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Polycystic ovary syndrome (PCOS) is a common metabolic and endocrine disorder characterized by abnormal elevation in hormone levels, with currently lacking effective treatment options. N-3 polyunsaturated fatty acids (PUFA) have broad pharmacological activity and play a beneficial role in the development of PCOS. In this study, we observed that n-3 PUFA-eicosatrienoic acid (ETA) improves the estrous cycle and ovarian morphology in dehydroepiandrosterone (DHEA)-induced PCOS mice, particularly serum hormone levels. Additionally, it suppresses the expression of CYP19A1 and E2 synthesis in human granulosa-like tumor cell line (KGN) cells. Further investigation revealed that ETA significantly upregulates the expression of CD36, cAMP, P-PKA, and FOXO1 in KGN cells and mouse ovaries to lower E2 levels. This conclusion was supported by inhibiting CD36 and FOXO1 at both the mouse and cellular levels. Additionally, ETA treatment decreased the expression of ESR1, Kiss1, Gnrh in the hypothalamus, and GnRHR, Lhβ, Egr1, Pitx1, Sf1 in the pituitary of PCOS mice. No differences were observed after ETA treatment in the CD36 and FOXO1 inhibitor groups, indicating that ETA improves PCOS mice by regulating the hypothalamic-pituitary axis through E2 synthesis inhibition. In summary, we have elucidated for the first time the mechanism by which CD36 regulates E2 synthesis in ovarian granulosa cells and demonstrated that ETA activates the CD36 receptor to inhibit E2 synthesis through the cAMP/PKA/FOXO1/CYP19A1 signaling pathway, thereby improving hormonal imbalance and treating PCOS. This provides a new strategy for the effective prevention and treatment of PCOS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Alzheimer's disease is associated both with imbalances in Al 3+ production and changes in viscosity in cells. Their simultaneous measurement could therefore provide valuable insights into Alzheimer's disease pathology. Their simultaneous measurement would therefore be of great value in investigating the pathological mechanism of Alzheimer's disease. We designed a fluorescent probe YM2T with AIE effect that is capable of selectively responding to Al 3+ by fluorescence colormetrics and to viscosity by fluorescence "turn on" modes. Additionally, Al 3+ and viscosity were simultaneously detected in PC12 cells using the low cytotoxic probe YM2T via blue and green fluorescence channels. More importantly, the YM2T probe was used to image mice with AD. Hence, the YM2T probe shows potential as a useful molecular instrument for studying the pathological impact of Al 3+ and viscosity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Bruton's tyrosine kinase inhibitors (BTKi) exhibit superior efficacy in relapsed/refractory primary central nervous system lymphoma (PCNSL), but few studies have evaluated patients with newly diagnosed PCNSL, and even fewer studies have evaluated differences in efficacy between treatment with BTKi and traditional chemotherapy. This study retrospectively analyzed the clinical characteristics of 86 patients with PCNSL and identified predictors of poor prognosis for overall survival (OS). After excluding patients who only received palliative care, 82 patients were evaluated for efficacy and survival. According to the induction regimen, patients were divided into the traditional chemotherapy, BTKi combination therapy, and radiotherapy groups; the objective response rates (ORR) of the three groups were 71.4%, 96.2%, and 71.4% (P = 0.037), respectively. Both median progression-free survival and median duration of remission showed statistically significant differences (P = 0.019 and P = 0.030, respectively). The median OS of the BTKi-containing therapy group was also longer than that of the traditional chemotherapy group (not reached versus 47.8 (32.5-63.1) months, P = 0.038).Seventy-one patients who achieved an ORR were further analyzed, and achieved an ORR after four cycles of treatment and maintenance therapy had prolonged OS (P = 0.003 and P = 0.043, respectively). In conclusion, survival, and prognosis of patients with newly diagnosed PCNSL are influenced by the treatment regimen, with the BTKi-containing regimen showing great potential., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Context: The safety and efficacy of nutritional management for pressure injuries (PIs) have been the subjects of ongoing interest. Some evidence demonstrated that nutrition is essential for skin and tissue viability, supporting tissue repair for healing the pressure injury., Objective: This investigation aimed to systematically review clinical practice guidelines (CPGs) for the nutritional management of PIs and furnish an evidence map to assess research trends and CPG gaps., Methods: The PubMed, Embase, and guidelines databases, and society websites were searched for CPGs for the nutritional management of PIs. The basic recommendations for the nutritional management of PIs, method quality, and reporting CPGs quality were identified and imported into Excel. Four researchers independently elucidated each CPG's quality via the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument and the Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist. All bubble charts were generated using Excel software., Results: This review included 12 CPGs with a combined 23 recommendations. The nutrition screening and assessment were summarized on the basis of the PI recommendations for 6 major items, 12 items on nutrition management, and 3 on PI education. The assessed CPGs had mixed quality, and the highest score  ± standard deviation based on the clarity of presentation was 83.46 ± 7.62, whereas the lowest mean score based on AGREE II applicability was 53.31 ± 16.90. Field 1 (basic information) in the RIGHT checklist had the greatest reporting rate (68.06%), whereas field 5 (review and quality assurance) had the lowest CPGs quality (41.67%)., Conclusion: This investigation furnishes an evidence map and provides new perspectives on the CPGs for the nutritional management of PIs. However, the CPGs included still need improvement, especially in the applicability and editorial independence domains., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

As a cancer with the highest incidence in recent years, lung cancer is mainly composed of three diseases: non-small cell lung cancer, small cell lung cancer and neuroendocrine tumor. The morbidity and mortality of this malignant tumor are the highest in both male and female populations worldwide. In my country, lung cancer has become the most common cancer disease and the leading cause of cancer death, so it is extremely important to find lung cancer therapeutic targets. Based on previous studies, we speculated that the TLR4-Myd88-NFκB pathway may be involved in hmgb1-induced EMT in A549 cells, and daphnetin may also inhibit hmgb1-induced EMT through the TLR4-Myd88-NFκB pathway in A549 cells, but related studies have not linked it to hmgb1-induced EMT. Therefore, the innovation of this study is to test these two conjectures and analyze how daphnetin affects the epithelial-mesenchymal transition (EMT) mechanism induced by HMGB1 in human lung adenocarcinoma cells (A549 cell line), aiming at lung adenocarcinoma cells, foundation for clinical treatment. The proliferation rate and the migrating cell number presented an obvious decrease in the HMGB1+TLR4-shRNA group and the HMGB1+daphnetin group relative to the HMGB1 group ( P  < 0.0001). The intracellular expression of TLR4, Myd88, NFκB, vimentin and snail1 proteins were significantly decreased ( P  < 0.001), while that of E-cadherin presented a remarkable increase ( P  < 0.001) in the HMGB1+TLR4-shRNA and HMGB1+daphnetin group compared with the HMGB1 group. TLR4-MyD88-NFκB pathway is associated with HMGB1-induced EMT in A549 cells. Daphnetin had an inhibitory effect on HMGB1-induced EMT via the TLR4-Myd88-NF-κB pathway in A549 cells.

