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ABSTRACT: Egg production is an important economic trait in layer ducks and understanding the genetics basis is important for their breeding. In this study, a genome-wide association study (GWAS) for egg production traits in 303 female Longyan Shan-ma ducks was performed based on a genotyping-by-sequencing strategy. Sixty-two single nucleotide polymorphisms (SNPs) associated with egg weight traits were identified (P < 9.48 × 10-5), including 8 SNPs at 5% linkage disequilibrium (LD)-based Bonferroni-corrected genome-wide significance level (P < 4.74 × 10-6). One hundred and nineteen SNPs were associated with egg number traits (P < 9.48 × 10-5), including 13 SNPs with 5% LD-based Bonferroni-corrected genome-wide significance (P < 4.74 × 10-6). These SNPs annotated 146 target genes which contained known candidate genes for egg production traits, such as prolactin and prolactin releasing hormone receptor. This study identified that these associated genes were significantly enriched in egg production-related pathways (P < 0.05), such as the oxytocin signaling, MAPK signaling, and calcium signaling pathways. It was notable that 18 genes were differentially expressed in ovarian tissues between higher and lower egg production in Shan-ma ducks. The identified potential candidate genes and pathways provide insight into the genetic basis underlying the egg production trait of layer ducks.

Abstract Arterial occlusion-induced ischemic stroke (IS) is a highly frequent stroke subtype. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that modulates antioxidant genes. Its role in IS is still unelucidated. The current study focused on constructing a transient middle cerebral artery occlusion (tMCAO) model for investigating the NRF2-related mechanism underlying cerebral ischemia/reperfusion (I/R) injury. Each male C57BL/6 mouse was injected with/with no specific NRF2 activator post-tMCAO. Changes in blood–brain barrier (BBB)-associated molecule levels were analyzed using western-blotting, PCR, immunohistochemistry, and immunofluorescence analysis. NRF2 levels within cerebral I/R model decreased at 24-h post-ischemia. NRF2 activation improved brain edema, infarct volume, and neurological deficits after MCAO/R. Similarly, sulforaphane (SFN) prevented the down-regulated tight junction proteins occludin and zonula occludens 1 (ZO-1) and reduced the up-regulated aquaporin 4 (AQP4) and matrix metalloproteinase 9 (MMP9) after tMCAO. Collectively, NRF2 exerted a critical effect on preserving BBB integrity modulating ferroptosis and inflammation. Because NRF2 is related to BBB injury regulation following cerebral I/R, this provides a potential therapeutic target and throws light on the underlying mechanism for clinically treating IS.

AbstractInterferon-beta (IFN-[Formula: see text]) is one of the classical drugs for immunomodulatory therapy in relapsing-remitting multiple sclerosis (RRMS) patients, but the drug responsiveness of different patients varies. Currently, there is no valid model to predict IFN-[Formula: see text] responsiveness. This research attempted to develop an IFN-[Formula: see text] responsiveness prediction model based on mRNA expression in RRMS patient peripheral blood mononuclear cells. Peripheral blood mononuclear cell mRNA expression datasets including 50 RRMS patients receiving IFN-[Formula: see text] treatment were obtained from GEO. Among the datasets, 24 cases from GSE24427 were included in a training set, and 18 and 9 cases from GSE19285 and GSE33464, respectively, were adopted as two independent test sets. In the training set, blood samples were collected immediately before first, second, month 1, 12, and 24 IFN-[Formula: see text] injection, and the mRNA expression data at four time points, namely, two days, one month, one year and two years after the onset of IFN-[Formula: see text] treatment, were compared with pre-treatment data to identify IFN-stimulated genes (ISGs). The ISGs at the one-month time point were used to construct the drug responsiveness prediction model. Next, the drug responsiveness model was verified in the two independent test sets to examine the performance of the model in predicting drug responsiveness. Finally, we used CIBERSORTx to estimate the content of cell subtypes in samples and evaluated whether differences in the proportions of cell subtypes were related to differences in IFN-[Formula: see text] responsiveness. Among the four time points, one month was the time point when the training set GSE24427 and test set GSE33464 had the highest number of ISGs. Functional analysis showed that these one-month ISGs were enriched in biological functions such as the innate immune response, type-I interferon signalling pathway, and other IFN-[Formula: see text]-associated functions. Based on these ISGs, we obtained a four-factor prediction model for IFN-[Formula: see text] responsiveness including MX1, MX2, XAF1, and LAMP3. In addition, the model demonstrated favourable predictive performance within the training set and two external test sets. A higher proportion of activated NK cells and lower naive CD4/total CD4 ratio might indicate better drug responsiveness. This research developed a polygene-based biomarker model that could predict RRMS patient IFN-[Formula: see text] responsiveness in the early treatment period. This model could probably help doctors screen out patients who would not benefit from IFN-[Formula: see text] treatment early and determine whether a current treatment plan should be continued.

Zhoupigan (Citrus reticulata cv. Manau Gan) is a local citrus variety in China. Its peel, known as Zangju peel (ZJP). The metabolic profile and bioactivity of ZJP have not been adequately studied, resulting in underutilization of ZJP and a serious waste of resources. In this study, GC–MS identified 46 components in ZJP, which defined ZJP's distinct aroma. Furthermore, UPLC-ESI-MS/MS detected 1506 metabolites in ZJP, and the differential metabolites were primarily involved in the biosynthesis of flavonoids and phenylacetone. Additionally, 56 key differential metabolites with metabolic pathways were identified. ZJP had significant antioxidant activity and the enzyme inhibitory activity ranking as pancreatic lipase (IC50 = 3.71 mg/mL) > α-glucosidase (IC50 = 6.28 mg/mL) > α-amylase (IC50 = 8.02 mg/mL). This study aimed to evaluate the potential of ZJP as natural antioxidant and functional food source and to serve as foundation for the further development of ZJP products with specific functional attributes.

Pyrrolizidine alkaloids (PAs) and their N-oxide (PANOs), as emerging environmental pollutants and chemical hazards in food, have become the focus of global attention. PAs/PANOs enter crops from soil and reach edible parts, but knowledge about their uptake and transport behavior in crops is currently limited. In this study, we chose tea (Camellia sinensis L.) as a representative crop and Sp/SpNO as typical PAs/PANOs to analyze their root uptake and transport mechanism. Tea roots efficiently absorbed Sp/SpNO, utilizing both passive and active transmembrane pathways. Sp predominantly concentrated in roots and SpNO efficiently translocated to above-ground parts. The prevalence of SpNO in cell-soluble fractions facilitated its translocation from roots to stems and leaves. In soil experiment, tea plants exhibited weaker capabilities for the uptake and transport of Sp/SpNO compared to hydroponic conditions, likely due to the swift degradation of these compounds in the soil. Moreover, a noteworthy interconversion between Sp and SpNO in tea plants indicated a preference for reducing SpNO to Sp. These findings represent a significant stride in understanding the accumulation and movement mechanisms of Sp/SpNO in tea plants. The insights garnered from this study are pivotal for evaluating the associated risks of PAs/PANOs and formulating effective control strategies.

Scented green tea (Camellia sinensis) is a type of reprocessed green tea produced by scenting with flowers. To investigate the differences in the volatiles of scented green tea processed with four different flowers (Jasminum sambac, Osmanthus fragrans, Michelia alba, and Rosa rugosa), gas chromatography–ion mobility spectrometry (GC–IMS) and gas chromatography–mass spectrometry (GC–MS) were employed to detect and identify the volatile compounds in the four types of scented teas. GC–IMS and GC–MS identified 108 and 101 volatile compounds, respectively. The key characteristic volatile compounds, namely indole, linalool, β-myrcene, benzyl acetate, and ethyl benzoate (jasmine tea); cedrol, (E)-β-ionone, γ-decalactone, and dihydro-β-ionol (osmanthus tea); geraniol, phenylethyl alcohol, jasmone, methyl jasmonate, hexadecanoic acid, 4-ethyl-benzaldehyde, 2-methylbutyl hexanoate, and indole (michelia tea); and 3,5-dimethoxytoluene, (E)-β-ionone, and 2-methylbutyl hexanoate (rose tea), were identified through chemometric analysis combined with relative odor activity values (ROAVs) and sensory evaluation. This study provides new insights into the formation of aroma molecular fingerprints during green tea scenting with flowers, providing theoretical guidance for infusing distinct aroma characteristics into green tea during scented tea processing.

