Evaluation of the clinical effect of 4D digital strabismus and amblyopia visual function correction system combined with traditional comprehensive treatment methods on anisometropic amblyopia.

PURPOSE: The objective of this study was to evaluate the clinical efficacy of a 4D digital strabismus and amblyopia visual function correction system (4D-DSAAVFCS) in combination with conventional modalities compared with conventional modalities alone in children with anisometropic amblyopia. METHODS: This nonrandomized controlled study collected data on best-corrected visual acuity (BCVA), simultaneous vision, fusion vision, near stereoscopic vision, the amplitude of P100 wave (graphic evoked visual potentials), and the latency of P100 wave from both eyes at the beginning of the treatment and one year later. The Mann‒Whitney U test was used to compare BCVA contrasts in different subgroups, and the independent samples t test was used to compare the amplitude and latency of P100 wave contrasts in different subgroups. The basic cure rate, simultaneous vision recovery rate, fusion vision recovery rate, and near stereoscopic vision recovery rate contrasts in different subgroups were compared via the chi-square test. RESULTS: This study included 393 children (217 boys and 176 girls) aged 3 to 12 years with anisometropic amblyopia who were treated at the Aier Eye Hospital of Wuhan University from January 2020 to December 2022. The children were divided into two groups, the 4D group (263 cases) and the traditional group (130 cases), on the basis of the treatment modality. The children in the traditional group received treatment through the conventional method of occlusion and regular training. Meanwhile, the children in the 4D group received treatment through the traditional method and the 4D-DSAAVFCS. The 4D group was divided into two age groups: 3 ~ 6 years (161 cases) and 6 ~ 12 years (102 cases). The basic cure rate of the 4D group was significantly better than that of the traditional group (χ2 = 4.318, P < 0.05). There were no statistically significant differences in the BCVA, the latency of P100 wave, or the amplitude of P100 wave between the 4D group and the traditional group before treatment (U=-0.117, t=-0.05, all P > 0.05 ). After one year of treatment, a statistically significant difference was observed between the 4D group and the conventional group in terms of BCVA, the latency of P100 wave, and the amplitude of P100 wave (U=-1.243, t=-0.853, t=-1.546, all P < 0.05). These results suggest that the therapeutic effect was greater in the 4D group than in the conventional group. The recovery rates of simultaneous vision, convergent fusion, divergent fusion, and near stereoscopic vision were significantly greater in the 4D group than in the conventional group (χ2 = 4.344, 4.726, 5.123, and 2.036, respectively; all P < 0.05). Additionally, the basic cure rate of children aged 3 ~ 6 years in the 4D group was significantly greater than that of children aged 6 ~ 12 years (χ2 = 2.365, P < 0.05). In this study, BCVA was significantly lower in the 3 ~ 6-year-old group than in the 6 ~ 12-year-old group (U = -1.267, P < 0.05). Similarly, the amplitude of P100 wave was also significantly greater in the 3 ~ 6-year-old group than in the 6 ~ 12-year-old group (t = -1877, P < 0.05). The latency of P100 wave was lower in the 3 ~ 6-year-old group than in the 6 ~ 12-year-old group (t=-0.998, P < 0.05). Additionally, the recovery rate of near stereoscopic vision was significantly greater in the 3 ~ 6-year-old group than in the 6 ~ 12-year-old group (χ2 = 4.534, P < 0.05). CONCLUSION: The combination of the traditional method with the 4D-DSAAVFCS was more effective than the traditional method alone in treating amblyopic children. This approach was particularly helpful in improving the visual acuity of the children and restoring their optic nerve conduction function, simultaneous vision, fusion vision, and near stereoscopic vision. The combination of the traditional method and the 4D-DSAAVFCS is more effective for younger children.

Probing the Interfacial Interaction Mechanisms of Nitrogen with Dodecane/Toluene: Implications for Foam Flooding.