Objective: The hippocampus and amygdala, as important components of the limbic system, play crucial roles in central remodeling in congenital hearing loss. This study aimed to investigate the morphological integrity and network properties of the subfields of hippocampus and amygdala in children with congenital hearing loss., Methods: A total of 24 children with congenital hearing loss and 17 age- and sex- matched healthy controls (HC) are included in the study. T1-weighted images are analyzed by segmenting the brain into cortical and subcortical regions. Intergroup difference of volumes were explored. Structural covariance networks for the whole brain and hippocampus-amygdala subregions were constructed. Between-group differences of network property are investigated by comparing area under a range of network sparsity., Results: Patients with congenital hearing loss exhibited significantly larger volumes in the right dentate gyrus and CA3 of the hippocampus. However, there were no significant differences in total hippocampal or showed decreased global efficiency and increased characteristic path length, indicating reduced network integration. Lower betweenness centrality was observed in the left hippocampal fissure in the hearing loss group. The changes in volume and network topological properties are not affected by age and sex., Conclusion: Children with congenital hearing loss display specific volumetric increases in hippocampal subregions, suggesting compensatory adaptations to auditory deprivation. The hippocampus-amygdala network shows significant reorganization, potentially underpinning cognitive and behavioral development issues associated with congenital hearing loss. These findings highlight the importance of targeted neural substrates in understanding and addressing the developmental challenges faced by children with congenital hearing loss., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Rationale: Tuberous sclerosis (TSC) is an autosomal dominant neurocutaneous syndrome resulting from mutations in the tumor suppressor genes TSC1 and TSC2. Unfortunately, the absence of accurate diagnosis has significantly impacted the well-being of both patients and their families. Furthermore, the pathogenicity of numerous variants remains unverified, which could potentially result in misinterpretation of their functional implications., Patient Concerns: Proband 1 was a 33-year-old Chinese male, this patient presents with hamartomas in multiple organ systems, accompanied by clinical symptoms such as intellectual disability, epilepsy, and lipid adenoma. The patient and their family members used targeted next-generation sequencing and Sanger sequencing to identify the pathogenic variant., Diagnoses: The TSC1 (c.2923G>T, c.2924C>T) variant was identified and the patient was diagnosed with TSC disease., Interventions: After the definite diagnosis, the patient was treated with valproic acid, oxcarbazepine, and various organ supports., Outcomes: At present, the patient has intellectual decline, multiple sebaceous adenomas, multiple fiber nodules on the back, palpable mass in the right subcostal and middle upper abdomen, and percussion pain in the right kidney area, 1 to 2 times a month seizure, poor intelligence than peers., Lessons: This finding strengthens the significant phenotypic variability associated with TSC and expands the mutational spectrum of this rare disease., Competing Interests: The authors have no conflicts of interest to discloses., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Growing evidence suggests that heart failure (HF) is associated with an increased risk of depressive disorders and anxiety. However, the existing studies were observational and may have confounded and not reflected true causal relationships. This study collected genetic instruments about HF, depression, and anxiety from publicly available genetic summary data. Two-sample Mendelian randomization (MR) analysis was performed, with inverse-variance weighted designated as the primary approach for determining causal effects. Secondary analyses included MR-Egger regression and the weighted media method. Additionally, we conducted MR pleiotropy residual sum and outlier to address horizontal pleiotropy. Cochran Q test, MR-Egger intercept test, and leave-one-out analysis were used to assess the robustness of the findings. The significance is determined by a P-value below .05. Gene prediction result revealed that HF did not exhibit a significant association with elevated incidence of depression by inverse-variance weighted method no matter HF from the Heart Failure Molecular Epidemiology for Therapeutic Targets Consortium (odds ratio [OR] = 1.05, 95% confidence interval [CI] = 0.93-1.18, P = .424 for major depressive disorder, MDD; OR = 1.01, 95% CI = 0.94-1.09, P = .782 for major depression) or the FinnGen Consortium (OR = 1.03, 95% CI = 0.92-1.15, P = .644 for MDD; OR = 1.00, 95% CI = 0.94-1.07, P = .962 for major depression). In contrast, the results of HF on anxiety exhibited inconsistency (OR = 1.60, 95% CI = 1.10-2.31, P = .013 for Heart Failure Molecular Epidemiology for Therapeutic Targets Consortium; OR = 1.42, 95% CI = 0.91-2.21, P = .123 for FinnGen Consortium); however, a combined effect analysis indicated support causal relationship between HF and the risk of anxiety (OR = 1.52, 95% CI = 1.07-2.00, P < .001). Our findings did not reveal evidence to confirm a causal association between HF and depression. However, our results provide support for a causal effect of HF on the risk of anxiety., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To explore the changes of Pigment Epithelium-Derived Factor (PEDF), Matrix Metalloproteinase-2 (MMP-2), and Transforming Growth Factor-β2 (TGF-β2) levels in the aqueous humor of cataract patients and their correlation with disease severity., Methods: 93 cataract patients and 56 healthy subjects were study objects. PEDF, MMP-2, and TGF-β2 levels of aqueous humor were compared, and the correlation between each index and Lens Opacity Classification System (LOCS) III classification was analyzed. ROC curve was used to analyze the evaluation value of the combined detection of each index on cataract development, and logistic regression to analyze the influence of the changes of each index on cataract development., Results: PEDF levels were lower and MMP-2 and TGF-β2 levels were higher in the aqueous humor of cataract patients than in healthy subjects. PEDF levels in the aqueous humor were negatively correlated with LOCS III classification, while MMP-2 and TGF-β2 levels were positively correlated with LOCS III classification. The AUC value of combined detection was higher than that of PEDF, MMP-2, and TGF-β2 in the aqueous humor alone. MMP-2 ≥ 15.13 pg/mL, TGF-β2 ≥ 385.91 pg/mL and PEDF < 198.85 ng/mL were risk factors for cataract development., Conclusion: The changes in PEDF, MMP-2, and TGF-β2 levels in the aqueous humor of cataract patients are related to LOCS III classification. The combined detection is valuable in evaluating cataract development., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Jasmonic acid (JA) is an important phytohormone used to defend against herbivores, but it does not respond to whitefly feeding. Conversely, another phytohormone, salicylic acid (SA), is induced when plants are fed upon by whiteflies. JA has a better anti-whitefly effect than SA; however, there is limited research on how to effectively improve plant resistance by utilizing the different responses of these phytohormones to whitefly feeding., Results: We discovered that protease inhibitors 8 (PI8) and terpene synthase 10 (TPS10) located downstream of the JA-regulated pathway in plants have anti-whitefly effects, but these two genes were not induced by whitefly feeding. To identify whitefly-inducible promoters, we compared the transcriptome data of tobacco fed upon by Bemisia tabaci with the control. We focused on pathogenesis-related (PR) genes because they are known to be induced by SA. Among these PR genes, we found that expression levels of pathogenes-related protein 1C-like (PR1) and glucose endo-1,3-beta-glucosidase (BGL) can be significantly induced by whitefly feeding and regulated by SA. We then engineered the whitefly-inducible promoters of BGL and PR1 to drive the expression of PI8 and TPS10. We found that compared with control plants that did not induce the expression of PI8 or TPS10, transformed plants expressing PI8 or TPS10 under the PR1 or BGL promoter showed a significant increase in the expression levels of PI8 and TPS10 after whitefly infection, significantly improving their resistance to whiteflies., Conclusion: Our findings suggest that using SA-inducible promoters as tools to drive the expression of JA-regulated defense genes can enhance plant resistance to whiteflies. Our study provides a novel pathway for the enhancement of plant resistance against insects. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Synthetic cannabinoids (SCs), which are among the most widely abused new psychoactive substances, are much more potent and have greater efficacy than natural cannabis. SCs can be disguised in various ways and are commonly sold in the form of electronic cigarette oil. SCs belong to a large family with structures consisting of a core with substituents, linker, ring with substituents, and tail. New SCs can be developed by adding substituents, such as halogen, alkyl, and alkoxy groups, to the aromatic ring system or by changing the alkyl chain length. Since the emergence of so-called first-generation SCs, subsequent developments have led to eighth-generation indole/indazole amide-based SCs. As of July 1, 2021, the entire category of SCs was added to the list of controlled substances, but implementation requires urgent improvements in detection technologies. Typically, each method is limited to a few SCs. Owing to the vast number of chemically diverse SCs and their fast update speed, the determination and identification of various types of SCs using a single method is challenging. Therefore, rapid, sensitive, and accurate quantitative methods that includes various types of SCs must be developed to meet the demand for the qualitative and quantitative analysis of new SCs in seized electronic cigarette oil. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of 102 SCs in electronic cigarette oil. The mass spectrometry and liquid-phase conditions influencing SC separation and determination were optimized. Using the external standard method, 102 SCs were successfully identified in electronic cigarette oil. The samples were extracted using methanol. Target analytes were separated on a Shimadzu Shim-pack GIST-HP C18 AQ column (100 mm×2.1 mm, 1.9 μm) at a column temperature of 40 ℃. The mobile phases consisted of (A) 0.1% formic acid aqueous solution and (B) methanol-acetonitrile (1∶1, v/v). The gradient elution conditions were as follows: 0-8 min, 55%A-15%A; 8-15 min, 15%A; 15-16 min, 15%A-55%A; 16-18 min, 55%A. The flow rate was 0.4 mL/min and the injection volume was 1 μL. Operating in the multiple reaction monitoring mode, the 102 SCs were identified within 18 min. Each SC exhibited a good linear relationship in the range of 1-100.0 μg/L with a correlation coefficient ( r )≥0.9915. The limits of detection were 0.01-0.30 μg/L and the limits of quantification were 0.04-0.99 μg/L, which meet the requirements for analyzing SCs in actual samples. Precision was determined using standard solutions with 2, 10, and 50 μg/L of the SCs. The precisions ( n =6) were 0.3%-6.0%. The recoveries of the 102 SCs, as evaluated by spiking electronic cigarette oil at low (2 μg/mL), medium (10 μg/mL), and high (50 μg/mL) levels, were 80.1%-119.8%. Good performance was observed for the analysis of real samples. The developed method is accurate, rapid, sensitive, and effective for the determination of the 102 SCs in electronic cigarette oil, satisfying the requirements for practical qualitative and quantitative analysis.

