AUXIN RESPONSE FACTOR 2 mediates repression of strawberry receptacle ripening via auxin-ABA interplay.

Cultivated strawberry (Fragaria × ananassa) is a popular, economically important fruit. The ripening of the receptacle (pseudocarp), the main edible part, depends on endogenously produced abscisic acid (ABA) and is suppressed by the high level of auxin produced from achenes (true fruit) during early development. However, the mechanism whereby auxin regulates receptacle ripening through inhibiting ABA biosynthesis remains unclear. Here, we identified AUXIN RESPONSE FACTOR 2 (FaARF2), which showed decreased expression with reduced auxin content in the receptacle, leading to increased ABA levels and accelerated ripening. Dual-luciferase, yeast one-hybrid, and electrophoretic mobility shift assays demonstrated that FaARF2 could bind to the AuxRE element in the promoter of 9-CIS-EPOXYCAROT-ENOID DIOXYGENASE 1 (FaNCED1), a key ABA biosynthetic gene, to suppress its transcriptional activity. Transiently overexpressing FaARF2 in the receptacles decreased FaNCED1 expression and ABA levels, resulting in inhibition of receptacle ripening and of development of quality attributes, such as pigmentation, aroma, and sweetness. This inhibition caused by overexpressing FaARF2 was partially recovered by the injection of exogenous ABA; conversely, transient silencing of FaARF2 using RNA interference produced the opposite results. The negative targeting of FaNCED1 by FaARF2 is a key link between auxin-ABA interactions and regulation of strawberry ripening.

Cortical-cerebellar circuits changes in preschool ASD children by multimodal MRI.

OBJECTIVE: To investigate the alterations in cortical-cerebellar circuits and assess their diagnostic potential in preschool children with autism spectrum disorder using multimodal magnetic resonance imaging. METHODS: We utilized diffusion basis spectrum imaging approaches, namely DBSI_20 and DBSI_combine, alongside 3D structural imaging to examine 31 autism spectrum disorder diagnosed patients and 30 healthy controls. The participants' brains were segmented into 120 anatomical regions for this analysis, and a multimodal strategy was adopted to assess the brain networks using a multi-kernel support vector machine for classification. RESULTS: The results revealed consensus connections in the cortical-cerebellar and subcortical-cerebellar circuits, notably in the thalamus and basal ganglia. These connections were predominantly positive in the frontoparietal and subcortical pathways, whereas negative consensus connections were mainly observed in frontotemporal and subcortical pathways. Among the models tested, DBSI_20 showed the highest accuracy rate of 86.88%. In addition, further analysis indicated that combining the 3 models resulted in the most effective performance. CONCLUSION: The connectivity network analysis of the multimodal brain data identified significant abnormalities in the cortical-cerebellar circuits in autism spectrum disorder patients. The DBSI_20 model not only provided the highest accuracy but also demonstrated efficiency, suggesting its potential for clinical application in autism spectrum disorder diagnosis.

Enhanced cerebral blood flow similarity of the somatomotor network in chronic insomnia: Transcriptomic decoding, gut microbial signatures and phenotypic roles.

Chronic insomnia (CI) is a complex disease involving multiple factors including genetics, gut microbiota, and brain structure and function. However, there lacks a unified framework to elucidate how these factors interact in CI. By combining data of clinical assessment, sleep behavior recording, cognitive test, multimodal MRI (structural, functional, and perfusion), gene, and gut microbiota, this study demonstrated that enhanced cerebral blood flow (CBF) similarities of the somatomotor network (SMN) acted as a key mediator to link multiple factors in CI. Specifically, we first demonstrated that only CBF but not morphological or functional networks exhibited alterations in patients with CI, characterized by increases within the SMN and between the SMN and higher-order associative networks. Moreover, these findings were highly reproducible and the CBF similarity method was test-retest reliable. Further, we showed that transcriptional profiles explained 60.4 % variance of the pattern of the increased CBF similarities with the most correlated genes enriched in regulation of cellular and protein localization and material transport, and gut microbiota explained 69.7 % inter-individual variance in the increased CBF similarities with the most contributions from Negativicutes and Lactobacillales. Finally, we found that the increased CBF similarities were correlated with clinical variables, accounted for sleep behaviors and cognitive deficits, and contributed the most to the patient-control classification (accuracy = 84.4 %). Altogether, our findings have important implications for understanding the neuropathology of CI and may inform ways of developing new therapeutic strategies for the disease.

