids, total cholesterol, total bilirubin, insulin like growth factor-1, eosinophil counts, interleukin 2, alcohol consumption, coffee consumption, apolipoprotein B on colorectal cancer risks, BMI, waist circumference, low-density lipoprotein (LDL), total testosterone, smoking on gastric cancer risks, BMI, fasting insulin, LDL, waist circumference, visceral adipose tissue (VAT), immune cells, type 2 diabetes mellitus (T2DM) on pancreatic cancer risks, waist circumference, smoking, T2DM on esophageal adenocarcinoma risks, and VAT, ferritin, transferrin, alcohol consumption, hepatitis B virus infection, rheumatoid arthritis on liver cancer risks, respectively. CONCLUSION: Larger, well-designed Mendelian randomization studies are practical in determining the causal status of risk factors for diseases.

Integrating network pharmacology and transcriptomics to study the potential mechanism of Jingzhi Niuhuang Jiedu tablet in rats with accumulation of heat in the lungs and stomach.

ETHNOPHARMACOLOGICAL RELEVANCE: Accumulation of heat in the lungs and stomach (AHLS) is an important syndrome within the realm of traditional Chinese medicine (TCM). It is the fundamental reason behind numerous illnesses, including mouth ulcers, dermatological conditions, acne, and pharyngitis. Jingzhi Niuhuang Jiedu tablet (JN) serves as the representative prescription for treatment of AHLS clinically. However, the effective components and mechanism of JN's impact on AHLS remain unexplored. AIM OF THE STUDY: The objective of this research was to analyze the effective components of JN and investigate the therapeutic effect and potential mechanism of JN on AHLS. MATERIALS AND METHODS: The effective compounds of JN extract were analyzed and identified using UHPLC-Q-Exactive/HRMS. Utilizing network pharmacology to investigate JN's multi-target, multi-pathway process in treating AHLS. Subsequently, anti-inflammatory activities of JN extract were evaluated in the RAW264.7 cells stimulated by lipopolysaccharide (LPS). In addition, a rat AHLS model induced by LPS and dried ginger was established. Pathological changes in rat lung and stomach tissues observed by HE staining and Masson's trichrome staining. Additionally, the expression of TNF-α, IL-6, and IL-1ß in bronchoalveolar lavage fluid (BALF) was identified through the ELISA assay. For a deeper understanding of how JN might affect AHLS, transcriptomics was utilized to examine differential genes and their underlying mechanisms. Concurrently, techniques like quantitative polymerase chain reaction (q-PCR), immunofluorescence, and western blotting (WB) were employed to confirm various mRNA and protein expression, including Il17ra, Il17re, IL-17A, IL-1ß, IL-6, PPARγ, PGC1-α and UCP1. RESULTS: We identified 178 potential effective components in the JN extract. Network pharmacology analysis showed that the 144 components in JN act on 200 key targets for the treatment of AHLS by suppressing inflammation, regulating energy metabolism, and gastric function. In addition, JN suppressed the LPS-stimulated generation of NO, TNF-α, IL-1ß, and IL-6 in RAW264.7 cells. And JN treatment effectively alleviated lung and stomach injury and reduced inflammation in rats. Analysis of RNA-seq from lung tissues revealed JN's substantial control over crucial genes in the IL-17 signaling pathway, including Il1b and Il17ra. Likewise, RNA sequencing of stomach tissues revealed that JN markedly decreased crucial genes in the Thermogenesis pathway, including Ppargc1a and Ppara. Additional experimental findings confirmed that treatment with JN significantly reduced the expression levels of mRNA (Il17ra, Il17re, Il1b, Ppargc1a and Ucp1), and the expression levels of protein (IL-17A, IL-1ß, IL-6, PPARγ, PGC1-α and UCP1). CONCLUSION: This study not only analyzes the effective components of JN but also reveals that JN could effectively ameliorate AHLS by inhibiting IL-17 signaling pathway and Thermogenesis pathway, which provides evidence for subsequent clinical studies and drug development.

Convergent evolution in high-altitude and marine mammals: Molecular adaptations to pulmonary fibrosis and hypoxia.

