The association between gout flares and monosodium urate burden assessed using musculoskeletal ultrasound in patients with gout.

Background: Ultrasound (US) has a high sensitivity in detecting monosodium urate (MSU) deposition in gout patients. However, the value of US in predicting gout flares has been reported only in a few monocentric studies. Objective: To investigate the association between gout flares in the previous year and US-detected MSU burden using two different US scores. Design: A retrospective study. Methods: Patients with gout were consecutively recruited to undergo musculoskeletal US examinations of their knees, ankles, and feet. The score derived from Outcome Measure in Rheumatology (hereinafter referred to as MSU score) and musculoskeletal US features-based (hereinafter referred to as MSKF score) were used to quantify the MSU burden of gout. Odds ratios for frequent gout flares were calculated. Results: We enrolled 1894 patients with gout (mean age: 45 years; gout duration: 5 years; males: 96.1%), experiencing a median of three flares over the past year. Of these, 428 (22.6%) patients reported frequent (⩾7) gout flares. The MSU and MSKF median scores were 6 and 9, respectively. For each five-point increase in MSU and MSKF score, the odds ratio of frequent gout flares increased 1.13-fold and 1.24-fold, respectively. The area under the curve (AUC) for the MSU and MSKF score was 0.635 [95% confidence interval (CI): 0.604-0.665] and 0.688 (95% CI: 0.659-0.718), respectively, (AUC difference 0.054, p value for AUC difference < 0.001). Conclusion: The MSU and MSKF scores were significantly associated with the number of gout flares in the previous year. The MSKF score outperformed the MSU score in terms of frequent gout flare discrimination.

Novel potential lncRNA biomarker in B cells indicates essential pathogenic pathway activation in patients with SLE.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a highly heterogeneous disease, and B cell abnormalities play a central role in the pathogenesis of SLE. Long non-coding RNAs (lncRNAs) have also been implicated in the pathogenesis of SLE. The expression of lncRNAs is finely regulated and cell-type dependent, so we aimed to identify B cell-expressing lncRNAs as biomarkers for SLE, and to explore their ability to reflect the status of SLE critical pathway and disease activity. METHODS: Weighted gene coexpression network analysis (WGCNA) was used to cluster B cell-expressing genes of patients with SLE into different gene modules and relate them to clinical features. Based on the results of WGCNA, candidate lncRNA levels were further explored in public bulk and single-cell RNA-sequencing data. In another independent cohort, the levels of the candidate were detected by RT-qPCR and the correlation with disease activity was analysed. RESULTS: WGCNA analysis revealed one gene module significantly correlated with clinical features, which was enriched in type I interferon (IFN) pathway. Among non-coding genes in this module, lncRNA RP11-273G15.2 was differentially expressed in all five subsets of B cells from patients with SLE compared with healthy controls and other autoimmune diseases. RT-qPCR validated that RP11-273G15.2 was highly expressed in SLE B cells and positively correlated with IFN scores (r=0.7329, p<0.0001) and disease activity (r=0.4710, p=0.0005). CONCLUSION: RP11-273G15.2 could act as a diagnostic and disease activity monitoring biomarker for SLE, which might have the potential to guide clinical management.

Prognostic Model Associated with Necroptosis in Colorectal Cancer based on Transcriptomic Analysis and Experimental Validation.

PURPOSE: Numerous studies have emphasised the importance of necroptosis in the malignant progression of colorectal cancer (CRC). However, whether necroptosis-related genes (NRGs) can be used to predict the prognosis of CRC remains to be revealed. METHODS: Patients with CRC were divided into two clusters based on the expression of NRGs, and prognosis was compared between the two clusters. A prognostic model was established based on NRGs, and its predictive efficiency was validated using Kaplan-Meier (K-M) curves, receiver operating characteristic (ROC) curves and a nomogram. Immune infiltration, single-cell and drug sensitivity analyses were used to examine the effects of NRGs on the prognosis of CRC. RESULTS: The prognostic model served as a valid and independent predictor of CRC prognosis. Immune infiltration and single-cell analyses revealed that the unique immune microenvironment of CRC was regulated by NRGs. Drug sensitivity analysis showed that patients in the high- and low-risk groups were sensitive to different drugs. In addition, H2BC18 was found to play an important role in regulating the malignant progression of CRC. CONCLUSION: This study provides novel insights into precision immunotherapy based on NRGs in CRC. The NRG-based prognostic model may help to identify targeted drugs and develop more effective and individualised treatment strategies for patients with CRC.

