A brain-derived insulin signal encodes protein satiety for nutrient-specific feeding inhibition.

The suppressive effect of insulin on food intake has been documented for decades. However, whether insulin signals can encode a certain type of nutrients to regulate nutrient-specific feeding behavior remains elusive. Here, we show that in female Drosophila, a pair of dopaminergic neurons, tritocerebrum 1-dopaminergic neurons (T1-DANs), are directly activated by a protein-intake-induced insulin signal from insulin-producing cells (IPCs). Intriguingly, opto-activating IPCs elicits feeding inhibition for both protein and sugar, while silencing T1-DANs blocks this inhibition only for protein food. Elevating insulin signaling in T1-DANs or opto-activating these neurons is sufficient to mimic protein satiety. Furthermore, this signal is conveyed to local neurons of the protocerebral bridge (PB-LNs) and specifically suppresses protein intake. Therefore, our findings reveal that a brain-derived insulin signal encodes protein satiety and suppresses feeding behavior in a nutrient-specific manner, shedding light on the functional specificity of brain insulin signals in regulating behaviors.

Orchestrating apoptosis and ferroptosis through enhanced sonodynamic therapy using amorphous UIO-66-CoOx.

The development of efficient and multifunctional sonosensitizers is crucial for enhancing the efficacy of sonodynamic therapy (SDT). Herein, we have successfully constructed a CoOx-loaded amorphous metal-organic framework (MOF) UIO-66 (A-UIO-66-CoOx) sonosensitizer with excellent catalase (CAT)- and glutathione-oxidase (GSH-OXD)-like activities. The A-UIO-66-CoOx exhibits a 2.6-fold increase in singlet oxygen (1O2) generation under ultrasound (US) exposure compared to crystalline UIO-66 sonosensitizer, which is attributed to its superior charge transfer efficiency and consistent oxygen (O2) supply. Additionally, the A-UIO-66-CoOx composite reduces the expression of glutathione peroxidase (GPX4) by depleting glutathione (GSH) through Co3+ and Co2+ valence changes. The high levels of highly cytotoxic 1O2 and deactivation of GPX4 can lead to lethal lipid peroxidation, resulting in concurrent apoptosis and ferroptosis. Both in vitro and vivo tumor models comprehensively confirmed the enhanced SDT antitumor effect using A-UIO-66-CoOx sonosensitizer. Overall, this study emphasizes the possibility of utilizing amorphization engineering to improve the effectiveness of MOFs-based sonosensitizers for combined cancer therapies.

Microstate dynamics and spectral components as markers of persistent and remittent attention-deficit/hyperactivity disorder.

OBJECTIVE: We leveraged microstate characteristics and power features to examine temporal and spectral deviations underlying persistent and remittent attention-deficit/hyperactivity disorder (ADHD). METHODS: 50 young adults with childhood ADHD (28 persisters, 22 remitters) and 28 demographically similar healthy controls (HC) were compared on microstates features and frequency principal components (f-PCs) of eye-closed resting state. Support vector machine model with sequential forward selection (SVM-SFS) was utilized to discriminate three groups. RESULTS: Four microstates and four comparable f-PCs were identified. Compared to HC, ADHD persisters showed prolonged duration in microstate C, elevated power of the delta component (D), and compromised amplitude of the two alpha components (A1 and A2). Remitters showed increased duration and coverage of microstate C, together with decreased activity of D, relatively intact amplitude of A1, and amplitude reduction in A2. The SVM-SFS algorithm achieved an accuracy of 93.59% in classifying persisters, remitters and controls. The most discriminative features selected were those exhibiting group differences. CONCLUSIONS: We found widespread anomalies in ADHD persisters in brain dynamics and intrinsic EEG components. Meanwhile, the neural features in remitters exhibited multiple patterns. SIGNIFICANCE: This study underlines the use of microstate dynamics and spectral components as potential markers of persistent and remittent ADHD.

Comparing perioperative outcomes between regional anesthesia and general anesthesia in patients undergoing hip fracture surgery: a systematic review and meta-analysis.