Cancer remains a highly lethal disease globally. The approach centered on REDOX-targeted mitochondrial therapy for cancer has displayed notable benefits. Plant polyphenols exhibit strong REDOX and anticancer properties, particularly by affecting mitochondrial function, yet their structural instability and low bioavailability hinder their utility. To overcome this challenge, researchers have utilized the inherent physical and chemical characteristics of polyphenols and their derivatives to develop innovative nanomedicines for targeting mitochondria. This review examines the construction strategies and anticancer properties of various types of polyphenol-based biological nanomedicine for regulating mitochondria in recent years, such as polyphenol self-assembly, metal–phenol network, polyphenol–protein, polyphenol–hydrogel, polyphenol–chitosan, and polyphenol–liposome. These polyphenolic nanomedicines incorporate enhanced features such as improved solubility, efficient photothermal conversion capability, regulation of mitochondrial homeostasis, and ion adsorption through diverse construction strategies. The focus is on how these polyphenol nanomedicines promote ROS production and their mechanism of targeting mitochondria to inhibit cancer. Furthermore, it delves into the benefits and applications of polyphenolic nanomedicine in cancer treatments, as well as the challenges for future research.

IntroductionDendrobium is an epiphytic herb plant with neuroprotective, gastroprotective, anti-inflammatory, and immunomodulatory effects. It is often found attached to tree trunks or rocks. With the development of the dendrobium industry, numerous epiphytic patterns exist, such as crushed stone, stump, and sawdust. The study of metabolites and endophytes of D. nobile under different epiphytic patterns, which revealed the effects of epiphytic patterns on D. nobile from the perspectives of metabolomics and microbiology, is of great significance for the healthy development of D. nobile.MethodsIn the study, the D. nobile under five epiphytic patterns grown in the same environment were selected. The metabolites were investigated by widely targeted metabolomics, and the endophytes were sequenced using high-throughput sequencing methods. Then, a correlation analysis between the different metabolites and endophytes was performed.ResultsA total of 1,032 metabolites were annotated in D. nobile. There are more flavonoids and phenolic acids accumulated on the epiphytic pattern of Danxia stone, whereas the accumulation of lipids on the other epiphytic patterns and 16 differential metabolites was screened out. The endophyte composition of D. nobile was dominated by Proteobacteria, Actinomycetes, unidentified bacteria, Firmicutes, and Cyanobacteria. For endophytic fungi, Basidiomycota and Ascomycota were the dominant phyla of D. nobile. The relative abundance of Spirosoma, Nocardioides, and Arrhenia in the Danxia stone was significantly higher than that of other epiphytic patterns. According to correlation analysis, we found a significant correlation between differential metabolites and Spirosoma, Nocardioides, and Arrheni.DiscussionThis study confirmed that Dendrobium quality was affected by its epiphytic patterns and revealed its possible causes from a microbiological point of view.

In this study, comprehensive and systematic nontargeted metabolomics analysis was performed with the metabolites of Zangju peel (Citrus reticulata cv. Manau Gan, CRZP, which has been cultivated for over 400 years in Derong County, China.) at four different mature stages. A total of 1878 metabolites were identified, among which flavonoids were the most abundant (62.04 %), and identified 62 key differential metabolites significantly affected by maturity. Based on biological activity measurements, CRZP showed better antioxidant activity, lipase inhibition ability, inhibition of adipogenic differentiation in 3TT-L1 cells and promotion of lipid metabolism, with the biological activity of CRZP at different maturity stages being associated with key differential metabolite. Thus, CRZP is natural antioxidants and possess anti-obesity potential, and industrial production needs to consider the Maturity stage of its collection.

Citrus is an important genus in the Rutaceae family, and citrus peels can be used in both food and herbal medicine. However, the bulk of citrus peels are discarded as waste by the fruit processing industry, causing environmental pollution. This study aimed to provide guidelines for the rational and effective use of citrus peels by elucidating the volatile and nonvolatile metabolites within them using metabolomics based on headspace-gas chromatography–ion mobility spectrometry and ultra-high-performance liquid chromatography–Q-Orbitrap high-resolution mass spectrometry. In addition, the antioxidant activities of the citrus peels were evaluated using DPPH radical scavenging, ABTS radical scavenging, and ferric reducing antioxidant power. In total, 103 volatile and 53 nonvolatile metabolites were identified and characterized. Alcohols, aldehydes, and terpenes constituted 87.36% of the volatile metabolites, while flavonoids and carboxylic acids accounted for 85.46% of the nonvolatile metabolites. Furthermore, (Z)-2-penten-1-ol, L-pipecolinic acid, and limonin were identified as characteristic components of Citrus reticulata Blanco cv. Ponkan (PK), C. reticulata ‘Unshiu’ (CLU), and C. reticulata ‘Wo Gan’ (WG), respectively. Principal component analysis and partial least squares discriminant analysis indicated that C. reticulata Blanco ‘Chun Jian’ (CJ), PK, CLU, and C. reticulata ‘Dahongpao’ (DHP) were clustered together. DHP is a traditional Chinese medicine documented in the Chinese Pharmacopoeia, suggesting that the chemical compositions of CJ, PK, and CLU may also have medicinal values similar to those of DHP. Moreover, DHP, PK, C. reticulata ‘Ai Yuan 38′(AY38), CJ, C. reticulata ‘Gan Ping’(GP), and C. reticulata ‘Qing Jian’(QJ) displayed better antioxidant activities, recommending their use as additives in cosmetics and food. Correlation analysis suggested that some polyphenols including tangeritin, nobiletin, skullcapflavone II, genistein, caffeic acid, and isokaempferide were potential antioxidant compounds in citrus peel. The results of this study deepen our understanding of the differences in metabolites and antioxidant activities of different citrus peel varieties and ultimately provide guidance for the full and rational use of citrus peels.

Chemotherapy exhibits numerous side effects in anti-tumour therapy. The clinical experiments indicated that deuterium-depleted water (DDW) monotherapy or in combination with chemotherapy was beneficial in inhibiting cancer development. To further understand the potential mechanism of DDW in cancer therapy, we performed a systematic review. The data from experiments published over the past 15 years were included. PubMed, Cochrane and Web of Science (January 2008 to November 2023) were systemically searched. Fifteen studies qualified for review, including fourteen in vivo and in vitro trials and one interventional trial. The results showed that DDW alone or in combination with chemotherapy effectively inhibited cancer progression in most experiments. The combination treatment enhances the therapeutic effect on cancer compared with chemotherapeutic monotherapy. The inhibitory role of DDW in tumours is through regulating the reactive oxygen species (ROS)-related genes in Kelch-like ECH-associated protein 1 (Keap 1) and Nuclear erythroid 2-related factor 2 (Nrf2) signalling pathways, further controlling ROS production. An abnormal amount of ROS can inhibit the tumour progression. More extensive randomized controlled trials should be conducted to evaluate the accurate effect of DDW in Keap1-Nrf2 signalling pathways.

Abstract Guillain–Barré syndrome (GBS) is an autoimmune disorder wherein the composition and gene expression patterns of peripheral blood immune cells change significantly. It is triggered by antigens with similar epitopes to Schwann cells that stimulate a maladaptive immune response against peripheral nerves. However, an atlas for peripheral blood immune cells in patients with GBS has not yet been constructed. This is a monocentric, prospective study. We collected 5 acute inflammatory demyelinating polyneuropathy (AIDP) patients and 3 healthy controls hospitalized in the First Affiliated Hospital of Harbin Medical University from December 2020 to May 2021, 3 AIDP patients were in the peak stage and 2 were in the convalescent stage. We performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from these patients. Furthermore, we performed cell clustering, cell annotation, cell–cell communication, differentially expressed genes (DEGs) identification and pseudotime trajectory analysis. Our study identified a novel clonally expanded CD14+ CD163+ monocyte subtype in the peripheral blood of patients with AIDP, and it was enriched in cellular response to IL1 and chemokine signaling pathways. Furthermore, we observed increased IL1β–IL1R2 cell–cell communication between CD14+ and CD16+ monocytes. In short, by analyzing the single-cell landscape of the PBMCs in patients with AIDP we hope to widen our understanding of the composition of peripheral immune cells in patients with GBS and provide a theoretical basis for future studies.