Efficacy and safety of orlistat in male patients with overweight/obesity and hyperuricemia: results of a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Obesity is associated with elevated serum uric acid (SUA) levels and frequent gout flares. Losing weight can reduce the SUA level and gout flares. The effect of orlistat on SUA levels and gout flares in patients with overweight/obesity and hyperuricemia (HUA) has not been extensively studied. This study investigated the effects of orlistat on SUA levels and gout flares compared to placebo in overweight and obese patients with HUA. METHODS: A total of 72 Chinese patients with overweight/obesity and HUA were randomly divided into a placebo group (35, 48.6%) and an orlistat group (37, 51.4%); the trial lasted 12 weeks. The primary endpoints were the relative changes in body weight, the SUA level, and gout flares in the per-protocol population. RESULTS: Orlistat reduced the proportion of patients with gout flares (log-rank P = 0.023, hazard ratio = 0.31, 95% confidence interval 0.11-0.85). There was no significant difference in SUA level between the two groups. The average weight loss of the orlistat group was 2.85 kg, and the average weight loss of the placebo group was 0.76 kg. The weight loss in the orlistat group was significantly greater than that in the control group (P < 0.05). CONCLUSIONS: This study is the first to demonstrate that orlistat has no significant effect on SUA levels in patients with overweight/obesity and HUA. The utility of orlistat as an adjunct therapy to prevent gout flares during weight loss in patients with HUA was emphasized. TRIAL REGISTRATION: Clinicaltrials.gov NCT05496075.

Aging and comprehensive molecular profiling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

Association of serum uric acid with women's ovarian reserve: observational study and Mendelian randomization analyses.

OBJECTIVE: To investigate the association between serum uric acid and women's ovarian reserve. DESIGN: Retrospective observational study and Mendelian randomization study. SETTING: University-affiliated in vitro fertilization center. PATIENTS: Observational analyses were undertaken using data from 8,257 women with infertility who finished their first in vitro fertilization treatments between May 2017 and December 2021. Mendelian randomization analyses were based on genome-wide association summary statistics from several biobanks of predominantly European ancestries. INTERVENTIONS: Observational study involved testing log2 transformed serum uric acid levels (for linear, negative regression, and logistic regression analyses); original uric acid levels (for nonlinear association analyses). Mendelian randomization study involved testing genetically predicted uric acid levels. MAIN OUTCOME MEASURES: Biomarkers including antimüllerian hormone, basal antral follicle count, follicle-stimulating hormone, luteinizing hormone, ratio of follicle-stimulating hormone to luteinizing hormone, estradiol; indices of ovarian response to stimulation including poor ovarian response according to different criteria and oocyte yield. RESULTS: In retrospective observational study, all ovarian reserve-related outcomes demonstrated significant differences across serum uric acid quartiles. A two-fold uric acid increase was associated with increased antimüllerian hormone (adjusted ß = 0.69; 95% confidence interval [CI], 0.43-0.95), antral follicle count (adjusted incidence rate ratio = 1.10, 95% CI, 1.05-1.14), luteinizing hormone (adjusted ß = 0.53, 95% CI, 0.28-0.78), decreased risks of Bologna poor ovarian response (adjusted odds ratio = 0.97; 95% CI, 0.95-0.99) and groups 2-4 Poseidon poor ovarian response (group 2: 0.63, 0.56-0.71; group 3: 0.71, 0.65-0.78; group 4: 0.50, 0.46-0.55), whereas an increased risk of group 1 (1.26, 1.13-1.41). Nonlinear analyses showed a common inflection point at 320-340 µmol/L of uric acid. Interactions between uric acid and antimüllerian hormone and antral follicle count were presented in association with oocyte yield. Mendelian randomization results suggested a significant association between genetically predicted uric acid levels and antimüllerian hormone levels (ß = 0.08; 95% CI, 0.04-0.12) but none for uric acid in relation to polycystic ovarian syndrome or other related hormones. CONCLUSION: Higher uric acid levels were associated with better ovarian reserve and increased levels of antimüllerian hormone albeit an increased risk of unexpected poor ovarian response.