Suppressor of Mek1 (Smek1) is a regulatory subunit of protein phosphatase 4. Genome-wide association studies have shown the protective effect of SMEK1 in Alzheimer's disease (AD). However, the physiological and pathological roles of Smek1 in AD and other tauopathies are largely unclear. Here, the role of Smek1 in preventing neurodegeneration is investigated in tauopathy. Smek1 is downregulated in the aged human brain. Through single-cell sequencing, a novel neuronal cluster is identified that possesses neurodegenerative characteristics in Smek1 -/- mice. Smek1 deficiency caused markedly more severe motor and cognitive impairments in mice, as well as neuronal loss, gliosis, and tau hyperphosphorylation at major glycogen synthase kinase 3β (Gsk3β) sites. Protein-protein interaction analysis revealed that the Ran-binding domain (RanBD) in the N-terminus of Smek1 facilitated binding with kinesin family member 2A (Kif2a). Depletion of Smek1 resulted in cytoplasmic aggregation of Kif2a, axon outgrowth defects, and impaired mitochondrial axonal trafficking. Downregulation of Kif2a markedly attenuated tau hyperphosphorylation and axon outgrowth defects in shSmek1 cells. For the first time, this study demonstrates that Smek1 deficiency progressively induces neurodegeneration by exacerbating tau pathology and mitochondrial dysfunction in an age-dependent manner., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The woody bamboos (Bambusoideae) exhibit distinctive biological traits within Poaceae, such as highly lignified culms, rapid shoot growth, monocarpic mass flowering and nutlike or fleshy caryopses. Much of the remarkable morphological diversity across the subfamily exists within a single hexaploid clade, the paleotropical woody bamboos (PWB), making it ideal to investigate the factors underlying morphological evolution in woody bamboos. However, the origin and biogeographical history of PWB remain elusive, as does the effect of environmental factors on the evolution of their morphological characters. We generated a robust and time-calibrated phylogeny of PWB using single nucleotide polymorphisms retrieved from optimized double digest restriction site associated DNA sequencing, and explored the evolutionary trends of habit, inflorescence, and caryopsis type in relation to environmental factors including climate, soil, and topography. We inferred that the PWB started to diversify across the Oligocene-Miocene boundary and formed four major clades, that is, Melocanninae, Racemobambosinae s.l. (comprising Dinochloinae, Greslanlinae, Racemobambosinae s.str. and Temburongiinae), Hickeliinae and Bambusinae s.l. (comprising Bambusinae s.str. plus Holttumochloinae). The ancestor of PWB was reconstructed as having erect habit, indeterminate inflorescence and basic caryopsis. The characters including climbing/scrambling habit, determinate inflorescence, and nucoid/bacoid caryopsis have since undergone multiple changes and reversals during the diversification of PWB. The evolution of all three traits was correlated with, and hence likely influenced by, aspects of climate, topography, and soil, with climate factors most strongly correlated with morphological traits, and soil factors least so. However, topography had more influence than climate or soil on the evolution of erect habit, whereas both factors had greater effect on the evolution of bacoid caryopsis than did soil. Our results provide novel insights into morphological diversity and adaptive evolution in bamboos for future ecological and evolutionary research., (© 2024 The Author(s). Journal of Integrative Plant Biology published by John Wiley & Sons Australia, Ltd on behalf of Institute of Botany, Chinese Academy of Sciences.)

Study Objectives: We assessed possible brain abnormalities in adult patients with moderate and severe obstructive sleep apnea using the mean kurtosis (MK) from diffusion kurtosis imaging and analyzed the correlation between MK and cognitive function., Methods: A total of 30 patients with moderate or severe obstructive sleep apnea and 30 healthy controls evaluated by the Montreal Cognitive Assessment scale were enrolled. All participants underwent diffusion kurtosis imaging and 3-dimensional T1-weighted imaging on a 3.0T magnetic resonance scanner. The MK values of gray and white matter brain regions were compared. Partial correlation analysis was used to analyze the correlation between respiratory sleep parameters/cognitive score and MK values in different brain regions., Results: Compared with the healthy controls, the MK of 20 brain regions (13 after false discovery rate correction) and cognitive scores in the obstructive sleep apnea group were significantly lower. In the obstructive sleep apnea group, apnea-hypopnea index was negatively correlated with the MK in the white matter of the right occipital lobe; lowest oxygen saturation was positively correlated with the MK in the bilateral parietal, precentral, and right postcentral cortex; total score on the Montreal Cognitive Assessment scale was positively correlated with MK in the left hippocampus; language function was positively correlated with MK in the white matter of the left parietal lobe; and delayed recall was positively correlated with the MK in right insula cortex and bilateral cingulate. After false discovery rate correction, only the correlations of lowest oxygen saturation with right precentral gyrus cortex and bilateral parietal cortex were significant., Conclusions: MK values of diffusion kurtosis imaging may provide valuable information in assessing the neurological impacts of obstructive sleep apnea., Citation: Zhang N, Peng K, Guo J-X, Liu Q, Xiao A-L, Jing H. Microstructural brain abnormalities and associated neurocognitive dysfunction in obstructive sleep apnea: a pilot study with diffusion kurtosis imaging. J Clin Sleep Med. 2024;20(10):1571-1578., (© 2024 American Academy of Sleep Medicine.)

Naturally derived compounds show promise as treatments for microbial infections. Polyphenols, abundantly found in various plants, fruits, and vegetables, are noted for their physiological benefits including antimicrobial effects. This study introduced a new set of acylated phloroglucinol derivatives, synthesized and tested for their antifungal activity in vitro against seven different pathogenic fungi. The standout compound, 3-methyl-1-(2,4,6-trihydroxyphenyl) butan-1-one ( 2b ), exhibited remarkable fungicidal strength, with EC 50 values of 1.39 μg/mL against Botrytis cinerea and 1.18 μg/mL against Monilinia fructicola , outperforming previously screened phenolic compounds. When tested in vivo, 2b demonstrated effective antifungal properties, with cure rates of 76.26% for brown rot and 83.35% for gray mold at a concentration of 200 μg/mL, rivaling the commercial fungicide Pyrimethanil in its efficacy against B. cinerea . Preliminary research suggests that 2b' s antifungal mechanism may involve the disruption of spore germination, damage to the fungal cell membrane, and leakage of cellular contents. These results indicate that compound 2b has excellent fungicidal properties against B. cinerea and holds potential as a treatment for gray mold.

Objective: High-risk neuroblastoma patients often have poor outcomes despite multi-treatment options. The risk stratification of high-risk MYCN-not-amplified (HR-MYCN-NA) patients remains difficult. This study aims to identify a gene set signature that can help further stratify HR-MYCN-NA patients for a potential personalized therapeutic strategy., Methods: Three microarrays and one single-cell RNA sequence dataset were acquired and analyzed. Firstly, the prognostic-related genes (PRGs) in HR-MYCN-NA tumor cells were identified using TARGET-NB and GSE137804 datasets. Then, the prognostic model was established by LASSO-Cox regression, and verified in external cohort (GSE49710, GSE45547). Moreover, a time-dependent receiver operating characteristic curve (ROC) and area under the ROC (AUC) was used to assess survival prediction. A nomogram was established to predict the 1-, 3- and 5-year overall survival (OS) of HR-MYCN-NA patients., Results: In the training set, a five-PRGs signature, which include GAL, GFRA3, MARCKS, PSMD13, and ZNHIT3 genes, was identified and successfully stratified HR-MYCN-NA patients into ultra-high risk (UHR) and high-risk (HR) subtypes (HR = 4.29, P < 0.001). ROC curve analysis confirmed its predictive power (AUC = 0.74-0.82), suggesting a good predictive efficacy. Consistently, high-risk scores also predicted worse OS (HR = 2, P = 0.033) in the external validation dataset (AUC = 0.67-0.71). Moreover, the overall C-index of the nomogram was 0.75 (P < 0.001), which indicated good agreement between the observed and predicted survival rates. Further integrating the five PRGs signature with clinical factors, these 5 gene signature (HR = 4.45, P < 0.001) and tumor grade (HR = 4.15, P = 0.02) were found to be independent prognostic factors for HR-MYCN-NA patients., Conclusion: The novel five PRGs signature could well predict the survival of HR-MYCN-NA patients, which may provide constructive information for these subsets., (© 2024. The Author(s).)

