Insights into "Yin Rhyme": Analysis of nonvolatile components in Tieguanyin oolong tea during the manufacturing process.

Tieguanyin (TGY) is renowned for its distinctive "Yin Rhyme" flavor. To elucidate the underlying formation mechanism, we conducted sensory evaluations, electronic tongue analysis, and widely-targeted metabolomics. Our sensory evaluations and electronic tongue results indicated that TGY exhibits a thick and mellow taste profile, contributing to the "Yin Rhyme" flavor. Metabolomics analysis of tea products revealed that TGY shows significantly higher concentrations of umami substances (L-glutamate, L-theanine) and bitter substances (valine, catechins) compared to Jinguanyin (JGY). Additionally, metabolomic analysis during different oolong tea processing stages revealed significant differences in 21 substances, including L-glutamate, L-theanine, valine, and catechins, between fresh leaves of both varieties. These substances exhibited distinct fluctuation patterns during processing, indicating that the cultivar plays a crucial role in developing the "Yin Rhyme" flavor, which was enhanced throughout processing. This study provides a theoretical foundation for understanding the formation of the unique "Yin Rhyme" flavor of TGY.

Comprehensive investigation on the flavor difference in five types of tea from JMD (Camellia sinensis 'Jinmudan').

BACKGROUND: Jinmudan (JMD) is a high-aroma variety widely cultivated in China. The current study primarily focuses on the key volatile metabolites in JMD black and oolong teas, and investigates the impact of processing technologies on the aroma quality of JMD tea. However, few studies have explored the suitability of JMD for producing a certain type of tea or the characteristic quality differences among various JMD teas using multivariate statistical analysis methods. RESULTS: The principal volatile metabolites contributing to the floral quality of JMD tea are linalool, geraniol, indole and phenethyl alcohol. In JMD black tea (BT), the key volatile metabolites include methyl salicylate, geraniol, (E)-ß-ocimene and phenethyl alcohol. In JMD oolong tea (OT), the key volatile metabolites include indole, linalyl valerate and phenethyl alcohol. In JMD yellow tea (YT), the key volatile metabolites include methyl salicylate, geraniol and terpinolene. In JMD white tea (WT), the key volatile metabolites include methyl salicylate, geraniol and terpinolene. In JMD green tea (GT), the key volatile metabolites include (E)-ß-ocimene, indole and geraniol. Comparative analysis and KEGG pathway enrichment analysis revealed that flavonoid biosynthesis is the primary metabolic pathway responsible for the taste differences among various tea types. GT exhibited higher levels of phloretin, dihydromyricetin and galangin. The contents of vitexin, tricetin in YT were relatively higher. The contents of aromadendrin and naringenin in BT were higher, while OT contained higher levels of kaempferol. Additionally, WT showed higher contents of 3-O-acetylpinobanksin and 3,5,7-pinobanksin. CONCLUSION: This study explained the reasons for the quality differences of different JMD tea and provided a reliable theoretical basis for the adaptability of JMD tea. © 2024 Society of Chemical Industry.

Genome-wide epigenetic dynamics of tea leaves under mechanical wounding stress during oolong tea postharvest processing.

Understanding the epigenetic responses to mechanical wounding stress during the postharvest processing of oolong tea provides insight into the reprogramming of the tea genome and its impact on tea quality. Here, we characterized the 5mC DNA methylation and chromatin accessibility landscapes of tea leaves subjected to mechanical wounding stress during the postharvest processing of oolong tea. Analysis of the differentially methylated regions and preferentially accessible promoters revealed many overrepresented TF-binding motifs, highlighting sets of TFs that are likely important for the quality of oolong tea. Within these sets, we constructed a chromatin accessibility-mediated gene regulatory network specific to mechanical wounding stress. In combination with the results of the TF-centred yeast one-hybrid assay, we identified potential binding sites of CsMYC2 and constructed a gene regulatory network centred on CsMYC2, clarifying the potential regulatory role of CsMYC2 in the postharvest processing of oolong tea. Interestingly, highly accessible chromatin and hypomethylated cytosine were found to coexist in the promoter region of the indole biosynthesis gene (tryptophan synthase ß-subunit, CsTSB) under wounding stress, which indicates that these two important epigenetic regulatory mechanisms are jointly involved in regulating the synthesis of indole during the postharvest processing of oolong tea. These findings improve our understanding of the epigenetic regulatory mechanisms involved in quality formation during the postharvest processing of oolong tea.