Mn(II) Optimized Sono/Chemodynamic Effect of Porphyrin-Metal-Organic Framework Nanosheets for MRI-Guided Colon Cancer Therapy and Metastasis Suppression.

Sonodynamic therapy (SDT) offers a remarkable non-invasive ultrasound (US) treatment by activating sonosensitizer and generating reactive oxygen species (ROS) to inhibit tumor growth. The development of multifunctional, biocompatible, and highly effective sonosensitizers remains a current priority for SDT. Herein, the first report that Mn(II) ions chelated Gd-TCPP (GMT) nanosheets (NSs) are synthesized via a simple reflux method and encapsulated with pluronic F-127 to form novel sonosensitizers (GMTF). The GMTF NSs produce a high yield of ROS under US irradiation due to the decreased highest occupied molecular orbital-lowest unoccupied molecular orbital gap energy (2.7-1.28 eV). Moreover, Mn(II) ions endow GMTF with a fascinating Fenton-like activity to produce hydroxyl radicals in support of chemodynamic therapy (CDT). It is also effectively used in magnetic resonance imaging (MRI) with high relaxation rate (r 1: 4.401 mM-1 s-1) to track the accumulation of NSs in tumors. In vivo results indicate that the SDT and CDT in combination with programmed cell death protein 1 antibody (anti-PD-1) show effective metastasis prevention effects, and 70% of the mice in the GMTF + US + anti-PD-1 group survived for 60 days. In conclusion, this study develops a sonosensitizer with promising potential for utilizing both MRI-guided SDT and CDT strategies.

Spontaneous Brain Activity Abnormalities in Patients With Temporal Lobe Epilepsy: A Meta-Analysis of 1474 Patients.

BACKGROUND: Abnormalities in resting-state functional brain activity have been detected in patients with temporal lobe epilepsy (TLE). The results of individual neuroimaging studies of TLE, however, are frequently inconsistent due to small and heterogeneous samples, analytical flexibility, and publication bias toward positive findings. PURPOSE: To investigate the most consistent regions of resting-state functional brain activity abnormality in patients with TLE through a quantitative meta-analysis of published neuroimaging data. STUDY TYPE: Meta-analysis. SUBJECTS: Exactly 1474 TLE patients (716 males and 758 females) from 31 studies on resting-state functional brain activity were included in this study. FIELD STRENGTH/SEQUENCE: Studies utilizing 1.5 T or 3 T MR scanners were included for meta-analysis. Resting-state functional MRI using gradient echo-planar imaging, T1-weighted imaging. ASSESSMENT: PubMed, Web of Science, Chinese National Knowledge Infrastructure, and WanFang databases were searched to identify studies investigating amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) at the whole-brain level between patients with TLE and healthy controls (HCs). STATISTICAL TESTS: Seed-based d Mapping with Permutation of Subject Images, standard randomization tests and meta-regression analysis were used. Results were significant if P < 0.05 with family-wise error corrected. RESULTS: Patients with TLE displayed resting-state functional brain activity which was a significant increase in the right hippocampus, and significant decrease in the right angular gurus and right precuneus. Additionally, the meta-regression analysis demonstrated that age (P = 0.231), sex distribution (P = 0.376), and illness duration (P = 0.184), did not show significant associations with resting state functional brain activity in patients with TLE. DATA CONCLUSION: Common alteration patterns of spontaneous brain activity were identified in the right hippocampus and default-model network regions in patients with TLE. These findings may contribute to understanding of the underlying mechanism for potentially effective intervention of TLE. TECHNICAL EFFICACY STAGE: Stage 2.

A Circular Network of Coregulated L-Threonine and L-Tryptophan Metabolism Dictates Acute Lower Limb Ischemic Injury.

