Corrigendum: Development of mini-barcode based on chloroplast genome and its application in metabarcoding molecular identification of Chinese medicinal material Radix Paeoniae Rubra (Chishao).

[This corrects the article DOI: 10.3389/fpls.2022.819822.].

Comparative transcriptome database for Camellia sinensis reveals genes related to the cold sensitivity and albino mechanism of 'Anji Baicha'.

Tea, a globally popular beverage, contains various beneficial secondary metabolites. Tea plants (Camellia sinensis) exhibit diverse genetic traits across cultivars, impacting yield, adaptability, morphology, and secondary metabolite composition. Many tea cultivars have been the subject of much research interest, which have led to the accumulation of publicly available RNA-seq data. As such, it has become possible to systematically summarize the characteristics of different cultivars at the transcriptomic level, identify functional genes, and infer gene functions through co-expression analysis. Here, the transcriptomes of 9 tea cultivars were assembled, and comparative analysis was conducted on the coding sequences of 13 cultivars. To give access to this data, we present TeaNekT (https://teanekt.sbs.ntu.edu.sg/), a web resource that facilitates the prediction of gene functions of various tea cultivars. We used TeaNekT to perform a cross-cultivar comparison of co-expressed gene clusters and tissue-specific gene expression. We observed that 'Anji Baicha' possesses the highest number of cultivar-specific genes and the second-highest number of expanded genes. These genes in 'Anji Baicha' tend to be enriched in functions associated with cold stress response, chloroplast thylakoid structure, and nitrogen metabolism. Notably, we identified three significantly expanded homologous genes in 'Anji Baicha' encoding the ICE1, SIZ1, and MAPKK2, which are closely associated with the cold sensitivity of 'Anji Baicha'. Additionally, one significantly expanded homologous gene in 'Anji Baicha' encoding regulatory factor RIQ may play a crucial role in the abnormal chloroplast structure and absence of thylakoid membranes in 'Anji Baicha'.

[Expression and Significance of PD-1/PD-L1 in MDS Blast Cells, T Lymphocyte Cell Subsets and Treg Cells].

OBJECTIVE: To investigate the expression and significance of PD-1/PD-L1 in MDS blast cells, T lymphocyte cell subsets and Treg cells. METHODS: Eighty-eight MDS patients and 19 AML patients were collectd as the study subjects, and Iron deficiency anemia and healthy bone marrow donors were used as control group. The expression of PD-1/PD-L1 in MDS/AML blast cells, T lymphocyte cell subsets and Treg cells was detected by flow cytometry, and the expression level of Th1/Th2/Th17-related cytokines in peripheral serum was detected. RESULTS: The expression of PD-1/PD-L1 in blast cells, T lymphocyte cell subsets and Treg cells in low risk MDS group were lower than that in control group, medium and high risk MDS group and AML group（all P < 0.01）, and Th1/Th17 type cytokines were dominant. The expression of PD-1/PD-L1 in blast cells, T lymphocyte cell subsets and Treg cells of intermediate and high risk MDS group and AML group were higher than that of control group and low risk MDS group (all P < 0.01), and Th2 type and Treg type (IL-10、TGF-ß) cytokines were dominant. After treatment, the differences of PD-1/PD-L1 expression were not statisticatly significant in blast cells, T lymphocyte cell subsets and Treg cells between the MDS remission group and the control group (all P >0.05). The expression of PD-1/PD-L1 in blast cells, T lymphocyte cell subsets and Treg cells in MDS non-remission group were significantly higher than that in remission group and control group (all P < 0.01). CONCLUSION: The high expression of PD-1/PD-L1, dominance of Treg (IL-10、TGF-ß) and Th2-related cytokines and inhibition of effector T lymphocyte cells in patients with MDS is conducive to tumor cell proliferation and immune escape, which may promote the progression of MDS disease.

Chiral inversion induced by aromatic interactions in short peptide assembly.