Four new homoisoflavonoids from Caesalpinia pulcherrima.

Four new homoisoflavonoids, 7-hydroxy-3-[hydroxy(4'-methoxyphenyl)methyl]-benzopyran-4-one (1), (3R)-7, 8-dihydroxy-3-(4'-methoxybenzyl)-chroman-4-one (2), 7-hydroxy-3-(2'-hydroxy-4'-methoxybenzyl)-chroman-4-one (3), and 7-hydroxy-3-(2'-hydroxy-4'-methoxybenzyl)-benzopyran-4-one (4), were isolated from the seeds of Caesalpinia pulcherrima. The structures of new compounds were elucidated by MS and NMR spectra. Their absolute configurations were assigned using electronic circular dichroism spectrum. Compounds 2 and 4 exhibited cytotoxic effects on MCF-7/TAM cells with the IC50 values of 101.4 ± 0.03 and 93.02 ± 0.03 µM, respectively.

Exosomal MicroRNAs modulate the cognitive function in fasudil treated APPswe/PSEN1dE9 transgenic (APP/PS1) mice model of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by cognitive decline stemming from the accumulation of beta-amyloid (Aß) plaques and the propagation of tau pathology through synapses. Exosomes, crucial mediators in neuronal development, maintenance, and intercellular communication, have gained attention in AD research. Yet, the molecular mechanisms involving exosomal miRNAs in AD remain elusive. In this study, we treated APPswe/PSEN1dE9 transgenic (APP/PS1) mice, a model for AD, with either vehicle (ADNS) or fasudil (ADF), while C57BL/6 (control) mice received vehicle (WT). Cognitive function was evaluated using the Y-maze test, and AD pathology was confirmed through immunostaining and western blot analysis of Aß plaques and phosphorylated tau. Exosomal RNAs were extracted, sequenced, and analyzed from each mouse group. Our findings revealed that fasudil treatment improved cognitive function in AD mice, as evidenced by increased spontaneous alternation in the Y-maze test and reduced Aß plaque load and phosphorylated tau protein expression in the hippocampus. Analysis of exosomal miRNAs identified three miRNAs (mmu-let-7i-5p, mmu-miR-19a-3p, mmu-miR-451a) common to both ADNS vs ADF and WT vs ADNS groups. Utilizing miRTarBase software, we predicted and analyzed target genes associated with these miRNAs. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of miRNA target genes indicated that mmu-miR-19a-3p and mmu-miR-451a are implicated in signal transduction, immune response, cellular communication, and nervous system pathways. Specifically, mmu-miR-19a-3p targeted genes involved in the sphingolipid signaling pathway, such as Pten and Tnf, while mmu-miR-451a targeted Nsmaf, Gnai3, and Akt3. Moreover, mmu-miR-451a targeted Myc in signaling pathways regulating the pluripotency of stem cells. In conclusion, fasudil treatment enhanced cognitive function by modulating exosomal MicroRNAs, particularly mmu-miR-451a and mmu-miR-19a-3p. These miRNAs hold promise as potential biomarkers and therapeutic targets for novel AD treatments.

The lethal K18-hACE2 knock-in mouse model mimicking the severe pneumonia of COVID-19 is practicable for antiviral development.