High-altitude and marine mammals inhabit distinct ecosystems but share a common challenge: hypoxia. To survive in low-oxygen environments, these species have evolved similar phenotypic pulmonary adaptations, characterized by a high density of elastic fibers. In this study, we explored the molecular mechanisms underlying these adaptations, focusing on pulmonary fibrosis and hypoxia tolerance through comparative genomics and convergent evolution analyses. We observed significant expansions and contractions in certain gene families across both high-altitude and marine mammals, closely associated with processes involved in pulmonary fibrosis. Notably, members of the keratin gene family, such as KRT17 and KRT14, appear to be associated with the development of the dense elastic fiber phenotype observed in the lungs of hypoxia-tolerant mammals. Through selection pressure and amino acid substitution analyses, we identified multiple genes exhibiting convergent accelerated evolution, positive selection, and amino acid substitution in these species, associated with adaptation to hypoxic environments. Specifically, the convergent evolution of ZFP36L1, FN1, and NEDD9 was found to contribute to the high density of elastic fibers in the lungs of both high-altitude and marine mammals, facilitating their hypoxia tolerance. Additionally, we identified convergent amino acid substitutions and gene loss events associated with sperm development, differentiation, and spermatogenesis, such as amino acid substitutions in SLC26A3 and pseudogenization of CFAP47, as confirmed by PCR. These genetic alterations may be linked to changes in the reproductive capabilities of these animals. Overall, this study offers novel perspectives on the genetic and molecular adaptations of high-altitude and marine mammals to hypoxic environments, with a particular emphasis on pulmonary fibrosis.

TRIM21 induces selective autophagic degradation of c-Myc and sensitizes regorafenib therapy in colorectal cancer.

Kirsten rat sarcoma virus (KRAS) mutation is associated with malignant tumor transformation and drug resistance. However, the development of clinically effective targeted therapies for KRAS-mutant cancer has proven to be a formidable challenge. Here, we report that tripartite motif-containing protein 21 (TRIM21) functions as a target of extracellular signal-regulated kinase 2 (ERK2) in KRAS-mutant colorectal cancer (CRC), contributing to regorafenib therapy resistance. Mechanistically, TRIM21 directly interacts with and ubiquitinates v-myc avian myelocytomatosis viral oncogene homolog (c-Myc) at lysine 148 (K148) via K63-linkage, enabling c-Myc to be targeted to the autophagy machinery for degradation, ultimately resulting in the downregulation of enolase 2 expression and inhibition of glycolysis. However, mutant KRAS (KRAS/MT)-driven mitogen-activated protein kinase (MAPK) signaling leads to the phosphorylation of TRIM21 (p-TRIM21) at Threonine 396 (T396) by ERK2, disrupting the interaction between TRIM21 and c-Myc and thereby preventing c-Myc from targeting autophagy for degradation. This enhances glycolysis and contributes to regorafenib resistance. Clinically, high p-TRIM21 (T396) is associated with an unfavorable prognosis. Targeting TRIM21 to disrupt KRAS/MT-driven phosphorylation using the antidepressant vilazodone shows potential for enhancing the efficacy of regorafenib in treating KRAS-mutant CRC in preclinical models. These findings are instrumental for KRAS-mutant CRC treatment aiming at activating TRIM21-mediated selective autophagic degradation of c-Myc.

Tumor-Selective Nano-Dispatcher Enforced Cancer Immunotherapeutic Effects via Regulating Lactate Metabolism and Activating Toll-Like Receptors.

The development of tumors relies on lactate metabolic reprogramming to facilitate their unchecked growth and evade immune surveillance. This poses a significant challenge to the efficacy of antitumor immunity. To address this, a tumor-selective nano-dispatcher, PIMDQ/Syro-RNP, to enforce the immunotherapeutic effect through regulation of lactate metabolism and activation of toll-like receptors is developed. By using the tumor-targeting properties of c-RGD, the system can effectively deliver monocarboxylate transporters 4 (MCT4) inhibitor (Syro) to inhibit lactate efflux in tumor cells, leading to decreased lactate levels in the tumor microenvironment (TME) and increased accumulation within tumor cells. The reduction of lactate in TME will reduce the nutritional support for regulatory T cells (Tregs) and promote the effector function of T cells. The accumulation of lactate in tumor cells will lead to tumor death due to cellular acidosis. In addition, it will also reduce the uptake of glucose by tumor cells, reduce nutrient plunder, and further weaken the inhibition of T cell function. Furthermore, the pH-responsive release of Toll-like receptors (TLR) 7/8 agonist IMDQ within the TME activates dendritic cells (DCs) and promotes the infiltration of T cells. These findings offer a promising approach for enhancing tumor immune response through targeted metabolic interventions.