PURPOSE: Nearly all patients with hip fractures undergo surgical treatment. The use of different anesthesia techniques during surgery may influence the clinical outcomes. The optimal anesthetic technique for patients undergoing hip fracture surgery is still controversial. We performed this updated systematic review and meta-analysis to compare clinical outcomes of patients undergoing hip fracture surgery with different anesthesia techniques. SOURCE: Articles published from 2000 to May 2023 were included from MEDLINE, Embase, Web of Science, and the Cochrane Library. We included randomized controlled trials and observational studies comparing general anesthesia (GA) with regional anesthesia (RA) for the outcomes of 30-day mortality, 90-day mortality, in-hospital mortality, perioperative complications, length of hospital stay, and length of surgery in patients undergoing hip fracture surgery. Subgroup analyses were performed for the outcomes based on study design (randomized controlled trials or observational studies). We used a random-effects model for all analyses. PRINCIPAL FINDINGS: In this meta-analysis, we included 12 randomized controlled trials. There was no difference in postoperative 30-day mortality between the two groups (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.44 to 1.74; I2 = 0%). The incidence of intraoperative hypotension was lower in patients who received RA vs GA (OR, 0.52; 95% CI, 0.38 to 0.72; I2 = 0%). No significant differences were observed in 90-day mortality, in-hospital mortality, postoperative delirium, pneumonia, myocardial infarction, venous thromboembolism, length of surgery, and length of hospital stay. CONCLUSION: In this updated systematic review and meta-analysis, RA did not reduce postoperative 30-day mortality in hip fracture surgery patients compared to GA. Fewer patients receiving RA had intraoperative hypotension than those receiving GA did. Apart from intraoperative hypotension, the data showed no differences in complications between the two anesthetic techniques. STUDY REGISTRATION: PROSPERO (CRD42023411854); registered 7 April 2023.

RéSUMé: OBJECTIF: Presque toutes les personnes ayant subi une fracture de la hanche se font opérer. L'utilisation de différentes techniques d'anesthésie pendant la chirurgie peut influencer les issues cliniques. La technique d'anesthésie optimale pour la patientèle bénéficiant de chirurgie de fracture de la hanche est encore controversée. Nous avons réalisé cette mise à jour par revue systématique et méta-analyse pour comparer les issues cliniques des personnes bénéficiant d'une chirurgie de fracture de la hanche avec différentes techniques d'anesthésie. SOURCES: Les articles publiés de 2000 à mai 2023 ont été inclus à partir des bases de données MEDLINE, Embase, Web of Science et Cochrane Library. Nous avons inclus des études randomisées contrôlées et des études observationnelles comparant l'anesthésie générale (AG) à l'anesthésie régionale (AR) pour les issues de mortalité à 30 jours, de mortalité à 90 jours, de mortalité intrahospitalière, de complications périopératoires, de durée de séjour à l'hôpital et de durée de la chirurgie pour les personnes bénéficiant d'une chirurgie de fracture de la hanche. Des analyses de sous-groupes ont été réalisées pour les issues en fonction de la méthodologie utilisée (étude randomisée contrôlée ou étude observationnelle). Un modèle à effets aléatoires a été utilisé pour toutes les analyses. CONSTATATIONS PRINCIPALES: Dans cette méta-analyse, nous avons inclus 12 études randomisées contrôlées. Il n'y avait pas de différence dans la mortalité postopératoire à 30 jours entre les deux groupes (rapport de cotes [RC], 0,88; intervalle de confiance à 95 % [IC], 0,44 à 1,74; I2 = 0 %). L'incidence d'hypotension peropératoire était plus faible chez les patient·es ayant reçu une AR vs une AG (RC, 0,52; IC 95 %, 0,38 à 0,72; I2 = 0 %). Aucune différence significative n'a été observée dans les issues de mortalité à 90 jours, de mortalité intrahospitalière, de delirium postopératoire, de pneumonie, d'infarctus du myocarde, de thromboembolie veineuse, de durée de la chirurgie, et de durée du séjour à l'hôpital. CONCLUSION: Dans cette revue systématique avec méta-analyse, l'anesthésie régionale n'a pas réduit la mortalité postopératoire à 30 jours chez les personnes ayant bénéficié d'une chirurgie de fracture de la hanche par rapport à l'anesthésie générale. Une proportion moindre de patient·es ayant reçu une AR présentaient une hypotension peropératoire par rapport aux personnes ayant reçu une AG. En dehors de l'hypotension peropératoire, les données n'ont montré aucune différence dans les complications entre les deux techniques anesthésiques. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42023411854); enregistrée le 7 avril 2023.

Review of the Protective Mechanism of Curcumin on Cardiovascular Disease.