Ketogenic diet ameliorates high-fat diet-induced insulin resistance in mouse skeletal muscle by alleviating endoplasmic reticulum stress.

OBJECTIVE: Ketogenic diets (KD) have been shown to alleviate insulin resistance (IR) by exerting anti-lipogenic and insulin sensitizing effects in the liver through a variety of pathways. The present study sought to investigate whether a ketogenic diet also improves insulin sensitization in skeletal muscle cells through alleviating endoplasmic reticulum stress. METHODS: High-fat diet-induced IR mice were allowed to a 2-week ketogenic diet. Insulin resistance and glucose tolerance were evaluated through GTT, ITT, and HOMA-IR. The C2C12 myoblasts exposed to palmitic acid were used to evaluate the insulin sensitization effects of ß-hydroxybutyric acid (ß-OHB). Molecular mechanisms concerning ER stress signaling activation and glucose uptake were assessed. RESULTS: The AKT/GSK3ß pathway was inhibited, ER stress signaling associated with IRE1, PERK, and BIP was activated, and the number of Glut4 proteins translocated to membrane decreased in the muscle of HFD mice. However, all these changes were reversed after 2 weeks of feeding on a ketogenic diet. Consistently in C2C12 myoblasts, the AKT/GSK3ß pathway was inhibited by palmitic acid (PA) treatment. The endoplasmic reticulum stress-related proteins, IRE1, and BIP were increased, and the number of Glut4 proteins on the cell membrane decreased. However, ß-OHB treatment alleviated ER stress and improved the glucose uptake of C2C12 cells. CONCLUSION: Our data reveal that KD ameliorated HFD-induced insulin resistance in skeletal muscle, which was partially mediated by inhibiting endoplasmic reticulum stress. The insulin sensitization effect of ß-OHB is associated with up regulation of AKT/GSK3ß pathway and the increase in the number of Glut4 proteins on the cell membrane.

Discovery of 6-Formylpyridyl Urea Derivatives as Potent Reversible-Covalent Fibroblast Growth Factor Receptor 4 Inhibitors with Improved Anti-Hepatocellular Carcinoma Activity.

Fibroblast growth factor receptor 4 (FGFR4) has been considered as a potential anticancer target due to FGF19/FGFR4 mediated aberrant signaling in hepatocellular carcinoma (HCC). Several FGFR4 inhibitors have been reported, but none have gained approval. Herein, a series of 5-formyl-pyrrolo[3,2-b]pyridine-3-carboxamides and a series of 6-formylpyridyl ureas were characterized as selective reversible-covalent FGFR4 inhibitors. The representative 6-formylpyridyl urea 8z exhibited excellent potency against FGFR4WT, FGFR4V550L, and FGFR4V550M with IC50 values of 16.3, 12.6, and 57.3 nM, respectively. It also potently suppressed proliferation of Ba/F3 cells driven by FGFR4WT, FGFR4V550L, and FGFR4V550M, and FGFR4-dependent Hep3B and Huh7 HCC cells, with IC50 values of 1.2, 13.5, 64.5, 15.0, and 20.4 nM, respectively. Furthermore, 8z displayed desirable microsomal stability and significant in vivo efficacy in the Huh7 HCC cancer xenograft model in nude mice. The study provides a promising new lead for anticancer drug discovery directed toward overcoming FGFR4 gatekeeper mutation mediated resistance in HCC patients.

Purine Metabolic Pathway Alterations and Serum Urate Changes after Oral Inosine Loading in Male Chinese Volunteers.