Different preferences for inorganic carbon influence CO2 flux under Cyanobacteria or Chlorophyta dominance days.

Algae play critical roles in the carbon dioxide (CO2) exchange between the water bodies and the atmosphere. However, the effects of prokaryotic and eukaryotic algae on carbon utilization, CO2 flux, and the underlying mechanisms remain poorly understood. Therefore, this study investigated the differences in carbon preferences and CO2 fluxes under different algal dominance days. Our research revealed that dissolved inorganic carbon (DIC) concentration fluctuations had a limited effect on the relative abundance of algae. However, shifts in dominant algal phyla induced changes in DIC, with Cyanobacteria preferring HCO3- and Chlorophyta preferring CO2. Analysis of the water chemistry balance indicated that the growth of Chlorophyta had a 15.59 times greater effect on CO2 sinks compared with that of Cyanobacteria. During the Cyanobacteria dominance days, the lower DIC concentration did not result in a reduction in CO2 emissions. However, increases in the dissolved organic carbon concentration provided a favorable environment for Cyanobacteria, which promoted CO2 emissions. The CCM model indicated that the growth of Chlorophyta resulted in CO2 uptake rates at least 3.57 times higher and CO2 leakage rates up to 0.97 times lower compared to Cyanobacteria, accelerating CO2 transport into the cell. Overall, CO2 sink was stronger on Chlorophyta dominance days than on Cyanobacteria dominance days. This study emphasized the influence of algal phyla on CO2 fluxes, revealing the significant CO2 sink associated with Chlorophyta. Further research should investigate how to manipulate environmental factors to favor Chlorophyta growth and effectively reduce CO2 emissions.

The prospective associations of 24-hour movement behaviors and domain-specific activities with executive function and academic achievement among school-aged children in Singapore.

Background: Physical activity (PA), sedentary behavior (SB), and sleep are collectively referred to as 24-h movement behaviors, which may be linked to cognitive development in children. However, most of the evidence was based on cross-sectional studies and/or solely relied on parent-reported information on children's behaviors, and it remains uncertain whether all domains/contexts of PA and SB are similarly associated with executive function and academic achievement. Objective: We investigated the prospective associations of accelerometer-measured 24 h-movement behaviors and domain-specific PA and SB with executive function and academic achievement among school-aged children in Singapore. Methods: The Growing Up in Singapore Toward healthy Outcomes (GUSTO) cohort used a wrist-worn accelerometer (Actigraph-GT3x+) to measure 24 h-movement behaviors data at ages 5.5 and 8 years. Executive function and academic achievement were assessed using NEuroPSYchology (NEPSY) and Wechsler Individual Achievement Tests at ages 8.5 and 9-years, respectively. Compositional data analyses were conducted to explore the associations of 24 h-movement behavior with outcomes, and multiple linear regression models to examine the associations of domain-specific PA and SB with outcomes (n = 432). Results: Among 432 children whose parents agreed to cognitive assessments (47% girls and 58% Chinese), the composition of 24 h-movement behaviors at ages 5.5 and 8 years was not associated with executive function and academic achievement. However, higher moderate-to-vigorous PA (MVPA) relative to remaining movement behaviors at age 5.5 years was associated with lower academic achievement [Mean difference (95% confidence interval): -0.367 (-0.726, -0.009) z-score], and reallocating MVPA time to sleep showed higher academic achievement scores [30 min from MVPA to sleep: 0.214 (0.023, 0.404) z-score]. Certain domains of PA and SB, notably organized PA/sports, outdoor play, and reading books were favorably associated with outcomes of interest, while indoor play and screen-viewing were unfavorably associated. Conclusion: The associations between movement behaviors and cognitive outcomes are multifaceted, influenced by specific domains of PA and SB. This study underscores the importance of participation in organized PA/sports, outdoor active play, and reading books, while ensuring adequate sleep and limiting screen viewing, to enhance cognitive outcomes. These findings underscore the need for further research into time-use trade-offs. Such studies could have major implications for revising current guidelines or strategies aimed at promoting healthier 24 h-movement behaviors in children. Study registration: https://clinicaltrials.gov/, NCT01174875.