Cardiovascular diseases (CVDs) are the most common cause of death worldwide and has been the focus of research in the medical community. Curcumin is a polyphenolic compound extracted from the root of turmeric. Curcumin has been shown to have a variety of pharmacological properties over the past decades. Curcumin can significantly protect cardiomyocyte injury after ischemia and hypoxia, inhibit myocardial hypertrophy and fibrosis, improve ventricular remodeling, reduce drug-induced myocardial injury, improve diabetic cardiomyopathy(DCM), alleviate vascular endothelial dysfunction, inhibit foam cell formation, and reduce vascular smooth muscle cells(VSMCs) proliferation. Clinical studies have shown that curcumin has a protective effect on blood vessels. Toxicological studies have shown that curcumin is safe. But high doses of curcumin also have some side effects, such as liver damage and defects in embryonic heart development. This article reviews the mechanism of curcumin intervention on CVDs in recent years, in order to provide reference for the development of new drugs in the future.

Facet joint tropism, pelvic incidence and intervertebral height index: associations with facet joint osteoarthritis in lumbar spinal stenosis.

BACKGROUND CONTEXT: Facet joint osteoarthritis (FJOA) is associated with lumbar disc degeneration and has a significant role in the development of lumbar spinal stenosis (LSS). The relationship between various radiographic parameters and the grade of FJOA is not well understood. PURPOSE: To explore radiographical parameters associated with FJOA in LSS without lumbar dynamic instability. STUDY DESIGN: Retrospective study analysis. PATIENT SAMPLE: A total of 122 patients diagnosed with LSS who visited our hospital between January 2015 and July 2022. OUTCOME MEASURES: We evaluated radiographic parameters of patients at L4-5 including lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), grades of FJOA, facet joint orientation (FO), facet joint tropism (FT), intervertebral height index (IHI) and the relative cross-sectional area (RCSA) of paraspinal muscles. METHODS: Patients diagnosed with LSS between January 2015 and July 2022 were enrolled. Demographic characteristics and radiographic parameters were collected. Spinopelvic parameters were measured through the preoperative lateral image of the whole spine, including LL, PI, pelvic tilt, and sacral slope. Lumbar computed tomography scan and magnetic resonance imaging were collected to measure the FO, FT, IHI, and the RCSA of paraspinal muscles respectively. Patients were divided into three groups according to the severity of FJOA graded by the Weishaupt classification: grade 0 and grade 1 were group A, grade 2 were group B, and grade 3 were group C. All variables were compared among the three groups, while the relationship between parameters and grades of FJOA were also analyzed. RESULTS: A total of 122 patients were included. PI was significantly greater in group C compared to group A (p = 0.025) and group B (p=0.022). FT was significantly greater in group C compared to group A (p<.001) and group B (p<.001). The RCSA of multifidus in group A were significantly greater than that in group B (p=0.02) and C (p=0.002). Additionally, FO in group C were significantly lower than group A (p<.001) and group B (p=0.028). The IHI in group C was significantly lower than group A (p=0.017). The correlation analysis indicated that grades of FJOA was positively related to Age, BMI (body mass index), PI, LL and FT, while negatively related to IHI, FO, RCSA of multifidus and RCSA of psoas major. Furthermore, the logistics regression showed that FT, PI, and IHI were important influence factors for FJOA. CONCLUSIONS: The current study confirmed that FT, PI and IHI were significantly associated with grades of FJOA at L4-5. Additionally, longitudinal studies are needed to understand the causal relationship between these parameters and FJOA.

Identification of potential diagnostic biomarkers for tenosynovial giant cell tumour by integrating microarray and single-cell RNA sequencing data.