Background: Areca nut (AN) is a traditional Chinese herbal medicine used for centuries to treat gastrointestinal (GI) disorders. Charred AN (CAN) is a processed product of AN with similar therapeutic effects. This study aimed to investigate the therapeutic mechanisms of AN and CAN for constipation via metabolomics and gut microbiota analysis., Methods: In this study, the rats were randomly divided into 5 groups ( n  = 6): control, constipation model, positive drug, AN treatment, and CAN treatment groups. Constipation was induced by intragastric administration of loperamide hydrochloride, followed by 14-day treatment with mosapride, AN, or CAN. The efficacy difference between AN and CAN was assessed by evaluating the weight gain, fecal water content, GI transit rate, colonic histopathology, serum levels of GI hormones, gut microbiota, and fecal metabolites., Results: The results demonstrated that both AN and CAN could alleviate loperamide-induced constipation. Furthermore, they significantly elevated the serum levels of motilin, vasoactive intestinal peptide, substance P, and acetylcholine. 16S rRNA analysis revealed that AN regulated the relative abundance of Bacillus , UCG-005 , norank&#95;f&#95;Muribaculaceae , Candidatus&#95;Saccharimonas , and Ruminococcus , whereas CAN modulate the relative abundance of Lactobacillus , Bacillus , norank&#95;f&#95;Muribaculaceae , Ruminococcus , unclassified&#95;f&#95;Oscillospiraceae , and unclassified&#95;f&#95;Prevotellaceae . Moreover, the metabolic profile of AN- and CAN-treated rats was also different, where AN treatment involved pathways of citrate cycle (TCA) and tyrosine, alanine, aspartate, and glutamate metabolisms. Whereas CAN treatment involved pathways of steroid and primary bile acid biosynthesis, as well as pyrimidine and purine metabolisms. Spearman correlation analysis indicated a close relationship between gut microbiota and fecal metabolites., Conclusion: In summary, this study revealed that AN may protect GI mucosa, enhance GI motility, and alleviate constipation symptoms by regulating the relative abundance of specific gut microbiota ( Bacillus , UCG-005 , norank&#95;f&#95;Muribaculaceae , Candidatus&#95;Saccharimonas , Ruminococcus ) as well as citrate cycle or tyrosine, alanine, aspartate, and glutamate metabolic pathways. Furthermore, CAN was observed to promote gastric emptying and intestinal propulsion, thereby alleviating constipation, by modulating the relative abundance of specific gut microbiota ( Lactobacillus , Bacillus , norank&#95;f&#95;Muribaculaceae , Ruminococcus , unclassified&#95;f&#95;Oscillospiraceae , unclassified&#95;f&#95;Prevotellaceae ) as well as steroid and primary bile acid biosynthesis, as well as pyrimidine and purine metabolic pathways., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Wu, Zhang, Huang, Jiang and Li.)

Nicotiana benthamiana, a widely acknowledged laboratory model plant for molecular studies, exhibits lethality to certain insect pests and can serve as a dead-end trap plant for pest control in the field. However, the underlying mechanism of N. benthamiana's resistance against insects remains unknown. Here, we elucidate that the lethal effect of N. benthamiana on the whitefly Bemisia tabaci arises from the toxic glandular trichome exudates. By comparing the metabolite profiles of trichome exudates, we found that 51 metabolites, including five O-acyl sugars (O-AS) with medium-chain acyl moieties, were highly accumulated in N. benthamiana. Silencing of two O-AS biosynthesis genes, branched-chain keto acid dehydrogenase (BCKD) and Isopropyl malate synthase-C (IPMS-C), significantly reduced the O-AS levels in N. benthamiana and its resistance against whiteflies. Additionally, we demonstrated that the higher expression levels of BCKD and IPMS-C in the trichomes of N. benthamiana contribute to O-AS synthesis and consequently enhance whitefly resistance. Furthermore, overexpression of NbBCKD and NbIPMS-C genes in the cultivated tobacco Nicotiana tabacum enhanced its resistance to whiteflies. Our study revealed the metabolic and molecular mechanisms underlying the lethal effect of N. benthamiana on whiteflies and presents a promising avenue for improving whitefly resistance., (© 2024 John Wiley & Sons Ltd.)

Background: The whitefly Bemisia tabaci is one of the world's foremost agricultural pests. Recently, we found that a wild relative of tobacco (Nicotiana benthamiana) demonstrates remarkable attractiveness and nearly 100% lethality towards whiteflies. Therefore, it can act as a dead-end trap crop for whitefly control in the field. However, the underlying mechanism of the significant attractiveness of N. benthamiana towards whiteflies is unclear., Results: Binary-choice assays and olfactory experiments showed that compared to common tobacco (N. tabacum), the volatile of N. benthamiana has a greater attraction to whiteflies. Then we analyzed and compared volatiles from these two Nicotiana species by thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS). We identified 16 chemical compounds that are more abundant in N. benthamiana than in N. tabacum. Seven compounds were further tested with olfactometer assays and we found that, among them, undecane strongly attracted whiteflies. Further experiments revealed that even 0.005 μg mL -1 undecane is attractive to whiteflies. We also silenced the genes that may influence the biosynthesis of undecane and found the production of undecane decreased after silencing NbCER3, and that N. benthamiana plants with less undecane lost their attraction to whiteflies. In addition, we found that applying 0.005 μg mL -1 undecane on yellow sticky traps can increase the number of stuck insects on the traps by ≈40%., Conclusion: Undecane from the volatile of N. benthamiana is a critical chemical signal that attracts whiteflies and NbCER3 involved in the biosynthesis of undecane. Undecane may be used to improve the efficiency of yellow sticky traps for whitefly control. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Sophora flavescens , a traditional Chinese herb, produces a wide range of secondary metabolites with a broad spectrum of biological activities. In this study, we isolated six isopentenyl flavonoids (1-6) from the roots of S. flavescens and evaluated their activities against phytopathogenic fungi. In vitro activities showed that kurarinone and sophoraflavanone G displayed broad spectrum and superior activities, among which sophoraflavanone G displayed excellent activity against tested fungi, with EC 50 values ranging from 4.76 to 13.94 μg/mL. Notably, kurarinone was easily purified and showed potential activity against Rhizoctonia solani , Botrytis cinerea , and Fusarium graminearum with EC 50 values of 16.12, 16.55, and 16.99 μg/mL, respectively. Consequently, we initially investigated the mechanism of kurarinone against B. cinerea . It was found that kurarinone disrupted cell wall components, impaired cell membrane integrity, increased cell membrane permeability, and affected cellular energy metabolism, thereby exerting its effect against B. cinerea . Therefore, kurarinone is expected to be a potential candidate for the development of plant fungicides.

Background: Although observational studies have reported a correlation between vitamin D deficiency and type 2 diabetes mellitus (T2DM), epidemiological evidence on the risk of obese subjects suffering T2DM due to a vitamin D deficiency is limited. Therefore, we investigated the correlation between T2DM and serum vitamin D, lipids, blood pressure, insulin indexes in an obese population., Methods: A total of 1440 participants including 450 healthy controls and 990 obese subjects, 470 without T2DM and 520 with T2DM. Serum vitamin D levels were measured, and the association between low levels and T2DM in obese subjects was examined using multinomial and linear regression analyses., Results: Of the participants, 35% had deficient or insufficient vitamin D levels (ie, <20 ng/mL). Compared with healthy controls, obese subjects, particularly those with T2DM had lower vitamin D levels. Multinomial logistic regression analysis showed that obese subjects with T2DM had a gradually increasing risk for desirable ( RO = 1.41, 95% CI 1.06-1.93, P = 0.027), insufficient ( RO = 1.83, 95% CI 1.27-2.84, P < 0.001), or deficient (( RO = 2.14, 95% CI 1.15-3.75, P = 0.014) vitamin D levels. In obese subjects with T2DM, vitamin D levels correlated inversely with the risk indicators for diabetes, such as the levels of HbA1c (β = -0.16, P = 0.002), fasting insulin (Fins; β = -0.31, P = 0.008), and HOMA-IR (β = -0.19, P < 0.001). In obese subjects without T2DM, vitamin D was associated negatively with the risk of having T2DM at five-year follow-up (relative risk = 0.93, 95% CI 0.79-0.97, P = 0.037)., Conclusion: This study demonstrates that low vitamin D levels correlate with the presence of T2DM in the obese population. This finding indicates that hypovitaminosis D may be a potential biological vulnerability factor for the development of T2DM in obese subjects., Competing Interests: The authors declare that they have no conflicts of interest for this work., (© 2024 Shen et al.)

The mechanism and function of the expression of Schwann characteristics by nevus cells in the mature zone of the dermis are unknown. Early growth response 3 (EGR3) induces Schwann cell-like differentiation of melanoma cells by simulating the process of nevus maturation, which leads to a strong phenotypic transformation of the cells, including the formation of long protrusions and a decrease in cell motility, proliferation, and melanin production. Meanwhile, EGR3 regulates the levels of myelin protein zero (MPZ) and collagen type I alpha 1 chain (COL1A1) through SRY-box transcription factor 10 (SOX10)-dependent and independent mechanisms, by binding to non-strictly conserved motifs, respectively. Schwann cell-like differentiation demonstrates significant benefits in both in vivo and clinical studies. Finally, a CD86-P2A-EGR3 recombinant mRNA vaccine is developed which leads to tumor control through forced cell differentiation and enhanced immune infiltration. Together, these data support further development of the recombinant mRNA as a treatment for cancer., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Phosphogypsum, a typical by-product in the phosphorus chemical industry, could generate a large amount of leachate containing phosphate and fluoride in the process of rainfall and long-term stacking, which not only causes serious environmental pollution, but also leads to a waste of resources. In this study, a united treatment of calcium hydroxide precipitation and lanthanum zeolite (La-ZFA) adsorption was proposed to achieve the recovery of phosphate and fluoride from phosphogypsum leachate. In phosphogypsum, most phosphorus could be leached except P in the residual occurrence form, while for fluoride, only water-soluble F could be effectively leached. The optimum leaching amounts of phosphate and fluoride were 22.59 and 4.64 mg/g, respectively, at liquid-solid ratio of 400:1, leaching time of 120 min, pH of 6.0, particle size of >200 mesh (<0.075 mm), and leaching temperature of 25°C. Using Ca(OH) 2 as the precipitant, the phosphate could be precipitated selectively from phosphogypsum leachate by controlling pH and time, and the concentrations of it decreased significantly to 0.29 mg/L at pH 10.0, with a removal efficiency of 99.48%. XRD, SEM and Visual MINTEQ software analysis proved that the main component of the precipitate was hydroxyapatite (Ca 5 (PO 4 ) 3 (OH)). After P precipitation, a series of sorbents for fluoride were investigated, and La-ZFA sorbent was chosen and utilized to recover the fluoride from the leachate through a cyclic fixed-bed column. The efficiency of La-ZFA was basically not affected by the high concentration sulfate, and it can selectively adsorb fluoride from phosphogypsum leachate, leading to a final fluoride concentration of 0.29 mg/L in the effluent. The characterization demonstrated that fluoride might be adsorbed onto the La-ZFA via ligand exchange with hydroxy groups. The proposed method in this study is expected to sequentially recover phosphate and fluorine from the leachate of phosphogypsum, and it has great guiding significance for resource utilization and management of phosphogypsum., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Two new norcassane-type diterpenoids, named 6 β -hydroxy-bisnorcass-13-en-12-one ( 1 ) and 6 β -hydroxy-bisnorcassan-12-one ( 2 ), were isolated from the seeds of Mezonevron sinense Hemsl. The structures of compounds 1 - 2 were determined by extensive spectroscopic analysis. Two compounds exhibited immunosuppressive activity with the IC 50 values of 19.35 ± 0.87 μM and 18.69 ± 0.88 μM in the ConA induced T cell model and 65.04 ± 0.83  μ M and 48.06 ± 0.76 μM in LPS induced B cell model, respectively.