Interfacial interactions between deformable bubbles and oil drops have attracted much attention in foam flooding. However, interactions involving nitrogen bubbles have not been reported. In this work, the interaction forces between nitrogen and dodecane/toluene in aqueous solutions were quantified using the atomic force microscopy bubble probe technique. The effects of the solution pH, ionic type, and solution concentration on the interactions were analyzed. The van der Waals (vdW), electric double layer (EDL), and hydrophobic (HB) interactions were involved in the low-concentration solutions. The EDL repulsion in NaCl increased with solution pH, while in CaCl2 and MgCl2, the EDL repulsion in general decreased and then increased with pH, attributed to the adsorption of OH- and divalent cations and their hydration products. The adsorption of divalent cations at the toluene/water interface was pronounced by cation-π interactions. At pH 10, precipitated divalent cation hydroxides at the bubble/water and oil/water interfaces adsorbed more cations, causing the increase of the surface potential. At high salinity, the EDL interaction was suppressed and the vdW repulsion became predominant. The vdW force of nitrogen with toluene was stronger than that with dodecane. Under all of the solution conditions, the attractive interaction could not overcome the total repulsive interaction at the minimum separation, and thus no bubble attachment was observed, which implied that a stable bubble/liquid/oil film was essential for maintaining foam stability. This work provides useful insights into the interfacial interaction mechanisms in nitrogen foam flooding. The findings can be readily extended to other engineering systems such as oil flotation and bubble-oil-water emulsions.

Serum cotinine levels and adolescents' sleep health outcomes from NHANES 2005 to 2018.

The association between tobacco smoke exposure and sleep has been widely discussed, but the correlation between serum cotinine levels and sleep health outcomes in adolescents has not been well described. This study aimed to further evaluate the association between serum cotinine levels and sleep health outcomes in adolescents using data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. This cross-sectional study included participants aged 16-19 years from the NHANES 2005-2018. A weighted multivariate logistic regression model was used for the primary analysis. A restricted cubic spline (RCS) model was employed to investigate the non-linear association between serum cotinine levels and trouble sleeping. Subgroup analyses based on population characteristics were also conducted. In total, 2630 participants were included, which are representative of the 11.5 million US adolescents. Higher serum cotinine levels (≥ 3 ng/ml) were significantly associated with trouble sleeping in the fully adjusted model (odds ratio [OR] 1.817). The RCS model revealed a non-linear relationship between serum cotinine levels and trouble sleeping. Subgroup analyses indicated that this relationship was consistent and stable across various population characteristics. Serum cotinine levels are associated with sleep health outcomes in adolescents, with high serum cotinine levels being linked to increased trouble sleeping and longer or shorter sleep duration.

CXCR4 orchestrates the TOX-programmed exhausted phenotype of CD8+ T cells via JAK2/STAT3 pathway.

Evidence from clinical trials suggests that CXCR4 antagonists enhance immunotherapy effectiveness in several cancers. However, the specific mechanisms through which CXCR4 contributes to immune cell phenotypes are not fully understood. Here, we employed single-cell transcriptomic analysis and identified CXCR4 as a marker gene in T cells, with CD8+PD-1high exhausted T (Tex) cells exhibiting high CXCR4 expression. By blocking CXCR4, the Tex phenotype was attenuated in vivo. Mechanistically, CXCR4-blocking T cells mitigated the Tex phenotype by regulating the JAK2-STAT3 pathway. Single-cell RNA/TCR/ATAC-seq confirmed that Cxcr4-deficient CD8+ T cells epigenetically mitigated the transition from functional to exhausted phenotypes. Notably, clinical sample analysis revealed that CXCR4+CD8+ T cells showed higher expression in patients with a non-complete pathological response. Collectively, these findings demonstrate the mechanism by which CXCR4 orchestrates CD8+ Tex cells and provide a rationale for combining CXCR4 antagonists with immunotherapy in clinical trials.