PURPOSE: Tenosynovial giant cell tumour (TGCT) is a benign hyperplastic and inflammatory disease of the joint synovium or tendon sheaths, which may be misdiagnosed due to its atypical symptoms and imaging features. We aimed to identify biomarkers with high sensitivity and specificity to aid in diagnosing TGCT. METHODS: Two scRNA-seq datasets (GSE210750 and GSE152805) and two microarray datasets (GSE3698 and GSE175626) were downloaded from the Gene Expression Omnibus (GEO) database. By integrating the scRNA-seq datasets, we discovered that the osteoclasts are abundant in TGCT in contrast to the control. The single-sample gene set enrichment analysis (ssGSEA) further validated this discovery. Differentially expressed genes (DEGs) of the GSE3698 dataset were screened and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were conducted. Osteoclast-specific up-regulated genes (OCSURGs) were identified by intersecting the osteoclast marker genes in the scRNA-seq and the up-regulated DEGs in the microarray and by the least absolute shrinkage and selection operator (LASSO) regression algorithm. The expression levels of OCSURGs were validated by an external dataset GSE175626. Then, single gene GSEA, protein-protein interaction (PPI) network, and gene-drug network of OCSURGs were performed. RESULT: 22 seurat clusters were acquired and annotated into 10 cell types based on the scRNA-seq data. TGCT had a larger population of osteoclasts compared to the control. A total of 159 osteoclast marker genes and 104 DEGs (including 61 up-regulated genes and 43 down-regulated genes) were screened from the scRNA-seq analysis and the microarray analysis. Three OCSURGs (MMP9, SPP1, and TYROBP) were finally identified. The AUC of the ROC curve in the training and testing datasets suggested a favourable diagnostic capability. The PPI network results illustrated the protein-protein interaction of each OCSURG. Drugs that potentially target the OCSURGs were predicted by the DGIdb database. CONCLUSION: MMP9, SPP1, and TYROBP were identified as osteoclast-specific up-regulated genes of the tenosynovial giant cell tumour via bioinformatic analysis, which had a reasonable diagnostic efficiency and served as potential drug targets.

Application of functional magnetic resonance imaging for evaluation of cartilage injury effect on knee joint function by recurrent patellar dislocation.

Explore the therapeutic effect of vastus medialis oblique plasty and the reliability and applicability of functional magnetic resonance imaging as a diagnostic method for early cartilage degeneration and injury diagnosis. From July 2020 to July 2022, there were 53 patients with recurrent patellar dislocation who met the inclusion criteria for surgery, including 34 women and 19 men, aged 11 to 53 years, with an average age of 24.4 years. After patient selection, functional magnetic resonance imaging was performed before surgery. According to the presence or absence of cartilage injury, they were divided into cartilage injury group (n = 28) and non-cartilage injury group (n = 25), and underwent vastus medialis oblique plasty. Preoperative patellar axial radiographs were performed in both groups of patients to measure the patellar tilt angle and lateral patellofemoral angle. The Lysholm, Kujala, and VAS (visual analogue scale) scores were applied to assess changes in knee joint function and anterior knee pain. All patients were postoperatively followed up. The patellar tilt angle and lateral patellofemoral angle of the 2 groups were significantly improved postoperatively (P < .05), with no statistical difference between the 2 groups (P > .05). Significant differences were observed in the VAS changes between the cartilage injury group and the non-cartilage injury group before and after operation (P < .05). There was a statistical difference in VAS score between the groups (P < .05). The changes in the Lysholm and Kujala scores before and after the operation in the cartilage injury and the non-cartilage injury groups were statistically different (P < .05). There was statistical difference between the 2 groups in Lysholm score and Kujala score after operation (P < .05). Vastus medialis oblique plasty significantly improved knee joint function and pain. Patients with cartilage injury had worse preoperative and postoperative knee function than patients without cartilage injury. Functional magnetic resonance imaging can reflect the early-stage changes in the biochemical cartilage components caused by recurrent patellar dislocation.

Functional reorganization of brain activity in children with attention-deficit/hyperactivity disorder: Evidence from the modulatory effect of cognitive demand during visuospatial attention task.

Previous studies reported that the inferior parietal lobule (IPL) had lower activation during visuospatial attention in children with attention-deficit/hyperactivity disorder (ADHD), while the functional connectivity (FC) between the IPL and other brain regions and how cognitive demand might modulate IPL's FC remain unclear. We performed a functional magnetic resonance imaging experiment recruiting two task conditions with relatively low and high cognitive demand of visuospatial attention. Forty-four children with ADHD and 36 age- and sex-matched healthy controls were included. IPL's regional activation and FC intensities were compared between groups and correlated with clinical measurements. We found that the IPL had significantly reduced activation in children with ADHD compared to healthy controls and this abnormal activation was not modulated by the cognitive demand of visuospatial attention. Importantly, further analysis revealed that the functional connectivity between IPL and inferior frontal gyrus was modulated by the cognitive demand of visuospatial attention in children with ADHD. These results revealed a modulatory effect of cognitive demand of visuospatial attention on IPL's functional connectivity but not IPL's activation in children with ADHD. More generally, these results highlight the functional reorganization of the brain activity as a possible compensatory strategy in response to the symptoms of ADHD.