IntroductionThe plant microbiome is the second genome of plants and is important for plant growth and health. Dendrobium is an epiphytic herbal plant of the family Orchidaceae that is often found attached to tree trunks or rocks and exhibits different cultivation modes. Microbiological and metabolite studies of Dendrobium denneanum Kerr (D. denneanum) in different cultivation modes can reveal important relationships between Dendrobium spp., their microbiomes, and their pharmacological substances, which is important for sustainable agricultural development and human health, particularly in the study of medicinal plants.MethodsIn this study, three cultivation modes, living tree epiphytic (LT), stone epiphytic (SE), and pot cultivation (PO) of D. denneanum in the same environment were selected, and the metabolites were using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Subsequently, differential metabolites were screened, the rhizosphere and root endosphere microorganisms were sequenced via high-throughput sequencing, and the 16S rRNA gene/ITS sequences were obtained.ResultsThe main microbial taxa in the rhizosphere and root endosphere of D. denneanum included bacteria belonging to Proteobacteria, Actinobacteria, and Actinobacteria, and the fungi Basidiomycota and Ascomycota, whose abundances varied in different cultivation modes. Soil properties affect the composition of D. denneanum metabolites and root microbiome, among which, soil total phosphorus (TP) and pH in particular are important factors for soil microorganisms. Studies of root microbial communities have shown that root endosphere fungi are similar to rhizosphere fungi with microbial enrichment occurring from the external environment to the internal structures. Root microbial communities and metabolites correlation analyses revealed significant correlations between rhizosphere microbes, as well as endophytes and metabolites. For example, the rhizosphere bacterium genus Occallatibacter and root endosphere fungus Clonostachys showed a significant negative correlation with the pharmacodynamic substance gigantol in D. denneanum (P

Background Foam cells play crucial roles in all phases of atherosclerosis. However, until now, the specific mechanisms by which these foam cells contribute to atherosclerosis remain unclear. We aimed to identify novel foam cell biomarkers and interventional targets for atherosclerosis, characterizing their potential mechanisms in the progression of atherosclerosis. Methods Microarray data of atherosclerosis and foam cells were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expression genes (DEGs) were screened using the “LIMMA” package in R software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Ontology (GO) annotation were both carried out. Hub genes were found in Cytoscape after a protein-protein interaction (PPI) enrichment analysis was carried out. Validation of important genes in the GSE41571 dataset, cellular assays, and tissue samples. Results A total of 407 DEGs in atherosclerosis and 219 DEGs in foam cells were identified, and the DEGs in atherosclerosis were mainly involved in cell proliferation and differentiation. CSF1R and PLAUR were identified as common hub genes and validated in GSE41571. In addition, we also found that the expression of CSF1R and PLAUR gradually increased with the accumulation of lipids and disease progression in cell and tissue experiments. Conclusion CSF1R and PLAUR are key hub genes of foam cells and may play an important role in the biological process of atherosclerosis. These results advance our understanding of the mechanism behind atherosclerosis and potential therapeutic targets for future development.

Apelin and Elabela (Ela) are peptides encoded by APLN and APELA, respectively, which act on their receptor APJ and play crucial roles in the body. Recent research has shown that they not only have important effects on the endocrine system, but also promote vascular development and maintain the homeostasis of myocardial cells. From a molecular biology perspective, we explored the roles of Ela and apelin in the cardiovascular system and summarized the mechanisms of apelin-APJ signaling in the progression of myocardial infarction, ischemia-reperfusion injury, atherosclerosis, pulmonary arterial hypertension, preeclampsia, and congenital heart disease. Evidences indicated that apelin and Ela play important roles in cardiovascular diseases, and there are many studies focused on developing apelin, Ela, and their analogues for clinical treatments. However, the literature on the therapeutic potential of apelin, Ela and their analogues and other APJ agonists in the cardiovascular system is still limited. This review summarized the regulatory pathways of apelin/ELA-APJ axis in cardiovascular function and cardiovascular-related diseases, and the therapeutic effects of their analogues in cardiovascular diseases were also included.

Abstract Egg production traits are economically important in laying ducks. Genetic molecular mechanisms and candidate genes underlying these traits remain unclear. In this study, whole genome variants were identified through whole-genome resequencing using three high-egg producing (HEN) and three low-egg producing (LEN) laying ducks. The gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genome (KEGG) pathways for the genes of common differential variants between HEN and LEN ducks were determined. Frizzled class receptor 6 (FZD6) was further genotyped using the Sequenom MassARRAY iPLEX platform. The association of FZD6 gene polymorphisms with 73 egg production and weight traits in 329 female ducks were estimated. A total of 65,535 single nucleotide polymorphisms (SNPs) and 4,702 indels were identified across the genome. Fourteen GO terms and 14 KEGG pathways were determined for the genes of common differential variants, including MAPK signaling, Wnt signaling, melanogenesis and calcium signaling pathways, which are key functional pathways for poultry egg production reported in previous reports. Further analysis showed that 27 SNPs of FZD6 were associated with three early egg production of duck and egg weight traits, including egg production at 17 weeks (EP17), 18 weeks (EP18) and 19 weeks (EP19) and egg weight at 59 weeks (EW59). The FZD6 should be considered a novel candidate gene for egg production traits in laying ducks.

Ningnanmycin is a widely used antibiotic in agricultural production that effectively controls fungal and viral diseases in tea trees and chrysanthemums. The polarity characteristic of ningnanmycin has posed limitations on the development of robust detection methods, thereby hindering effective monitoring and control measures. By combining cation exchange solid phase extraction (SPE) with hydrophilic interaction chromatography tandem mass spectrometry (HILIC-MS/MS), we have effectively tackled the issue pertaining to the separation and retention of ningnanmycin. The average recoveries of ningnanmycin in green tea, black tea, and chrysanthemum were 77.3–82.0%, 80.1–81.5%, and 74.0–80.0%, respectively. The intraday and interday relative standard deviations (RSDs) were below and equal to 7.7%. Good linearity was observed in the concentration range of 1–1000 μg/L (R2 > 0.998). The limits of detection (LODs) ranged from 1.1 μg/kg to 7.1 μg/kg, and the limits of quantification (LOQs) ranged from 3.6 μg/kg to 23.7 μg/kg for ningnanmycin. These results indicate the good accuracy, repeatability, reproducibility, and sensitivity of the method. It is suitable for detecting ningnanmycin in tea and chrysanthemum.

In this paper, the effects of Ni content on the room and elevated temperature (250 °C) tensile strength of Al-7Si-1.5Cu-0.4Mg-0.3Mn-0.1RE-xNi (x = 0, 0.3, 0.6, 0.9 wt.%) alloys were investigated, along with microstructure characterization and tensile testing. In the as-cast state, the dominant Ni-rich phases were primarily the γ-Al7Cu4Ni and δ-Al3CuNi phases. Following the solution heat treatment, a significant reduction in the γ-Al7Cu4Ni phase was noted, accompanied by the emergence of numerous small ε-Al3Ni phases. Both room temperature strength and high temperature strength at 250 °C exhibited a consistent increase with rising Ni content, reaching 405 MPa and 261 MPa, respectively, at 0.9 Ni content, which were increased by 6.4% and 16.8%, respectively, compared with 0 Ni content. The elongation exhibited an oscillating increase within the Ni content range of 0 to 0.6, reaching peak values of 2.6% in room temperature and 4.3% in high temperature at 0.6 Ni, followed by a rapid decline. At 0.6 Ni content, the alloy demonstrated a well-balanced combination of mechanical properties, featuring commendable strength and plasticity.