Plasma Cell-Free DNA Concentration and Fragmentomes Predict Neoadjuvant Chemotherapy Response in Cervical Cancer Patients.

Cervical cancer remains one of the most lethal gynecological malignancies. However, biomarkers for more precise patient care are an unmet need. Herein, the concentration of 285 plasma cell-free DNA (cfDNA) samples are analyzed from 84 cervical patients and the clinical significance of cfDNA fragmentomic characteristics across the neoadjuvant chemotherapy (NACT) treatment. Patients with poor NACT response exhibit a significantly greater escalation in cfDNA levels following the initial cycle of treatment, in comparison to patients with a favorable response. Distinctive end motif profiles and promoter coverages of cfDNA in initial plasma are observed between patients with differing NACT responses. Notably, the DNASE1L3 analysis further demonstrates the intrinsic association between cfDNA characteristics and chemotherapy resistance. The cfDNA and motif ratios show a good discriminative capacity for predicting non-responders from responders (area under the curve (AUC) > 0.8). In addition, transcriptional start sites (TSS) coverages around promoters discern the alteration of biological processes associated with chemotherapy resistance and reflect the potential value in predicting chemotherapy response. These findings in predictive biomarkers may optimize treatment selection, minimize unnecessary treatment, and assist in establishing personalized treatment strategies for cervical cancer patients.

Exogenous selenium mitigates cadmium uptake and accumulation in two rice (Oryza sativa L.) varieties in cadmium-contaminated soil.

Rice grown in cadmium (Cd)-contaminated soil, is a potential threat to human health, but exogenous selenium (Se) application on rice can mitigate Cd toxicity. However, the mechanisms underlying Se mitigation of Cd stress in ratoon rice (RR) are still poorly understood. We conducted a pot experiment with moderate Cd-contaminated yellow-brown paddy soil on two rice varieties 'Taoyouxiangzhan' (TX) and 'Liangyou 6326'(LY). For all treatments, 1.0 mg kg-1 sodium selenite solution was added to soil. Treatment T1 was sodium selenite only, and in the other treatments 100 mg L-1 Se solution was sprayed on the leaves at seedling stage (T2), at tillering stage (T3), and in early anthesis stage (T4). Se treatments decreased Cd accumulation in rice grains and herbage. Under foliar spraying 100 mg L-1 Se at the seedling + 1.0 mg kg-1 Se in soil (T2), leaf Cd content decreased 16.95% in the current season and grains content decreased 46.67% in the subsequent season. Furthermore, grain Se content increased 0.94 mg kg-1 for the TX variety combined with the analysis of Cd bio-accumulation factor in grains, and Se treatments effectively decreased Cd grain concentrations due to reduced Cd translocation from roots to grains. TX variety rice showed a more pronounced response to Se treatments than LY.

Resveratrol stimulates brown of white adipose via regulating ERK/DRP1-mediated mitochondrial fission and improves systemic glucose homeostasis.

PURPOSE: Diabetes mellitus and metabolic homeostasis disorders may benefit from white adipose tissue (WAT) browning, which is associated with mitochondrial fission. Resveratrol, a dietary polyphenol, exhibits beneficial effects against abnormalities related to metabolic diseases. However, it remains unknown whether resveratrol contributes to WAT browning by regulating mitochondrial fission. METHODS: We administered resveratrol (0.4% mixed with control) to db/db mice for 12 weeks, measuring body weight, oral glucose tolerance, insulin tolerance, and histological changes. The uncoupling protein 1 (UCP1) and dynamin-related protein 1 (DRP1) expressions in the epididymal WAT were assessed via immunoblotting. RESULTS: We found that resveratrol improved systemic glucose homeostasis and insulin resistance in db/db mice, which was associated with increased UCP1 in epididymal WAT. Resveratrol-treated mice exhibited more fragmented mitochondria and increased phosphorylation of DRP1 in the epididymal WAT of the db/db mice. These results were further confirmed in vitro, where resveratrol induced extracellular signal-regulated kinase (ERK) signaling activation, leading to phosphorylation of DRP1 at the S616 site (p-DRP1S616) and mitochondrial fission, which was reversed by an ERK inhibitor in 3T3-L1 adipocytes. CONCLUSION: Resveratrol plays a role in regulating the phosphorylation of ERK and DRP1, resulting in the promotion of beige cells with epididymal WAT and the improvement of glucose homeostasis. Our present study provides novel insights into the potential mechanism of resveratrol-mediated effects on WAT browning, suggesting that it is, at least in part, mediated through ERK/DRP1-mediated mitochondrial fission.