Although hydrophobic interactions provide the main driving force for initial peptide aggregation, their role in regulating suprastructure handedness of higher-order architectures remains largely unknown. We here interrogate the effects of hydrophobic amino acids on handedness at various assembly stages of peptide amphiphiles. Our studies reveal that relative to aliphatic side chains, aromatic side chains set the twisting directions of single ß-strands due to their strong steric repulsion to the backbone, and upon packing into multi-stranded ß-sheets, the side-chain aromatic interactions between strands form the aromatic ladders with a directional preference. This ordering not only leads to parallel ß-sheet arrangements but also induces the chiral flipping over of single ß-strands within a ß-sheet. In contrast, the lack of orientational hydrophobic interactions in the assembly of aliphatic peptides implies no chiral inversion upon packing into ß-sheets. This study opens an avenue to harness peptide aggregates with targeted handedness via aromatic side-chain interactions.

Bioinspired Three-Component System to Prepare Full-Color Functional Biomimetic Pigments.

Nature provides a great source of inspiration for the development of sustainable materials with excellent properties, among which melanin with optical, electronic, and radiation protection properties are considered to be promising coloring materials. However, compared to chemical pigments, the single color, complex oxidation process, and poor solubility of natural melanin strongly limit their further applications. Here, we introduce a series of melanin-like polymeric pigments with amino acid-encoded physicochemical properties by a simple three-component reaction system. Our protocol enables artificial control of the chromophore structures through the rational design of the substrates and dopants, thereby combining the safety and functionality of biopigments with the color richness of chemical dyes. Similar to the photoprotective effect of natural melanin, the polymeric pigments showed excellent antioxidant activity in reducing free radicals and have the advantages of iridescent color, strong tinting strength, stability, and affordability. Furthermore, due to their ability to dye substrates, these biomimetic are expected to become new low-cost bioactive chromophores and find various biochemical applications such as in clothing and hair dyeing, food addition, and anticounterfeiting detection.

Biochemical insights into tea foam: A comparative study across six categories.

Tea foam properties, crucial indicators of tea quality, have gained renewed interest due to their potential applications in innovative beverages and foods. This study investigated the foaming properties and chemical foundations of six major tea categories through morphological observations and biochemical analyses. White tea exhibited the highest foaming ability at 56.28%, while black tea showed the best foam stability at 84.01%. Conversely, green tea had the lowest foaming ability (10.83%) and foam stability (54.24%). These superior foaming characteristics are attributed to the relatively low lipid content and acidic pH values. Surprisingly, no significant correlation was found between tea saponin content and foaming properties. Instead, specific amino acids (including Tyr, Gaba, Phe, Ile, and Leu) and catechins (GA and CG) were identified as potential contributors. These results deepen our understanding of tea foam formation and offer insights into utilizing tea-derived plant-based foams in food products.

Analyzing urinary hippuric acid as a metabolic health biomarker through a supramolecular architecture.

The prevalence of metabolic disorders has been found to increase concomitantly with alternations in habitual diet and lifestyle, indicating the importance of metabolic health monitoring for early warning of high-risk status and suggesting effective intervention strategies. Hippuric acid (HA), as one of the most abundant metabolites from the gut microbiota, holds potential as a regulator of metabolic health. Accordingly, it is imperative to establish an efficient, sensitive, and affordable method for large-scale population monitoring, revealing the association between HA level and metabolic disorders. Upon systematic screening of macrocycle•dye reporter pair, a supramolecular architecture (guanidinomethyl-modified calix[5]arene, GMC5A) was employed to sense urinary HA by employing fluorescein (Fl), whose complexation behavior was demonstrated by theoretical calculations, accomplishing quantification of HA in urine from 249 volunteers in the range of 0.10 mM and 10.93 mM. Excitedly, by restricted cubic spline, urinary HA concentration was found to have a significantly negative correlation with the risk of metabolic disorders when it exceeded 0.76 mM, suggesting the importance of dietary habits, especially the consumption of fruits, coffee, and tea, which was unveiled from a simple questionnaire survey. In this study, we accomplished a high throughput and sensitive detection of urinary HA based on supramolecular sensing with the GMC5A•Fl reporter pair, which sheds light on the rapid quantification of urinary HA as an indicator of metabolic health status and early intervention by balancing the daily diet.