Exploration of diagnostic biomarkers, microenvironment characteristics, and ursolic acid's therapeutic effect for benign prostate hyperplasia.

Benign prostatic hyperplasia (BPH) and early-stage prostate cancer (PC) have similar symptoms, making it challenging to differentially diagnose these two conditions. The study used Weighted Gene Co-Expression Network Analysis, as well as two machine learning strategies to identify BPH-specific biomarkers based on an integrated transcriptome data from 922 samples. Eight prognostic genes (ALCAM, COL6A2, CRISP2, FOXF2, IGF1, PTN, SCN7A, and UAP1) were identified to be BPH-specific biomarkers with high accuracy and specificity. Moreover, we constructed a seven-gene diagnostic classifier to distinguish BPH from PC. The infiltrations of plasmacytoid dendritic cells and neutrophil cells showed distinct differences between BPH and non-BPH groups. Additionally, ursolic acid can reverse transcriptional features associated with the occurrence and progression of BPH. Both in vivo and in vitro experiments have confirmed that it induces apoptosis of BPH cells and inhibits cell proliferation by promoting cell cycle S-phase arrest. The diagnostic biomarkers, microenvironment characteristics, and therapeutic effect of ursolic acid explored in this study offer new diagnostic and therapeutic strategies for BPH.

Insulin-Like Growth Factor 1 Receptor Deficiency Alleviates Angiotensin II-Induced Cardiac Fibrosis Through the Protein Kinase B/Extracellular Signal-Regulated Kinase/Nuclear Factor-κB Pathway.

Background The renin-angiotensin system plays a crucial role in the development of heart failure, and Ang II (angiotensin II) acts as the critical effector of the renin-angiotensin system in regulating cardiac fibrosis. However, the mechanisms of cardiac fibrosis are complex and still not fully understood. IGF1R (insulin-like growth factor 1 receptor) has multiple functions in maintaining cardiovascular homeostasis, and low-dose IGF1 treatment is effective in relieving Ang II-induced cardiac fibrosis. Here, we aimed to investigate the molecular mechanism of IGF1R in Ang II-induced cardiac fibrosis. Methods and Results Using primary mouse cardiac microvascular endothelial cells and fibroblasts, in vitro experiments were performed. Using C57BL/6J mice and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9)-mediated IGF1R heterozygous knockout (Igf1r+/-) mice, cardiac fibrosis mouse models were induced by Ang II for 2 weeks. The expression of IGF1R was examined by quantitative reverse transcription polymerase chain reaction, immunohistochemistry, and Western blot. Mice heart histologic changes were evaluated using Masson and picro sirius red staining. Fibrotic markers and signal molecules indicating the function of the Akt (protein kinase B)/ERK (extracellular signal-regulated kinase)/nuclear factor-κB pathway were detected using quantitative reverse transcription polymerase chain reaction and Western blot. RNA sequencing was used to explore IGF1R-mediated target genes in the hearts of mice, and the association of IGF1R and G-protein-coupled receptor kinase 5 was identified by coimmunoprecipitation. More important, blocking IGF1R signaling significantly suppressed endothelial-mesenchymal transition in primary mouse cardiac microvascular endothelial cells and mice in response to transforming growth factor-ß1 or Ang II, respectively. Deficiency or inhibition of IGF1R signaling remarkably attenuated Ang II-induced cardiac fibrosis in primary mouse cardiac fibroblasts and mice. We further observed that the patients with heart failure exhibited higher blood levels of IGF1 and IGF1R than healthy individuals. Moreover, Ang II treatment significantly increased cardiac IGF1R in wild type mice but led to a slight downregulation in Igf1r+/- mice. Interestingly, IGF1R deficiency significantly alleviated cardiac fibrosis in Ang II-treated mice. Mechanistically, the phosphorylation level of Akt and ERK was upregulated in Ang II-treated mice, whereas blocking IGF1R signaling in mice inhibited these changes of Akt and ERK phosphorylation. Concurrently, phosphorylated p65 of nuclear factor-κB exhibited similar alterations in the corresponding group of mice. Intriguingly, IGF1R directly interacted with G-protein-coupled receptor kinase 5, and this association decreased ≈50% in Igf1r+/- mice. In addition, Grk5 deletion downregulated expression of the Akt/ERK/nuclear factor-κB signaling pathway in primary mouse cardiac fibroblasts. Conclusions IGF1R signaling deficiency alleviates Ang II-induced cardiac fibrosis, at least partially through inhibiting endothelial-mesenchymal transition via the Akt/ERK/nuclear factor-κB pathway. Interestingly, G-protein-coupled receptor kinase 5 associates with IGF1R signaling directly, and it concurrently acts as an IGF1R downstream effector. This study suggests the promising potential of IGF1R as a therapeutic target for cardiac fibrosis.