Lower limb ischemia is characterized by reduced arterial perfusion in the lower limbs, leading to tissue ischemia and cell death. It is primarily caused by thrombosis and the rupture of arterial plaques, resulting in damage to ischemic muscle tissues. Metabolic processes are crucial in its development. Herein we combined single-cell data with metabolomics data to explore the pathways and mechanisms influencing lower limb ischemia. We analyzed single-cell and metabolomics data. In single-cell analysis, we identified different cell subpopulations and key regulatory genes, and biological enrichment analysis was performed to understand their functions and relationships. For metabolomics, mass spectrometry and chromatography techniques were employed to analyze metabolites in clinical samples. We performed differential analysis, correlation analysis, and Mendelian randomization to determine the relationships between key metabolites and genes. Nebl, Dapl1, Igfbp4, Lef1, Klrd1, Ciita, Il17f, Cd8b1, Il17a, Cd180, Il17re, Trim7, and Slc6a19 were identified to play a crucial role in lower limb ischemia. Important metabolites included L-threonine and L-tryptophan. The metabolism of L-threonine and L-tryptophan is linked to lower limb ischemia and thrombosis. B0AT1, encoded by SLC6A19, is closely related to these metabolites and appears to play a key role in lower limb ischemia development. Our analysis revealed the roles of key genes and metabolites in lower limb ischemia. These findings enhance our understanding of the pathogenesis of lower limb ischemia and provide new insights into its prevention and treatment.

Targeted blood-brain barrier penetration and precise imaging of infiltrative glioblastoma margins using hybrid cell membrane-coated ICG liposomes.

Surgical resection remains the primary treatment modality for glioblastoma (GBM); however, the infiltrative nature of GBM margins complicates achieving complete tumor removal. Additionally, the blood-brain barrier (BBB) poses a formidable challenge to effective probe delivery, thereby hindering precise imaging-guided surgery. Here, we introduce hybrid cell membrane-coated indocyanine green (ICG) liposomes (HM-Lipo-ICG) as biomimetic near-infrared (NIR) fluorescent probes for targeted BBB penetration and accurate delineation of infiltrative GBM margins. HM-Lipo-ICG encapsulates clinically approved ICG within its core and utilizes a hybrid cell membrane exterior, enabling specific targeting and enhanced BBB permeation. Quantitative assessments demonstrate that HM-Lipo-ICG achieves BBB penetration efficiency 2.8 times higher than conventional ICG liposomes. Mechanistically, CD44 receptor-mediated endocytosis facilitates BBB translocation of HM-Lipo-ICG. Furthermore, HM-Lipo-ICG enables high-contrast NIR imaging, achieving a signal-to-background ratio of 6.5 in GBM regions of an orthotopic glioma mouse model, thereby improving tumor margin detection accuracy fourfold (84.4% vs. 22.7%) compared to conventional ICG liposomes. Application of HM-Lipo-ICG facilitates fluorescence-guided precision surgery, resulting in complete resection of GBM cells. This study underscores the potential of hybrid cell membrane-coated liposomal probes in precisely visualizing and treating infiltrative GBM margins.

DNA methylation controlling abscisic acid catabolism responds to light to mediate strawberry fruit ripening.

Phytohormones, epigenetic regulation and environmental factors regulate fruit ripening but their interplay during strawberry fruit ripening remains to be determined. In this study, bagged strawberry fruit exhibited delayed ripening compared with fruit grown in normal light, correlating with reduced abscisic acid (ABA) accumulation. Transcription of the key ABA catabolism gene, ABA 8'-hydroxylase FaCYP707A4, was induced in bagged fruit. With light exclusion whole genome DNA methylation levels were up-regulated, corresponding to a delayed ripening process, while DNA methylation levels in the promoter of FaCYP707A4 were suppressed, correlating with increases in transcript and decreased ABA content. Experiments indicated FaCRY1, a blue light receptor repressed in bagged fruit and FaAGO4, a key protein involved in RNA-directed DNA methylation, could bind to the promoter of FaCYP707A4. The interaction between FaCRY1 and FaAGO4, and an increased enrichment of FaAGO4 directed to the FaCYP707A4 promoter in fruit grown under light suggests FaCRY1 may influence FaAGO4 to modulate the DNA methylation status of the FaCYP707A4 promoter. Furthermore, transient overexpression of FaCRY1, or an increase in FaCRY1 transcription by blue light treatment, increases the methylation level of the FaCYP707A4 promoter, while transient RNA interference of FaCRY1 displayed opposite phenotypes. These findings reveal a mechanism by which DNA methylation influences ABA catabolism, and participates in light-mediated strawberry ripening.

[Synergistic effect and compatibility structure of active anti-inflammatory ingredients from Lamiophlomis rotata based on network pharmacology and component structure theory].

