Hydrogel Nanoparticles Enable Nucleation Barrier Regulation and Ion Anchoring as an Alternative Pathway for Monosodium Urate Monohydrate Crystallization Control.

Gout flare-up, commonly resulting from monosodium urate monohydrate (MSUM) crystallization, has led to painful inflammatory arthritis among hundreds of millions of people. Herein, a kind of hydrogel nanoparticles (HNPs) with specific properties was developed, aimed at providing a promising pathway for MSUM crystallization control. The experimental and molecular dynamics simulation results synchronously indicate that the fabricated HNPs achieve efficient inhibition of MSUM crystallization governed by the mechanism of "host-guest interaction" even under very low-dose administration. HNPs as the host dispersed in the hyperuricemic model effectively lift the relative heterogeneous nucleation barrier of the MSUM crystal and hinder solute aggregation with strong electronegativity and hydrophobicity. The initial appearance of MSUM crystals was then delayed from 94 to 334 h. HNPs as the guest on the surface of the formed crystal can decelerate the growth rate by anchoring ions and occupying the active sites on the surface, and the terminal yield of the MSUM crystal declined to less than 1% of the control group. The good biocompatibility of HNPs (cell viability > 94%) renders it possible for future clinical applications. This study can guide the rational design of inhibitory nanomaterials and the development of their application in the control of relevant pathological crystallization.

Targeting Moonlighting Enzymes in Cancer.

Moonlighting enzymes are multifunctional proteins that perform multiple functions beyond their primary role as catalytic enzymes. Extensive research and clinical practice have demonstrated their pivotal roles in the development and progression of cancer, making them promising targets for drug development. This article delves into multiple notable moonlighting enzymes, including GSK-3, GAPDH, and ENO1, and with a particular emphasis on an enigmatic phosphatase, PTP4A3. We scrutinize their distinct roles in cancer and the mechanisms that dictate their ability to switch roles. Lastly, we discuss the potential of an innovative approach to develop drugs targeting these moonlighting enzymes: target protein degradation. This strategy holds promise for effectively tackling moonlighting enzymes in the context of cancer therapy.

Design, synthesis, and biological evaluation of first-in-class FABP1 inhibitors for the treatment of NASH.

The fatty acid-binding protein 1 (FABP1) is a fatty acid transporter protein that is considered as an emerging target for metabolic diseases. Despite forceful evidence that the inhibition of FABP1 is essential for ameliorating NASH, pharmacological control and validation of FABP1 are hindered by a lack of relevant inhibitors as pharmacological tool. Therefore, the development of effective FABP1 inhibitors is a current focus of research. Herein, we firstly reported the comprehensive structure-activity relationship (SAR) study of novel FABP1 inhibitors derived from high throughput screening of our in-house library, which resulting in the identification of the optimal compound 44 (IC50 = 4.46 ± 0.54 µM). Molecular docking studies revealed that 44 forms stable hydrogen bonds with amino acids around the active pocket of FABP1. Moreover, 44 alleviated the typical histological features of fatty liver in NASH mice, including steatosis, lobular inflammation, ballooning and fibrosis. Additionally, 44 has been demonstrated to have lipid metabolism regulating, anti-oxidative stress and hepatoprotective properties. This study might be provided a promising insight into the field of NASH and inspiration for the development of FABP1 inhibitors.

Measuring General Health Literacy in Chinese adults: validation of the HLS19-Q12 instrument.