Comparison of surface microscopy coil and ankle joint special phased array coil magnetic resonance imaging in assessing preoperative osteochondral lesions of the talus.

Background: Lesion size is a major determinant of treatment strategies and predictor of clinical outcomes for osteochondral lesions of the talus (OLTs). Although magnetic resonance imaging (MRI) has been commonly used in the preoperative evaluation of OLTs, MRI has low reliability and usually overestimates or underestimates lesion size compared with intraoperative assessment. This study aims to determine whether the surface microscopy coil (SMC) can improve the accuracy of assessment of preoperative OLTs compared with conventional coil MRI, ankle joint special phased array coil (ASC). Methods: A total of 43 patients diagnosed with OLTs undertook preoperative MRI examination with both SMC and ASC were included in this prospective study from 2019 to 2022. The diameter of the lesion was measured in sagittal plane and coronal plane at its widest point and then the lesion area was calculated. Then MRI measurements were compared with arthroscopy or open-surgery measurements. Results: The mean lesion area measured with ASC was significantly greater than that measured intraoperatively (95.07±44.60 vs. 52.74±29.86 mm2, P<0.001), while there was no significant difference between lesion area measured in SMC and intraoperatively (55.28±36.06 vs. 52.74±29.86 mm2, P=0.576). Diameter measured in ASC was significantly greater than that measured intraoperatively in both coronal plane (8.95±2.48 vs. 6.67±1.81, P<0.001) and sagittal plane (13.12±3.76 vs. 9.58±3.98, P<0.001). No significant difference between lesion diameter measured in SMC and intraoperatively in both coronal plane (6.44±2.59 vs. 6.67±1.81, P=0.608) or sagittal plane (10.23±3.69 vs. 9.58±3.98, P=0.194). Compared with surgical assessment, 39 of 43 cases were consistent with SMC assessment while only 26 of 43 cases were consistent with ASC assessment (39/43 vs. 26/43, P=0.002). Conclusions: Diameter measured with SMC was much more accurate than ASC MRI. Compared with ASC MRI, the SMC had a much higher concordance rate between preoperative assessment and surgical assessment.

Causal relationship between type 2 diabetes mellitus and bone mineral density: a Mendelian randomization study in an East Asian population.

It remains unclear whether the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) reflects causality in East Asian populations. Herein, a Mendelian randomization study conducted in East Asian population enhances the current clinical cognition that T2DM is not associated with reduction in BMD. PURPOSE: A Mendelian randomization (MR) approach was utilized to investigate the relationship between type 2 diabetes mellitus (T2DM) and bone mineral density (BMD) in East Asian populations. METHODS: Genome-wide association study summary data from BioBank Japan were used to identify genetic variants strongly related to T2DM risk (36,614 cases and 155,150 controls) and osteoporosis (7788 cases and 204,665 controls). Heel BMD GWAS data of 1260 East Asian people from ieu open gwas project was considered as a second outcome. Inverse variance-weighted (IVW) analysis was mainly applied; MR-Egger and the weighted median were also used to obtain robust estimates. A series of sensitivity analyses including Cochran's Q test, MR-Egger regression, and leave-one-out analysis were used to detect pleiotropy or heterogeneity. RESULTS: In the main analysis, IVW estimates indicated that T2DM significantly associated with the risk of osteoporosis (odds ratio = 0.92, 95% CI: 0.86-0.99, p = 0.016) and with higher BMD (OR: 1.25, 95% CI: 1.06-1.46, p = 6.49 × 10-3). Results of comprehensive sensitivity analysis were consistent with the main causality estimate. Horizontal pleiotropy and heterogeneity were absent in our MR study. CONCLUSIONS: T2DM is not associated with reduction in BMD in terms of genetic polymorphism in East Asian populations.