Development of amphipathic derivatives of thymol and carvacrol as potent broad-spectrum antibacterial agents.

In the current study, to discover novel antibacterial agents, we designed and synthesized 72 carvacrol and thymol derivatives by biomimicking the structure and function of cationic antimicrobial peptides (AMPs). Many of the derivatives showed good antibacterial activity, and compound thy2I exhibited the most potent antibacterial activity with minimum inhibitory concentration (MIC) values ranging from 0.5 µg/mL to 8 µg/mL. Compound thy2I could kill both gram-positive and gram-negative bacteria via a membrane-targeting mechanism of action with a low frequency of resistance. In addition, thy2I had the advantages of good membrane selectivity, low toxicity in vitro and in vivo, and good plasma stability. The in vivo activity results revealed that thy2I exhibited a positive therapeutic effect in a mouse skin abscess model induced by Staphylococcus aureus ATCC29213. After thy2I treatment (10 mg/kg), the bacterial load of the S. aureus-infected abscesses was reduced by approximately 99.65 %. Our study suggests that thy2I may serve as an antibacterial lead for further clinical evaluation.

PTEN in kidney diseases: a potential therapeutic target in preventing AKI-to-CKD transition.

Renal fibrosis, a critical factor in the development of chronic kidney disease (CKD), is predominantly initiated by acute kidney injury (AKI) and subsequent maladaptive repair resulting from pharmacological or pathological stimuli. Phosphatase and tensin homolog (PTEN), also known as phosphatase and tensin-associated phosphatase, plays a pivotal role in regulating the physiological behavior of renal tubular epithelial cells, glomeruli, and renal interstitial cells, thereby preserving the homeostasis of renal structure and function. It significantly impacts cell proliferation, apoptosis, fibrosis, and mitochondrial energy metabolism during AKI-to-CKD transition. Despite gradual elucidation of PTEN's involvement in various kidney injuries, its specific role in AKI and maladaptive repair after injury remains unclear. This review endeavors to delineate the multifaceted role of PTEN in renal pathology during AKI and CKD progression along with its underlying mechanisms, emphasizing its influence on oxidative stress, autophagy, non-coding RNA-mediated recruitment and activation of immune cells as well as renal fibrosis. Furthermore, we summarize prospective therapeutic targeting strategies for AKI and CKD-treatment related diseases through modulation of PTEN.

Insights into the methods for separation and chromatographic determination of nucleotides/nucleosides in Cordyceps spp.