Animal models of COVID-19 facilitate the development of vaccines and antivirals against SARS-CoV-2. The efficacy of antivirals or vaccines may differ in different animal models with varied degrees of disease. Here, we introduce a mouse model expressing human angiotensin-converting enzyme 2 (ACE2). In this model, ACE2 with the human cytokeratin 18 promoter was knocked into the Hipp11 locus of C57BL/6J mouse by CRISPR - Cas9 (K18-hACE2 KI). Upon intranasal inoculation with high (3 × 105 PFU) or low (2.5 × 102 PFU) dose of SARS-CoV-2 wildtype (WT), Delta, Omicron BA.1, or Omicron BA.2 variants, all mice showed obvious infection symptoms, including weight loss, high viral loads in the lung, and interstitial pneumonia. 100% lethality was observed in K18-hACE2 KI mice infected by variants with a delay of endpoint for Delta and BA.1, and a significantly attenuated pathogenicity was observed for BA.2. The pneumonia of infected mice was accompanied by the infiltration of neutrophils and pulmonary fibrosis in the lung. Compared with K18-hACE2 Tg mice and HFH4-hACE2 Tg mice, K18-hACE2 KI mice are more susceptible to SARS-CoV-2. In the antivirals test, REGN10933 and Remdesivir had limited antiviral efficacies in K18-hACE2 KI mice upon the challenge of SARS-CoV-2 infections, while Nirmatrelvir, monoclonal antibody 4G4, and mRNA vaccines potently protected the mice from death. Our results suggest that the K18-hACE2 KI mouse model is lethal and stable for SARS-CoV-2 infection, and is practicable and stringent to antiviral development.

Decoding the ribosome's hidden language: rRNA modifications as key players in cancer dynamics and targeted therapies.

Ribosomal RNA (rRNA) modifications, essential components of ribosome structure and function, significantly impact cellular proteomics and cancer biology. These chemical modifications transcend structural roles, critically shaping ribosome functionality and influencing cellular protein profiles. In this review, the mechanisms by which rRNA modifications regulate both rRNA functions and broader cellular physiological processes are critically discussed. Importantly, by altering the translational output, rRNA modifications can shift the cellular equilibrium towards oncogenesis, thus playing a key role in cancer development and progression. Moreover, a special focus is placed on the functions of mitochondrial rRNA modifications and their aberrant expression in cancer, an area with profound implications yet largely uncharted. Dysregulation in these modifications can lead to metabolic dysfunction and apoptosis resistance, hallmark traits of cancer cells. Furthermore, the current challenges and future perspectives in targeting rRNA modifications are highlighted as a therapeutic approach for cancer treatment. In conclusion, rRNA modifications represent a frontier in cancer research, offering novel insights and therapeutic possibilities. Understanding and harnessing these modifications can pave the way for breakthroughs in cancer treatment, potentially transforming the approach to combating this complex disease.

Alternative pre-mRNA splicing in stem cell function and therapeutic potential: A critical review of current evidence.

Alternative splicing is a crucial regulator in stem cell biology, intricately influencing the functions of various biological macromolecules, particularly pre-mRNAs and the resultant protein isoforms. This regulatory mechanism is vital in determining stem cell pluripotency, differentiation, and proliferation. Alternative splicing's role in allowing single genes to produce multiple protein isoforms facilitates the proteomic diversity that is essential for stem cells' functional complexity. This review delves into the critical impact of alternative splicing on cellular functions, focusing on its interaction with key macromolecules and how this affects cellular behavior. We critically examine how alternative splicing modulates the function and stability of pre-mRNAs, leading to diverse protein expressions that govern stem cell characteristics, including pluripotency, self-renewal, survival, proliferation, differentiation, aging, migration, somatic reprogramming, and genomic stability. Furthermore, the review discusses the therapeutic potential of targeting alternative splicing-related pathways in disease treatment, particularly focusing on the modulation of RNA and protein interactions. We address the challenges and future prospects in this field, underscoring the need for further exploration to unravel the complex interplay between alternative splicing, RNA, proteins, and stem cell behaviors, which is crucial for advancing our understanding and therapeutic approaches in regenerative medicine and disease treatment.

New frontiers in salivary extracellular vesicles: transforming diagnostics, monitoring, and therapeutics in oral and systemic diseases.