To evaluate the Vaccine Effectiveness (VE) of the Influenza Vaccine (InfV) during pregnancy in Gansu province. A retrospective cohort of pregnant women vaccinated with InfV was constructed using the electronic case system and immunization planning system of Gansu province. Outcome information of Influenza-Like Illness (ILI) in pregnant women after vaccination with InfV during the influenza epidemic seasons from 2019 to 2021 was collected. The log-binomial model was used to estimate the adjusted Risk Ratio ( RR ), VE, and their Confidence Intervals ( CI ). The incidence rates of the InfV vaccination group and the non-vaccination group during pregnancy in Gansu province were 4.70% (54/1,150) and 6.91% (16,990/245,754), respectively. The adjusted RR was 0.78 (95% CI 0.43-0.75), and the adjusted VE was 22.20 (95% CI 0.79-40.30). Vaccination with InfV during pregnancy in Gansu province from 2019 to 2021 has a protective effect against ILI in pregnant women, and there is no difference in vaccination at different stages of pregnancy.

Aquaculture has suffered significant financial losses as a result of the infection of zoonotic Aeromonas hydrophila, which has a high level of resistance to classic antibiotics. In this study, we isolated an A. hydrophila strain B3 from diseased soft-shelled turtle (Pelodiscus sinensis), which is one of the most commercially significant freshwater farmed reptiles in East Asia, and found that A. hydrophila was its dominant pathogen. To better understand the inhibition effect and action mechanism of Chinese herbs on A. hydrophila, we conducted Chinese herbs screening and found that Lonicera japonica had a significant antibacterial effect on A. hydrophila B3. Experimental therapeutics of L. japonica on soft-shelled turtle showed that the supplement of 1% L. japonica to diet could significantly upregulate the immunity-related gene expression of soft-shelled turtle and protect soft-shelled turtle against A. hydrophila infection. Histopathological section results validated the protective effect of L. japonica. As the major effective component of L. japonica, chlorogenic acid demonstrated significant inhibitory effect on the growth of A. hydrophila with MIC at 6.4 mg/mL. The in vitro assay suggested that chlorogenic acid could inhibit the hemolysin/protease production and biofilm formation of A. hydrophila and significantly decrease the expression of quorum sensing, biofilm formation, and hemolysin-related genes in A. hydrophila. Our results showed that the Chinese herb L. japonica would be a promising candidate for the treatment of A. hydrophila infections in aquaculture, and it not only improves the immune response of aquatic animals but also inhibits the virulence factor (such as biofilm formation) expression of A. hydrophila. KEY POINTS: • A. hydrophila was the dominant pathogen of the diseased soft-shelled turtle. • L. japonica can protect soft-shelled turtle against A. hydrophila infection. • Chlorogenic acid inhibits the growth and biofilm formation of A. hydrophila., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Although anesthesia provides favorable conditions for surgical procedures, recent studies have revealed that the brain remains active in processing noxious signals even during anesthesia. However, whether and how these responses affect the anesthesia effect remains unclear. The ventrolateral periaqueductal gray (vlPAG), a crucial hub for pain regulation, also plays an essential role in controlling general anesthesia. Hence, it was hypothesized that the vlPAG may be involved in the regulation of general anesthesia by noxious stimuli. Here, we found that acute noxious stimuli, including capsaicin-induced inflammatory pain, acetic acid-induced visceral pain, and incision-induced surgical pain, significantly delayed recovery from sevoflurane anesthesia in male mice, whereas this effect was absent in the spared nerve injury-induced chronic pain. Pretreatment with peripheral analgesics could prevent the delayed recovery induced by acute nociception. Furthermore, we found that acute noxious stimuli, induced by the injection of capsaicin under sevoflurane anesthesia, increased c-Fos expression and activity in the GABAergic neurons of the ventrolateral periaqueductal gray. Specific reactivation of capsaicin-activated vlPAG GABA neurons mimicked the effect of capsaicin and its chemogenetic inhibition prevented the delayed recovery from anesthesia induced by capsaicin. Finally, we revealed that the vlPAG GABA neurons regulated the recovery from anesthesia through the inhibition of ventral tegmental area dopaminergic neuronal activity, thus decreasing dopamine (DA) release and activation of DA D 1 -like receptors in the brain. These findings reveal a novel, cell- and circuit-based mechanism for regulating anesthesia recovery by nociception, and it is important to provide new insights for guiding the management of the anesthesia recovery period., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

The epoxy propanol molecular cage bonded silica stationary phase, RCC3-GLD@silica, synthesized through the ring-opening reaction of secondary amine with epoxy propanol using RCC3-R as the scaffold unit, was successfully prepared as confirmed by infrared spectroscopy, thermogravimetric analysis, and nitrogen adsorption-desorption characterization. This stationary phase demonstrated excellent separation performance in both reversed-phase and hydrophilic chromatography modes, effectively separating a wide variety of compounds including alkylbenzenes, polycyclic aromatic hydrocarbons, phenols, anilines, sulfonamides, nucleosides, amino acids, sugars, and acids. The development of RCC3-GLD@silica benefits from the synergistic effects of its hydrophobic and hydrophilic actions, as evidenced by the U-shaped characteristic of the retention factor for nucleoside compounds with changes in the aqueous content of the mobile phase, further confirming the simultaneous presence of reversed-phase and hydrophilic chromatography mechanisms. Not only did this stationary phase successfully separate 33 compounds in reversed-phase chromatography mode, but it also separated 54 compounds in hydrophilic interaction chromatography mode, showcasing its broad separation capability from weakly polar to strongly polar compounds on a single chromatographic column. This indicates a wide application prospect in the field of chromatographic analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The unique high isoelectric point of lysozyme (LYZ) restricts its application in composite antibacterial coating due to the unfavorable liability to electrostatic interaction with other components. In this work, the antibacterial activity of a dispersible LYZ-carboxymethyl konjac glucomannan (CMKGM) polyelectrolyte complex was evaluated. Kinetic analysis revealed that, compared with free LYZ, the complexed enzyme exhibited decreased affinity (K m ) but markedly increased V max against Micrococcus lysodeikticus, and QCM and dynamic light scattering analysis confirmed that the complex could bind with the substrate but in a much lower ratio. The complexation with CMKGM did not alter the antibacterial spectrum of LYZ, and the complex exerted antibacterial function by delaying the logarithmic growth phase and impairing the cell integrity of Staphylococcus aureus. Since the LYZ-CMKGM complex is dispersible in water and could be assembled easily, it has great potential as an edible coating in food preservation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jun-Xia Xiao reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Receptor-interacting protein kinase 1 (RIPK1) is a therapeutic target in treating neurodegenerative diseases and cancers. RIPK1 has three distinct functional domains, with the center domain containing a receptor-interacting protein homotypic interaction motif (RHIM), which mediates amyloid formation. The functional amyloid formed by RIPK1 and/or RIPK3 is a crucial intermediate in regulating cell necroptosis. In this study, the amyloid structure of mouse RIPK1, formed by an 82-residue sequence centered at RHIM, is presented. It reveals the "N"-shaped folding of the protein subunit in the fibril with four β-strands. The folding pattern is shared by several amyloid structures formed by proteins with RHIM, with the central β-strand formed by the most conserved tetrad sequence I/VQI/VG. However, the solid-state NMR results indicate a structural difference between mouse RIPK1 and mouse RIPK3. A change in the structural rigidity is also suggested by the observation of weakened signals for mouse RIPK3 upon mixing with RIPK1 to form the RIPK1/RIPK3 complex fibrils. Our results provide vital information to understand the interactions between different proteins with RHIM, which will help us further comprehend the regulation mechanism in cell necroptosis., (© 2024. The Author(s).)