The synergistic effect and compatibility structure of active anti-inflammatory ingredients(iridoid glycosides: shanzhiside methylester and 8-O-acetylshanzhiside methyl ester, flavonoid glycoside: luteoloside, and phenylethanoid glycoside: forsythoside B) from Lamiophlomis rotata were explored based on network pharmacology and component structure theory. In network pharmacology, CTD, SwisseTargetPrediction, and PharmMapper databases were used to collect and screen the targets of all active ingredients. The inflammation-related targets were obtained from CTD and GeneCards databases. The core targets were obtained by Venny 2.1.0, STRING, and Cytoscape 3.9.1. Core targets were annotated by the GO function and enriched by the KEGG pathway based on the DAVID database. In terms of component structure, based on a uniform design method and xylene-induced ear swelling model in mice, tumor necrosis factor-α and interleukin-6 were taken as the dependent variables, and the compatibility relationship among anti-inflammatory ingredients from L. rotata was explored through the quadratic polynomial stepwise regression. In addition, in vivo pharmacological experiments were conducted to verify the results. A network pharmacology study showed that compared with a single ingredient, the combined action of the three ingredients can synergistically exert anti-inflammatory effects through more biological processes, pathways, and targets. Component structure study showed that the optimal structural ratio of shanzhiside methylester and 8-O-acetylshanzhiside methyl ester in the iridoid glycoside ingredient was 1.21∶1. The optimal structural ratio among the three types of ingredients(iridoid glycosides∶phenylethanol glycoside∶flavonoid glycoside) was 4.8∶1.6∶1. In conclusion, each anti-inflammatory ingredient from L. rotata can work synergistically, and there is an optimal compatibility ratio relationship among these ingredients. This work provides a new experimental basis for the intrinsic quality control of L. rotata.

A Direct-Contact Photocurrent-Direction-Switching Biosensing Platform Based on In Situ Formation of CN QDs/TiO2 Nanodiscs and Double-Supported 3D DNA Walking Amplification.

Herein, a direct-contact photocurrent-direction-switching photoelectrochemical (PEC) biosensing platform for the ultrasensitive and selective detection of soluble CD146 (sCD146) is reported for the first time via in situ formation of carbon nitride quantum dots (CN QDs)/titanium dioxide (TiO2 ) nanodiscs with the double-supported 3D DNA walking amplification. In this platform, metal organic frameworks (MOFs)-derived porous TiO2 nanodiscs exhibit excellent anodic photocurrent, whereas a single-stranded auxiliary DNA (ssDNA) as biogate is absorbed onto the TiO2 nanodiscs to block active sites. Subsequently, with the help of intermediate DNAs from target sCD146-induced double-supported 3D DNA walking signal amplification, the ssDNA can leave away from the surface of TiO2 nanodiscs due to the specific hybridization with intermediate DNAs. Afterward, the successful direct contact of CN QDs on TiO2 nanodiscs by porosity and electrostatic adsorption, leads to the effective photocurrent-direction switching from anodic to cathodic photocurrent. Based on direct-contact photocurrent-direction-switching CN QDs/TiO2 nanodiscs system and double-supported 3D DNA walking signal amplification, sCD146 is detected sensitively with a wide linear range (10 fg mL-1 to 5 ng mL-1 ) and a low limit of detection (2.1 fg mL-1 ). Also, the environmentally friendly and direct-contact photocurrent-direction-switching PEC biosensor has an application prospect for cancer biomarker detection.

Preliminary Diffusion-Tensor Imaging Evidence for Trans-Synaptic Axonal Degeneration in Dysthyroid Optic Neuropathy Due to Thyroid-Associated Ophthalmopathy.