BACKGROUND: Health literacy measurement lays a solid foundation to identify associations with health outcomes and monitor population health literacy levels over time. In mainland China, most existing health literacy instruments are either knowledge-based or practice-based, making health literacy results incomparable between China and other countries. This study aimed to examine the reliability and validity of the 12-item Health Literacy Population Survey (HLS19-Q12) in a general population of Chinese adults. METHODS: A cross-sectional study was conducted to recruit primary carers of students from 11 schools in Zhengzhou, Henan Province, using convenience cluster sampling. Participants completed an online self-administered survey that collected information on key sociodemographics, health literacy (HLS19-Q12 and a comparison tool: Health Literacy Questionnaire (HLQ)), and health-related outcomes. Using the COnsensus-based Standards for the selection of health status Measurement Instruments (COSMIN) checklist as a guideline, we tested internal consistency, test-retest reliability, content validity, structural validity, concurrent predictive validity, and convergent validity of the HLS19-Q12. RESULTS: Overall, 14,184 participants completed the full survey. The HLS19-Q12 showed excellent internal consistency (Cronbach's α = 0.93), moderate test-retest reliability (intra-class correlation coefficient = 0.54), satisfactory content validity (based on the 12-matrix health literacy model), and strong structural validity (comparative fit index = 0.94, Tucker and Lewis's index of fit = 0.93, root mean square error of approximation = 0.095). Concurrent predictive validity results showed health literacy was associated with both health determinants and health-related outcomes. The HLS19-Q12 had weak to strong correlations (coefficients = 0.24 to 0.42) with the nine scales of the HLQ. Respondents had an average score of 81.6 (± 23.0) when using the HLS19-Q12, with 35.0% and 7.5% having problematic and inadequate levels of health literacy, respectively. CONCLUSIONS: The HLS19-Q12 is a reliable and valid instrument to measure health literacy in our sample. Further validation is needed with a more nationally representative sample of Chinese adults. The HLS19-Q12 could be used as a comprehensive, skills-based, and easy-to-administer health literacy assessment tool integrated into population surveys and intervention evaluations.

Higher Circulating Lymphocytes and the Incidence of Pre-eclampsia and Eclampsia.

Excessive immune activation contributes to the onset of early dysfunction of the maternal-fetal interface, and it is closely linked to the development of pre-eclampsia. However, the effect of specific immune cells on the risk of pre-eclampsia and eclampsia remains controversial. We investigated the causal relationship between immune cells and pre-eclampsia and eclampsia. For exposure, we extracted genetic variants associated with immune cell-related traits, and for outcomes, we used summary genetic data of pre-eclampsia/eclampsia. A two-sample Mendelian randomization (MR) analysis was then performed to assess the causal relationship. Robustness of the MR results was then evaluated through colocalization analysis. We found that genetically proxied circulating lymphocyte absolute count was causally associated with total eclampsia (odds ratio (OR) = 1.53, 95% confidence interval (CI) (1.31-1.79), p = 1.15E - 07) and pre-eclampsia (OR = 1.50, 95% CI (1.28-1.77), p = 9.18E - 07); T cell absolute count was causally associated with total eclampsia (OR = 1.49, 95% CI (1.28-1.73), p = 2.73E - 07) and pre-eclampsia (OR = 1.47, 95% CI (1.25-1.72), p = 1.76E - 06). And CD28- CD25+ CD8+ T cell absolute count was causally associated with total eclampsia (OR = 1.83, 95% CI (1.44-2.32), p = 7.11E - 07) and pre-eclampsia (OR = 1.77, 95% CI (1.38-2.26), p = 6.55E - 06). Colocalization analysis revealed that immune cell-related traits shared the same variant with pre-eclampsia/eclampsia. Our study suggested causal effects of genetic predisposition to high lymphocyte absolute count levels, T cell absolute count, and CD28- CD25+ CD8+ T cell absolute count on eclampsia, particularly pre-eclampsia risk, providing crucial new insights into the potential prevention target for eclampsia and pre-eclampsia.

High performance on-chip polarization beam splitter at visible wavelengths based on a silicon nitride small-sized ridge waveguide.

Due to sensitive scaling of the wavelength and the visible-light absorption properties with the device dimension, traditional passive silicon photonic devices with asymmetric waveguide structures cannot achieve polarization control at the visible wavelengths. In this work, a simple and small polarization beam splitter (PBS) for a broad visible-light band, using a tailored silicon nitride (Si3N4) ridge waveguide, is presented, which is based on the distinct optical distribution of two fundamental orthogonal polarized modes in the ridge waveguide. The bending loss for different bending radii and the optical coupling properties of the fundamental modes for different Si3N4 ridge waveguide configurations are analyzed. A PBS composed of a bending ridge waveguide structure and a triple-waveguide directional coupler was fabricated on the Si3N4 thin film. The TM excitation of the device based on a bending ridge waveguide structure shows a polarization extinction ratio (PER) of ≥ 20 dB with 33 nm bandwidth (624-657 nm) and insertion loss (IL) ≤ 1 dB at the through port. The TE excitation of the device, based on a triple-waveguide directional coupler with coupling efficiency distinction between the TE0 and TM0 modes, shows a PER of ≥ 18 dB with 50 nm bandwidth (580-630 nm) and insertion loss (IL) ≤ 1 dB at the cross port. The on-chip Si3N4 PBS device is found to possess the highest known PER at a visible broadband range and small (43 µm) footprint. It should be useful for novel photonic circuit designs and further exploration of Si3N4 PBSs.