Abstract Background The assembly of the rhizomicrobiome, i.e., the microbiome in the soil adhering to the root, is influenced by soil conditions. Here, we investigated the core rhizomicrobiome of a wild plant species transplanted to an identical soil type with small differences in chemical factors and the impact of these soil chemistry differences on the core microbiome after long-term cultivation. We sampled three natural reserve populations of wild rice (i.e., in situ) and three populations of transplanted in situ wild rice grown ex situ for more than 40 years to determine the core wild rice rhizomicrobiome. Results Generalized joint attribute modeling (GJAM) identified a total of 44 amplicon sequence variants (ASVs) composing the core wild rice rhizomicrobiome, including 35 bacterial ASVs belonging to the phyla Actinobacteria, Chloroflexi, Firmicutes, and Nitrospirae and 9 fungal ASVs belonging to the phyla Ascomycota, Basidiomycota, and Rozellomycota. Nine core bacterial ASVs belonging to the genera Haliangium, Anaeromyxobacter, Bradyrhizobium, and Bacillus were more abundant in the rhizosphere of ex situ wild rice than in the rhizosphere of in situ wild rice. The main ecological functions of the core microbiome were nitrogen fixation, manganese oxidation, aerobic chemoheterotrophy, chemoheterotrophy, and iron respiration, suggesting roles of the core rhizomicrobiome in improving nutrient resource acquisition for rice growth. The function of the core rhizosphere bacterial community was significantly (p < 0.05) shaped by electrical conductivity, total nitrogen, and available phosphorus present in the soil adhering to the roots. Conclusion We discovered that nitrogen, manganese, iron, and carbon resource acquisition are potential functions of the core rhizomicrobiome of the wild rice Oryza rufipogon. Our findings suggest that further potential utilization of the core rhizomicrobiome should consider the effects of soil properties on the abundances of different genera. Video Abstract

The DUF26 domain-containing protein is an extracellular structural protein, which plays an important role in signal transduction. Dongxiang wild rice (Oryza rufipogon Griff.) is the northern-most common wild rice in China. Using domain analysis, 85 DUF26 domain-containing genes were identified in Dongxiang wild rice (DXWR) and further divided into four categories. The DUF26 domain-containing genes were unevenly distributed on chromosomes, and there were 18 pairs of tandem repeats. Gene sequence analysis showed that there were significant differences in the gene structure and motif distribution of the DUF26 domain in different categories. Motifs 3, 8, 9, 13, 14, 16, and 18 were highly conserved in all categories. It was also found that there were eight plasmodesmata localization proteins (PDLPs) with a unique motif 19. Collinearity analysis showed that DXWR had a large number of orthologous genes with wheat, maize, sorghum and zizania, of which 17 DUF26 domain-containing genes were conserved in five gramineous crops. Under the stress of anaerobic germination and seedling submergence treatment, 33 DUF26 domain-containing genes were differentially expressed in varying degrees. Further correlation analysis with the expression of known submergence tolerance genes showed that these DUF26 domain-containing genes may jointly regulate the submergence tolerance process with these known submergence tolerance genes in DXWR.

IntroductionP. ternata is a perennial herb of the family Araceae that grows in China and has various medicinal properties and applications. At present, the artificial cultivation of P. ternata is constrained by seedling propagation. To address the problems of low seedling breeding propagation efficiency and high cost, our group has developed a highly efficient cultivation technology for "hydroponic cuttings of P. ternata "for the first time. P. ternata is used as the source material and is grown in a hydroponic system, increasing the seedling production rate 10-fold compared with the traditional cultivation mode. However, the callus formation mechanism in cuttings from hydroponic cultivation is still remains unclear.MethodsIn order to better understand the biological process of callus formation in cuttings from hydroponic P. ternata, anatomical characterization, endogenous hormone content determination and transcriptome sequencing were performed on five callus stages from early growth to early senescence.ResultsRegarding the four major hormones during the callus developmental stages of P. ternata hydroponic cuttings, cytokinins showed an increasing trend during callus formation. IAA(indole-3-acetic acid) and abscisic acid contents increased at 8d and then decreased, while jasmonic acid content gradually decreased. A total of 254137 unigenes were identified by transcriptome sequencing in five callus formation stages. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differentially expressed genes (DEGs) that differentially expressed unigenes were involved in various plant hormone signaling and hormone synthesis-related pathways. The expression patterns of 7 genes were validated using quantitative real-time PCR.DiscussionThis study presented integrated transcriptomic and metabolic analysis approach to obtain insights into the underlying biosynthetic mechanisms and function of key hormones involved in the callus formation process from hydroponic P. ternata cuttings.

IntroductionCitrus reticulata ‘Chachi’ peel (CRCP), which is named “Guangchenpi” in China, is a geographical indication product with unique flavor properties. CRCP has been used for centuries as a traditional genuine herb because of its excellent therapeutic effects. In addition, owing to its unique odor and high nutrition, it is widely used in various food preparations. Volatile organic compounds (VOCs) are regarded as an important quality marker for CRCP and are highly susceptible to effects in the drying process due to their thermal instability.MethodsIn the current study, the main VOCs in CRCP were processed using different drying methods, including sun-drying, hot air drying, and vacuum-freeze drying. The VOCs were identified by the electronic nose (E-nose), gas chromatography-ion mobility spectrometry (GC-IMS), and headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS).ResultsThe results showed that the CRCP dried by vacuum-freeze exhibited the highest VOCs contents and retained the richest compounds compared to those dried by other methods, which indicated that vacuum-freeze drying is the most suitable for CRCP production. Furthermore, the chemometrics analysis revealed that the primary differential metabolites of the samples generated using different drying methods were terpenes and esters.DiscussionOverall, our study would help better understand the VOCs present in CRCP with different drying methods. The outcomes of the current study would guide the drying and processing of CRCP, which is beneficial for large-scale storage and industrial production of CRCP.

Background: To reveal candidate genes and the molecular genetic mechanism underlying primary feather color trait in ducks, a genome-wide association study (GWAS) for the primary feather color trait was performed based on the genotyping-by-sequencing (GBS) technology for a native Chinese female duck, Longyan Shan-ma ducks.Methods: Blood genomic DNA from 314 female Longyan Shan-ma duck were genotyped using GBS technology. A GWAS for the primary feather color trait with genome variations was performed using an univariate linear mixed model based on all SNPs in autosomes.Results: Seven genome-wide significant single nucleotide polymorphisms (SNPs, Bonferroni-adjusted p-value

BackgroundImmune infiltration plays an important role in the course of ischemic stroke (IS) progression. Cuproptosis is a newly discovered form of programmed cell death. To date, no studies on the mechanisms by which cuproptosis-related genes regulate immune infiltration in IS have been reported.MethodsIS-related microarray datasets were retrieved from the Gene Expression Omnibus (GEO) database and standardized. Immune infiltration was extracted and quantified based on the processed gene expression matrix. The differences between the IS group and the normal group as well as the correlation between the infiltrating immune cells and their functions were analyzed. The cuproptosis-related DEGs most related to immunity were screened out, and the risk model was constructed. Finally, Gene Ontology (GO) function, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and drug target were performed using the Enrichr website database. miRNAs were predicted using FunRich software. Finally, cuproptosis-related differentially expressed genes (DEGs) in IS samples were typed, and Gene Set Variation Analysis (GSVA) was used to analyze the differences in biological functions among the different types.ResultsSeven Cuproptosis-related DEGs were obtained by merging the GSE16561 and GSE37587 datasets. Correlation analysis of the immune cells showed that NLRP3, NFE2L2, ATP7A, LIPT1, GLS, and MTF1 were significantly correlated with immune cells. Subsequently, these six genes were included in the risk study, and the risk prediction model was constructed to calculate the total score to analyze the risk probability of the IS group. KEGG analysis showed that the genes were mainly enriched in the following two pathways: D-glutamine and D-glutamate metabolism; and lipids and atherosclerosis. Drug target prediction found that DMBA CTD 00007046 and Lithocholate TTD 00009000 were predicted to have potential therapeutic effects of candidate molecules. GSVA showed that the TGF-β signaling pathway and autophagy regulation pathways were upregulated in the subgroup with high expression of cuproptosis-related DEGs.ConclusionsNLRP3, NFE2L2, ATP7A, LIPT1, GLS and MTF1 may serve as predictors of cuproptosis and play an important role in the pathogenesis of immune infiltration in IS.