Salivary extracellular vesicles (EVs) have emerged as key tools for non-invasive diagnostics, playing a crucial role in the early detection and monitoring of diseases. These EVs surpass whole saliva in biomarker detection due to their enhanced stability, which minimizes contamination and enzymatic degradation. The review comprehensively discusses methods for isolating, enriching, quantifying, and characterizing salivary EVs. It highlights their importance as biomarkers in oral diseases like periodontitis and oral cancer, and underscores their potential in monitoring systemic conditions. Furthermore, the review explores the therapeutic possibilities of salivary EVs, particularly in personalized medicine through engineered EVs for targeted drug delivery. The discussion also covers the current challenges and future prospects in the field, emphasizing the potential of salivary EVs in advancing clinical practice and disease management.

Unveiling characteristic metabolic accumulation over enzymatic-catalyzed process of Tieguanyin oolong tea manufacturing by DESI-MSI and multiple-omics.

To achieve an integrative understanding of the spatial distribution and chronological flavoring compounds accumulation, desorption-electrospray-ionization coupled mass-spectrometry-imaging (DESI-MSI) and multi-omics techniques were performed on the leaf samples collected from the enzymatic-catalyzed-process (ECP) stage of Tieguanyin oolong tea manufacturing. The result of DESI-MSI visualization indicated transform or re-distribution of catechins, flavonols and amino acids were on-going attributing to the multi-stress over ECP stage. Out of identified 2621 non-volatiles and 45,771 transcripts, 43 non-volatiles and 12 co-expressed pathways were screened out as biomarkers and key cascades in response to adverse conditions. The targeted metabolic analysis on the characteristic flavoring compounds showed that the accumulations of free amino acids were enhanced, while catechins, flavonol glycosides, and alkaloids exhibited dynamic changes. This result suggests withering and turning-over process are compatible and collectively regulate the metabolic accumulation and development of flavoring metabolites, facilitating to the development of characteristic quality of Tieguanyin tea.

Widely targeted metabolomics analysis reveals the formation of nonvolatile flavor qualities during oolong tea manufacturing: a case study of Jinguanyin.

Background: The manufacturing processes of oolong tea significantly impact its nonvolatile components, leading to the emergence of distinct flavor attributes. Understanding the dynamic changes in nonvolatile components during the manufacturing stages of the Jinguanyin (JGY) cultivar is crucial for unraveling the potential mechanism behind flavor formation. Methods: Comprehensive metabolomics and sensomics analyses were conducted to investigate the dynamic changes in nonvolatile components throughout various phases of oolong tea processing, focusing on the JGY cultivar. Results: A total of 1,005 nonvolatile metabolites were detected, with 562 recognized as significant differential metabolites during various phases of oolong tea processing. Notably, the third turning-over, third setting, and high-temperature treatments exhibited the most significant effects on the nonvolatile metabolites of oolong tea. JGY finished tea demonstrated a characteristic flavor profile, marked by mellowness, sweetness in aftertaste, and a significant Yin rhyme. This flavor profile was collectively promoted by the accumulation of amino acids and organic acids, the decrease in flavonols (3-O-glycosides) and sugar substances, the alteration of phenolic acids, and the stabilization of caffeine. Conclusion: This study contribute to the understanding of the formation of oolong tea flavor qualities. The dynamic changes observed in various types of nonvolatile compounds during oolong tea processing shed light on the intricate interplay of metabolites and their influence on the final flavor characteristics.

Scene-adaptive pattern coding-based fringe projection profilometry: diffuse surfaces identification and 3-D reconstruction in cluttered scenes.

