Glutathione-Activated Emission of Ultrasmall Gold Nanoparticles in the Second Near-Infrared Window for Imaging of Early Kidney Injury.

Biomarker-activatable luminescent probes with high sensitivity and specificity show great promise in advanced bioimaging applications. However, the lack of stable biomarkers at an early stage is currently a major obstacle for sensitive early disease imaging. Herein, we develop a facile in vivo ligand exchange strategy to achieve renal-clearable activatable luminescent gold nanoparticles (AuNPs), which are independent of biomarkers for sensitive and long-time imaging of early kidney injury. Significantly activated emission in the second near-infrared region (∼1026 nm) is realized from the ligand exchange of triphenylphosphine-3,3',3″-trisulfonic acid (TPPTS)-coated AuNPs (∼1.4 nm, TPPTS-AuNPs) with quantitative amounts of glutathione (GSH). The abundant GSH in cells, particularly in liver sinusoids, is then demonstrated successfully to activate the emission of TPPTS-AuNPs with an extremely low background for both cell imaging and in vivo visualization of visceral organs (e.g., liver and kidneys). In addition, the in vivo GSH-exchanged TPPTS-AuNPs show enhanced interactions with acidic renal tubular epithelial cells, resulting in sensitive (contrast index, ∼3.9) and long-time (>6.5 h) noninvasive monitoring of acidosis-induced early kidney injury. This facile ligand exchange strategy opens new possibilities for designing activatable luminescent probes independent of biomarkers for earlier disease diagnosis and treatment.

The association between bilirubin and hypertension among a Chinese ageing cohort: a prospective follow-up study.

BACKGROUND: Hypertension is highly prevalent and associated with the elevated risks of cardiovascular diseases, dementia, and physical disabilities among adults. Although the correlation between bilirubin and hypertension has been reported, the observation in quinquagenarian population is scarce. We aimed to examine bilirubin-hypertension association in Guankou Ageing Cohort Study. METHODS: Participants ≥ 55 years were recruited and their questionnaires and physical examination data were collected. Kaplan-Meier survival analysis and Cox proportional hazards regression were implemented to assess the hypertension risk. The non-liner dose-response relationships of bilirubin-hypertension were determined by restricted cubic spline (RCS) models. Receiver operating characteristic (ROC) curves and multiple factors analysis (MFA) were performed to evaluate the predictive abilities. RESULTS: 1881 eligible participants (male 43.75%, female 56.25%) with the median age of 61.00 (59.00-66.00) were included. The hazard ratio (HR, 95% CI) of serum total bilirubin (STB) and unconjugated bilirubin (UCB) were 1.03 (1.01-1.05) and 1.05 (1.03-1.07), while conjugated bilirubin (CB) showed a weak protective effect with the HR of 0.96 (0.92-0.99), and the associations remained significant in all models. RCS analyses further indicated the similar bidirectional effects of STB and UCB with the cut-off of 12.17 µmol/L and 8.59 µmol/L, while CB exhibited inverse bidirectional dose-response relationship with a cut-off of 3.47 µmol/L. ROC curves and MFA showed baseline STB combined with age, BMI, and waist circumference could well discriminate the low and high of hypertension risk. CONCLUSIONS: Our findings suggested the higher levels of total and unconjugated bilirubin were hazardous factors of hypertension, while an inverse effect presented when more bilirubin was conjugated.

Inflammatory markers in postoperative cognitive dysfunction for patients undergoing total hip arthroplasty: a meta-analysis.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a poorly understood disorder, very common even after total hip arthroplasty (THA). It is widely considered that inflammation response play a role in the pathogenesis of POCD. AIMS: The aim of the present study was to investigate whether inflammation cytokine concentrations could serve as biomarkers for POCD in patients undergoing THA. METHODS: A systematic search of databases was conducted to retrieve publications measuring circulating inflammatory markers of patients with and without POCD after THA. Inflammatory markers identified in more than two studies were pooled. The standardized mean difference (SMD) and the 95% confidence interval (95% CI) were calculated for each outcome. Fail-safe N statistics was calculated to estimate possible publication bias. RESULTS: The pooled incidence rate of POCD after THA by combining 11 cohort studies was 31%. A total of five inflammatory markers, CRP, S-100B, IL-1ß, IL-6 and TNF-α, were assessed. Significantly higher pre-operative CRP (P = 0.012) and S-100B (P < 0.0001) as well as post-operative CPR (P = 0.005) and IL-6 (P < 0.0001) at 6 h were found in POCD compared with non-POCD patients undergoing THA. Fail-safe N statistics revealed that these results are robust. DISCUSSION: The current evidence suggests that some of the inflammatory markers, including CRP, S-100B, and IL-6, were correlated with the occurrence of POCD after THA. CONCLUSION: Monitor of inflammatory markers might help early diagnosis of POCD after THA and development of preventive strategies.

Single-cell and spatial sequencing identifies senescent and germinal tumor cells in adamantinomatous craniopharyngiomas.