Construction of Smartphone-Integrated Nanozyme Sensor Based on Amino Acid-Modulated Gold Nanoparticles.

Amino acids are not only the building blocks of proteins but also lead to the development of novel nanomaterials with unique properties. Herein, we proposed a simple strategy to produce gold nanoparticles (Au NPs) with peroxidase-like (POD-like) activities by using a series of amino acids as reducing agents, named Au NPs@M (M represents different amino acids). The Au NPs@His was identified as the nanozyme with the most potent catalytic performance, which was used in combination with smartphones to achieve rapid detection of hydrogen peroxide with a detection limit of 0.966 µM. It also enables rapid detection of glucose with a detection limit of 2.904 µM, highlighting the significant contribution of Au NPs@His in expediting the detection of critical biomolecules. This work not only provides a convenient and highly efficient method to identify glucose but also shows the potential of histidine as a reducing agent in constructing Au nanomaterials exerting enzyme-like catalysis.

Black tea preserves intestinal homeostasis through balancing barriers and microbiota in mice.

Introduction: Black tea, a beverage consumed worldwide, possesses favorable effects on gastrointestinal tract, including nourishing stomach and promoting digestion. Nevertheless, its specific effects on intestinal homeostasis remains inconclusive. Methods: We applied black tea to mice prior to inducing colitis with DSS and then monitored their body weight and disease activity index (DAI) daily. When sacrificed, we measured intestinal permeability and conducted analyses of mucin and tight junction proteins. We detected inflammatory cytokines, immune cells, and related inflammatory signaling pathways. In addition, the gut microbiota was analyzed through 16S rRNA sequencing, and the concentrations of short-chain fatty acids (SCFAs) were also measured. Results: The results showed that black tea-treated group significantly rescued the DSS-disrupted intestinal structure. It reduced the relative abundance of the pathogenic bacterium Turicibacter, while increased the abundance of beneficial bacteria norank_f_Muribaculaceae and restored the contents of SCFAs such as acetate, propionate, and butyrate. It also protected the intestinal barrier by reducing the levels of immune response-related factors (e.g., TNF-α, IL-6, IL-1ß) and increasing the expression of tight junction proteins (TJs) (e.g., ZO-1, occludin). Furthermore, black tea exhibited the capacity to suppress the expression of MMP-9 and ICAM-1, as well as to inhibit the activation of NF-κB signaling pathway. Discussion: Our findings provide a theoretical framework that elucidates the mechanisms by which black tea preserves intestinal homeostasis, highlighting its potential as a preventive strategy against intestinal disruptions. This study contributes to the understanding of the dietary effects of black tea on gastrointestinal health.

Fungal fermentation of Fuzhuan brick tea: A comprehensive evaluation of sensory properties using chemometrics, visible near-infrared spectroscopy, and electronic nose.

Fuzhuan brick tea (FBT) fungal fermentation is a key factor in achieving its unique dark color, aroma, and taste. Therefore, it is essential to develop a rapid and reliable method that could assess its quality during FBT fermentation process. This study focused on using electronic nose (e-nose) and spectroscopy combination with sensory evaluations and physicochemical measurements for building machine learning (ML) models of FBT. The results showed that the fused data achieved 100 % accuracy in classifying the FBT fermentation process. The SPA-MLR method was the best prediction model for FBT quality (R2 = 0.95, RMSEP = 0.07, RPD = 4.23), and the fermentation process was visualized. Where, it was effectively detecting the degree of fermentation relationship with the quality characteristics. In conclusion, the current study's novelty comes from the established real-time method that could sensitively detect the unique post-fermentation quality components based on the integration of spectral, and e-nose and ML approaches.

Development of a paper-based transcription aptasensor for convenient urinary uric acid self-testing.