BACKGROUND: Oral inosine loading is a new method to evaluate the effects of purine on urate metabolism. However, individuals respond differently to acute purine intake, and the effects on the metabolism of other purines remain to be explored. METHODS: 35 male participants are recruited. Participants received 500 mg of inosine orally after an overnight fast, and blood and urine samples are collected before and at various time points over 180 min after inosine administration. RESULTS: The serum urate concentration is significantly different between the hyperuricemia (n = 14) and non-hyperuricemia (n = 16) groups before inosine intake, but there is no in urate change after inosine intake. When grouped according to the baseline estimated glomerular filtration rate (eGFR), the increase in urate level in the high-eGFR group is significantly higher than that in the low-eGFR group (p  =  0.047). The high-eGFR group showed higher levels of serum xanthine and xanthine oxidase (XOD), the key enzyme in urate synthesis, after inosine loading (p < 0.01). CONCLUSIONS: The increase in urate level is positively related to eGFR after oral acute inosine administration, which may have been due to a higher level of XOD.

Cross-sectional network analysis of plasma proteins/metabolites correlated with pathogenesis and therapeutic response in acute promyelocytic leukemia.

The treatment of PML/RARA+ acute promyelocytic leukemia (APL) with all-trans-retinoic acid and arsenic trioxide (ATRA/ATO) has been recognized as a model for translational medicine research. Though an altered microenvironment is a general cancer hallmark, how APL blasts shape their plasma composition is poorly understood. Here, we reported a cross-sectional correlation network to interpret multilayered datasets on clinical parameters, proteomes, and metabolomes of paired plasma samples from patients with APL before or after ATRA/ATO induction therapy. Our study revealed the two prominent features of the APL plasma, suggesting a possible involvement of APL blasts in modulating plasma composition. One was characterized by altered secretory protein and metabolite profiles correlating with heightened proliferation and energy consumption in APL blasts, and the other featured APL plasma-enriched proteins or enzymes catalyzing plasma-altered metabolites that were potential trans-regulatory targets of PML/RARA. Furthermore, results indicated heightened interferon-gamma signaling characterizing a tumor-suppressing function of the immune system at the first hematological complete remission stage, which likely resulted from therapy-induced cell death or senescence and ensuing supraphysiological levels of intracellular proteins. Overall, our work sheds new light on the pathophysiology and treatment of APL and provides an information-rich reference data cohort for the exploratory and translational study of leukemia microenvironment.

Aerobic exercise-induced decrease of chemerin improved glucose and lipid metabolism and fatty liver of diabetes mice through key metabolism enzymes and proteins.

Our previous studies have implicated an important role of adipokine chemerin in exercise-induced improvements of glycolipid metabolism and fatty liver in diabetes rat, but the underlying mechanisms remain unknown. This study first used an exogenous chemerin supplement to clarify the roles of decreased chemerin in exercised diabetes mice and possible mechanisms of glucose and lipid metabolism key enzymes and proteins [such as adipose triglyceride lipase (ATGL), lipoprotein lipase (LPL), phosphoenolpyruvate carboxykinase (PEPCK), and glucose transporter 4 (GLUT4)]. In addition, two kinds of adipose-specific chemerin knockout mice were generated to demonstrate the regulation of chemerin on glucose and lipid metabolism enzymes and proteins. We found that in diabetes mice, exercise-induced improvements of glucose and lipid metabolism and fatty liver, and exercise-induced increases of ATGL, LPL, and GLUT4 in liver, gastrocnemius and fat were reversed by exogenous chemerin. Furthermore, in chemerin knockdown mice, chemerin(-/-)∙adiponectin mice had lower body fat mass, improved blood glucose and lipid, and no fatty liver; while chemerin(-/-)∙fabp4 mice had hyperlipemia and unchanged body fat mass. Peroxisome proliferator-activated receptor γ (PPARγ), ATGL, LPL, GLUT4 and PEPCK in the liver and gastrocnemius had improve changes in chemerin(-/-)·adiponectin mice while deteriorated alterations in chemerin(-/-)·fabp4 mice, although PPARγ, ATGL, LPL, and GLUT4 increased in the fat of two kinds of chemerin(-/-) mice. CONCLUSIONS: Decreased chemerin exerts an important role in exercise-induced improvements of glucose and lipid metabolism and fatty liver in diabetes mice, which was likely to be through PPARγ mediating elevations of ATGL, LPL and GLUT4 in peripheral metabolic organs.