BACKGROUND: The mechanism driving dysthyroid optic neuropathy (DON) is unclear. Diffusion-tensor imaging (DTI) allows for noninvasively assessing the microstructure of the entire visual pathway and may facilitate a better understanding of the mechanism of DON. PURPOSE: To assess microstructural changes of the whole visual pathway and to investigate the potential mechanism of trans-synaptic damage（TSD） pathogenesis in DON with DTI. STUDY TYPE: Cross-sectional. POPULATION: Sixty-four patients with bilateral thyroid-associated ophthalmopathy (TAO), 30 with and 34 without DON, and 30 age- and sex-matched healthy controls (HCs). FIELD STRENGTH/SEQUENCE: 3 T/DTI (A single-shot diffusion-weighted echo-planar imaging sequence). ASSESSMENT: Differences in DTI parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in each segment (optic nerve, tract, and radiation) of the entire visual pathway among the groups were compared. The parameters of visual evoked potentials (VEPs), visual field tests, and mean retinal nerve fiber layer (mRNFL) thickness on optical coherence tomography were also compared across patients. STATISTICAL TESTS: Student's t-test, chi-square test; ANOVA with post-hoc testing, interclass correlation coefficient, and correlation analysis. Significance level: P < 0.05. RESULTS: TAO patients with DON showed significantly reduced mRNFL thickness and abnormal VEPs. There was a tendency for gradually reduced FA and AD, and increased RD and MD from HCs, with non-DON to with DON in optic nerve and tract, statistically. For radiation, the RD and MD showed statistical increase, the AD and FA just showed numerical decrease (P = 0.119 and 0.059, respectively). For DON, the FA and MD of visual pathway segments showed correlations with abnormal VEPs. DATA CONCLUSION: DTI may be a useful tool for detecting microstructural changes in the entire visual pathway in DON. The changes in RNFL thickness and DTI parameters suggested TSD as a potential pathogenic mechanism of DON. EVIDENCE LEVEL: 4 Technical Efficacy: Stage 5.

Aberrant spontaneous brain activity in patients with thyroid-associated ophthalmopathy with and without optic neuropathy: a resting-state functional MRI study.

OBJECTIVES: To investigate the brain functional alterations in dysthyroid optic neuropathy (DON) by evaluating spontaneous neural activity, using functional magnetic resonance imaging (fMRI) with regional homogeneity (ReHo), and its relationship with ophthalmologic performance. METHODS: Forty-seven patients with thyroid-associated ophthalmopathy (TAO; 20 with DON, 27 with non-DON) and 33 age-, sex-, and education-matched healthy controls (HCs) underwent fMRI. ReHo values were compared using one-way analysis of variance (ANOVA) with post hoc pairwise comparisons (voxel-level p < 0.01, Gaussian random field correction, cluster-level p < 0.05). Correlations between ReHo values and ophthalmological metrics were assessed for DONs, with Bonferroni correction for multiple comparisons (p < 0.004). ROC curves were applied to evaluate the diagnostic performance of ReHo metrics. RESULTS: ReHo values were significantly lower in the left insula and right superior temporal gyrus, and higher in the left posterior cingulate cortex (LPCC), of DON than of non-DON patients. ReHo values were also significantly lower in the right middle temporal, left insula, and left precentral gyrus in DON than in HCs. Meanwhile, ReHo values were higher in LPCC in non-DON than in HCs. ReHo values correlated with ophthalmic examinations to varying degrees in DON. For distinguishing DON, the ReHo values in LPCC showed optimal individually (AUC = 0.843), the combination of the ReHo in both the left insula and LPCC performed better (AUC = 0.915). CONCLUSION: Spontaneous brain activity differed between TAO with and without DON, which may reflect the underlying pathological mechanism of DON. The ReHo index can be considered a diagnostic biomarker. CLINICAL RELEVANCE STATEMENT: Spontaneous brain activity in DON differed from that in TAO without DON, which may reflect the underlying pathological mechanism of DON. The ReHo index can be considered a diagnostic biomarker for early detection of DON. KEY POINTS: • Dysthyroid optic neuropathy (DON) affects brain activity, which contributes in the understanding of its visual dysfunction. • Regional homogeneity values differ between thyroid-associated ophthalmopathy with and without DON in various brain regions. • Regional homogeneity values can be used as a biomarker in the differential diagnosis of DON.

Procoagulant effect of extracellular vesicles in patients after transcatheter aortic valve replacement or transcatheter aortic valve replacement with percutaneous coronary intervention.