Adamantinomatous craniopharyngioma (ACP) is a clinically aggressive tumor without effective treatment method. Previous studies proposed a paracrine tumorigenesis model, in which oncogenic ß-catenin induces senescence in pituitary stem cells and the senescent cells lead the formation of paracrine tumors through secretion of pro-tumorigenic factors. However, there lacks characterization on senescent cells in ACPs. Here, we profiled 12 ACPs with single-cell RNA and TCR-sequencing to elucidate the cellular atlas in ACPs and 3 of them were also subject to spatial sequencing to localize different subpopulations of the tumor cells. In total, we obtained the transcriptome profiles of 70,682 cells. Tumor cells, which were unambiguously identified through the cellular mutation status of the driver CTNNB1 mutations, were clustered into 6 subsets. The whorl-like cluster (WC) cells show distinct molecular features from the other tumor cells and the palisading epithelium (PE) cells consists of a proliferating subset. Other than typical PE and WC, we identified two novel subpopulations of the tumor cells. In one subpopulation, the cells express a high level of cytokines, e.g., FDCSP and S100A8/A9, and are enriched with the senescence-associated secretory phenotype (SASP) factors. Hematoxylin and eosin staining reveals that these SASP cells lack an ordered structures and their nuclei are elongated. In the other subpopulation, the cell sizes are small and they are tightly packed together with an unusual high density expressing a high level of mitochondrial genes (median 10.9%). These cells are the origin of the tumor developmental trajectories revealed by RNA velocity and pseudo-time analysis. Single-cell RNA and TCR analysis reveals that some ACPs are infiltrated with clonally expanded cytotoxic T cells. We propose a hypothesis that WC and PE are formed via different negative regulation mechanisms of the overactivated WNT/ß-catenin signaling which provides a new understanding on the tumorigenesis of ACPs. The study lays a foundation for future studies on targeting senescent cells in ACPs with senolytic compounds or other therapeutic agents.

Multi-omics analysis of adamantinomatous craniopharyngiomas reveals distinct molecular subgroups with prognostic and treatment response significance.

BACKGROUND: Adamantinomatous craniopharyngioma (ACP) is the commonest pediatric sellar tumor. No effective drug is available and interpatient heterogeneity is prominent. This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles, imaging findings, and histological features, in order to predict the response to anti-inflammatory treatment and immunotherapies. METHODS: Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled, including 119 ACPs and 23 papillary craniopharyngiomas. Whole-exome sequencing (151 tumors, including recurrent ones), RNA sequencing (84 tumors), and DNA methylome profiling (95 tumors) were performed. Consensus clustering and non-negative matrix factorization were used for subgrouping, and Cox regression were utilized for prognostic evaluation, respectively. RESULTS: Three distinct molecular subgroups were identified: WNT, ImA, and ImB. The WNT subgroup showed higher Wnt/ß-catenin pathway activity, with a greater number of epithelial cells and more predominantly solid tumors. The ImA and ImB subgroups had activated inflammatory and interferon response pathways, with enhanced immune cell infiltration and more predominantly cystic tumors. Mitogen-activated protein kinases (MEK/MAPK) signaling was activated only in ImA samples, while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group, mostly consisting of children. The degree of astrogliosis was significantly elevated in the ImA group, with severe finger-like protrusions at the invasive front of the tumor. The molecular subgrouping was an independent prognostic factor, with the WNT group having longer event-free survival than ImB (Cox, P = 0.04). ImA/ImB cases were more likely to respond to immune checkpoint blockade (ICB) therapy than the WNT group ( P <0.01). In the preliminary screening of subtyping markers, CD38 was significantly downregulated in WNT compared with ImA and ImB ( P = 0.01). CONCLUSIONS: ACP comprises three molecular subtypes with distinct imaging and histological features. The prognosis of the WNT type is better than that of the ImB group, which is more likely to benefit from the ICB treatment.

3-D Deconvolutional Networks for the Unsupervised Representation Learning of Human Motions.

Data representation learning is one of the most important problems in machine learning. Unsupervised representation learning becomes meritorious as it has no necessity of label information with observed data. Due to the highly time-consuming learning of deep-learning models, there are many machine-learning models directly adapting well-trained deep models that are obtained in a supervised and end-to-end manner as feature abstractors to distinct problems. However, it is obvious that different machine-learning tasks require disparate representation of original input data. Taking human action recognition as an example, it is well known that human actions in a video sequence are 3-D signals containing both visual appearance and motion dynamics of humans and objects. Therefore, the data representation approaches with the capabilities to capture both spatial and temporal correlations in videos are meaningful. Most of the existing human motion recognition models build classifiers based on deep-learning structures such as deep convolutional networks. These models require a large quantity of training videos with annotations. Meanwhile, these supervised models cannot recognize samples from the distinct dataset without retraining. In this article, we propose a new 3-D deconvolutional network (3DDN) for representation learning of high-dimensional video data, in which the high-level features are obtained through the optimization approach. The proposed 3DDN decomposes the video frames into spatiotemporal features under a sparse constraint in an unsupervised way. In addition, it also can be regarded as a building block to develop deep architectures by stacking. The high-level representation of input sequential data can be used in multiple downstream machine-learning tasks, we evaluate the proposed 3DDN and its deep models in human action recognition. The experimental results from three datasets: 1) KTH data; 2) HMDB-51; and 3) UCF-101, demonstrate that the proposed 3DDN is an alternative approach to feedforward convolutional neural networks (CNNs), that attains comparable results.