Zangju (Citrus reticulata cv. Manau Gan) is the main citrus cultivar in Derong County, China, with unique aroma and flavour characteristics, but the use of Zangju peel (CRZP) is limited due to a lack of research on its peel. In this study, electronic nose, headspace-gas chromatography–ion mobility spectrometry (HS-GC–IMS), and partial least squares-discriminant analysis (PLS-DA) methods were used to rapidly and comprehensively evaluate the volatile compounds of dried CRZP and to analyse the role of dynamic changes at different maturation stages. The results showed that seventy-eight volatile compounds, mainly aldehydes (25.27%) and monoterpenes (55.88%), were found in the samples at four maturity stages. The contents of alcohols and aldehydes that produce unripe fruit aromas are relatively high in the immature stage (October to November), while the contents of monoterpenoids, ketones and esters in ripe fruit aromas are relatively high in the full ripening stage (January to February). The PLS-DA model results showed that the samples collected at different maturity stages could be effectively discriminated. The VIP method identified 12 key volatile compounds that could be used as flavour markers for CRZP samples collected at different maturity stages. Specifically, the relative volatile organic compounds (VOCs) content of CRZP harvested in October is the highest. This study provides a basis for a comprehensive understanding of the flavour characteristics of CRZP in the ripening process, the application of CRZP as a byproduct in industrial production (food, cosmetics, flavour and fragrance), and a reference for similar research on other C. reticulata varieties.

Apolipoproteins (APOs), the primary protein moiety of lipoproteins, are known for their crucial role in lipid traffic and metabolism. Despite extensive exploration of APOs in cardiovascular diseases, their roles in cancers did not attract enough attention. Recently, research focusing on the roles of APOs in cancers has flourished. Multiple studies demonstrate the interaction of APOs with classical pathways of tumorigenesis. Besides, the dysregulation of APOs may indicate cancer occurrence and progression, thus serving as potential biomarkers for cancer patients. Herein, we summarize the mechanisms of APOs involved in the development of various cancers, their applications as cancer biomarkers and their genetic polymorphism associated with cancer risk. Additionally, we also discuss the potential anti-cancer therapies by virtue of APOs. The comprehensive review of APOs in cancers may advance the understanding of the roles of APOs in cancers and their potential mechanisms. We hope that it will provide novel clues and new therapeutic strategies for cancers.

Edible herbal medicines contain macro- and micronutrients and active metabolites that can take part in biochemical processes to help achieve or maintain a state of well-being. Citri Reticulatae Pericarpium (CRP) is an edible and medicinal herb used as a component of the traditional Chinese medicine (TCM) approach to treating COVID-19 in China. However, the material basis and related mechanistic research regarding this herb for the treatment of COVID-19 are still unclear. First, a wide-targeted UPLC-ESI-MS/MS-based comparative metabolomics analysis was conducted to screen for the active metabolites of CRP. Second, network pharmacology was used to uncover the initial linkages among these metabolites, their possible targets, and COVID-19. Each metabolite was then further studied via molecular docking with the identified potential SARS-CoV-2 targets 3CL hydrolase, host cell target angiotensin-converting enzyme II, spike protein, and RNA-dependent RNA polymerase. Finally, the most potential small molecule compound was verified by in vitro and in vivo experiments, and the mechanism of its treatment of COVID-19 was further explored. In total, 399 metabolites were identified and nine upregulated differential metabolites were screened out as potential key active metabolites, among which isorhamnetin have anti-inflammatory activity in vitro validation assays. In addition, the molecular docking results also showed that isorhamnetin had a good binding ability with the key targets of COVID-19. Furthermore, in vivo results showed that isorhamnetin could significantly reduced the lung pathological injury and inflammatory injury by regulating ATK1, EGFR, MAPK8, and MAPK14 to involve in TNF signaling pathway, PI3K-Akt signalling pathway, and T cell receptor signaling pathway. Our results indicated that isorhamnetin, as screened from CRP, may have great potential for use in the treatment of patients with COVID-19. This study has also demonstrated that comparative metabolomics combined with network pharmacology strategy could be used as an effective approach for discovering potential compounds in herbal medicines that are effective against COVID-19.

Ischemia/reperfusion (I/R) injury is a common clinical problem after coronary angioplasty, cardiopulmonary resuscitation, and organ transplantation, which can lead to cell damage and death. Mitsugumin 53 (MG53), also known as Trim72, is a conservative member of the TRIM family and is highly expressed in mouse skeletal and cardiac muscle, with minimal amounts in humans. MG53 has been proven to be involved in repairing cell membrane damage. It has a protective effect on I/R injury in multiple oxygen-dependent organs, such as the heart, brain, lung, kidney, and liver. Recombinant human MG53 also plays a unique role in I/R, sepsis, and other aspects, which is expected to provide new ideas for related treatment. This article briefly reviews the pathophysiology of I/R injury and how MG53 mitigates multi-organ I/R injury.

Alzheimer’s disease (AD) has become a worldwide disease affecting human health and resulting in a heavy economic burden on the healthcare system. Polygonati rhizoma (PR), a kind of traditional Chinese medicine (TCM), is known to improve learning and memory abilities. However, its AD-treating material basis and therapeutic potential for the treatment of AD have remained unclear. Therefore, the present study aimed to uncover the key active ingredients of PR and its therapeutic potential for the treatment of AD. First, we used comparative metabolomics to identify the potential key active ingredients in the edible and medicinal PR. Second, network pharmacology was used to decipher the effects and potential targets of key active ingredients in the PR for the treatment of AD, and molecular docking was further used to identify the binding ability of those active ingredients with AD-related target of AChE. The rate of acetylcholinesterase (AChE) inhibition, oxidative stress, neuroprotective effects, and anti-inflammatory activity were assessed in vitro to screen the potential active ingredients in the PR with therapeutic potential against AD. Finally, APPswe/PS1dE9 AD mice were used to screen the therapeutic components in the PR. Seven overlapping upregulated differential metabolites were identified as the key active ingredients, among which cafestol, isorhamnetin, and rutin have AChE inhibitory activity, anti-inflammatory activity, and neuroprotective effects in vitro validation assays. Furthermore, in vivo results showed that cafestol, isorhamnetin, and rutin displayed several beneficial effects in AD transgenic mice by reducing the number of Aβ-positive spots and the levels of inflammatory cytokines, inhibiting the AChE activity, and increasing the antioxidant levels. Each compound is involved in a different function in the early stages of AD. In conclusion, our results corroborate the current understanding of the therapeutic effects of PR on AD. In addition, our work demonstrated that the proposed network pharmacology-integrated comparative metabolomics strategy is a powerful way of identifying key active ingredients and mechanisms contributing to the pharmacological effects of TCM.

Pericarpium Citri Reticulatae (PCR) is a natural citrus by-product with beneficial health and nutritive properties that is used widely in food and is an ingredient in traditional Chinese medicine. PCR improves gradually with aging. However, the present research has not yet revealed the reasons for this. Some data prove the important role of microorganisms in the quality of tobacco and fermented tea with the time of the aging of these foods. Our studies further proved that the coexisting Aspergillus niger plays an important role in the change of flavonoids and volatile oil in PCR during this process. Therefore, we put forward that longer storage is better for PCR and is highly correlated with the change of the coexisting microbial population structure caused by environmental factors. Samples of PCR aged in Beijing, Sichuan, Guangdong, and Yunnan were collected at different time points. Using GC/MS and high throughput 16S rDNA and ITS sequencing techniques, massive changes in volatile profile and microbial communities were observed during aging. Spearman correlation analysis indicated that Exobasidium, Xeromyces, Pseudocercospora, Russula, Aspergillus, Herbaspirillum, Sphingomonas, and Streptococcus, which are the dominant microbial genera in Sichuan and Guangdong showed strong connections with volatile components of chemical markers. It was preliminarily verified that the changes of volatile components for PCR are highly correlated with the change of the coexisting microbial population structure caused by environmental factors, providing a new idea for the research on the aging mechanism of PCR and key influencing factors of aging quality.