The abnormal uric acid (UA) level in urine can serve as warning signals of many diseases, such as gout and metabolic cardiovascular diseases. The current methods for detecting UA face limitations of instrument dependence and the requirement for non-invasiveness, making it challenging to fulfill the need for home-based application. In this study, we designed an aptasensor that combined UA-specific transcriptional regulation and a fluorescent RNA aptamer for convenient urinary UA testing. The concentration of UA can be translated into the intensity of fluorescent signals. The aptasensor showed higher sensitivity and more robust anti-interference performance. UA levels in the urine of different volunteers could be accurately tested using this method. In addition, a paper-based aptasensor for UA self-testing was manufactured, in which the urinary UA levels could be determined using a smartphone-based colorimetric approach. This work not only demonstrates a new approach for the design of disease-associated aptasensor, but also offers promising ideas for home-based detection of UA.

Study on Quality Characteristic of Chebulae Fructus and Its Adulterants and Degradation Pathway of Hydrolyzable Tannins.

Chebulae Fructus (CF) is known as one of the richest sources of hydrolyzable tannins (HTs). In this study, ultra-performance liquid chromatography coupled with a photodiode array detector method was established for simultaneous determination of the 12 common phenolcarboxylic and tannic constituents (PTCs). Using this method, quantitative analysis was accomplished in CF and other four adulterants, including Terminaliae Belliricae Fructus, Phyllanthi Fructus, Chebulae Fructus Immaturus, and Canarii Fructus. Based on a quantitative analysis of the focused compounds, discrimination of CF and other four adulterants was successfully accomplished by hierarchical cluster analysis and principal component analysis. Additionally, the total contents of the 12 compounds that we focused on in this study were unveiled as 148.86 mg/g, 96.14 mg/g, and 18.64 mg/g in exocarp, mesocarp, and endocarp and seed of CF, respectively, and PTCs were witnessed to be the most abundant in the exocarp of CF. Noticeably, the HTs (chebulagic acid, chebulanin acid, chebulinic acid, and punicalagin) were observed to be ultimately degraded to chebulic acid, gallic acid, and ellagic acid during sunlight-drying of the fresh fruits. As a result, our study indicated that CF and its adulterants could be distinguished by the observed 12 PTCs, which were mainly distributed in the exocarp of the fruits. The HTs were prone to degrade into the three simple phenolcarboxylic acids during drying or processing, allowing us to obtain a more comprehensive understanding of the PTCs, with great significance in the improved quality of CF and related products.

Antimicrobial therapy based on self-assembling peptides.

The emergence of drug-resistant microorganisms has threatened global health, and microbial infections have severely limited the use of medical materials. For example, the attachment and colonization of pathogenic bacteria to medical implant materials can lead to wound infections, inflammation and complications, as well as implant failure, shortening their lifespan and even resulting in patient death. In the era of antibiotic resistance, antimicrobial drug discovery needs to prioritize unconventional therapies that act on new targets or adopt new mechanisms. In this regard, supramolecular antimicrobial peptides have emerged as attractive therapeutic platforms, both as bactericides for combination antibiotics and as delivery vehicles. By taking advantage of their programmable intermolecular and intramolecular interactions, peptides can be modified to form higher-order structures (including nanofibers and nanoparticles) with unique functionality. This paper begins with an analysis of the relationship between peptide self-assembly and antimicrobial activity, describes in detail the research and development of various self-assembled antimicrobial peptides in recent years, and finally explores different combinatorial strategies for self-assembling antimicrobial peptides.

A method for mining condition-specific co-expressed genes in Camellia sinensis based on k-means clustering.