High Detectivity of PbS Films Deposited on Quartz Substrates: The Role of Enhanced Photogenerated Carrier Separation.

PbS films grown on quartz substrates by the chemical bath deposition method were annealed in an O2 atmosphere to investigate the role of oxygen in the sensitization process at different annealing temperatures. The average grain size of the PbS films gradually increased as the annealing temperature increased from 400 °C to 700 °C. At an annealing temperature of 650 °C, the photoresponsivity and detectivity reached 1.67 A W-1 and 1.22 × 1010 cm Hz1/2 W-1, respectively. The role of oxides in the sensitization process was analyzed in combination with X-ray diffraction and scanning electron microscopy results, and a three-dimensional network model of the sensitization mechanism of PbS films was proposed. During the annealing process, O functioned as a p-type impurity, forming p+-type PbS layers with high hole concentrations on the surface and between the PbS grains. As annealing proceeds, the p+-type PbS layers at the grain boundaries interconnect to form a three-dimensional network structure of hole transport channels, while the unoxidized p-type PbS layers act as electron transport channels. Under bias, photogenerated electron-hole pairs were efficiently separated by the formed p+-p charge separation junction, thereby reducing electron-hole recombination and facilitating a higher infrared response.

Tailored hydrogel composite membrane for the regulated crystallization of monosodium urate monohydrate within coffee's metabolites system.

Herein, a facile bionic research platform with fabricated hydrogel composite membrane (HCM) is constructed to uncover the effects of the main components of coffee's metabolites on MSUM crystallization. Tailored and biosafety polyethylene glycol diacrylate/N-isopropyl acrylamide (PEGDA/NIPAM) HCM allows the proper mass transfer of coffee's metabolites and can well simulate the process of coffee's metabolites acting in the joint system. With the validations of this platform, it is shown that chlorogenic acid (CGA) can hinder the MSUM crystals formation from 45 h (control group) to 122 h (2 mM CGA), which is the most likely reason that reduces the risk of gout after long-term coffee consumption. Molecular dynamics simulation further indicates that the high interaction energy (Eint) between CGA and MSUM crystal surface and the high electronegativity of CGA both contribute to the restraint of MSUM crystal formation. In conclusion, the fabricated HCM, as the core functional materials of the research platform, presents the understanding of the interaction between coffee consumption and gout control.

Integrated analysis of single-cell and bulk transcriptome identifies a signature based on NK cell marker genes to predict prognosis and therapeutic response in clear cell renal cell carcinoma.

Background: Accumulating evidence has highlighted the effects of natural killer (NK) cells on shaping anti-tumor immunity. This study aimed to construct an NK cell marker gene signature (NKMS) to predict prognosis and therapeutic response of clear cell renal cell carcinoma (ccRCC) patients. Methods: Publicly available single-cell and bulk RNA profiles with matched clinical information of ccRCC patients were collected from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), ArrayExpress, and International Cancer Genome Consortium (ICGC) databases. A novel NKMS was constructed, and its prognostic value, associated immunogenomic features and predictive capability to immune checkpoint inhibitors (ICIs) and anti-angiogenic therapies were evaluated in ccRCC patients. Results: We identified 52 NK cell marker genes by single-cell RNA-sequencing (scRNA-seq) analysis in GSE152938 and GSE159115. After least absolute shrinkage and selection operator (LASSO) and Cox regression, the most prognostic 7 genes (CLEC2B, PLAC8, CD7, SH3BGRL3, CALM1, KLRF1, and JAK1) composed NKMS using bulk transcriptome from TCGA. Survival and time-dependent receiver operating characteristic (ROC) analysis exhibited exceptional predictive capability of the signature in the training set and two independent validation cohorts (E-MTAB-1980 and RECA-EU cohorts). The seven-gene signature was able to identify patients within high Fuhrman grade (G3-G4) and American Joint Committee on Cancer (AJCC) stage (III-IV). Multivariate analysis confirmed the independent prognostic value of the signature, and a nomogram was built for clinical utility. The high-risk group was characterized by a higher tumor mutation burden (TMB) and greater infiltration of immunocytes, particularly CD8+ T cells, regulatory T (Treg) cells and follicular helper T (Tfh) cells, in parallel with higher expression of genes negatively regulating anti-tumor immunity. Moreover, high-risk tumors exhibited higher richness and diversity of T-cell receptor (TCR) repertoire. In two therapy cohorts of ccRCC patients (PMID32472114 and E-MTAB-3267), we demonstrated that high-risk group showed greater sensitivity to ICIs, whereas the low-risk group was more likely to benefit from anti-angiogenic therapy. Conclusions: We identified a novel signature that can be utilized as an independent predictive biomarker and a tool for selecting the individualized treatment for ccRCC patients.