Patients with severe aortic stenosis (AS) after replacement of the transcatheter aortic valve (TAVR) are more likely to develop thrombotic complications such as cerebral embolism and artificial valve thrombosis. However, the mechanism is not yet well defined. We aimed to explore the plasma extracellular vesicles (EVs) levels and their role in the induction of procoagulant activity (PCA) in patients receiving TAVR alone or TAVR with percutaneous coronary intervention (PCI). EVs were analyzed with flow cytometer. Markers of platelet and endothelial cell activation were quantified using selective enzyme-linked immunosorbent assay (ELISA) kits. Procoagulant activity (PCA) was assessed by clotting time, purified clotting complex assays, and fibrin production assays. Our results confirmed that EVs with positive phosphatedylserin (PS+EV), platelet EVs (PEVs) and positive tissue factor EVs (TF+EVs) were higher in patients following TAVR than before TAVR, particularly in TAVR with PCI. Furthermore, endothelial-derived EVs (EEVs) were also higher in patients after TAVR with PCI than pre-TAVR, however, the EEVs levels in TAVR alone patients were gradually reduce than pre-TAVR. In addition, we further proved that total EVs contributed to dramatically shortened coagulation time, increased intrinsic/extrinsic factor Xa and thrombin generation in patients after TAVR, especially in TAVR with PCI. The PCA was markedly attenuated by approximately 80% with lactucin. Our study reveals a previously unrecognized link between plasma EV levels and hypercoagulability in patients after TAVR, especially TAVR with PCI. Blockade of PS+EVs may improve the hypercoagulable state and prognosis of patients.

Imaging investigation of cervicocranial artery dissection by using high resolution magnetic resonance VWI and MRA: qualitative and quantitative analysis at different stages.

BACKGROUND: To explore the value of magnetic resonance angiography (MRA) and high resolution magnetic resonance vessel wall imaging (HRMR-VWI) in cervicocranial artery dissection (CCAD) for the disease diagnosis, course staging and treatment. On the basis of qualitative evaluation, this study also extract the changes of different stages in vessel wall in different vessel segments to identify imaging indicators for the quantitative evaluation of CCAD. METHODS: We retrospectively enrolled 34 patients with CCAD (38branches) with conventional MRA and HRMR-VWI examinations. Two radiologists independently analyzed imaging features of vessel wall and lumen in the different stages, and the typical sign detection of artery dissection were compared between MRA and HRMR-VWI. Then the parameters of vessel wall was quantitatively evaluated by the post-processing software (Vesselmass, Leiden University Medical Center, Leiden, The Netherlands. RESULTS: HRMR-VWI revealed typical sign detection of artery dissection in all patients in the acute and subacute stage. Among them, the intimal flap/double lumen sign ditection were more common than the MRA, there was significant difference (P = 0.012). MRA revealed typical sign detection of artery dissection in more than half the patients, and the detection was no significant difference at the chronic stage between MRA and HRMR-VWI (P = 1.000/1.000/0.761). In the acute and subacute stage, the typical sign detection of intramural hematoma and Grade II enhancement revealed by HR-MRI was higher than the observations in the chronic stage (P = 0.000/0.000/0.016), while there was no significant difference by MRA (P = 0.902). The values of wall thickness, relative signal intensity of vessel wall enhancement, relative signal intensity of intramural hematoma (IMH), and percentage of stenosis in CCAD decreased from acute to subacute and then to chronic stages. Each quantitative parameter in patients with CCAD in the early stages (i.e., acute and subacute stages) was significantly different from that in patients with CCAD in the recovered group at chronic stage (P < 0.05). Wall thickness and relative signal intensity of vessel wall enhancement in patients with CCAD in the early stages were not significantly different from those in patients with CCAD in the incompletely recovered group at chronic stage (P > 0.05). CONCLUSIONS: As the only noninvasive imaging technology, HRMR-VWI displays the structure of the vessel wall in vivo, showing not only excellent performance in the early diagnosis of CCAD, but also describing the changes of different stages in the qualitative and quantitative characteristics of vessel wall. It also helps to guide the diseasediagnosis, course staging and treatment of CCAD. Although the diagnostic efficacy of MRA was not as good as HRMR-VWI, it should be the first choice of method for routine examination in evaluating CCAD, especially at the chronic stage of CCAD.

Juvenile hormone suppresses the FoxO-takeout axis to shorten longevity in male silkworm.