Background: The threats to the safety of humans and the environment and the resistance of agricultural chemicals to plant pathogenic fungi and bacteria highlight an urgent need to find safe and efficient alternatives to chemical fungicides and bactericides. In this study, a series of Berberine (BBR) derivatives were designed, synthesized and evaluated for in vitro and in vivo antimicrobial activity against plant pathogenic fungi and bacteria., Results: Bioassay results indicated that compounds A11, A14, A20, A21, A22, A25, A26, E1, E2, E3, Z1 and Z2 showed high inhibitory activity against Sclerotinia sclerotiorum and Botrytis cinerea. Especially, A25 showed a broad spectrum and the highest antifungal activity among these compounds. Its EC 50 value against Botrytis cinerea was 1.34 μg mL -1 . Compound E6 possessed high inhibitory activity against Xanthomonas oryzae and Xanthomonas Campestris, with MIC 90 values of 3.12 μg mL -1 and 1.56 μg mL -1 . A Topomer CoMFA model was generated for 3D-QSAR studies based on anti-B. cinerea effects, with high predictive accuracy, showed that the addition of an appropriate substituent group at the para-position of benzyl of BBR derivatives could effectively improve the anti-B. cinerea activity. In addition, compound A25 could significantly inhibit the spore germination of Botrytis cinerea at low concentration, and compound F4 exhibited remarkable curative and protective efficiencies on rice bacterial leaf blight., Conclusion: This study indicates that the BBR derivatives are hopeful for further exploration as the lead compound with novel antimicrobial agents. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Daylily ( Hemerocallis citrina ) is a perennial herb of the genus Hemerocallis of Liliaceae. It is also an economically important crop and is widely cultivated. Daylily has nutritional, medicinal and ornamental values. The research literature shows that daylily is a high-quality food raw material rich in soluble sugars, ascorbic acid, flavonoids, dietary fiber, carotenoids, mineral elements, polyphenols and other nutrients, which are effective in clearing heat and diuresis, resolving bruises and stopping bleeding, strengthening the stomach and brain, and reducing serum cholesterol levels. This article reviews the main nutrients of daylily and summarizes the drying process of daylily. In addition, due to the existence of active ingredients, daylily also has a variety of biological activities that are beneficial to human health. This article also highlights the nutritional quality of daylily, the research progress of dried vegetable rehydration technology and dried daylily. In the end, the undeveloped molecular mechanism and functional research status of daylily worldwide are introduced in order to provide reference for the nutritional quality research and dried processing industry of daylily., Competing Interests: The authors declare that they have no competing interests., (© 2024 Li-Xiang et al.)

Background: Perimenopausal syndrome (PMS) is a chronic disease associated with estrogen deficiency. Because of the unsatisfactory outcomes of current conventional treatments for this condition, its treatment must be continuously explored and optimized., Aim: To assess the clinical effectiveness of γ-oryzanol in combination with Femoston for PMS., Methods: A total of 119 patients with PMS were selected from June 2023 to December 2023, which included 59 and 60 patients in the control and observation group, respectively. The control and observation groups were treated with Femoston and γ-oryzanol + Femoston, respectively. Comparative analyses were performed in terms of clinical effectiveness, safety (dizziness and headache, nausea and vomiting, and breast tenderness), sex hormones [estradiol (E 2 ), luteinizing hormone (LH), and follicle-stimulating hormone (FSH)], lumbar spine (L1-4) and bilateral femoral bone mineral density (BMD), and sleep quality (sleeping time and frequency of awakenings from sleep)., Results: Compared with the control group, the observation group had statistically higher total effective rates of treatment; lower overall incidence of adverse events; higher post-treatment E 2 levels and L1-4 and bilateral femoral BMD; and lower LH and FSH levels, sleeping time, and frequency of awakenings from sleep after treatment., Conclusion: Therefore, for the treatment of PMS, γ-oryzanol combined with Femoston is significantly better than Femoston alone in terms of clinical effectiveness, exhibiting more pronounced clinical advantages in improving safety, sex hormone levels, BMD, and sleep quality., Competing Interests: Conflict-of-interest statement: All authors have no conflicts of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

In this study, we analyzed the clinical efficacy of Zishen Yutai pills (ZSYTP) combined with metformin hydrochloride on infertile women diagnosed with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization and embryo transfer (IVF-ET). Patients were assigned into 3 groups: the ZSYTP group (n = 50), the metformin group (n = 50), and the combination group (ZSYTP combined with metformin hydrochloride, n = 50), based on their respective and the indicated treatments before undergoing IVF-ET. Then, their glucose metabolism indices, sex hormone indices, traditional Chinese medicine (TCM) syndrome scores, and outcomes of IVF-ET were compared. Baseline characteristics were not significantly different between the 2 groups. After treatment, various parameters such as body mass index (BMI), fasting plasma glucose (FPG), fasting insulin (FIN), homeostatic model assessment of insulin resistance (HOMA-IR), luteinizing hormone (LH), estradiol (E2), follicle-stimulating hormone (FSH), testosterone (T) levels, and TCM syndrome scores were found to be reduced compared to pretreatment levels in both groups. Moreover, the improvement observed in the treatment group exceeded that of the control group. Specifically, the observation group displayed significantly lower gonadotropin (Gn) dosage and duration, as well as a reduced abortion rate compared to the control group. Furthermore, the observation group had higher numbers of obtained eggs, high-quality embryos, eggs obtained through IVF-ET, average transferred embryos, clinical pregnancy rate, and embryo implantation rate compared to the control group. Pretreatment with ZSYTP combined with metformin before IVF-ET in PCOS patients improves the outcome of IVF-ET., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To identify important MRI features to differentiate hepatic mucinous cystic neoplasms (MCN) from septated hepatic cysts (HC) using random forest and compared with logistic regression algorithm., Methods: Pathologically diagnosed hepatic cysts and hepatic MCNs with pre-operative contrast-enhanced MRI in our hospital from 2010 to 2023 were collected and only septated lesions on enhanced MRI were enrolled. A total of 21 septated HC and 18 MCNs were included in this study. Eighteen MRI features were analyzed and top important features were identified based on random forest (RF) algorithm. The results were evaluated by the prediction performance of a RF model combining the important features and compared with the performance of the logistic regression (LR) algorithm. Finally, for each identified feature, diagnostic probability, sensitivity, and specificity were calculated and compared., Results: Four variables, i.e., the septation arising from wall without indentation, multiseptate, intracapsular cyst sign, and solitary lesion were extracted as top important features with significance for MCNs by the random forest algorithm. The RF model using these variables had an AUC of 0.982 (0.95CI, 0.950-1.000), compared with the LR model based on two identified features with AUC of 0.931 (0.95CI, 0.846-1.000), p = 0.202. Among the four important features, multiseptate had the highest specificity (95.2%) and good sensitivity (72.2%, lower than the septation from wall without indentation, 94.4%) to diagnose MCNs., Conclusion: Four out of 18 MRI features were extracted as reliably important factors to differ hepatic MCNs from septated HC. The combination of these four features in a RF model could achieve satisfactory diagnostic efficacy., (© 2024. The Author(s) under exclusive licence to Japan Radiological Society.)