Polarization Splitting at Visible Wavelengths with the Rutile TiO2 Ridge Waveguide.

On-chip polarization control is in high demand for novel integrated photonic applications such as polarization division multiplexing and quantum communications. However, due to the sensitive scaling of the device dimension with wavelength and the visible-light absorption properties, traditional passive silicon photonic devices with asymmetric waveguide structures cannot achieve polarization control at visible wavelengths. In this paper, a new polarization-splitting mechanism based on energy distributions of the fundamental polarized modes in the r-TiO2 ridge waveguide is investigated. The bending loss for different bending radii and the optical coupling properties of the fundamental modes in different r-TiO2 ridge waveguide configurations are analyzed. In particular, a polarization splitter with a high extinction ratio operating at visible wavelengths based on directional couplers (DCs) in the r-TiO2 ridge waveguide is proposed. Polarization-selective filters based on micro-ring resonators (MRRs) with resonances of only TE or TM polarizations are designed and operated. Our results show that polarization-splitters for visible wavelengths with a high extinction ratio in DC or MRR configurations can be achieved with a simple r-TiO2 ridge waveguide structure.

Effect of intergenerational exchange patterns and intergenerational relationship quality on depressive symptoms in the elderly: An empirical study on CHARLS data.

Background: As the population ages with fewer children, depression symptoms are increasing among the elderly who lack companionship. Intergenerational support is closely related to depression in the elderly; hence how the behavioral patterns and emotional quality of intergenerational support affect depressive symptoms in the elderly should be further explored. Objective: To study the effects of intergenerational exchange patterns and intergenerational relationship quality on depressive symptoms in the elderly. Methods: A total of 8,015 people over 60 years old in CHARLS in 2018 were selected as the object of this study. First, the correlation between demographics, economic conditions, health status, intergenerational support patterns, intergenerational relationship quality, and depressive symptoms in the elderly were analyzed. Three regression analysis models were established to analyze the relationship between control variables, intergenerational support patterns, intergenerational relationship quality, and depressive symptoms in the elderly. Results: Among the intergenerational economic, care, and emotional exchange modes, the risk of depressive symptoms in the elderly in the mutual support group was 31.8, 38.4, and 25.5% lower than that in the non-communication group. Compared with the elderly with very poor intergenerational relationship quality, the elderly with good, very good, and excellent intergenerational relationship quality had 74.5, 84.0, and 85.6% lower risk of depressive symptoms. Discussion: Different cultural backgrounds also affect intergenerational exchange patterns and depression in the elderly. During the study of depressive symptoms, two aspects relating to intergenerational support should be considered behaviorally and emotionally: the intergenerational exchange model and the intergenerational relationship quality. As depression in the elderly is affected by multiple factors, the participation and joint efforts of the whole society are required to reduce depressive symptoms in the elderly and realize active aging. Conclusion: The intergenerational exchange pattern of mutual support and the higher quality of the intergenerational relationship can significantly reduce the depressive symptoms of the elderly.

Characterization of fatty acid metabolism-related lncRNAs in lung adenocarcinoma identifying potential novel prognostic targets.

Lung adenocarcinoma (LUAD), a malignant respiratory tumor with an extremely poor prognosis, has troubled the medical community all over the world. According to recent studies, fatty acid metabolism (FAM) and long non-coding RNAs (lncRNAs) regulation have shown exciting results in tumor therapy. In this study, the original LUAD patient data was obtained from the TCGA database, and 12 FAM-related lncRNAs (AL390755.1, AC105020.6, TMPO-AS1, AC016737.2, AC127070.2, LINC01281, AL589986.2, GAS6-DT, AC078993.1, LINC02198, AC007032.1, and AL021026.1) that were highly related to the progression of LUAD were finally identified through bioinformatics analysis, and a risk score model for clinical reference was constructed. The window explores the immunology and molecular mechanism of LUAD, aiming to shed the hoping light on LUAD treatment.