SPX-domain proteins (small proteins with only the SPX domain) have been proven to be involved in phosphate-related signal transduction and regulation pathways. Except for OsSPX1 research showing that it plays a role in the process of rice adaptation to cold stress, the potential functions of other SPX genes in cold stress are unknown. Therefore, in this study, we identified six OsSPXs from the whole genome of DXWR. The phylogeny of OsSPXs has a strong correlation with its motif. Transcriptome data analysis showed that OsSPXs were highly sensitive to cold stress, and real-time PCR verified that the levels of OsSPX1, OsSPX2, OsSPX4, and OsSPX6 in cold-tolerant materials (DXWR) during cold treatment were higher than that of cold-sensitive rice (GZX49). The promoter region of DXWR OsSPXs contains a large number of cis-acting elements related to abiotic stress tolerance and plant hormone response. At the same time, these genes have expression patterns that are highly similar to cold-tolerance genes. This study provides useful information about OsSPXs, which is helpful for the gene-function research of DXWR and genetic improvements during breeding.

According to the 2020 global cancer data released by the World Cancer Research Fund (WCRF) International, gastric cancer (GC) is the fifth most common cancer worldwide, with yearly increasing incidence and the second-highest fatality rate in malignancies. Despite the contemporary ambiguous molecular mechanisms in GC pathogenesis, numerous in-depth studies have demonstrated that zinc finger proteins (ZFPs) are essential for the development and progression of GC. ZFPs are a class of transcription factors with finger-like domains that bind to Zn2+ extensively and participate in gene replication, cell differentiation and tumor development. In this review, we briefly outline the roles, molecular mechanisms and the latest advances in ZFPs in GC, including eight principal aspects, such as cell proliferation, epithelial–mesenchymal transition (EMT), invasion and metastasis, inflammation and immune infiltration, apoptosis, cell cycle, DNA methylation, cancer stem cells (CSCs) and drug resistance. Intriguingly, the myeloid zinc finger 1 (MZF1) possesses reversely dual roles in GC by promoting tumor proliferation or impeding cancer progression via apoptosis. Therefore, a thorough understanding of the molecular mechanism of ZFPs on GC progression will pave the solid way for screening the potentially effective diagnostic indicators, prognostic biomarkers and therapeutic targets of GC.

Zinc (Zn2+) is the second most abundant necessary trace element in the human body, exerting a critical role in many physiological processes such as cellular proliferation, transcription, apoptosis, growth, immunity, and wound healing. It is an essential catalyst ion for many enzymes and transcription factors. The maintenance of Zn2+ homeostasis is essential for the central nervous system, in which Zn2+ is abundantly distributed and accumulates in presynaptic vesicles. Synaptic Zn2+ is necessary for neural transmission, playing a pivotal role in neurogenesis, cognition, memory, and learning. Emerging data suggest that disruption of Zn2+ homeostasis is associated with several central nervous system disorders including Alzheimer’s disease, depression, Parkinson’s disease, multiple sclerosis, schizophrenia, epilepsy, and traumatic brain injury. Here, we reviewed the correlation between Zn2+ and these central nervous system disorders. The potential mechanisms were also included. We hope that this review can provide new clues for the prevention and treatment of nervous system disorders.

Abstract Background Rice, which serves as a staple food for more than half of the world’s population, is grown worldwide. The hybridization of wild and cultivated rice has enabled the incorporation of resistance to varying environmental conditions. Endophytic microbiota are known to be transferred with their host plants. Although some studies have reported on the endophytic microbiota of wild and cultivated rice, the inheritance from wild and cultivated rice accessions in next generations, in terms of endophytic microbiota, has not been examined. Results In the present study, the endophytic microbial community structures of Asian and African wild and cultivated rice species were compared with those of their F1 offspring. High-throughput sequencing data of bacterial 16S rDNA and fungal internal transcribed spacer regions were used to classify the endophytic microbiota of collected samples of rice. Results indicated that when either African or Asian wild rice species were crossed with cultivated rice accessions, the first generation harbored a greater number of root endophytic fungi than the cultivated parent used to make the crosses. Network analysis of the bacterial and fungal operational taxonomic units revealed that Asian and African wild rice species clustered together and exhibited a greater number of significant correlations between fungal taxa than cultivated rice. The core bacterial genus Acidovorax and the core fungal order Pleosporales, and genera Myrothecium and Bullera connected African and Asian wild rice accessions together, and both the wild rice accessions with their F1 offspring. On the other hand, the core bacterial genus Bradyrhizobium and the core fungal genera Dendroclathra linked the African and Asian cultivated rice accessions together. Conclusions This study has theoretical significance for understanding the effect of breeding on the inheritance of endophytic microbiota of rice and identifying beneficial endophytic bacteria and fungi among wild and cultivated rice species, and their F1 offspring.

Background: Ischemic stroke is the most common stroke incident. Sphingosine-1-phosphate (S1P) receptor 3 (S1PR3) is a member of the downstream G protein-coupled receptor family of S1P. The effect of S1PR3 on ischemic stroke remains elusive.Methods: We downloaded two middle cerebral artery occlusion (MCAO) microarray datasets from the Gene Expression Omnibus (GEO) database and screened differentially expressed genes (DEGs). Then, we performed a weighted gene coexpression network analysis (WGCNA) and identified the core module genes related to ischemic stroke. We constructed a protein–protein interaction (PPI) network for the core genes in which DEGs and WGCNA intersected. Finally, we discovered that S1PR3 was involved as the main member of the red proteome. Then, we explored the mechanism of S1PR3 in the mouse tMCAO model. The S1PR3-specific inhibitor CAY10444 was injected into the abdominal cavity of mice after cerebral ischemia/reperfusion (I/R) injury, and changes in the expression of blood–brain barrier-related molecules were measured using PCR, western blotting, and immunofluorescence staining.Results: Both GEO datasets showed that S1PR3 was upregulated during cerebral I/R in mice. WGCNA revealed that the light yellow module had the strongest correlation with the occurrence of IS. We determined the overlap with DEGs, identified 146 core genes that are potentially related to IS, and constructed a PPI network. Finally, S1PR3 was found to be the main member of the red proteome. In the mouse cerebral I/R model, S1PR3 expression increased 24 h after ischemia. After the administration of CAY10444, brain edema and neurological deficits in mice were ameliorated. CAY10444 rescued the decreased expression of the tight junction (TJ) proteins zonula occludens 1 (ZO1) and occludin after ischemia induced by transient MCAO (tMCAO) and reduced the increase in aquaporin 4 (AQP4) levels after tMCAO, preserving the integrity of the BBB. Finally, we found that S1PR3 is involved in regulating the mitogen-activated protein kinase (MAPK) and (phosphatidylinositol-3 kinase/serine-threonine kinase) PI3K-Akt signaling pathways.Conclusion: S1PR3 participates in the regulation of blood–brain barrier damage after cerebral I/R. S1PR3 is expected to be an indicator and predictor of cerebral ischemia, and drugs targeting S1PR3 may also provide new ideas for clinical medications.