BACKGROUND: As one of the world's most important beverage crops, tea plants (Camellia sinensis) are renowned for their unique flavors and numerous beneficial secondary metabolites, attracting researchers to investigate the formation of tea quality. With the increasing availability of transcriptome data on tea plants in public databases, conducting large-scale co-expression analyses has become feasible to meet the demand for functional characterization of tea plant genes. However, as the multidimensional noise increases, larger-scale co-expression analyses are not always effective. Analyzing a subset of samples generated by effectively downsampling and reorganizing the global sample set often leads to more accurate results in co-expression analysis. Meanwhile, global-based co-expression analyses are more likely to overlook condition-specific gene interactions, which may be more important and worthy of exploration and research. RESULTS: Here, we employed the k-means clustering method to organize and classify the global samples of tea plants, resulting in clustered samples. Metadata annotations were then performed on these clustered samples to determine the "conditions" represented by each cluster. Subsequently, we conducted gene co-expression network analysis (WGCNA) separately on the global samples and the clustered samples, resulting in global modules and cluster-specific modules. Comparative analyses of global modules and cluster-specific modules have demonstrated that cluster-specific modules exhibit higher accuracy in co-expression analysis. To measure the degree of condition specificity of genes within condition-specific clusters, we introduced the correlation difference value (CDV). By incorporating the CDV into co-expression analyses, we can assess the condition specificity of genes. This approach proved instrumental in identifying a series of high CDV transcription factor encoding genes upregulated during sustained cold treatment in Camellia sinensis leaves and buds, and pinpointing a pair of genes that participate in the antioxidant defense system of tea plants under sustained cold stress. CONCLUSIONS: To summarize, downsampling and reorganizing the sample set improved the accuracy of co-expression analysis. Cluster-specific modules were more accurate in capturing condition-specific gene interactions. The introduction of CDV allowed for the assessment of condition specificity in gene co-expression analyses. Using this approach, we identified a series of high CDV transcription factor encoding genes related to sustained cold stress in Camellia sinensis. This study highlights the importance of considering condition specificity in co-expression analysis and provides insights into the regulation of the cold stress in Camellia sinensis.

Dan-shen Yin promotes bile acid metabolism and excretion to prevent atherosclerosis via activating FXR/BSEP signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Dan-shen Yin (DSY), a traditional prescription, has been demonstrated to be effective in decreasing hyperlipidemia and preventing atherosclerosis (AS), but its mechanism remains unknown. We hypothesized that DSY activates farnesoid X receptor (FXR) to promote bile acid metabolism and excretion, thereby alleviating AS. AIM OF THE STUDY: This study was designed to explore whether DSY reduces liver lipid accumulation and prevents AS by activating FXR and increasing cholesterol metabolism and bile acid excretion. MATERIALS AND METHODS: The comprehensive chemical characterization of DSY was analyzed by UHPLC-MS/MS. The AS models of ApoE-/- mice and SD rats was established by high-fat diet and high-fat diet combined with intraperitoneal injection of vitamin D3, respectively. The aortic plaque and pathological changes were used to evaluate AS. Lipid levels, H&E staining and oil red O staining were used to evaluate liver lipid accumulation. The cholesterol metabolism and bile acid excretion were evaluated by enzyme-linked immunosorbent assay, UPLC-QQQ/MS. In vitro, the lipid and FXR/bile salt export pump (BSEP) levels were evaluated by oil red O staining, real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. RESULTS: A total of 36 ingredients in DSY were identified by UPLC-MS/MS analysis. In vivo, high-dose DSY significantly inhibited aortic intimal thickening, improved arrangement disorder, tortuosity, and rupture of elastic fibers, decreased lipid levels, and reduced the number of fat vacuoles and lipid droplets in liver tissue in SD rats and ApoE-/- mice. Further studies found that high-dose DSY significantly reduced liver lipid and total bile acids levels, increased liver ursodeoxycholic acid (UDCA) and other non-conjugated bile acids levels, increased fecal total cholesterol (TC) levels, and augmented FXR, BSEP, cholesterol 7-alpha hydroxylase (CYP7A1), ATP binding cassette subfamily G5/G8 (ABCG5/8) expression levels, while decreasing ASBT expression levels. In vitro studies showed that DSY significantly reduced TC and TG levels, as well as lipid droplets, while also increasing the expression of ABCG5/8, FXR, and BSEP in both HepG2 and Nr1h4 knockdown HepG2 cells. CONCLUSION: This study demonstrated that DSY promotes bile acid metabolism and excretion to prevent AS by activating FXR. For the prevent of AS and drug discovery provided experimental basis.