Background: Drug addiction is a social and medical problem that must be urgently addressed. The nucleus accumbens (NAc) is closely related to addiction-related learning memory, and γ-aminobutyric acid type B receptor (GABA B R) is a potential target for the treatment of drug addiction. However, the role of GABA B R activity levels in the NAc in cocaine addiction is unclear., Methods: In this study, we established an animal model of cocaine dependence, modulated the level of GABA B R activity, applied a conditioned place preference assay (CPP) to assess the role of the NAc in reconsolidation of addiction memory, evaluated learning and memory functions by behavioral experiments, examined the expression of GB1, GB2, cyclic adenosine monophosphate response element binding protein (CREB), p-CREB, protein kinase A (PKA), protein kinase (ERK), and Brain-derived neurotrophic factor (BDNF) in the NAc by molecular biology experiments, and screened differentially significantly expressed genes by transcriptome sequencing., Results: Our study showed that the GABA B receptor agonist baclofen (BLF) had a significant effect on locomotor distance in rats, promoted an increase in GABA levels and significantly inhibited the PKA and ERK1/2/CREB/BDNF signaling pathways. Moreover, transcriptome sequencing showed that GABA B R antagonist intervention identified a total of 21 upregulated mRNAs and 21 downregulated mRNAs. The differentially expressed (DE) mRNA genes were mainly enriched in tyrosine metabolism; however, further study is needed., Conclusion: GABA B R activity in the NAc is involved in the regulation of cocaine addiction and may play an important role through key mRNA pathways., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Introduction: EGFR-mutated NSCLC is characterized by an immunosuppressive microenvironment that confers limited clinical effectiveness to anti-PD-1 or PD-L1 antibodies. Despite the discouraging outcomes of immunotherapy, novel immune checkpoints are constantly emerging, among which the specific vulnerability for therapeutic intervention in the context of EGFR-mutated NSCLC remains unresolved., Methods: Data sets of patient- and cell line-levels were used for screening and mutual validation of association between EGFR mutation and a panel of immune checkpoint-related genes. Regulatory mechanism was elucidated through in vitro manipulation of EGFR signaling pathway and evaluated by immunoblot analysis, quantitative polymerase chain reaction, flow cytometry, immunofluorescence staining, and chromatin immunoprecipitation. In vivo investigation of different therapeutic strategies were conducted using both immunocompetent and immunodeficient mouse models., Results: Among all screened immune checkpoints, CD47 emerged as the candidate most relevant to EGFR activation. Mechanistically, EGFR mutation constitutively activated downstream ERK and AKT pathways to respectively up-regulate the transcriptional factors c-Myc and NF-κB, both of which structurally bound to the promotor region of CD47 and actively transcribed this "don't eat me" signal. Impaired macrophage phagocytosis was observed on introduction of EGFR-sensitizing mutations in NSCLC cell line models, whereas CD47 blockade restored the phagocytic capacity and augmented tumor cell killing in both in vitro and in vivo models. Remarkably, the combination of anti-CD47 antibody with EGFR tyrosine kinase inhibitor revealed an additive antitumor activity compared with monotherapy of either antitumor agent in both immunocompetent and adaptive immunity-deficient mouse models., Conclusions: EGFR-sensitizing mutation facilitates NSCLC's escape from innate immune attack through up-regulating CD47. Combination therapy incorporating CD47 blockade holds substantial promise for clinical translation in developing more effective therapeutic approaches against EGFR-mutant NSCLC., Competing Interests: Disclosure Dr. Wu is an employee of Shenzhen Engineering Center for Translational Medicine of Precision Cancer Immunodiagnosis and Therapy, YuceBio Technology Co., Ltd. The remaining authors declare no conflict of interest, (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 ., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Breast cancer (BRCA) is the most common cancer among women. Adriamycin (ADR), also known as doxorubicin (Dox), is a commonly used chemotherapeutic agent for BRCA patients, however, the susceptibility of tumor cells to develop resistance to Dox has severely limited its clinical use. One new promising therapeutic target for breast cancer patients is exosomes. The objective of this study was to investigate the role of exosomes in regulating Dox resistance in BRCA. In this study, the exosomes from both types of cells were extracted by differential centrifugation. The effect of exosomes on drug resistance was assessed by laser confocal microscopy, MTT assay, and qRT-PCR. The miRNA was transfected into cells using Lipofectamine 2000, which was then evaluated for downstream genes and changes in drug resistance. Exosomes from MCF-7 cells (MCF-7/exo) and MCF-7/ADR cells (ADR/exo) were effectively extracted in this study. The ADR/exo was able to endocytose MCF-7 cells and make them considerably more resistant to Dox. Moreover, we observed a significant difference in miR-34a-5p expression in MCF-7/ADR and ADR/exo compared to MCF-7 and MCF-7/exo. Among the miR-34a-5p target genes, NOTCH1 displayed a clear change with a negative correlation. In addition, when miR-34a-5p expression was elevated in MCF-7/ADR cells, the expression of miR-34a-5p in ADR/exo was also enhanced alongside NOTCH1, implying that exosomes may carry miRNA into and out of cells and perform their function. In conclusion, exosomes can influence Dox resistance in breast cancer cells by regulating miR-34a-5p/NOTCH1. These findings provide novel insights for research into the causes of tumor resistance and the enhancement of chemotherapy efficacy in breast cancer., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Alteration of DNA methylation leads to diverse diseases, and the dynamic changes of DNA methylation (DNAm) on sets of CpG dinucleotides in mammalian genomes are termed "DNAm age" and "epigenetic clocks" that can predict chronological age. However, whether and how dysregulation of DNA methylation promotes cyst progression and epigenetic age acceleration in autosomal dominant polycystic kidney disease (ADPKD) remains elusive. Here, we show that DNA methyltransferase 1 (DNMT1) is upregulated in cystic kidney epithelial cells and tissues and that knockout of Dnmt1 and targeting DNMT1 with hydralazine, a safe demethylating agent, delays cyst growth in Pkd1 mutant kidneys and extends life span of Pkd1 conditional knockout mice. With methyl-CpG binding domain (MBD) protein-enriched genome sequencing (MBD-seq), DNMT1 chromatin immunoprecipitation (ChIP)-sequencing and RNA-sequencing analysis, we identified two novel DNMT1 targets, PTPRM and PTPN22 (members of the protein tyrosine phosphatase family). PTPRM and PTPN22 function as mediators of DNMT1 and the phosphorylation and activation of PKD-associated signaling pathways, including ERK, mTOR and STAT3. With whole-genome bisulfide sequencing in kidneys of patients with ADPKD versus normal individuals, we found that the methylation of epigenetic clock-associated genes was dysregulated, supporting that epigenetic age is accelerated in the kidneys of patients with ADPKD. Furthermore, five epigenetic clock-associated genes, including Hsd17b14, Itpkb, Mbnl1, Rassf5 and Plk2, were identified. Thus, the diverse biological roles of these five genes suggest that their methylation status may not only predict epigenetic age acceleration but also contribute to disease progression in ADPKD., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Allergic asthma is a complex inflammatory disorder predominantly orchestrated by T helper 2 (Th2) lymphocytes. The anti-inflammatory protein Clara Cell 10-kDa (CC10), also known as secretoglobin family 1A member 1 (SCGB1A1), shows promise in modulating respiratory diseases. However, its precise role in asthma remains unclear. This study examines the potential of CC10 to suppress allergic asthma inflammation, specifically assessing its regulatory effects on Th2 cell responses and dendritic cells (DCs). Lower CC10 levels in asthma were observed and correlated with increased IgE and lymphocytes. Cc10 -/- mice exhibited exacerbated allergic airway inflammation marked by increased inflammatory cell infiltration, Th2 cytokines, serum antigen-specific IgE levels, and airway hyperresponsiveness (AHR) in house dust mite (HDM)-induced models. Conversely, recombinant CC10 significantly attenuated these inflammatory responses. Intriguingly, CC10 did not directly inhibit Th cell activation but significantly downregulated the population of CD11b + CD103 - DCs subsets in lungs of asthmatic mice and modulated the immune activation functions of DCs through NF-κB signaling pathway. The mixed lymphocyte response assay revealed that DCs mediated the suppressive effect of CC10 on Th2 cell responses. Collectively, CC10 profoundly mitigates Th2-type allergic inflammation in asthma by modulating lung DC phenotype and functions, highlighting its therapeutic potential for inflammatory airway conditions and other related immunological disorders., (© 2024. The Author(s).)

Single-cluster catalysts (SCCs) representing structurally well-defined metal clusters anchored on support tend to exhibit tunable catalytic performance for complex redox reactions in heterogeneous catalysis. Here we report a theoretical study on an SCC of Ru 3 @Mo 2 CO 2 MXene for N 2 -to-NH 3 thermal conversion. Our results show that Ru 3 @Mo 2 CO 2 can effectively activate N 2 and promotes its conversion to NH 3 through an association mechanism, in which the rate-determining step of NH 2 * + H* → NH 3 * has a low energy barrier of 1.29 eV. Notably, with the assistance of Mo 2 CO 2 support, the positively charged Ru 3 cluster active site can effectively adsorb and activate N 2 , leading to 0.74 |e| charge transfer from Ru 3 @Mo 2 CO 2 to the adsorbed N 2 . The supported Ru 3 also acts as an electron reservoir to regulate the charge transfer for various intermediate steps of ammonia synthesis. Microkinetic analysis shows that the turnover frequency of the N 2 -to-NH 3 conversion on Ru 3 @Mo 2 CO 2 is as high as 1.45 × 10 -2 s -1 site -1 at a selected thermodynamic condition of 48 bar and 700 K, the performance of which even surpasses that of the Ru B5 site and Fe 3 /θ-Al 2 O 3 (010) reported before. Our work provides a theoretical understanding of the high stability and catalytic mechanism of Ru 3 @Mo 2 CO 2 and guidance for further designing and fabricating MXene-based metal SCCs for ammonia synthesis under mild conditions., (© The Author(s) 2024. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Diabetes accelerates vascular senescence, which is the basis for atherosclerosis and stiffness. The activation of NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and oxidative stress are closely associated with the deteriorative senescence in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). For decades, Sodium Tanshinone IIA Sulfonate (STS) has been utilized as a cardiovascular medicine with acknowledged anti-inflammatory and anti-oxidative properties. Nevertheless, the impact of STS on vascular senescence remains unexplored in diabetes. Diabetic mice, primary ECs and VSMCs were transfected with the NLRP3 overexpression/knockout plasmid, the tumor necrosis factor alpha-induced protein 3 (TNFAIP3/A20) overexpression/knockout plasmid, and treated with STS to detect senescence-associated markers. In diabetic mice, STS treatment maintained catalase (CAT) level and vascular relaxation, reduced hydrogen peroxide probe (ROSgreen) fluorescence, p21 immunofluorescence, Senescence β-Galactosidase Staining (SA-β-gal) staining area, and collagen deposition in aortas. Mechanistically, STS inhibited NLRP3 phosphorylation (serine 194), NLRP3 dimer formation, NLRP3 expression, and NLRP3-PYCARD (ASC) colocalization. It also suppressed the phosphorylation of IkappaB alpha (IκBα) and NFκB, preserved A20 and CAT levels, reduced ROSgreen density, and decreased the expression of p21 and SA-β-gal staining in ECs and VSMCs under HG culture. Our findings indicate that STS mitigates vascular senescence by modulating the A20-NFκB-NLRP3 inflammasome-CAT pathway in hyperglycemia conditions, offering novel insights into NLRP3 inflammasome activation and ECs and VSMCs senescence under HG culture. This study highlights the potential mechanism of STS in alleviating senescence in diabetic blood vessels, and provides essential evidence for its future clinical application., (© 2024. The Author(s).)