Bioinspired trimesic acid anchored electrocatalysts with unique static and dynamic compatibility for enhanced water oxidation.

Layered double hydroxides are promising candidates for the electrocatalytic oxygen evolution reaction. Unfortunately, their catalytic kinetics and long-term stabilities are far from satisfactory compared to those of rare metals. Here, we investigate the durability of nickel-iron layered double hydroxides and show that ablation of the lamellar structure due to metal dissolution is the cause of the decreased stability. Inspired by the amino acid residues in photosystem II, we report a strategy using trimesic acid anchors to prepare the subsize nickel-iron layered double hydroxides with kinetics, activity and stability superior to those of commercial catalysts. Fundamental investigations through operando spectroscopy and theoretical calculations reveal that the superaerophobic surface facilitates prompt release of the generated O2 bubbles, and protects the structure of the catalyst. Coupling between the metals and coordinated carboxylates via C‒O‒Fe bonding prevents dissolution of the metal species, which stabilizes the electronic structure by static coordination. In addition, the uncoordinated carboxylates formed by dynamic evolution during oxygen evolution reaction serve as proton ferries to accelerate the oxygen evolution reaction kinetics. This work offers a promising way to achieve breakthroughs in oxygen evolution reaction stability and dynamic performance by introducing functional ligands with static and dynamic compatibilities.

Clinical study on single-port endoscopic resection via a gasless transaxillary approach in the treatment of breast fibroadenoma in adolescents.

BACKGROUND: Breast fibroadenoma is the most common benign breast tumour. This study aimed to investigate the advantages and disadvantages of endoscopic-assisted resection via a gas-less transaxillary single-port approach for breast fibroadenoma in adolescent patients, compared with a traditional approach. METHODS: The clinical data of 83 patients with breast fibroadenoma treated in our hospital from October 2019 to October 2021 were collected for retrospective analysis. These patients were divided into an endoscopic-assisted surgery (ES) group (n = 39) and a traditional open surgery (OS) group (n = 44) according to the surgical approach. The operative time, intraoperative blood loss, incision length, postoperative complications, and patient satisfaction were compared between the two groups. RESULTS: The surgical cost was (5.1 ± 0.6) thousand Yuan [(0.7 ± 0.1) thousand US dollars] in the ES group and (3.5 ± 2.7) thousand Yuan [(0.5 ± 0.4) thousand US dollars] in the OS group, showing a statistically significant difference (p < 0.001). There was no significant difference in surgical time, intraoperative blood loss, incision length, or the rate of postoperative complications between the two groups. Stratified analysis revealed that the ES group had a significantly shorter operative time [(57.00 ± 10.26) min vs. (78.27 ± 7.63)] (p < 0.001), a smaller incision length [(3.73 ± 0.34) cm vs. (4.42 ± 0.44) cm] (p < 0.001), and a lower complication incidence rate (11.1% vs. 63.6) (p = 0.011) than the OS group in the cases with a nodule number ≥ 3. The satisfaction score using the BREAST-Q scale indicated that psychosocial well-being and patient satisfaction with the breast in the ES group were significantly superior to those in the OS group [(91.18 ± 3.12) points vs. (87.00 ± 4.45) points and (91.03 ± 6.80) points vs. (84.45 ± 6.06) points, respectively] (p < 0.001). CONCLUSION: ES is a safe and effective method for the treatment of fibroadenoma. In patients with multiple fibroadenomas (≥ 3 tumours), ES has a shorter operative time and fewer postoperative complications. ES demonstrates a significant, prominent advantage in cosmetic appearance. However, it should be noted that ES is associated with higher costs than OS.