Fringe projection profilometry (FPP) is one of the most widely used optical three-dimensional (3-D) perceiving techniques. However, when applied to cluttered scenes, acquiring accurate 3-D shapes is difficult because of the influences of indirect light caused by non-diffuse surfaces. In this paper, we first theoretically analyze and model the influences of indirect light in FPP, and then propose a scene-adaptive pattern coding-based method, which can design projection patterns based on the reflective properties of the scene's surfaces, to achieve accurate 3-D perceiving in cluttered scenes. Specifically, the scene confidence analysis method is first proposed to identify the reflective properties of various surfaces and localize the camera pixels of the diffuse surface. The illumination status (i.e., "0" or "1") of each projector pixel can be determined according to the camera-projection coordinate mapping and spatial pattern coding, where only diffuse surfaces can be illuminated, thus fundamentally preventing the influences of indirect light from the point of view of the light source. The 3-D shapes of diffuse surfaces can be accurately reconstructed in cluttered scenes. Different from traditional reflective properties change or light separation solutions, the proposed method can achieve accurate 3-D perceiving of cluttered scenes without additional hardware or expensive calculation. Extensive experiments verify that the proposed method outperforms the traditional methods in terms of accuracy and robustness.

FPP-SLAM: indoor simultaneous localization and mapping based on fringe projection profilometry.

Simultaneous localization and mapping (SLAM) plays an important role in autonomous driving, indoor robotics and AR/VR. Outdoor SLAM has been widely used with the assistance of LiDAR and Global Navigation Satellite System (GNSS). However, for indoor applications, the commonly used LiDAR sensor does not satisfy the accuracy requirement and the GNSS signals are blocked. Thus, an accurate and reliable 3D sensor and suited SLAM algorithms are required for indoor SLAM. One of the most promising 3D perceiving techniques, fringe projection profilometry (FPP), shows great potential but does not prevail in indoor SLAM. In this paper, we first introduce FPP to indoor SLAM, and accordingly propose suited SLAM algorithms, thus enabling a new FPP-SLAM. The proposed FPP-SLAM can achieve millimeter-level and real-time mapping and localization without any expensive equipment assistance. The performance is evaluated in both simulated controlled and real room-sized scenes. The experimental results demonstrate that our method outperforms other state-of-the-art methods in terms of efficiency and accuracy. We believe this method paves the way for FPP in indoor SLAM applications.

Vaccination with Span, an antigen guided by SARS-CoV-2 S protein evolution, protects against challenge with viral variants in mice.

SARS-CoV-2 continues to accumulate mutations to evade immunity, leading to breakthrough infections after vaccination. How researchers can anticipate the evolutionary trajectory of the virus in advance in the design of next-generation vaccines requires investigation. Here, we performed a comprehensive study of 11,650,487 SARS-CoV-2 sequences, which revealed that the SARS-CoV-2 spike (S) protein evolved not randomly but into directional paths of either high infectivity plus low immune resistance or low infectivity plus high immune resistance. The viral infectivity and immune resistance of variants are generally incompatible, except for limited variants such as Beta and Kappa. The Omicron variant has the highest immune resistance but showed high infectivity in only one of the tested cell lines. To provide cross-clade immunity against variants that undergo diverse evolutionary pathways, we designed a new pan-vaccine antigen (Span). Span was designed by analyzing the homology of 2675 SARS-CoV-2 S protein sequences from the NCBI database before the Delta variant emerged. The refined Span protein harbors high-frequency residues at given positions that reflect cross-clade generality in sequence evolution. Compared with a prototype wild-type (Swt) vaccine, which, when administered to mice, induced serum with decreased neutralization activity against emerging variants, Span vaccination of mice elicited broad immunity to a wide range of variants, including those that emerged after our design. Moreover, vaccinating mice with a heterologous Span booster conferred complete protection against lethal infection with the Omicron variant. Our results highlight the importance and feasibility of a universal vaccine to fight against SARS-CoV-2 antigenic drift.

Electrically Copolymerized Polydopamine Melanin/Poly(3,4-ethylenedioxythiophene) Applied for Bioactive Multimodal Neural Interfaces with Induced Pluripotent Stem Cell-Derived Neurons.