Compounds identification and mechanism prediction of YuXueBi capsule in the treatment of arthritis by integrating UPLC/IM-QTOF-MS and network pharmacology.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that seriously affects the life quality of patients. As a patent medicine of Chinese traditional medicine, YuXueBi capsule (YXBC) is widely used for treating RA with significant effects. However, its active compounds and therapeutic mechanisms are not fully illuminated, encumbering the satisfactory clinical application. In this study, we developed a method for identifying the chemical compounds of YXBC and the absorbed compounds into blood of rats using ultra performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry (UPLC/IM-QTOF-MS) combined with UNIFI analysis software. A total of 58 compounds in YXBC were unambiguously or tentatively identified, 16 compounds from which were found in serum of rats after administration of YXBC. By network pharmacology, these prototype compounds identified in serum were predicted to regulate 30 main pathways (including HIF-1 signaling pathway, neuroactive ligand-receptor interaction, IL-17 signaling pathway, and so on) through 146 targets, resulting in promoting blood circulation and removing blood stasis, analgesia, and anti-inflammatory activities. This study provides a scientific basis for the clinical efficacy of YXBC in the treatment of RA.

Identifying the temporal contributors and their interactions during dynamic formation of black tea cream.

Tea cream formed in hot and strong tea infusion while cooling deteriorates quality and health benefits of tea. However, the interactions among temporal contributors during dynamic formation of tea cream are still elusive. Here, by deletional recombination experiments and molecular dynamics simulation, it was found that proteins, caffeine (CAF), and phenolics played a dominant role throughout the cream formation, and the contribution of amino acids was highlighted in the early stage. Furthermore, CAF was prominent due to its extensive binding capacity and the filling complex voids property, and caffeine-theaflavins (TFs) complexation may be the core skeleton of the growing particles in black tea infusion. In addition to TFs, the unidentified phenolic oxidation-derived products (PODP) were confirmed to contribute greatly to the cream formation.

Overcoming Endosomal Escape Barriers in Gene Drug Delivery Using De Novo Designed pH-Responsive Peptides.

A major challenge in using nanocarriers for intracellular drug delivery is their restricted capacity to escape from endosomes into the cytosol. Here, we significantly enhance the drug delivery efficiency by accurately predicting and regulating the transition pH (pH0) of peptides to modulate their endosomal escape capability. Moreover, by inverting the chirality of the peptide carriers, we could further enhance their ability to deliver nucleic acid drugs as well as antitumor drugs. The resulting peptide carriers exhibit versatility in transfecting various cell types with a high efficiency of up to 90% by using siRNA, pDNA, and mRNA. In vivo antitumor experiments demonstrate a tumor growth inhibition of 83.4% using the peptide. This research offers a potent method for the rapid development of peptide vectors with exceptional transfection efficiencies for diverse pathophysiological indications.

MetDIT: Transforming and Analyzing Clinical Metabolomics Data with Convolutional Neural Networks.

Clinical metabolomics is growing as an essential tool for precision medicine. However, classical machine learning algorithms struggle to comprehensively encode and analyze the metabolomics data due to their high dimensionality and complex intercorrelations. This article introduces a new method called MetDIT, designed to analyze intricate metabolomics data effectively using deep convolutional neural networks (CNN). MetDIT comprises two components: TransOmics and NetOmics. Since CNN models have difficulty in processing one-dimensional (1D) sequence data efficiently, we developed TransOmics, a framework that transforms sequence data into two-dimensional (2D) images while maintaining a one-to-one correspondence between the sequences and images. NetOmics, the second component, leverages a CNN architecture to extract more discriminative representations from the transformed samples. To overcome the overfitting due to the small sample size and class imbalance, we introduced a feature augmentation module (FAM) and a loss function to improve the model performance. Furthermore, we systematically optimized the model backbone and image resolution to balance the model parameters and computational costs. To demonstrate the performance of the proposed MetDIT, we conducted extensive experiments using three different clinical metabolomics data sets and achieved better classification performance than classical machine learning methods used in metabolomics, including Random Forest, SVM, XGBoost, and LightGBM. The source code is available at the GitHub repository at https://github.com/Li-OmicsLab/MetDIT, and the WebApp can be found at http://metdit.bioinformatics.vip/.