Effects of biochar on plant growth and hydro-chemical properties of recycled concrete aggregate.

Biochar has been used as a sustainable amendment to mitigate environmental risks, improve plant growth and soil properties. This study conducted laboratory column tests to investigate the effects of plant-biochar interactions on shrub growth, hydraulic properties and nutrient contents of recycled concrete aggregates (RCAs). In total, three test conditions, namely, vegetated RCA without biochar (R), with 5 % biochar (R5) and 10 % biochar (R10) were subject to drying. With biochar application, total N, P and K of RCA increased by >100 %, 200 % and 31 %, respectively, while pH reduced to 8.3. With shrub growth, the lowest RCA pH was reduced to 7.8. The leaf area index (LAI) of shrub increased by 51 % due to biochar amendment, while the differences in shoot height were insignificant. The water retention capacity of RCA was enhanced by improving the saturated water content and air-entry value by 27 % and 100 %. The slope of the soil suction-LAI correlation for biochar amend cases was 1.6 times lower than R. This indicates that biochar may limit the increase of matric suction and prevent excessive water loss during drying. However, the differences between R5 and R10 were not significant. Therefore, 5 % biochar amendment is highly suggested as it can substantially improve plant growth and soil hydraulic properties during drying.

Live imaging reveals chromatin compaction transitions and dynamic transcriptional bursting during stem cell differentiation in vivo.

Stem cell differentiation requires dramatic changes in gene expression and global remodeling of chromatin architecture. How and when chromatin remodels relative to the transcriptional, behavioral, and morphological changes during differentiation remain unclear, particularly in an intact tissue context. Here, we develop a quantitative pipeline which leverages fluorescently-tagged histones and longitudinal imaging to track large-scale chromatin compaction changes within individual cells in a live mouse. Applying this pipeline to epidermal stem cells, we reveal that cell-to-cell chromatin compaction heterogeneity within the stem cell compartment emerges independent of cell cycle status, and instead is reflective of differentiation status. Chromatin compaction state gradually transitions over days as differentiating cells exit the stem cell compartment. Moreover, establishing live imaging of Keratin-10 (K10) nascent RNA, which marks the onset of stem cell differentiation, we find that Keratin-10 transcription is highly dynamic and largely precedes the global chromatin compaction changes associated with differentiation. Together, these analyses reveal that stem cell differentiation involves dynamic transcriptional states and gradual chromatin rearrangement.

Better timing for HoLEP: a retrospective analysis of patients treated with HoLEP over a 10-year period with a 1-year follow-up.

The aim of this study was to explore the optimal timing of holmium laser enucleation of the prostate (HoLEP) in patients presenting benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS). A retrospective analysis was conducted based on the perioperative and postoperative outcome data of 1212 patients who underwent HoLEP in Shanghai Ninth People's Hospital (Shanghai, China) between January 2009 and December 2018. According to the preoperative International Prostate Symptom Score (IPSS), all patients whom we analyzed were divided into Group A (IPSS of 8-18) and Group B (IPSS of 19-35). Peri- and postoperative outcome data were obtained during the 1-year follow-up. IPSS changes were the main postoperative outcomes. The postoperative IPSS, quality of life, peak urinary flow rate, postvoid residual, and overactive bladder symptom score (OABSS) improved significantly. The IPSS improved further in the group with severe LUTS symptoms, but the postoperative IPSS was still higher than that in the moderate LUTS group. OABSSs showing moderate and severe cases after follow-up were more frequent in Group B (9.1%) than in Group A (5.2%) (P < 0.05). There were no significant intergroup differences in the intraoperative American Society of Anesthesiologists or hospitalization expense scores, and the medication costs, as well as the total costs, were significantly higher in Group B. In this retrospective study, HoLEP was an effective treatment for symptomatic BPH. For patients with LUTS, earlier surgery in patients with moderate severity may result in a marginally better 12-month IPSS than that in men with severe symptoms.

A randomized controlled study of remote computerized cognitive, neurofeedback, and combined training in the treatment of children with attention-deficit/hyperactivity disorder.