Multimodal neural interfaces include combined functions of electrical neuromodulation and synchronic monitoring of neurochemical and physiological signals in one device. The remarkable biocompatibility and electrochemical performance of polystyrene sulfonate-doped poly(3,4-ethylenedioxythiophene) (PEDOT:PSS) have made it the most recommended conductive polymer neural electrode material. However, PEDOT:PSS formed by electrochemical deposition, called PEDOT/PSS, often need multiple doping to improve structural instability in moisture, resolve the difficulties of functionalization, and overcome the poor cellular affinity. In this work, inspired by the catechol-derived adhesion and semiconductive properties of polydopamine melanin (PDAM), we used electrochemical oxidation polymerization to develop PDAM-doped PEDOT (PEDOT/PDAM) as a bioactive multimodal neural interface that permits robust electrochemical performance, structural stability, analyte-trapping capacity, and neural stem cell affinity. The use of potentiodynamic scans resolved the problem of copolymerizing 3,4-ethylenedioxythiophene (EDOT) and dopamine (DA), enabling the formation of PEDOT/PDAM self-assembled nanodomains with an ideal doping state associated with remarkable current storage and charge transfer capacity. Owing to the richness of hydrogen bond donors/acceptors provided by the hydroxyl groups of PDAM, PEDOT/PDAM presented better electrochemical and mechanical stability than PEDOT/PSS. It has also enabled high sensitivity and selectivity in the electrochemical detection of DA. Different from PEDOT/PSS, which inhibited the survival of human induced pluripotent stem cell-derived neural progenitor cells, PEDOT/PDAM maintained cell proliferation and even promoted cell differentiation into neuronal networks. Finally, PEDOT/PDAM was modified on a commercialized microelectrode array system, which resulted in the reduction of impedance by more than one order of magnitude; this significantly improved the resolution and reduced the noise of neuronal signal recording. With these advantages, PEDOT/PDAM is anticipated to be an efficient bioactive multimodal neural electrode material with potential application to brain-machine interfaces.

[The albino mechanism of a new theanine-rich tea cultivar 'Fuhuang 2'].

To explore the mechanism of tea albino variation and high theanine formation, 'Fuyun 6' and a new theanine-rich tea cultivar 'Fuhuang 2' were as materials in this study, pigment content, metabolome and transcriptome of the two cultivars were analyzed by ultramicroelectron microscopy, widely targeted metabolomics, targeted metabolomics and transcriptomics. The results showed that five catechins, theobromine, caffeine, and 20 free amino acids, including theanine, glutamine, arginine, etc., were identified by targeted metabolomics. The amino acid content of 'Fuhuang 2' was significantly higher than that of 'Fuyun 6', and the theanine content was as high as 57.37 mg/g in 'Fuhuang 2'. The ultrastructure of leaves showed that the chloroplast cell structure of 'Fuhuang 2' was fuzzy, most of the grana lamellae were arranged in disorder, with large gaps, and the thylakoids were filiform. The determination of pigments showed that compared with 'Fuyun 6', the contents of chlorophyll A and B, carotenoids, flavonoids and other pigments of 'Fuhuang 2' decreased significantly, some important pigment-related-genes, such as chlorophyllase (CLH), 9-cis-epoxycarotenoid dioxygenase (NCED), flavonoid 3ß-hydroxylase (F3H) and flavonoid 3', 5'-hydroxylase (F3'5'H) were significantly changed. Compared with 'Fuyun 6', 'Fuhuang 2' identified 138 significantly changed metabolites (SCMs) and 658 differentially expressed genes (DEGs). KEGG enrichment analysis showed that SCMs and DEGs were significantly enriched in amino acid biosynthesis, glutathione metabolism and TCA cycle. In general, the albino phenotype of 'Fuhuang 2' may be caused by a deficiency in photosynthetic proteins, chlorophyll metabolism genes and chlorophyll content. The accumulation of high theanine in 'Fuhuang 2' may be due to the low nitrogen consumption in yellowed leaves and the lack of carbon skeleton, amino and nitrogen resources are stored more effectively, resulting in the up regulation of metabolites and related gene expression in the amino acid synthesis pathway, theanine has become a significant accumulation of nitrogen-containing compounds in yellowed leaves.