Cordyceps genus is entomopathogenic mushrooms that have traditionally been used in ethnomedicine in Asian countries. Nucleosides (Ns), nucleotide(Nt), Nucleobases (Nb) and their analogues play a critically physiological role and have a great potential in drug development, such as pentostatin and cordycepin (COR). Due to their significance bioactivity, several Nt/Ns were used as markers for quality evaluation for medicinal Cordyceps, including adenosine, inosine, guanosine, uridine and COR. Among them, COR is the most considerable adenosine analogue, exhibiting significant therapeutic potential and has many intracellular targets. Nt/Ns contains polar compounds and the phosphate groups of Nt deprotonate and carry negative charges with a broad range of pH values. Recent years, various advanced methods of extraction and separation, and nanomaterials have been developed to extract, isolate and determine these molecules, such as ultrasound-assisted extraction (UAE), Supercritical fluid extraction (SFE) and pressurized liquid extraction (PLE) for the extraction, the solid phase extraction (SPE) methods (microextraction SPE (SPME), magnetic SPE (MSPE), and unique SPE materials based on the boronate affinity for the separation, and chromatography methods employing ultraviolet (UV), fluorescence, MS detection and electrospray ionization (ESI), along with matrix-assisted laser desorption/ ionization (MALDI) for the determination. COR derived from adenosine and its structure is very similar to that of 2'-deoxyadenosine (2'-dA) and adenosine, resulting in an incorrect identification, which will influence its therapeutic effects. Therefore, this review primarily focused on the characteristics of Nt/Ns, the advanced methods, strategies, nanomaterials for extracting and determining Nt/Ns (COR in particular) in Cordyceps spp, as well as the methods for distinguishing COR from its structure analogs.

Total Syntheses and Anti-Inflammatory Studies of Three Natural Coumarins: Glycycoumarin, Glycyrin, and 3-O-Methylglycyrol.

Licorice (Glycyrrhiza uralensis Fisch), a significant traditional Chinese herbal medicine, has been extensively utilized in China to treat various ailments. Natural bioactive coumarins, glycycoumarin, glycyrin, and 3-O-methylglycyrol, were isolated from licorice, and they exhibited various pharmacological properties. In this report, we have accomplished the total synthesis of glycycoumarin, glycyrin, and 3-O-methylglycyrol in 5-7 linear steps from commercially available 2,4,6-trihydroxybenzaldehyde with yields of 12.3-21.2%. Additionally, their anti-inflammatory activities were studied and compared. Glycycoumarin, glycyrin, and 3-O-methylglycyrol exhibited different levels of anti-inflammatory activities, with glycyrin being the most potent. Mechanistic studies indicated that glycyrin exerted its anti-inflammatory properties by inhibiting the activation of TNF-α, IL-6, and IL-1ß, making it a potential anti-inflammatory lead compound for further optimization and discovery of new agents.

Spatial multi-omics: deciphering technological landscape of integration of multi-omics and its applications.

The emergence of spatial multi-omics has helped address the limitations of single-cell sequencing, which often leads to the loss of spatial context among cell populations. Integrated analysis of the genome, transcriptome, proteome, metabolome, and epigenome has enhanced our understanding of cell biology and the molecular basis of human diseases. Moreover, this approach offers profound insights into the interactions between intracellular and intercellular molecular mechanisms involved in the development, physiology, and pathogenesis of human diseases. In this comprehensive review, we examine current advancements in multi-omics technologies, focusing on their evolution and refinement over the past decade, including improvements in throughput and resolution, modality integration, and accuracy. We also discuss the pivotal contributions of spatial multi-omics in revealing spatial heterogeneity, constructing detailed spatial atlases, deciphering spatial crosstalk in tumor immunology, and advancing translational research and cancer therapy through precise spatial mapping.

Exploring factors affecting the acceptance of fall detection technology among older adults and their families: a content analysis.

BACKGROUND: This study conducted in-depth interviews to explore the factors that influence the adoption of fall detection technology among older adults and their families, providing a valuable evaluation framework for healthcare providers in the field of fall detection, with the ultimate goal of assisting older adults immediately and effectively when falls occur. METHODS: The method employed a qualitative approach, utilizing semi-structured interviews with 30 older adults and 29 families, focusing on their perspectives and expectations of fall detection technology. Purposive sampling ensured representation from older adults with conditions such as Parkinson's, dementia, and stroke. RESULTS: The results reveal key considerations influencing the adoption of fall-detection devices, including health factors, reliance on human care, personal comfort, awareness of market alternatives, attitude towards technology, financial concerns, and expectations for fall detection technology. CONCLUSIONS: This study identifies seven key factors influencing the adoption of fall detection technology among older adults and their families. The conclusion highlights the need to address these factors to encourage adoption, advocating for user-centered, safe, and affordable technology. This research provides valuable insights for the development of fall detection technology, aiming to enhance the safety of older adults and reduce the caregiving burden.