Shield-armed probiotic delivery system based on co-deposition of poly-dopamine and poly-l-lysine helps Lactiplantibacillus plantarum relieve hyperuricemia.

Hyperuricemia (HUA) is a disease characterized by an abnormal metabolism of purine. Lactic acid bacteria (LAB) have attracted much attention for their safe and effective treatment of HUA by inhibiting xanthine oxidase (XOD) and regulating gut microbiota. However, the effectiveness of probiotics can be compromised by the harsh environment of the gastrointestinal tract. In preliminary experiments, Lactiplantibacillus plantarum DY1, which is generally regarded as safe (GRAS), can lower uric acid. We have devised a straightforward and efficient technique for encapsulating DY1 using a coating comprising polydopamine (PDA) co-deposited with poly-l-lysine (PLL) to obtain DY1@PDLL. TEM, SEM, FT-IR and DLS tests showed that DY1 was successfully coated. Incubate at SGF or SIF for 3 h, the number of viable bacteria of free probiotics and DY1@PDLL decreased by 0.92 and 0.46 log cfu/mL, 1.66 and 0.66 log cfu/mL, respectively. The fluorescence intensity of the intestines of the DY1@PDLL treated mice was 3.96 times that of free probiotic. Notably, DY1@PDLL can reduce the uric acid levels of HUA mice by 31.63 % and free probiotics by 18.72 % (≈1.69 times). DY1@PDLL could also regulate gut microbiota and serum metabolic profile. These findings unequivocally highlight the remarkable potential of DY1@PDLL as an exceptional oral probiotic delivery system.

Neuroprotective effect and preparation methods of berberine.

Berberine (BBR) is a natural alkaloid, which has played an important role in the field of medicine since its discovery in the late 19th century. However, the low availability of BBR in vivo prevents its full effect. In recent years, a large number of studies confirmed that BBR has a protective effect on the nervous system through various functions, yet the issue of the inability to systematically understand the protection of BBR on the nervous system remains a gap that needs to be addressed. Many existing literature introductions about berberine in neurodegenerative diseases, but the role of berberine in the nervous system goes far beyond these. Different from these literatures, this review is divided into three parts: preparation method, mechanism, and therapeutic effect. Various dosage forms of BBR and their preparation methods are added, in order to provide a reasonable choice of BBR, and help to solve the problem of low bioavailability in treatment. More importantly, we more comprehensively summarize the mechanism of BBR to protect the nervous system, in addition to the treatment of neurodegenerative diseases (anti-oxidative stress, anti-neuroinflammation, regulation of apoptosis), two extra mechanisms of berberine for the protection of the nervous system were also introduced: bidirectional regulation of autophagy and promote angiogenesis. Also, we have clarified the precise mechanism by which BBR has a therapeutic effect not only on neurodegenerative illnesses but also on multiple sclerosis, gliomas, epilepsy, and other neurological conditions. To sum up, we hope that these can evoke more efforts to comprehensively utilize of BBR nervous system, and to promote the application of BBR in nervous system protection.

Ethanol extract of Vanilla planifolia stems reduces PAK6 expression and induces cell death in glioblastoma cells.

Glioblastoma multiforme (GBM) is a malignant tumour with a poor prognosis. Therefore, potential treatment strategies and novel therapeutic targets have gained increased attention. Our data showed that the ethanol extract of Vanilla planifolia stem (VAS) significantly decreased the viability and the colony formation of GBM cells. Moreover, VAS induced the cleavage of MAP1LC3, a marker of autophagy. Further RNA-seq and bioinformatic analysis revealed 4248 differentially expressed genes (DEGs) between VAS-treated GBM cells and the control cells. Protein-protein interactions between DEGs with fold changes less than -3 and more than 5 were further analysed, and we found that 16 and 9 hub DEGs, respectively, were correlated with other DEGs. Further qPCR experiments confirmed that 14 hub DEGs was significantly downregulated and 9 hub DEGs was significantly upregulated. In addition, another significantly downregulated DEG, p21-activated kinase 6 (PAK6), was correlated with the overall survival of GBM patients. Further validation experiments confirmed that VAS significantly reduced the mRNA and protein expression of PAK6, which led to the abolition of cell viability and colony formation. These findings demonstrated that VAS reduced cell viability, suppressed colony formation and induced autophagy and revealed PAK6 and other DEGs as potential therapeutic targets for GBM treatment.