Tunable Grain Orientation of Chalcogenide Film and Its Application for Second Harmonic Generation.

To date, the second harmonic generation (SHG) has a great effect on photonic devices. However, it is a formidable challenge to achieve reconfigurable SHG. Hereby, we experimentally demonstrate the SHG response from the oriented Ge2Sb2Te5 (GST) grains induced by polarized laser pulses for the first time. The orientation of GST grains is found to be perpendicular to the polarization direction of the pump laser. Such unique ordered structures result in a periodic change of SHG intensity with the input polarization angle of the pump laser rotating every 180°. These findings may pave avenues for generating nonlinear optical sources with a simple process, scalability, and switchable functionality.

Serum Irisin Levels and Clinical Implication in Elderly Patients With Type 2 Diabetes Mellitus.

BACKGROUND: The aim of this study is to evaluate the level and role of serum irisin in elderly patients with type 2 diabetes mellitus (T2DM) using case-control study. METHODS: A total of 71 patients with T2DM were selected as the case group according to the inclusion criteria and exclusion criteria; and the ratio of 1:1 was calculated according to the inclusion rate of the residents. The cohort established in Guankou Town, Jimei District, Xiamen City, Fujian Province, China and the residents of this cohort were selected at the age of 60 and above. A total of 71 healthy subjects were included as the control group with the same gender and the age with a difference of ± 5 years old. The clinical data of the subjects were collected to determine their previous history, blood pressure, body mass index (BMI), hemoglobin (HB), liver function test, renal function test, fasting blood glucose and serum lipid. The irisin level in serum was measured by enzyme-linked immunosorbent assay (ELISA). The data were analyzed by using SPSS17.0 software. Single factor analysis using Chi-square test or t-test was performed to compare the differences between T2DM patients with the control group of the general data, clinical indicators and irisin level in serum. Logistic regression was used to analyze the protective factors and risk factors of diabetes mellitus. RESULTS: The results of single factor analysis showed that the level of irisin in T2DM group was significantly lower than that in the control group (703.37 ± 241.51 ng/mL and 800.22 ± 275.59 ng/mL, respectively). The levels of BMI, systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG) and fasting plasma glucose (FPG) in T2DM group were higher than those in control group, and differences were statistically significant. Logistic regression analysis indicated that irisin may be a protective factor for type 2 diabetes (odds ratio (OR) = 0.997, 95% confidence interval (CI): 0.994 - 0.999). CONCLUSIONS: The serum irisin level in T2DM group was significantly lower than that in control group, suggesting that irisin may be a protective factor for type 2 diabetes.

Degradation kinetics of Ti-Cu compound layer in transient liquid phase bonded graphite/copper joints.

The continuous Ti-Cu compound layer produced in brazing of graphite to copper with Ti foil is found to be seriously detrimental to joint properties due to its brittleness. In this work, a transient liquid phase (TLP) bonding method with a diffusion process below melting point is developed to realize a Ti-Cu compound layer free joint. The degradation of Ti-Cu compound layer depends on two simultaneously occurring processes, namely flow of titanium atoms to copper substrate and that to TiC layer on graphite. The latter is determined by growth kinetics of TiC layer based on carbon diffusion process. A degradation model is proposed and applied to optimize the TLP bonding. The improved graphite/copper joints without Ti-Cu compound layer show 20.8% higher in shear strength compared with that of brazing joints.

Enhanced and Stable Upconverted White-light Emission in Ho3+/Yb3+/Tm3+-doped LiNbO3 Single Crystal via Mg2+ Ion Doping.

A strategy to enhance the upconversion white-light intensity via Mg2+ ion doping was demonstrated in Ho3+/Yb3+/Tm3+/LiNbO3 single crystal. It is found Mg2+ ion doping affects the crystal field symmetry around RE3+ ions and enhance the upconversion emission intensity. Bright white-light is obtained when the Mg2+ ion concentration is 0.5 mol% in the melt. And the CIE coordinates are hardly changed with Mg2+ ion doping. In addition, the upconversion mechanism is discussed in detail. It is observed the longer lifetimes of intermediate levels result in the lower upconversion photon numbers, which are beneficial to the upconversion process. Therefore, Mg2+ ion doped Ho3+/Yb3+/Tm3+/LiNbO3 single crystals would have potential applications in stable white-light devices and photoelectric instruments.