Abstract Pericarpium Citri Reticulatae (PCR), the mature fruit peel of Citrus reticulata Blanco and its different cultivars, is an important citrus by‐product with beneficial health and nutritive properties. However, due to the lack of value‐added methods for its development and utilization, a large amount of PCR is discarded or wasted. To explore a possibly more effective method to utilize PCR, we compared the chemical and biological differences before (CK) and after (CP) microbial transformation of PCR by Aspergillus niger. UPLC‐ESI‐MS/MS, HPLC, and LC‐MS methods were used to compare the chemical profiles of CK and CP. The results demonstrated that microbial biotransformation by A. niger could transform flavonoid compounds by utilizing the carbohydrate and amino acid nutrients in PCR. This could also promote the accumulation of polyhydroxyflavones compounds in CP. The antioxidant assay demonstrated that CP had significantly greater free radical‐scavenging activity than CK. The higher antioxidant activity of CP may result from the high level of flavonoids with associated phenolic hydroxyl groups. Microbial biotransformation is an effective method for improving the antioxidant capacity of PCR and may be effective and useful in other natural product situations.

Abstract Background Violaceins have attracted much attention as potential targets used in medicines, food additives, insecticides, cosmetics and textiles, but low productivity was the key factor to limit their large-scale applications. This work put forward a direct RBS engineering strategy to engineer the violacein biosynthetic gene cluster cloned from Chromobacterium violaceum ATCC 12,472 to efficiently improve the fermentation titers. Results Through four-rounds of engineering of the native RBSs within the violaceins biosynthetic operon vioABCDE, this work apparently broke through the rate-limiting steps of intermediates conversion, resulting in 2.41-fold improvement of violaceins production compared to the titers of the starting strain Escherichia coli BL21(DE3) (Vio12472). Furthermore, by optimizing the batch-fermentation parameters including temperature, concentration of IPTG inducer and fermentation time, the maximum yield of violaceins from (BCDE)m (tnaA −) reached 3269.7 µM at 2 mM tryptophan in the medium. Interestingly, rather than previous reported low temperature (20 ℃), we for the first time found the RBS engineered Escherichia coli strain (BCDE)m worked better at higher temperature (30 ℃ and 37 ℃), leading to a higher-level production of violaceins. Conclusions To our knowledge, this is the first time that a direct RBS engineering strategy is used for the biosynthesis of natural products, having the potential for a greater improvement of the product yields within tryptophan hyperproducers and simultaneously avoiding the costly low temperature cultivation for large-scale industrial production of violaciens. This direct RBS engineering strategy could also be easily and helpfully used in engineering the native RBSs of other larger and value-added natural product biosynthetic gene clusters by widely used site-specific mutagenesis methods represented by inverse PCR or CRISPR-Cas9 techniques to increase their fermentation titers in the future.

BackgroundIschemic stroke (IS) is a common disease endangering human life and health. Cerebral ischemia triggers a series of complex harmful events, including excitotoxicity, inflammation and cell death, as well as increased nitric oxide production through the activation of nitric oxide synthase (NOS). Oxidative stress plays a major role in cerebral ischemia and reperfusion. Sphingosine 1-phosphate receptor subtype 3 (S1PR3), a member of S1P’s G protein-coupled receptors S1PR1-S1PR5, is involved in a variety of biological effects in the body, and its role in regulating oxidative stress during cerebral ischemia and reperfusion is still unclear.MethodsTransient middle cerebral artery occlusion (tMCAO) mice were selected as the brain ischemia–reperfusion (I/R) injury model. Male C57/BL6 mice were treated with or without a selective S1PR3 inhibition after tMCAO, and changes in infarct volume, Nissl staining, hematoxylin-eosin (H&E) staining and NOS protein, nitric oxide (NO), superoxide dismutase (SOD), and malondialdehyde (MDA) content after tMCAO were observed.ResultsIn the cerebral ischemia–reperfusion model, inhibition of S1PR3 improved the infarct volume and neuronal damage in mice after tMCAO. Similarly, inhibition of S1PR3 can reduce the expression of NO synthase subtype neuronal NOS (nNOS) and reduce the production of NO after cerebral ischemia. After cerebral ischemia and reperfusion, the oxidative stress response was enhanced, and after the administration of the S1PR3 inhibitor, the SOD content increased and the MDA content decreased, indicating that S1PR3 plays an important role in regulating oxidative stress response.ConclusionInhibiting S1PR3 attenuates brain damage during I/R injury by regulating nNOS/NO and oxidative stress, which provides a potential new therapeutic target and mechanism for the clinical treatment of IS.

BackgroundMultiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) mediated by autoimmunity. No objective clinical indicators are available for the diagnosis and prognosis of MS. Extracellular proteins are most glycosylated and likely to enter into the body fluid to serve as potential biomarkers. Our work will contribute to the in-depth study of the functions of extracellular proteins and the discovery of disease biomarkers.MethodsMS expression profiling data of the human brain was downloaded from the Gene Expression Omnibus (GEO). Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases. GO and KEGG were used to analyze the function and pathway of EP-DEGs. STRING, Cytoscape, MCODE and Cytohubba were used to construct a protein-protein interaction (PPI) network and screen key EP-DEGs. Key EP-DEGs levels were detected in the CSF of MS patients. ROC curve and survival analysis were used to evaluate the diagnostic and prognostic ability of key EP-DEGs.ResultsWe screened 133 EP-DEGs from DEGs. EP-DEGs were enriched in the collagen-containing extracellular matrix, signaling receptor activator activity, immune-related pathways, and PI3K-Akt signaling pathway. The PPI network of EP-DEGs had 85 nodes and 185 edges. We identified 4 key extracellular proteins IL17A, IL2, CD44, IGF1, and 16 extracellular proteins that interacted with IL17A. We clinically verified that IL17A levels decreased, but Del-1 and resolvinD1 levels increased. The diagnostic accuracy of Del-1 (AUC: 0.947) was superior to that of IgG (AUC: 0.740) with a sensitivity of 82.4% and a specificity of 100%. High Del-1 levels were significantly associated with better relapse-free and progression-free survival.ConclusionIL17A, IL2, CD44, and IGF1 may be key extracellular proteins in the pathogenesis of MS. IL17A, Del-1, and resolvinD1 may co-regulate the development of MS and Del-1 is a potential biomarker of MS. We used bioinformatics methods to explore the biomarkers of MS and validated the results in clinical samples. The study provides a theoretical and experimental basis for revealing the pathogenesis of MS and improving the diagnosis and prognosis of MS.

Pesticides are widely used to maintain tea yields. For achieving satisfactory effects on pests, multiple pesticides in a low application dose have been the trend at present. In this study, we investigated the dissipation and dietary risk assessment of thiacloprid and tolfenpyrad. A method for the determination of thiacloprid and tolfenpyrad was developed. The recoveries ranged from 73% to 105% with standard deviations between 0.7% and 8.3%. Limits of quantification were 0.01 mg/kg for both pesticides. Field trials were conducted in China in 2021. The half-lives were in ranges of 3.22 to 8.45 days for thiacloprid and 2.91 to 10.50 days for tolfenpyrad. The terminal residues were in the range of 0.04–2.55 mg/kg for thiacloprid and

According to the global cancer burden data for 2020 issued by the World Health Organization (WHO), colorectal cancer has risen to be the third-most frequent cancer globally after breast and lung cancer. Despite advances in surgical treatment and chemoradiotherapy for colon cancer, individuals with extensive liver metastases still have depressing prognoses. Numerous studies suggest ZFPs are crucial to the development of colon cancer. The ZFP family is encoded by more than 2% of the human genome sequence and is the largest transcriptional family, all with finger-like structural domains that could combine with Zn2+. In this review, we summarize the functions, molecular mechanisms and recent advances of ZFPs in colon cancer. We also discuss how these proteins control the development and progression of colon cancer by regulating cell proliferation, EMT, invasion and metastasis, inflammation, apoptosis, the cell cycle, drug resistance, cancer stem cells and DNA methylation. Additionally, several investigations have demonstrated that Myeloid zinc finger 1 (MZF1) has dual functions in colon cancer, which may both promote cancer proliferation and inhibit cancer progression through apoptosis. Generally, a comprehensive understanding of the action mechanisms of ZFPs in colon cancer will not only shed light on the discovery of new diagnostic and prognosis indicators but will also facilitate the design of novel targeted therapies.