Nanopore actuation of a DNA-tracked nanovehicle.

As a kind of nanomachine that has great potential for applications in nanoscale sensing and manipulation, nanovehicles with unique shapes and functions have received extensive attention in recent years. Different from the existing common method of using synthetic chemistry to design and manufacture a nanovehicle, here we theoretically report a molecularly assembled DNA-tracked nanovehicle that can move on a solid-state surface using molecular dynamics simulations. A graphene membrane with four nanopores acts as the chassis of the nanoscale vehicle, and two circular ssDNAs across the nanopores serve as the wheels. The electroosmotic flows induced by independently charged nanopores with different surface charge densities under external electric fields were found to be the main power to actuate the controlled rotary motion of circular ssDNAs across every two nanopores. By tuning the rotary speed of each circular ssDNA, the linear and turning movements of the designed nanovehicle were realized. The designed nanovehicle makes it possible to have access to almost everywhere in the human body, which would lead to significant breakthroughs in the fields of nanoscale surgery, drug delivery and so on. The research not only enriches the family of nanorobots, but also opens another way for designing nanovehicles.

Genome-wide identification and functional characterization of borneol dehydrogenases in Wurfbainia villosa.

MAIN CONCLUSION: Genome-wide screening of short-chain dehydrogenases/reductases (SDR) family reveals functional diversification of borneol dehydrogenase (BDH) in Wurfbainia villosa. Wurfbainia villosa is an important medicinal plant, the fruits of which accumulate abundant terpenoids, especially bornane-type including borneol and camphor. The borneol dehydrogenase (BDH) responsible for the conversion of borneol to camphor in W. villosa remains unknown. BDH is one member of short-chain dehydrogenases/reductases (SDR) family. Here, a total of 115 classical WvSDR genes were identified through genome-wide screening. These WvSDRs were unevenly distributed on different chromosomes. Seven candidate WvBDHs based on phylogenetic analysis and expression levels were selected for cloning. Of them, four BDHs can catalyze different configurations of borneol and other monoterpene alcohol substrates to generate the corresponding oxidized products. WvBDH1 and WvBDH2, preferred (+)-borneol to (-)-borneol, producing the predominant ( +)-camphor. WvBDH3 yielded approximate equivalent amount of (+)-camphor and (-)-camphor, in contrast, WvBDH4 generated exclusively (+)-camphor. The metabolic profiles of the seeds showed that the borneol and camphor present were in the dextrorotatory configuration. Enzyme kinetics and expression pattern in different tissues suggested WvBDH2 might be involved in the biosynthesis of camphor in W. villosa. All results will increase the understanding of functional diversity of BDHs.

Comparing genomes of Fructus Amomi-producing species reveals genetic basis of volatile terpenoid divergence.

Wurfbainia longiligularis and Wurfbainia villosa are both rich in volatile terpenoids and are 2 primary plant sources of Fructus Amomi used for curing gastrointestinal diseases. Metabolomic profiling has demonstrated that bornyl diphosphate (BPP)-related terpenoids are more abundant in the W. villosa seeds and have a wider tissue distribution in W. longiligularis. To explore the genetic mechanisms underlying the volatile terpenoid divergence, a high-quality chromosome-level genome of W. longiligularis (2.29 Gb, contig N50 of 80.39 Mb) was assembled. Functional characterization of 17 terpene synthases (WlTPSs) revealed that WlBPPS, along with WlTPS 24/26/28 with bornyl diphosphate synthase (BPPS) activity, contributes to the wider tissue distribution of BPP-related terpenoids in W. longiligularis compared to W. villosa. Furthermore, transgenic Nicotiana tabacum showed that the GCN4-motif element positively regulates seed expression of WvBPPS and thus promotes the enrichment of BPP-related terpenoids in W. villosa seeds. Systematic identification and analysis of candidate TPS in 29 monocot plants from 16 families indicated that substantial expansion of TPS-a and TPS-b subfamily genes in Zingiberaceae may have driven increased diversity and production of volatile terpenoids. Evolutionary analysis and functional identification of BPPS genes showed that BPP-related terpenoids may be distributed only in the Zingiberaceae of monocot plants. This research provides valuable genomic resources for breeding and improving Fructus Amomi with medicinal and edible value and sheds light on the evolution of terpenoid biosynthesis in Zingiberaceae.