Juvenile hormone (JH) plays a crucial endocrine regulatory role in insect metamorphosis, reproduction, and longevity in multiple organisms, such as flies, honeybees, and migratory monarch butterflies. However, the molecular mechanism of JH affecting longevity remains largely unknown. In this study, we showed that JH III and its analog methoprene shortened the survival days significantly in the adulthood of male silkworm. At the same time, the allatostatin, a neuropeptide that inhibits the secretion of JH by the corpora allata, could extend the survival days dramatically after adult eclosion in male silkmoth. Interestingly, a central pro-longevity FoxO transcription factor was reduced upon JH stimulation in silkworm individuals and BmN-SWU1 cells. Furthermore, the analysis of the upstream sequence of the FoxO gene identified a JH response element which suggested that FoxO might be regulated as a target of JH. Surprisingly, we identified a Bmtakeout (BmTO) gene that encodes a JH-binding protein and contains a FoxO response element. As expected, FoxO overexpression and knockdown up- and down-regulated the expression of BmTO respectively, indicating that BmTO functions as a FoxO target. BmTO overexpression could release the inhibitory effect of JH on the BmFoxO gene by reducing JH bioavailability to block its signal transduction. Collectively, these results may provide insights into the mechanism of the JH-FoxO-TO axis in aging research and pest control.

Effects of medical insurance system on the hospitalization cost of acute myocardial infarction patients.

BACKGROUND: Acute myocardial infarction is still a burden on Chinese patients. Whether different medical insurance system have any influence on the hospitalization cost and therapeutic effect of acute myocardial infarction patient needs further investigation. METHOD: In this study, 600 patients were stratified by health insurance status to investigate the cost effectiveness. RESULT: Compared with free medical care, patients with other health insurance status have a significantly lower age (P Ë‚ 0.05-0.001), the youngest of which is new rural cooperative medical system. The hospital expense, nursing fee, length of stay, daily hospitalization cost, daily drug cost, daily nursing cost and percent of nursing cost of different health insurance status were statistically significant. ANCOVA analyses controlling for age showed that the differences of hospital expenses, nursing fee, length of stay and daily hospitalization cost were still statistically significant. Further studies found that health insurance status was the leading factors influencing length of stay (ß = - 0.305, P = 0.0000001), nursing costs (ß = - 0.319, P = 0.004), daily hospitalization costs (ß = 0.296, P = 0.0001) and occurrence of clinical events (ß = - 0.186, OR = 0.830, 95% CI 0.694-0.993, P = 0.041). CONCLUSIONS: The hospitalization cost, length of stay, nursing work and therapeutic effect of acute myocardial infarction patients are affected by different health insurance status and age.

[Varieties and standards of Corydalis medicinal plants].

Through literature research and standard retrieval, Corydalis-derived medicinal materials, the origins, and related standards were summarized. Finally, 27 medicinal materials were screened out, involving 71 species(varieties). Among them, only 11 are recorded in Chinese Pharmacopoeia(2020), National Standard for Chinese Patent Drugs·Tibetan Medicine, Tibetan Medicine Standards, and other local standards, including Corydalis Bungeanae Herba and Corydalis Herba. The names and original plants of the medicinal materials are different in different standards, and the phenomena of "same medicinal material with different names" and "same name for different medicinal materials" are prominent. Most standards only include the traits, microscopic identification, and physico-chemical property identification, with unsound quality criteria. Thus, efforts should be made to strengthen the sorting of Corydalis medicinal plants, herbal textual research, and investigation of the resources and utilization. Moreover, via modern techniques, the chemical components and medicinal material basis of different original plants should be explored and sound quality standards should be established to improve the safety and quality of Corydalis-derived medicinal materials. Summarizing Corydalis medicinal plants, Corydalis-derived medicinal materials, and related standards, this study is expected to provide a reference for the standard formulation, quality evaluation, expansion of drug sources, and rational development and utilization of Corydalis resources.

Progressive gray matter hypertrophy with severity stages of insomnia disorder and its relevance for mood symptoms.