Palindrome sequence mediated target recycling integrating with self-priming assisted signal reaction for sensitive miRNA detection.

The development of a sensitive and isothermal technique with a greatly enhanced miRNA detection signal is still technically problematic due to the low abundance of miRNA and high sequence similarities with homologous miRNAs. Herein, we propose a novel fluorescence approach for sensitive and reliable miRNA detection by integrating the palindrome sequence mediated target recycling with self-priming assisted signal reaction. In this method, a dual toehold DNA nano-probe (HT) with two functional arms is designed to mediate specific target recognition and signal amplification. In the presence of target miRNA, it binds to the recognition module of HT probe, releasing the "2" sequence to initiate strand displacement amplification (SDA) and a self-priming-induced signal reaction. Based on the elegant design, the proposed method exhibits a wide linear response range exceeding five orders of magnitude and a low limit of detection of 0.96 fM according to the 3δ rule. The non-specific signal is below 5 % for non-target miRNA detection. Taking the merits of excellent sensitivity, desirable specificity, and superior anti-interference ability, the proposed approach shows a promising prospect for detecting miRNAs in complicated biological environments and early diagnosis of diseases.

Advances in biosynthesis and metabolic engineering strategies of cordycepin.

Cordyceps militaris, also called as bei-chong-cao, is an insect-pathogenic fungus from the Ascomycota phylum and the Clavicipitaceae family. It is a valuable filamentous fungus with medicinal and edible properties that has been utilized in traditional Chinese medicine (TCM) and as a nutritious food. Cordycepin is the bioactive compound firstly isolated from C. militaris and has a variety of nutraceutical and health-promoting properties, making it widely employed in nutraceutical and pharmaceutical fields. Due to the low composition and paucity of wild resources, its availability from natural sources is limited. With the elucidation of the cordycepin biosynthetic pathway and the advent of synthetic biology, a green cordycepin biosynthesis in Saccharomyces cerevisiae and Metarhizium robertsii has been developed, indicating a potential sustainable production method of cordycepin. Given that, this review primarily focused on the metabolic engineering and heterologous biosynthesis strategies of cordycepin.

Luteolin and its analog luteolin-7-methylether from Leonurus japonicus Houtt suppress aromatase-mediated estrogen biosynthesis to alleviate polycystic ovary syndrome by the inhibition of tumor progression locus 2.

ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt (L. japonicus, Chinese motherwort), known as Yi Mu Cao which means "good for women", has long been widely used in China and other Asian countries to alleviate gynecological disorders, often characterized by estrogen dysregulation. It has been used for the treatment of polycystic ovary syndrome (PCOS), a common endocrine disorder in women but the underlying mechanism remains unknown. AIM OF THE STUDY: The present study was designed to investigate the effect and mechanism of flavonoid luteolin and its analog luteolin-7-methylether contained in L. japonicus on aromatase, a rate-limiting enzyme that catalyzes the conversion of androgens to estrogens and a drug target to induce ovulation in PCOS patients. MATERIALS AND METHODS: Estrogen biosynthesis in human ovarian granulosa cells was examined using ELISA. Western blots were used to explore the signaling pathways in the regulation of aromatase expression. Transcriptomic analysis was conducted to elucidate the potential mechanisms of action of compounds. Finally, animal models were used to assess the therapeutic potential of these compounds in PCOS. RESULTS: Luteolin potently inhibited estrogen biosynthesis in human ovarian granulosa cells stimulated by follicle-stimulating hormone. This effect was achieved by decreasing cAMP response element-binding protein (CREB)-mediated expression of aromatase. Mechanistically, luteolin and luteolin-7-methylether targeted tumor progression locus 2 (TPL2) to suppress mitogen-activated protein kinase 3/6 (MKK3/6)-p38 MAPK-CREB pathway signaling. Transcriptional analysis showed that these compounds regulated the expression of different genes, with the MAPK signaling pathway being the most significantly affected. Furthermore, luteolin and luteolin-7-methylether effectively alleviated the symptoms of PCOS in mice. CONCLUSIONS: This study demonstrates a previously unrecognized role of TPL2 in estrogen biosynthesis and suggests that luteolin and luteolin-7-methylether have potential as novel therapeutic agents for the treatment of PCOS. The results provide a foundation for further development of these compounds as effective and safe therapies for women with PCOS.