Origin of ultrahigh-performance barium titanate-based piezoelectrics: Stannum-induced intrinsic and extrinsic contributions.

Despite the pivotal role of stannum doping in achieving ultrahigh piezoelectric performance in barium titanate-based ceramics, the fundamental mechanisms underlying this enhancement remain elusive. Here, we introduce a single variable nonstoichiometric stannum strategy in lead-free barium titanate-based ceramics with giant piezoelectricity, revealing that stannum doping contributes intrinsically and extrinsically to enhance piezoelectricity. Density functional theory calculations elucidate the intrinsic enhancement of polarization arising from lattice distortion and increased space for titanium-oxygen bonds induced by optimal stannum doping, which is corroborated by Rayleigh analysis. A phase transition from ferroelectric multiphase coexistence to paraelectric phase is observed, alongside a rapid miniaturized and eventually disappeared domains with increasing stannum doping. This evolution in phase structure and domain configuration induces a nearly vanishing polarization anisotropy and low domain wall energy, facilitating easy polarization rotation and domain wall motion, thereby significantly contributing to the extrinsic piezoelectric response. Consequently, the origins of ultrahigh performance can be attributed to the synergistic effect of stannum-induced intrinsic and extrinsic contributions in barium titanate-based ceramics. This study provides fundamental insights into the role of doping elements and offers guidance for the design of high-performance piezoelectrics.

Phylogenomics of Bivalvia Using Ultraconserved Elements (UCEs) Reveal New Topologies for Pteriomorphia and Imparidentia.

Despite significant advances in phylogenetics over the past decades, the deep relationships within Bivalvia (phylum Mollusca) remain inconclusive. Previous efforts based on morphology or several genes have failed to resolve many key nodes in the phylogeny of Bivalvia. Advances have been made recently using transcriptome data, but the phylogenetic relationships within Bivalvia historically lacked consensus, especially within Pteriomorphia and Imparidentia. Here, we inferred the relationships of key lineages within Bivalvia using matrices generated from specifically designed ultraconserved elements (UCEs) with 16 available genomic resources and 85 newly sequenced specimens from 55 families. Our new probes (Bivalve UCE 2k v.1) for target sequencing captured an average of 849 UCEs with 1085-bp in mean length from in vitro experiments. Our results introduced novel schemes from six major clades (Protobranchina, Pteriomorphia, Palaeoheterodonta, Archiheterodonta, Anomalodesmata and Imparidentia), though some inner nodes were poorly resolved, such as paraphyletic Heterodonta in some topologies potentially due to insufficient taxon sampling. The resolution increased when analyzing specific matrices for Pteriomorphia and Imparidentia. We recovered three Pteriomorphia topologies different from previously published trees, with the strongest support for ((Ostreida + (Arcida + Mytilida)) + (Pectinida + (Limida + Pectinida))). Limida were nested within Pectinida, warranting further studies. For Imparidentia, our results strongly supported the new hypothesis of (Galeommatida + (Adapedonta + Cardiida)), while the possible non-monophyly of Lucinida was inferred but poorly supported. Overall, our results provide important insights into the phylogeny of Bivalvia and show that target enrichment sequencing of UCEs can be broadly applied to study both deep and shallow phylogenetic relationships.

The effect of frailty on mortality and functional outcomes in spontaneous intracerebral haemorrhage.