A novel LUAD prognosis prediction model based on immune checkpoint-related lncRNAs.

Lung adenocarcinoma (LUAD) is a malignant disease with an extremely poor prognosis, and there is currently a lack of clinical methods for early diagnosis and precise treatment and management. With the deepening of tumor research, more and more attention has been paid to the role of immune checkpoints (ICP) and long non-coding RNAs (lncRNAs) regulation in tumor development. Therefore, this study downloaded LUAD patient data from the TCGA database, and finally screened 14 key ICP-related lncRNAs based on ICP-related genes using univariate/multivariate COX regression analysis and LASSO regression analysis to construct a risk prediction model and corresponding nomogram. After multi-dimensional testing of the model, the model showed good prognostic prediction ability. In addition, to further elucidate how ICP plays a role in LUAD, we jointly analyzed the immune microenvironmental changes in LAUD patients and performed a functional enrichment analysis. Furthermore, to enhance the clinical significance of this study, we performed a sensitivity analysis of common antitumor drugs. All the above works aim to point to new directions for the treatment of LUAD.

Effect of familiarity and recollection during constrained retrieval on incidental encoding for new "foil" information.

Behavioral studies have demonstrated differences in the effect of constrained retrieval of semantic vs. non-semantic information on the encoding of foils. However, the impact of recognition on foils between semantic and non-semantic trials remains unclear. This study thus examines the roles of recognition-familiarity and recollection-in constrained retrieval for foils. We applied the event-related brain potentials (ERPs) data of new/old effects to elucidate the neural mechanisms underlying the "foil effect." Participants encoded semantic and non-semantic tasks (Phase 1), were tested in a blocked memory task with new words presented as foils (Phase 2), and performed a surprise recognition task involving foils and completely new words (Phase 3). Behavioral results showed better recognition performance regarding reaction times and accuracy by hit and correct reject for semantic vs. non-semantic trials in Phase 2. Conversely, inferior recognition performance in reaction times and accuracy by hit and correct reject was noted for semantic vs. non-semantic foils in Phase 3. ERP results showed more positive Frontal N400 (FN400) for hit in non-semantic trials, more positive late positive component (LPC) for correct rejects in semantic trials in Phase 2, and more positive LPC for hits in both semantic and non-semantic trials only in Phase 3. Through dual-processing theory, we prove that different task types in constrained retrieval depend on different retrieval processes. Particularly, familiarity may be applied more often in non-semantic trials, and recollection in semantic trials. The difference in processes between semantic and non-semantic trials during constrained retrieval affects incidental encoding of foils.

Euonymine inhibits in-stent restenosis through enhancing contractile phenotype of vascular smooth muscle cells via modulating the PTEN/AKT/mTOR signaling pathway.