Methyl-CpG-binding protein 2 regulates CYP27A1-induced myometrial contraction during preterm labor.

Persistent and intense uterine contraction is a risk factor for preterm labor. We previously found that methyl-CpG-binding protein 2 (MeCP2), as a target of infection-related microRNA miR-212-3p, may play an inhibitory role in regulating myometrium contraction. However, the molecular mechanisms by which MeCP2 regulates myometrial contraction are still unknown. In this study, we found that MeCP2 protein expression was lower in myometrial specimens obtained from preterm labor cases, compared to those obtained from term labor cases. Herein, using RNA sequence analysis of global gene expression in human uterine smooth muscle cells (HUSMCs) following siMeCP2, we show that MeCP2 silencing caused dysregulation of the cholesterol metabolism pathway. Notably, MeCP2 silencing resulted in the upregulation of CYP27A1, the key enzyme involved in regulating cholesterol homeostasis, in HUSMCs. Methylation-specific PCR, chromatin immunoprecipitation, and dual luciferase reporter gene technology indicated that MeCP2 could bind to the methylated CYP27A1 promoter region and repress its transcription. Administration of siCYP27A1 in a lipopolysaccharide (LPS)-induced preterm labor mouse model delayed the onset of preterm labor. Human preterm myometrium and the LPS-induced preterm labor mouse model both showed lower expression of MeCP2 and increased expression of CYP27A1. These results demonstrated that aberrant upregulation of CYP27A1 induced by MeCP2 silencing is one of the mechanisms facilitating inappropriate myometrial contraction. CYP27A1 could be exploited as a novel therapeutic target for preterm birth.

The high-quality genome of Grona styracifolia uncovers the genomic mechanism of high levels of schaftoside, a promising drug candidate for treatment of COVID-19.

Recent study has evidenced that traditional Chinese medicinal (TCM) plant-derived schaftoside shows promise as a potential drug candidate for COVID-19 treatment. However, the biosynthetic pathway of schaftoside in TCM plants remains unknown. In this study, the genome of the TCM herb Grona styracifolia (Osbeck) H.Ohashi & K.Ohashi (GSO), which is rich in schaftoside, was sequenced, and a high-quality assembly of GSO genome was obtained. Our findings revealed that GSO did not undergo recent whole genome duplication (WGD) but shared an ancestral papilionoid polyploidy event, leading to the gene expansion of chalcone synthase (CHS) and isoflavone 2'-hydroxylase (HIDH). Furthermore, GSO-specific tandem gene duplication resulted in the gene expansion of C-glucosyltransferase (CGT). Integrative analysis of the metabolome and transcriptome identified 13 CGTs and eight HIDHs involved in the biosynthetic pathway of schaftoside. Functional studies indicated that CGTs and HIDHs identified here are bona fide responsible for the biosynthesis of schaftoside in GSO, as confirmed through hairy root transgenic system and in vitro enzyme activity assay. Taken together, the ancestral papilionoid polyploidy event expanding CHSs and HIDHs, along with the GSO-specific tandem duplication of CGT, contributes, partially if not completely, to the robust biosynthesis of schaftoside in GSO. These findings provide insights into the genomic mechanisms underlying the abundant biosynthesis of schaftoside in GSO, highlighting the potential of GSO as a source of bioactive compounds for pharmaceutical development.