INTRODUCTION: Limited data in patients with spontaneous intracerebral haemorrhage (SICH) showed that frailty was associated with mortality; however, there was insufficient data on functional outcomes. This study aimed to investigate the effect of frailty on overall mortality and 90-day functional outcomes in SICH. MATERIALS AND METHODS: We conducted a retrospective study of 1223 patients diagnosed with SICH from January 2014 to December 2020. Frailty was defined as a clinical frailty scale (CFS) score of 4-9. Binary cut-offs were defined using receiver operating curve analysis. 90-day poor functional outcomes (PFO) were defined as modified Rankin Scale (mRS) ≥3, and utility-weighted mRS (UW-mRS) were based on previous validated studies respectively. Regression analyses were conducted to investigate the association between frailty and outcomes. Confounders adjusted for included demographics, cardiovascular risk factors and haematoma characteristics. RESULTS: 1091 patients met the inclusion criterion. 167 (15.3 %) had 30-day mortality and 730 (66.9 %) had 90-day PFO. Frailty was significantly associated with lower overall survival (HR: 1.54; 95 % CI: 1.11-2.14, p=0.010), 90-day PFO (OR: 1.90; 95 % CI: 1.32-2.74; p<0.001) and poorer UW-mRS (ß: -0.06; 95 % CI: (-0.08 to -0.04); p<0.001) even after adjusting for confounders. CONCLUSIONS: Frailty was significantly associated with greater mortality and PFO after incident SICH, even after adjusting for a priori confounders. Frail male individuals may be predisposed to poorer outcomes from higher prevalence of cortical atrophy. The use of CFS in younger individuals may aid management by predicting outcomes after incident SICH. Identifying frail individuals with incident SICH could aid in decision-making and the surgical management of SICH.

Portable multimodal platform with carbon nano-onions as colorimetric and fluorescent signal output for trypsin detection.

Multimodal biosensors with independent signaling pathways can self-calibrate and improve the reliability of disease biomarker detection. Herein, a colorimetric-fluorescent dual-mode paper-based biosensor with PAN/Fe(III)-CNOs (FPCs) as core components has been developed, which information is recognized by smartphone and naked eye. Using 1-(2-pyridylazo)-2-naphthol (PAN) as a mediator, Fe(III) is enriched on the surface of carbon nano-onions (CNOs), endowing FPCs with excellent mimetic enzyme activity and photothermal conversion ability, which allows it to output amplified colorimetric signals under laser irradiation. In addition, the complexation of PAN with Fe(III) broadens its absorption spectrum, which makes FPCs more suitable to be energy acceptors to quench fluorescence of polymer dots (Pdots), resulting in the changes of output fluorescent signal. Based on the above design, a portable colorimetric-fluorescent dual-mode biosensor is proposed for trypsin detection with Pdots as fluorescence sources and FPCs as fluorescence quenchers and nanoenzymes. This work provides a convenient way for constructing portable visual multimodal biosensors, which is expected to applied in various disease diagnosis.

Computational Study on Flavin-Catalyzed Aerobic Dioxygenation of Alkenyl Thioesters: Decomposition of Anionic Peroxides.

Flavin-dependent catalysts are widely applied to aerobic monooxygenation/oxidation reactions. In contrast, flavin-catalyzed aerobic dioxygenation reactions exhibit higher atomic economy but are less reported, not to mention the relevant mechanistic studies. Herein, a density functional theory study on flavin-catalyzed aerobic epoxidation-oxygenolysis of alkenyl thioesters was performed for the first time. Different from the previous mechanistic proposal, a pathway featuring two catalytic stages, monoanionic flavin-C(4a)-peroxide/oxide intermediates, and a reverse reaction sequence (epoxidation goes prior to oxygenolysis) was revealed. In comparison, the pathways involving dianionic flavin catalysts, monoanionic flavin-N(5)-(hydro)peroxide/C(10a)-peroxide, or neutral flavin-C(4a)-hydroperoxide/hydroxide/N(5)-oxide, and the pathways where oxygenolysis goes prior to epoxidation are less favored. Epoxidation goes through intramolecular substitution of the O-O bond of anionic flavin-C(4a)-peroxide by ß-carbon, while the resulting flavin-C(4a)-oxide accomplishes the oxygenolysis. Furthermore, two other reaction modes, i.e., concerted O-O cleavage/1,2-shift of α-substituents and dyotropic rearrangement were discovered for the decomposition of other anionic peroxides, and preliminary rules were summarized for understanding the chemoselectivity for this process. This study sheds light on the different reaction features of numerous flavin-dioxygen derivatives, providing deeper insights into flavin-catalyzed dioxygenation reactions, and is expected to inspire experimental design based on unconventional anionic peroxides.

Anisomycin alleviates cognitive impairments and pathological features in 3xTg-AD mice.