Effects of turning over intensity on fatty acid metabolites in postharvest leaves of Tieguanyin oolong tea (Camellia sinensis).

Fatty acid derived volatiles (FADVs) are major contributors to the aroma quality of oolong tea (Camellia sinensis). Most of the processing time for oolong tea is taken up by turning over treatments, but the full profile of fatty acid metabolic changes during this process remains unclear. In this study, we detected fatty acids, their derived volatiles, and related genes of Tieguanyin oolong tea using biochemical and molecular biology methods. The results showed that with an increase in turning over intensities, the content of total unsaturated fatty acids continuously dropped and the content of characteristic FADVs, such as hexanoic acid (Z)-3-Hexenly ester and 2-exenal, continued to increase. Lipoxygenase (LOX), a key gene family in the fatty acid metabolic pathway, showed different patterns, and CsLOX1 (TEA025499.1) was considered to be a key gene during the turning over processes. We found that fruit-like aroma (Z)-3-Hexen-1-ol acetate had a strong correlation with the expression levels of eight Camelia sinensis LOX family genes. Tieguanyin had relatively rich pleasant volatile compounds with moderate turning over intensity (five times turning over treatments). This study provides an overall view of how fatty acid metabolites change and affect the quality of oolong tea with different turning over intensities during processing.

A Broad Antiviral Strategy: Inhibitors of Human DHODH Pave the Way for Host-Targeting Antivirals against Emerging and Re-Emerging Viruses.

New strategies to rapidly develop broad-spectrum antiviral therapies are urgently required for emerging and re-emerging viruses. Host-targeting antivirals (HTAs) that target the universal host factors necessary for viral replication are the most promising approach, with broad-spectrum, foresighted function, and low resistance. We and others recently identified that host dihydroorotate dehydrogenase (DHODH) is one of the universal host factors essential for the replication of many acute-infectious viruses. DHODH is a rate-limiting enzyme catalyzing the fourth step in de novo pyrimidine synthesis. Therefore, it has also been developed as a therapeutic target for many diseases relying on cellular pyrimidine resources, such as cancers, autoimmune diseases, and viral or bacterial infections. Significantly, the successful use of DHODH inhibitors (DHODHi) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection further supports the application prospects. This review focuses on the advantages of HTAs and the antiviral effects of DHODHi with clinical applications. The multiple functions of DHODHi in inhibiting viral replication, stimulating ISGs expression, and suppressing cytokine storms make DHODHi a potent strategy against viral infection.

B-Cell-Epitope-Based Fluorescent Quantum Dot Biosensors for SARS-CoV-2 Enable Highly Sensitive COVID-19 Antibody Detection.

A new antibody diagnostic assay with more rapid and robust properties is demanded to quantitatively evaluate anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity in a large population. Here, we developed a nanometer-scale fluorescent biosensor system consisting of CdSe-ZnS quantum dots (QDs) coupled with the highly sensitive B-cell epitopes of SARS-CoV-2 that could remarkably identify the corresponding antibody with a detection limit of 100 pM. Intriguingly, we found that fluorescence quenching of QDs was stimulated more obviously when coupled with peptides than the corresponding proteins, indicating that the energy transfer between QDs and peptides was more effective. Compared to the traditional enzyme-linked immunosorbent assay (ELISA), the B-cell-epitope-based QD-biosensor could robustly distinguish coronavirus disease 2019 (COVID-19) antibody-positive patients from uninfected individuals with a higher sensitivity (92.3-98.1% positive rates by QD-biosensor vs. 78.3-83.1% positive rates by ELISAs in 207 COVID-19 patients' sera) in a more rapid (5 min) and labor-saving manner. Taken together, the 'QD-peptides' biosensor provided a novel real-time, quantitative, and high-throughput method for clinical diagnosis and home-use tests.