Rice, a cold-sensitive crop, is a staple food for more than 50% of the world’s population. Low temperature severely compromises the growth of rice and challenges China’s food safety. Dongxiang wild rice (DXWR) is the most northerly common wild rice in China and has strong cold tolerance, but the genetic basis of its cold tolerance is still unclear. Here, we report quantitative trait loci (QTLs) analysis for seedling cold tolerance (SCT) using a high-density single nucleotide polymorphism linkage map in the backcross recombinant inbred lines that were derived from a cross of DXWR, and an indica cultivar, GZX49. A total of 10 putative QTLs were identified for SCT under 4 °C cold treatment, each explaining 2.0–6.8% of the phenotypic variation in this population. Furthermore, transcriptome sequencing of DXWR seedlings before and after cold treatment was performed, and 898 and 3413 differentially expressed genes (DEGs) relative to 0 h in cold-tolerant for 4 h and 12 h were identified, respectively. Gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) analysis were performed on these DEGs. Using transcriptome data and genetic linkage analysis, combined with qRT-PCR, sequence comparison, and bioinformatics, LOC_Os08g04840 was putatively identified as a candidate gene for the major effect locus qSCT8. These findings provided insights into the genetic basis of SCT for the improvement of cold stress potential in rice breeding programs.

Pyrrolizidine alkaloids (PAs) are common constituents of plants and have serious hepatotoxicity. Intermedine (Im) and lycopsamine (La) are two monoesters of PAs that frequently coexist in the PA-containing plants (e.g., comfrey and tea). The present study aimed to explore the combined hepatotoxicity and toxicity mechanism of the Im and La mixture. In vitro, the combined cytotoxicity of the Im and La mixture on human hepatocytes (HepD) was examined by CCK-8, colony formation, wound healing, and Annexin V/PI staining assays. The combination of Im and La inhibited the ability of HepD cells to proliferate, colonize, and migrate and induced hepatocytes apoptosis in a dose-dependent manner. In addition to significantly causing a burst of intracellular reactive oxygen species (ROS), mitochondrial apoptosis, and endoplasmic reticulum (ER) stress, the Im and La mixture can also cause an increase in intracellular Ca2+, triggering the PERK/eIF2α/ATF4/CHOP apoptosis pathway. This study provided the first direct evidence that the combined PAs induced hepatotoxicity through ER-mediated apoptosis. These results supplemented the basic toxicity data for the combined PAs and provided a new perspective for the risk assessment of combined PA toxicity.

The cytosolic PNGase (peptide:N-glycanase), also known as peptide-N4-(N-acetyl-β-glucosaminyl)-asparagine amidase, is a well-conserved deglycosylation enzyme (EC 3.5.1.52) which catalyzes the non-lysosomal hydrolysis of an N(4)-(acetyl-β-d-glucosaminyl) asparagine residue (Asn, N) into a N-acetyl-β-d-glucosaminyl-amine and a peptide containing an aspartate residue (Asp, D). This enzyme (NGLY1) plays an essential role in the clearance of misfolded or unassembled glycoproteins through a process named ER-associated degradation (ERAD). Accumulating evidence also points out that NGLY1 deficiency can cause an autosomal recessive (AR) human genetic disorder associated with abnormal development and congenital disorder of deglycosylation. In addition, the loss of NGLY1 can affect multiple cellular pathways, including but not limited to NFE2L1 pathway, Creb1/Atf1-AQP pathway, BMP pathway, AMPK pathway, and SLC12A2 ion transporter, which might be the underlying reasons for a constellation of clinical phenotypes of NGLY1 deficiency. The current comprehensive review uncovers the NGLY1’ssdetailed structure and its important roles for participation in ERAD, involvement in CDDG and potential treatment for NGLY1 deficiency.

Abstract Aspergillus is a fungal genus widely studied all over the world because some species are known allergens and opportunistic human pathogens. The dynamic growth of Aspergillus is a prerequisite for establishing safe storage time of orange peel. In this paper, high‐throughput sequencing technique was used for the first time to analyze the diversity and structure of fungi in the same batch of samples at different periods of time, and 20 batches of fresh orange peel and 56 batches of dried peel were verified. Results shown that the orange peel gradually began to grow Aspergillus fungal after storing for 240 days, and the abundance became maximum at 270 days and then decreased. These results suggest the safe storage time should be from January to August. And orange peel should be dried in August to prevent rapid propagation or metabolic toxicity production of Aspergillus fungi.

Zinc (Zn) is the second most abundant necessary trace element in the human body. It is reported that zinc deficiency (ZD) promotes many types of cancer progression through multiple signal pathways. It is well known that oxidative stress, DNA damage, DNA repair, cell cycle, cell apoptosis, metabolic alterations, microRNAs abnormal expression, and inflammation level are closely related to cancer development. Cumulative evidence suggests that ZD influences these biological functions. This review explores the latest advances in understanding the role of ZD in tumorigenesis. Fully comprehending the potential mechanisms of ZD-induced tumors may provide novel clues for prevention and clinical treatment of cancers.

Aiming at the problem that it is difficult to extract the characteristics of the draft tube pressure fluctuation signal under the background of strong noise, this study proposes a dual noise reduction method based on adaptive local iterative filtering (ALIF) and singular value decomposition (SVD). First, perform ALIF decomposition of the signal to be decomposed to obtain a series of IMF components, calculate the sample entropy of each component, select some IMF components to reconstruct according to the set sample entropy threshold, and then perform SVD decomposition on the reconstructed signal, and according to the location of the singular value difference spectrum mutation point, the appropriate number of reconstructions is selected for reconstruction, so as to achieve the double noise reduction effect. The ALIF-SVD dual noise reduction method proposed in this study is compared with the single ALIF, EMD, and EMD-SVD dual noise reduction method through simulation, and the correlation coefficient, signal-to-noise ratio, and mean square error are used to evaluate the noise reduction. It is found that the ALIF-SVD dual noise reduction method avoids the phenomenon of modal aliasing in the decomposition process, effectively removes the noise, and can retain the useful information of the original signal, and the noise reduction effect is better. A unit of a hydropower station in China is further selected as the research object, and its draft tube pressure fluctuation data were analyzed for noise reduction. It was found that this method can accurately extract the signal characteristics under strong noise background, so as to determine the type of pressure fluctuation of the unit, which is helpful to improve the fault recognition rate of hydraulic turbines. And it provides some technical support for the safe and stable operation of hydropower units and the promotion of condition-based maintenance strategy and improves the intelligent level of hydropower station operation management.

Citrus cultivars are widely spread worldwide, and some of them only differ by specific mutations along the genome. It is difficult to distinguish them by traditional morphological identification. To accurately identify such similar cultivars, the subtle differences between them must be detected. In this study, UPLC-ESI-MS/MS-based widely targeted metabolomics analysis was conducted to study the chemical differences between two closely related citrus cultivars, Citrus reticulata 'DHP' and C. reticulata 'BZH'. Totally 352 metabolites including 11 terpenoids, 35 alkaloids, 80 phenolic acids, 25 coumarins, 7 lignans, 184 flavonoids and 10 other compounds were detected and identified; Among them, 15 metabolites are unique to DHP and 16 metabolites are unique to BZH. Hierarchical cluster analysis (HCA), principal component analysis (PCA), and orthogonal signal correction and partial least squares-discriminant analysis (OPLS-DA) can be used to clearly discriminate between DHP and BZH. 93 metabolites including 36 down-regulated and 57 up-regulated are significantly different in DHP and BZH. They are mainly involved in the biosynthesis of flavonoids, flavones, flavonols, and isoflavonoids. In addition, the relative content levels of flavonoids, alkaloids, and terpenoids are much higher in the peel of DHP than that of BZH, the presence of which may correlate with the quality difference of the peels. The results reported herein indicate that metabolite analysis based on UPLC-ESI-MS/MS is an effective means of identifying cultivars with different genotypes, especially those that cannot be distinguished based on traditional identification methods.