Neuroinflammation plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). Anisomycin is a pyrrolidine antibiotic isolated from Streptomyces griseolus, which is an efficient anti-inflammatory agent that functions both in vivo and in vitro. However, it is not clear whether anisomycin can exert neuroprotective effect in AD. In the present study, anisomycin was intragastrically administrated to female triple-transgenic AD (3xTg-AD) model mice, then Morris water maze test was used to observe the long-term spatial memory of mice, the in vivo hippocampal field potential recording was performed to evaluate the synaptic plasticity, the Western blot and immunofluorescence were employed to detect pathological changes, and the bioinformatics analysis was used to predict the potential target of anisomycin exerting effects in AD. The results showed that anisomycin ameliorated the long-term spatial memory deficits, improved LTP depression and increased the expression of PSD-95, reduced the Aß and tau pathologies, and alleviated the activation of microglia and astrocytes in the brains of 3xTg-AD mice. In addition, the results from bioinformatics analysis showed that the potential target of anisomycin focused on inflammatory pathway. These results indicated that anisomycin exerts neuroprotective effects in 3xTg-AD mice by alleviating neuroinflammation, but the potential mechanism of anisomycin exerting neuroprotective effects needs to be further investigated.

Rich-silicon rice husk ash increases iron plaque formation and decreases cadmium and arsenic accumulation in rice seedlings.

Combined Cd (cadmium) and As (arsenic) pollution in cultivated land affects the safety of crops production and endangers human health. Rice (Oryza sativa L.) is a crop that uptakes Si (silicon), and Si can effectively promote rice growth and mitigate heavy metal toxicity. This study examined the effect and mechanism of Si-rich amendment (HA) prepared by aerobic combustion of rice husk on Cd and As accumulation in iron plaque and rice seedlings via hydroponic experiments. HA enhanced the vitality of rice growth because of its Si content and increased the amount of amorphous fraction iron plaques, furthermore, Cd content was decreased while the As was increased in both amorphous fraction and crystalline fraction iron plaques, resulting in the contents of Cd and As decreases by 10.0%-38.3% and 9.6%-42.8% for the shoots, and by 13.4%-45.2% and 9.9%-20.0% for the roots, respectively. In addition, X-ray diffraction and X-ray photoelectron spectroscopy illustrated significantly more Fe2O, MnO2 and MnO in the iron plaque after HA supply and the simultaneous existence of Mn-As and Mn-Si compounds. This result revealed less Cd from iron plaque and more As retention with HA supply, reducing the amount of Cd and As up taking and accumulation by rice seedlings. HA is beneficial to rice growth and reduce the absorption of heavy metals in plants. At the same time, HA is environmentally friendly, it can be used for the remediation of paddy fields contaminated by Cd and As.

Effect of concentration, temperature, and time on the stability of hepatitis C virus nucleic acid in serum.

To explore the influence of storage temperature and time on the stability of different concentrations of hepatitis C virus nucleic acid (HCV RNA) samples and to provide data reference for laboratory quality control. Serum samples of 10 patients with HCV RNA detection quantitation of 106-108 IU/mL were collected. The samples of each patient were diluted into three concentrations: high, medium, and low. Then the samples of each concentration were divided into 21, which were divided into three groups according to the storage conditions of -20°C, 4°C, and 25°C, with seven samples in each group. The samples were selected from each group for quantitative detection of HCV RNA on day 0, day 1, day 3, day 5, day 7, day 14, and day 30. The results of each concentration and storage temperature sample remained stable within 5 days. Based on the mixed-effect linear model, the main effects of temperature, time, and concentration were statistically significant (P < 0.01). There was an interaction effect between concentration and time (P = 0.0448), and there was also an interaction effect between temperature and time (P < 0.01). There was no interaction effect between concentration and temperature (P = 0.11) or between concentration, temperature, and time (P = 0.90). The results of serum samples with different concentrations of the HCV RNA remained stable within 5 days. The lower the initial concentration of HCV RNA serum sample, the worse the stability; the higher the storage temperature, the worse the stability. If conditions permit, the laboratory should store such samples at -20°C. IMPORTANCE: Previously, there were few reports about the influence of different concentrations of sample nucleic acid on the stability of samples at various temperatures and times in various literatures. Therefore, it is necessary to analyze the influence of concentration factors on the stability of samples and test results at different storage times and temperatures. This study took the concentration of hepatitis C virus nucleic acid as the research object to further understand the stability of hepatitis C virus nucleic acid test samples under various storage conditions, to provide data reference for the treatment of hepatitis C virus nucleic acid and RNA test samples before clinical laboratory test, and provide guidance and help for the improvement of laboratory quality control.