Purpose: Kinase interacting with stathmin (KIS) is a serine/threonine kinase involved in RNA processing and protein phosphorylation. Increasing evidence has suggested its involvement in cancer progression. The aim of this study was to investigate the role of KIS in the development of lung adenocarcinoma (LUAD). Dual luciferase assay was used to explore the relationship between KIS and SOX4, and its effect on ID1/β-catenin pathway., Methods: Real-time qPCR and western blot were used to assess the levels of KIS and other factors. Cell proliferation, migration, and invasion were monitored, and xenograft animal model were established to investigate the biological functions of KIS in vitro and in vivo., Results: In the present study, KIS was found to be highly expressed in LUAD tissues and cell lines. KIS accelerated the proliferative, migratory and invasive abilities of LUAD cells in vitro, and promoted the growth of LUAD in a mouse tumor xenograft model in vivo. Mechanistically, KIS activated the β-catenin signaling pathway by modulating the inhibitor of DNA binding 1 (ID1) and was transcriptionally regulated by SOX4 in LUAD cells., Conclusion: KIS, a target of SOX4, regulates the ID1-mediated enhancement of β-catenin to facilitate LUAD cell invasion and metastasis., (© 2024. The Author(s).)

The current study presents the development process and initial validation of the Engagement in Athletic Training Scale (EATS), which was designed to evaluate athletes' engagement in athletic training. In study 1, item generation and initial content validity of the EATS were achieved. In study 2, the factor structure of the EATS was examined using exploratory factor analysis (EFA) and exploratory structural equation modeling (ESEM). Internal consistency reliabilities of the subscales were examined ( N  = 460). In study 3, factor structure, discriminant validity, internal consistency reliability, and nomological validity of the EATS were further examined in an independent sample ( N  = 513). Meanwhile, measurement invariance of the EATS across samples (study 2 and study 3) and genders was evaluated. Overall, results from the 3 rigorous studies provided initial psychometric evidence for the 19-item EATS and suggested that the EATS could be used as a valid and reliable measure to evaluate athletes' engagement in athletic training., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Liu, Wu, Zou, Wang, Zhang, Hu and Liu.)

Background: Hyperlipidemia damages vascular wall and serves as a foundation for diseases such as atherosclerosis, hypertension and stiffness. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is implicated in vascular dysfunction associated with hyperlipidemia-induced vascular injury. Sodium tanshinone IIA sulfonate (STS), a well-established cardiovascular protective drug with recognized anti-inflammatory, antioxidant, and vasodilatory properties, is yet to be thoroughly investigated for its impact on vascular relaxant imbalance induced by hyperlipidemia., Methods: In this study, we treated ApoE-knockout (ApoE-/-) mouse with STS and assessed the activation of the NLRP3 inflammasome, expression of MMP2/9, integrity of elastic fibers, and vascular constriction and relaxation., Results: Our findings reveal that STS intervention effectively preserves elastic fibers, significantly restores aortic relaxation function in ApoE-/- mice, and reduces their excessive constriction. Furthermore, STS inhibits the phosphorylation of spleen tyrosine kinase (SYK), suppresses NLRP3 inflammasome activation, and reduces MMP2/9 expression., Conclusions: These results demonstrate that STS protects vascular relaxation against hyperlipidemia-induced damage through modulation of the SYK-NLRP3 inflammasome-MMP2/9 pathway. This research provides novel insights into the mechanisms underlying vascular relaxation impairment in a hyperlipidemic environment and uncovers a unique mechanism by which STS preserves vascular relaxation, offering valuable foundational research evidence for its clinical application in promoting vascular health., (© 2024. The Author(s).)

Background: Central nervous system involvement in chronic lymphocytic leukemia rarely occurs, and there is no standard therapy for central nervous system involvement in chronic lymphocytic leukemia. This article aims to analyze the diagnosis and treatment of central nervous system involvement in chronic lymphocytic leukemia., Case Presentation: It reports two cases of central nervous system involvement in chronic lymphocytic leukemia describing the clinical course, therapy, and prognosis. Case 1 is a 67-year-old Asian male patient, he experienced complications with central nervous system involvement after developing resistance to ibrutinib, bendamustine, and rituximab (BR) chemotherapies. The central nervous system lesion was controlled with high-dose methotrexate combined with pomalidomide, but Richter transformation occurred several months later. Case 2 is a 62-year-old Asian female patient, she had central nervous system involvement at initial diagnosis, and bone marrow and central nervous system lesions were controlled by ibrutinib therapy., Conclusion: Central nervous system involvement in chronic lymphocytic leukemia is rare and can be diagnosed on the basis of clinical features, cerebrospinal fluid testing, and radiographic evaluation. Ibrutinib, pomalidomide, and other drugs that can cross the blood-brain barrier may be effective for treating central nervous system involvement in chronic lymphocytic leukemia., (© 2024. The Author(s).)

Plant life history is determined by two transitions, germination and flowering time, in which the phosphatidylethanolamine-binding proteins (PEBPs) FLOWERING LOCUS T (FT) and TERMINAL FLOWER1 (TFL1) play key regulatory roles. Compared with the highly conserved TFL1-like genes, FT-like genes vary significantly in copy numbers in gymnosperms, and monocots within the angiosperms, while sporadic duplications can be observed in eudicots. Here, via a systematic analysis of the PEBPs in angiosperms with a special focus on 12 representative species featuring high-quality genomes in the order Lamiales, we identified a successive lineage-specific but systematic expansion of FT-like genes in the families of core Lamiales. The first expansion event generated FT1-like genes mainly via a core Lamiales-specific whole-genome duplication (cL-WGD), while a likely random duplication produced the FT2-like genes in the lineages containing Scrophulariaceae and the rest of the core Lamiales. Both FT1- and FT2-like genes were further amplified tandemly in some families. These expanded FT-like genes featured highly diverged expression patterns and structural variation, indicating functional diversification. Intriguingly, some core Lamiales contained the relict MOTHER OF FT AND TFL1 like 2 (MFT2) that probably expanded in the common ancestor of angiosperms. Our data showcase the highly dynamic lineage-specific expansion of the FT-like genes, and thus provide important and fresh evolutionary insights into the gene regulatory network underpinning flowering time diversity in Lamiales and, more generally, in angiosperms., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Brassicaceae represents an important plant family from both a scientific and economic perspective. However, genomic features related to the early diversification of this family have not been fully characterized, especially upon the uplift of the Tibetan Plateau, which was followed by increasing aridity in the Asian interior, intensifying monsoons in Eastern Asia, and significantly fluctuating daily temperatures. Here, we reveal the genomic architecture that accompanied early Brassicaceae diversification by analyzing two high-quality chromosome-level genomes for Meniocus linifolius (Arabodae; clade D) and Tetracme quadricornis (Hesperodae; clade E), together with genomes representing all major Brassicaceae clades and the basal Aethionemeae. We reconstructed an ancestral core Brassicaceae karyotype (CBK) containing 9 pseudochromosomes with 65 conserved syntenic genomic blocks and identified 9702 conserved genes in Brassicaceae. We detected pervasive conflicting phylogenomic signals accompanied by widespread ancient hybridization events, which correlate well with the early divergence of core Brassicaceae. We identified a successive Brassicaceae-specific expansion of the class I TREHALOSE-6-PHOSPHATE SYNTHASE 1 (TPS1) gene family, which encodes enzymes with essential regulatory roles in flowering time and embryo development. The TPS1s were mainly randomly amplified, followed by expression divergence. Our results provide fresh insights into historical genomic features coupled with Brassicaceae evolution and offer a potential model for broad-scale studies of adaptive radiation under an ever-changing environment., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)