BACKGROUND: Percutaneous coronary intervention (PCI) is an effective treatment for acute myocardial infarction, but the postoperative in-stent re-stenosis (ISR) remains a major risk factor that affects the prognosis of PCI. Clinically, drug-eluting stents (DES) are widely applied to prevent and treat ISR. However, only a few stent coating drugs are currently available for clinical use, including paclitaxel and rapamycin (sirolimus) and their derivatives. These stent-coated drugs have led to a decrease in restenosis rates, but the major adverse outcomes, such as delayed endothelial healing and increased in-stent thrombosis, seriously reduce their therapeutic effects. PURPOSE: Herein, we explored the potential efficacy of Euonymine (Euo), an alkaloid extracted from Tripterygium Hypoglaucum (Levl) Hutch (THH, Lei gong Teng), for the prevention against ISR after PCI. STUDY DESIGN: Our study depicts the potential efficacy of Euo in treating ISR and explores its mechanism with in vitro and in vivo models. METHODS: Primary vascular smooth muscle cells (VSMCs) from the rabbit thoracic aorta were cultured, and the proliferation and migration of VSMCs were monitored. Apoptosis was measured by Transmission Electron Microscopy and TUNEL staining assay. Protein and gene levels were measured to explore the underlying molecular mechanisms. In vivo models of porcine coronary implantation and rabbit carotid balloon injury are used to validate the efficacy of Euo in inhibiting ISR after PCI. RESULTS: With an ox-LDL-injured cell model, we showed that Euo suppressed the proliferation and migration of the rabbit thoracic aorta primary VSMCs, while inducing their apoptosis. We next established a rabbit carotid balloon injury model in which the phosphorylation levels of PI3K and AKT1 (Ser473) as well as mTOR activity were significantly elevated compared to the sham-operated control. These activities were significantly attenuated by the Euo intervention. Additionally, the balloon angioplasty significantly increased the expression of Bcl-2, while decreased the expression of Bax and caspase-3. Euo intervention significantly increased the ratio of Bax/Bcl-2 and the level of caspase-3. Taken together, Euo may enhance the VSMCs contractile phenotype by modulating the PTEN/AKT/mTOR signaling pathway. Furthermore, with two in vivo models, the porcine coronary artery implantation model, and the rabbit carotid balloon injury model, we demonstrated that Euo-eluting stents indeed inhibited ISR after PCI. CONCLUSION: For the first time, this study delineates the potential efficacy of Euo, derived from Tripterygium Hypoglaucum (Levl) Hutch, in ameliorating ISR after PCI with two in vivo models. The phytochemical targets PTEN/AKT/mTOR signaling pathway to increase the contractile phenotype of VSMCs and exerts anti-proliferative, anti-migratory as well as pro-apoptotic effects, thereby inhibiting the ISR.

Multiple Mechanistic Models Reveal the Neuroprotective Effects of Diterpene Ginkgolides against Astrocyte-Mediated Demyelination via the PAF-PAFR Pathway.

Currently, therapies for ischemic stroke are limited. Ginkgolides, unique Folium Ginkgo components, have potential benefits for ischemic stroke patients, but there is little evidence that ginkgolides improve neurological function in these patients. Clinical studies have confirmed the neurological improvement efficacy of diterpene ginkgolides meglumine injection (DGMI), an extract of Ginkgo biloba containing ginkgolides A (GA), B (GB), and K (GK), in ischemic stroke patients. In the present study, we performed transcriptome analyses using RNA-seq and explored the potential mechanism of ginkgolides in seven in vitro cell models that mimic pathological stroke processes. Transcriptome analyses revealed that the ginkgolides had potential antiplatelet properties and neuroprotective activities in the nervous system. Specifically, human umbilical vein endothelial cells (HUVEC-T1 cells) showed the strongest response to DGMI and U251 human glioma cells ranked next. The results of pathway enrichment analysis via gene set enrichment analysis (GSEA) showed that the neuroprotective activities of DGMI and its monomers in the U251 cell model were related to their regulation of the sphingolipid and neurotrophin signaling pathways. We next verified these in vitro findings in an in vivo cuprizone (CPZ, bis(cyclohexanone)oxaldihydrazone)-induced model. GB and GK protected against demyelination in the corpus callosum (CC) and promoted oligodendrocyte regeneration in CPZ-fed mice. Moreover, GB and GK antagonized platelet-activating factor (PAF) receptor (PAFR) expression in astrocytes, inhibited PAF-induced inflammatory responses, and promoted brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) secretion, supporting remyelination. These findings are critical for developing therapies that promote remyelination and prevent stroke progression.

AGs-Unet: Building Extraction Model for High Resolution Remote Sensing Images Based on Attention Gates U Network.