OBJECTIVE: To investigate the gray matter (GM) alterations in patients with insomnia disorder (ID) at different severity stages and the relationship between GM alterations and sleep, mood, and cognitive measures. METHODS: One hundred one ID patients and 63 healthy controls (HC) were included. Each patient underwent structural MRI and completed sleep-, mood-, and cognitive-related questionnaires. The ID patients were further grouped into subthreshold insomnia (SI) group and clinical insomnia (CI) group. We investigated changes in GM volumes in ID patients via diffeomorphic anatomical registration through exponentiated lie algebra voxel-based morphometry (DARTEL-VBM). We first compared voxel-wise differences in GM volumes between the HC group and the ID group. Analysis of variance was performed on individual GM maps in the SI, CI, and HC groups to further investigate the effects of different stages of ID severity on GM volumes. Multiple regression was used to model the relationship between altered GM volumes in SI and CI groups and clinical measures. RESULTS: GM hypertrophies in the left anterior and middle cingulate gyrus, right middle and inferior temporal gyrus, and right cerebellum Crus II were detected in ID. Increased GM volume in the right middle temporal gyrus was detected in the SI group, whereas all three regions in the CI group. Regression analysis showed that mood- and cognitive-related measures had a positive correlation with GM volumes, while sleep-related measures had a negative correlation with GM volumes in the CI group. CONCLUSIONS: Our findings of the progressively increased GM volumes in ID suggest that a hypertrophic cortical morphological mechanism may underlie the altered neuroanatomy induced by insomnia. KEY POINTS: • Insomnia-induced GM hypertrophies in the cingulate gyrus, temporal gyrus, and cerebellum Crus II. • The middle temporal gyrus was early detectable in the SI group. • The increased GM volumes in the CI group were correlated with clinical measures.

Rapid synthesis of monodispersed Au-Ag alloy nanosponges using selective laser melting and dealloying for sensitive near-infrared surface-enhanced Raman scattering.

We developed a rapid synthesis method for monodispersed Au-Ag alloy nanosponges (NSs) with high density of 'hotspots' for near-infrared surface enhanced Raman scattering (NIR-SERS) by a selective laser-irradiation melting and chemical dealloying process. Au@Ag core-shell nanocubes were firstin situconverted into solid alloyed Au-Ag nanospheres by a rapid laser irradiation igniting quick fusion and quenching process within two minutes. The alloyed Au-Ag nanospheres transformed into Au-Ag alloy NSs after treated by a chemical dealloying process. Different from traditional thermal annealing, it thus can effectively avoid the heat fusion between nanoparticles, and maintain the alloyed Au-Ag nanospheres and NSs in high monodispersity. Importantly, due to the strong plasmonic coupling in nanopores (pore size less than 10 nm), the obtained Au-Ag alloy NSs show a broad and intense localized surface plasmon resonances absorption ranging from visible to near-Infrared region (500-1200 nm). The accessibly open structures for absorbing targets and high-density of 'NIR-hotspots' endow the Au-Ag alloy NSs substrate with superior sensitivity in NIR-SERS detection of 4-aminothiophenol with an enhancement factor of ∼107. This work not only provides a simple pathway for rapid preparation of NIR-SERS substrate for biosensing, but also might open up a new horizon for fabricating spongy nanostructures with other elements.

Abnormal white matter within brain structural networks is associated with high-impulse behaviour in codeine-containing cough syrup dependent users.

Codeine-containing cough syrup (CCS) is considered as one of the most popular drug of dependence among adolescents because of its inexpensiveness and easy availability. However, its relationship with neurobiological effects remains sparsely explored. Herein, we examined how high-impulse behaviours relate to changes in the brain structural networks. Forty codeine-containing cough syrup dependent (CCSD) users and age-, gender-, and number of cigarettes smoked per day -matched forty healthy control (HC) subjects underwent structural brain imaging via MRI. High-impulse behaviour was assessed using the 30-item self-rated Barratt Impulsiveness Scale (BIS-11), and structural networks were constructed using diffusion tensor imaging and AAL-90 template. Between-group topological metrics were compared using nonparametric permutations. Benjamin-Hochberg false discovery rate correction was used to correct for multiple comparisons (P < 0.05). The relationships between abnormal network metrics and clinical characteristics of CCS dependent (BIS-11 total score, CCS- dependent duration and mean dose) were examined by Spearman's correlation. Structural networks of the CCSD group demonstrated lower small-world properties than those of the HC group. Abnormal changes in nodal properties among CCSD users were located mainly in the frontal gyrus, inferior parietal lobe and olfactory cortex. NBS analysis further indicated disrupted structural connections between the frontal gyrus and multiple brain regions. There were significant correlations between abnormal nodal properties of the frontal gyrus and clinical characteristics (BIS-11 total score, CCS dependent duration and mean dose) in the CCSD group. These findings suggest that the high-impulse behavioural expression in CCS addiction is associated with widespread brain regions, particularly within those in the frontal cortex. Aberrant brain regions and disrupted connectivity of structural network may be the bases of neuropathology for underlying symptoms of high-impulse behaviours in CCSD users, which may provide a novel sight to better treat and prevent codeine dependency in adolescents.