There is an increasing interest in non-pharmacological treatments for children with attention-deficit/hyperactivity disorder (AD/HD), especially digital techniques that can be remotely delivered, such as neurofeedback (NFT) and computerized cognitive training (CCT). In this study, a randomized controlled design was used to compare training outcomes between remotely delivered NFT, CCT, and combined NFT/CCT training approaches. A total of 121 children with AD/HD were randomly assigned to the NFT, CCT, or NFT/CCT training groups, with 80 children completing the training program. Pre- and post-training symptoms (primary outcome), executive and daily functions were measured using questionnaires as well as resting EEG during eyes-closed (EC) and eyes-open (EO) conditions. After 3 months of training, the inattentive and hyperactive/impulsive symptoms, inhibition, working memory, learning and life skills of the three groups of children were significantly improved. The objective EEG activity showed a consistent increase in the relative alpha power in the EO condition among the three training groups. Training differences were not observed between groups. There was a positive correlation between pre-training EO relative alpha power and symptom improvement scores of inattention and hyperactivity/impulsivity, as well as a negative correlation between pre-training inattention scores and change in EO relative alpha. This study verified the training effects of NFT, CCT, and combined NFT/CCT training in children with AD/HD and revealed an objective therapeutic role for individual relative alpha activity. The verified feasibility and effectiveness of home-based digital training support promotion and application of digital remote training.

Epilepsy gene prickle ensures neuropil glial ensheathment through regulating cell adhesion molecules.

Human PRICKLE1 gene has been associated with epilepsy. However, the underlying pathogenetic mechanisms remain elusive. Here we report a Drosophila prickle mutant pk IG1-1 exhibiting strong epileptic seizures and, intriguingly, abnormal glial wrapping. We found that pk is required in both neurons and glia, particularly neuropil ensheathing glia (EGN), the fly analog of oligodendrocyte, for protecting the animal from seizures. We further revealed that Pk directly binds to the membrane skeleton binding protein Ankyrin 2 (Ank2), thereby regulating the cell adhesion molecule Neuroglian (Nrg). Such protein interactions also apply to their human homologues. Moreover, nrg and ank2 mutant flies also display seizure phenotypes, and expression of either Nrg or Ank2 rescues the seizures of pk IG1-1 flies. Therefore, our findings indicate that Prickle ensures neuron-glial interaction within neuropils through regulating cell adhesion between neurons and ensheathing glia. Dysregulation of this process may represent a conserved pathogenic mechanism underlying PRICKLE1-associated epilepsy.

Information-based multivariate decoding reveals imprecise neural encoding in children with attention deficit hyperactivity disorder during visual selective attention.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in school-age children. Attentional orientation is a potential clinical diagnostic marker to aid in the early diagnosis of ADHD. However, the underlying pathophysiological substrates of impaired attentional orienting in childhood ADHD remain unclear. Electroencephalography (EEG) was measured in 135 school-age children (70 with childhood ADHD and 65 matched typically developing children) to directly investigate target localization during spatial selective attention through univariate ERP analysis and information-based multivariate pattern machine learning analysis. Compared with children with typical development, a smaller N2pc was found in the ADHD group through univariate ERP analysis. Children with ADHD showed a lower parieto-occipital multivariate decoding accuracy approximately 240-340 ms after visual search onset, which predicts a slower reaction time and larger standard deviation of reaction time. Furthermore, a significant correlation was found between N2pc and decoding accuracy in typically developing children but not in children with ADHD. These observations reveal that impaired attentional orienting in ADHD may be due to inefficient neural encoding responses. By using a personalized information-based multivariate machine learning approach, we have advanced the understanding of cognitive deficits in neurodevelopmental disorders. Our study provides potential research directions for the early diagnosis and optimization of personalized intervention in children with ADHD.

Role of fractional high harmonics with non-integer OAM on the generation of a helical attosecond pulse train.

Extreme-ultraviolet pulses of attosecond duration carrying orbital angular momentum (OAM) can be produced by spectrally filtering vortex high harmonics generated in a gas medium. Here we reveal that fractional high harmonics (FHHs) with non-integer OAM generated by a short duration Laguerre-Gaussian laser beam are origins for the change of helical attosecond pulse train (APT) with azimuthal angle. We show that these harmonics have gap and minimum structures in the annular intensity profile and discontinue phase distribution along azimuthal angle. And each FHH can be expressed as a superposition of OAM modes with integer topological charges. Features of FHH can be identified by coherently combining selected OAM modes. We also uncover that these features are formed after FHH is propagated in gas medium and in vacuum. We finally demonstrate that the generation of FHHs and the dependence of helical APTs on azimuthal angle are changed by varying the macroscopic condition.