Building contour extraction from high-resolution remote sensing images is a basic task for the reasonable planning of regional construction. Recently, building segmentation methods based on the U-Net network have become popular as they largely improve the segmentation accuracy by applying 'skip connection' to combine high-level and low-level feature information more effectively. Meanwhile, researchers have demonstrated that introducing an attention mechanism into U-Net can enhance local feature expression and improve the performance of building extraction in remote sensing images. In this paper, we intend to explore the effectiveness of the primeval attention gate module and propose the novel Attention Gate Module (AG) based on adjusting the position of 'Resampler' in an attention gate to Sigmoid function for a building extraction task, and a novel Attention Gates U network (AGs-Unet) is further proposed based on AG, which can automatically learn different forms of building structures in high-resolution remote sensing images and realize efficient extraction of building contour. AGs-Unet integrates attention gates with a single U-Net network, in which a series of attention gate modules are added into the 'skip connection' for suppressing the irrelevant and noisy feature responses in the input image to highlight the dominant features of the buildings in the image. AGs-Unet improves the feature selection of the attention map to enhance the ability of feature learning, as well as paying attention to the feature information of small-scale buildings. We conducted the experiments on the WHU building dataset and the INRIA Aerial Image Labeling dataset, in which the proposed AGs-Unet model is compared with several classic models (such as FCN8s, SegNet, U-Net, and DANet) and two state-of-the-art models (such as PISANet, and ARC-Net). The extraction accuracy of each model is evaluated by using three evaluation indexes, namely, overall accuracy, precision, and intersection over union. Experimental results show that the proposed AGs-Unet model can improve the quality of building extraction from high-resolution remote sensing images effectively in terms of prediction performance and result accuracy.

Branched-chain amino acid supplementation impairs insulin sensitivity and promotes lipogenesis during exercise in diet-induced obese mice.

OBJECTIVE: Branched-chain amino acids (BCAAs) are popular dietary supplements for exercise. However, increased BCAA levels positively correlate with obesity and diabetes. The metabolic impact of BCAA supplementation on insulin sensitivity during exercise is less understood. METHODS: Male C57BL/6 mice were fed for 12 weeks with a high-fat diet, normal chow diet, or BCAA-restricted high-fat diet. They were subjected to running exercise with or without BCAA treatment for another 12 weeks. RESULTS: Exercise reduced body weight, improved insulin sensitivity, lowered BCAAs in plasma, and inhibited the upregulation of BCAAs and metabolites caused by BCAA supplementation in the subcutaneous white adipose tissue (sWAT) of obese mice. BCAA supplementation reversed insulin sensitivity ameliorated by exercise. The phosphorylation of protein kinase B (Ser473 and Ser474) was decreased by BCAAs in the sWAT of obese mice. However, BCAA supplementation had no such effects in lean mice. BCAAs also increased the expression of fatty acid synthase and other lipogenesis genes in the sWAT of exercised obese mice. BCAA restriction had no effect on body weight and insulin sensitivity in obese mice. CONCLUSIONS: BCAA supplementation impaired the beneficial effect of exercise on glycolipid metabolism in obese but not lean mice. Caution should be taken regarding the use of BCAAs for individuals with obesity who exercise.

Individualized 3D printing-assisted repair and reconstruction of neoplastic bone defects at irregular bone sites: exploration and practice in the treatment of scapular aneurysmal bone cysts.

BACKGROUND: The irregular anatomical shape and complex structures of irregular bones make it more difficult to repair and reconstruct bone defects in irregular bones than in the long bones of the extremities. Three-dimensional (3D) printing technology can help to overcome the technical limitations of irregular bone repair by generating simulations that enable structural integration of the lesion area and bone structure of the donor site in all directions and at multiple angles. Thus, personalized and accurate treatment plans for restoring anatomical structure, muscle attachment points, and maximal function can be made. The present study aimed to investigate the ability of 3D printing technology to assist in the repair and reconstruction of scapular aneurysmal ABC defects. METHODS: The study included seven patients with ABCs of the scapula. Based on computed tomography (CT) data for the patient, the scapula (including the defect) and pelvis were reconstructed using Mimics Medical software. The reconstructed scapula model was printed using a 3D printer. Before the operation, the model was used to design the surgical approach and simulate the operation process, to determine the length and radius of the plate and the number and direction of screws, and to determine the bone mass of the ilium and develop reasonable strategies for segmentation and distribution. The operation time, amount of bleeding, length and radius of the plate, and direction and number of screws were recorded. RESULTS: The average duration of follow-up was 25.6 months, and none of the seven patients experienced recurrence during the follow-up period. The surgical approach, the length and radius of internal fixation, and the number and direction of screws were consistent with the designed operation plan. Patients gradually recovered the anatomical structure of the scapula and function of the shoulder joint. CONCLUSIONS: In the treatment of bone defects caused by irregular bone tumors, 3D printing technology combined with surgery has the advantages of less trauma, short operation time, less bleeding and reducing the difficulty of operation, which can reduce the waste of bone graft, and more complete reconstruction of the anatomical structure of the defective bone.