Correlation between Polyphenol Contents and Antioxidant Activities in Different Echinacea Purpurea Varieties.

OBJECTIVE: Polyphenols are complex compounds containing multiple phenolic hydroxyl groups. They are widely distributed in plants and have antioxidant activities. Whether the antioxidant activities of the cultivated varieties of Echinacea are similar to or better than those of the wild ones and the relationship between the accumulation of polyphenols and their antioxidant activities are still not clear. METHODS: Folin-Ciocalteu method, high performance liquid chromatography (HPLC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, ferric ion reducing antioxidant power (FRAP) assay, 2,2'-azino-bis(3-ethylbenzothiazoline-6)-sulfonic acid (ABTS) radical scavenging assay, and Fe2+ chelating ability assay were used, respectively, to detect the total polyphenols and 5 kinds of caffeic acid derivatives (chicoric acid, caffeic acid, caftaric acid, chlorogenic acid, and 1,5-dicaffeoylquinic acid) in the roots, stems, leaves, and flowers, and the antioxidant activities of 3 varieties of Echinacea: E. purpurea L., cultivar E. purpurea 'Aloha', and E. purpurea 'White Swan'. RESULTS: E. purpurea L. had the highest contents of total polyphenols, 5 caffeic acid derivatives and antioxidant activities, followed by E. purpurea 'White Swan' and E. purpurea 'Aloha', respectively. E. purpurea 'White Swan' had the strongest ability to remove the DPPH, ABTS•+ and free radicals, and to chelate Fe2+; E. purpurea L. had the strongest ability to reduce FRAP. The correlation analyses revealed that the contents of total polyphenols and caffeic acid derivatives of E. purpurea L. and E. purpurea 'White Swan' were correlated with their antioxidant activities. CONCLUSION: E. purpurea L. was the most appropriate material for the development of medicinal plants. E. purpurea 'White Swan' could be used as a substitute for E. purpurea L. in terms of its antioxidant activity.

Detection of multiple types of cancer driver mutations using targeted RNA sequencing in non-small cell lung cancer.

BACKGROUND: DNA-based next-generation sequencing has been widely used in the selection of target therapies for patients with nonsmall cell lung cancer (NSCLC). RNA-based next-generation sequencing has been proven to be valuable in detecting fusion and exon-skipping mutations and is recommended by National Comprehensive Cancer Network guidelines for these mutation types. METHODS: The authors developed an RNA-based hybridization panel targeting actionable driver oncogenes in solid tumors. Experimental and bioinformatics pipelines were optimized for the detection of fusions, single-nucleotide variants (SNVs), and insertion/deletion (indels). In total, 1253 formalin-fixed, paraffin-embedded samples from patients with NSCLC were analyzed by DNA and RNA panel sequencing in parallel to assess the performance of the RNA panel in detecting multiple types of mutations. RESULTS: In analytical validation, the RNA panel achieved a limit of detection of 1.45-3.15 copies per nanogram for SNVs and 0.21-6.48 copies per nanogram for fusions. In 1253 formalin-fixed, paraffin-embedded NSCLC samples, the RNA panel identified a total of 124 fusion events and 26 MET exon 14-skipping events, in which 14 fusions and six MET exon 14-skipping mutations were missed by DNA panel sequencing. By using the DNA panel as the reference, the positive percent agreement and the positive predictive value of the RNA panel were 98.08% and 98.62%, respectively, for detecting targetable SNVs and 98.15% and 99.38%, respectively, for detecting targetable indels. CONCLUSIONS: Parallel DNA and RNA sequencing analyses demonstrated the accuracy and robustness of the RNA sequencing panel in detecting multiple types of clinically actionable mutations. The simplified experimental workflow and low sample consumption will make RNA panel sequencing a potentially effective method in clinical testing.