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Background Recombinant human growth hormone (rhGH) therapy has shown to improve height and body composition in children with Prader–Willi syndrome (PWS), the evidence of early rhGH treatment on motor and mental development is still accumulating. This study explored the time effect on psychomotor development, anthropometric indexes, and safety for infants and young children with PWS. Methods A phase 3, single-arm, multicenter, self-controlled study was conducted in six sites. Patients received rhGH at 0.5 mg/m2/day for first four weeks, and 1 mg/m2/day thereafter for up to 52 weeks. Motor development was measured using Peabody Developmental Motor Scales-second edition, mental development using Griffiths Development Scales-Chinese (GDS-C). Height standard deviation score (SDS), body weight SDS, and body mass index (BMI) SDS were also assessed. Results Thirty-five patients were enrolled totally. Significant improvements were observed in height, body weight, and BMI SDS at week 52; GDS-C score showed significant improvement in general quotient (GQ) and sub-quotients. In a linear regression analysis, total motor quotient (TMQ), gross motor quotient (GMQ), and fine motor quotient were negatively correlated with age; however, treatment may attenuate deterioration of TMQ and GMQ. Changes in GQ and locomotor sub-quotient in Conclusion Fifty-two-week treatment with rhGH improved growth, BMI, mental development, and lessened the deterioration of motor function in infants and young children with PWS. Improved mental development was more pronounced when instituted in patients

Most information used to evaluate diabetic statuses is collected at a special time-point, such as taking fasting plasma glucose test and providing a limited view of individual's health and disease risk. As a new parameter for continuously evaluating personal clinical statuses, the newly developed technique "continuous glucose monitoring" (CGM) can characterize glucose dynamics. By calculating the complexity of glucose time series index (CGI) with refined composite multi-scale entropy analysis of the CGM data, the study showed for the first time that the complexity of glucose time series in subjects decreased gradually from normal glucose tolerance to impaired glucose regulation and then to type 2 diabetes (P for trend0.01). Furthermore, CGI was significantly associated with various parameters such as insulin sensitivity/secretion (all P0.01), and multiple linear stepwise regression showed that the disposition index, which reflects β-cell function after adjusting for insulin sensitivity, was the only independent factor correlated with CGI (P0.01). Our findings indicate that the CGI derived from the CGM data may serve as a novel marker to evaluate glucose homeostasis.

With the diverse applications to industry and domain-specific context, multi-source information extraction on semi-structured and unstructured data, as well as across data models, is becoming more common. However, multi-model information extraction often requires the deployment of multiple data model management, storage, and analysis subsystems on the cloud, many subsystems are not high-resource utilization at the same time, and the resource waste phenomenon is often serious. Therefore, an adaptive scalable multi-model big data analysis and information extraction system is designed and implemented in this paper, which can support data maintenance and cross-model query of relational, graph, document, key and other data models, and can provide efficient cross-model information extraction. On this basis, we can achieve the system resource allocation on demand and fast scaling mechanism, according to the real-time requirements of multi-model big data analysis, and dynamic adjustment of each subsystem resource allocation. Therefore, our solution not only guarantees multi-model query and information extraction performance and quality of service, but also significantly reduces the total consumption of system resources and cost.

Objectives To evaluate robustness of dual-energy CT (DECT) radiomics features of virtual unenhanced (VUE) image and virtual monoenergetic image (VMI) among different imaging platforms. Methods A phantom with sixteen clinical-relevant densities was scanned on ten DECT platforms with comparable scan parameters. Ninety-four radiomic features were extracted via Pyradiomics from VUE images and VMIs at energy level of 70 keV (VMI70keV). Test–retest repeatability was assessed by Bland–Altman analysis. Inter-platform reproducibility of VUE images and VMI70keV was evaluated by coefficient of variation (CV) and quartile coefficient of dispersion (QCD) among platforms, and by intraclass correlation coefficient (ICC) and concordance correlation coefficient (CCC) between platform pairs. The correlation between variability of CT number radiomics reproducibility was estimated. Results 92.02% and 92.87% of features were repeatable between scan–rescans for VUE images and VMI70keV, respectively. Among platforms, 11.30% and 28.39% features of VUE images, and 15.16% and 28.99% features of VMI70keV were with CV 0.90 and CCC > 0.90 between platform pairs were 10.00% and 9.86% in VUE images and 11.23% and 11.23% in VMI70keV. The CT number inter-platform reproducibility using CV and QCD showed negative correlations with percentage of the first-order radiomics features with CV 70keV (r2 0.3870–0.6178, all p Conclusions The majority of DECT radiomics features were non-reproducible. The differences in CT number were considered as an indicator of inter-platform DECT radiomics variation. Critical relevance statement: The majority of radiomics features extracted from the VUE images and the VMI70keV were non-reproducible among platforms, while synchronizing energy levels of VMI to reduce the CT number value variability may be a potential way to mitigate radiomics instability. Graphical Abstract

Objects with different shapes, materials and temperatures can emit distinct polarizations and spectral information in mid-infrared band, which provides a unique signature in the transparent window for object identification. However, the crosstalk among various polarization and wavelength channels prevents from accurate mid-infrared detections at high signal-to-noise ratio. Here, we report full-polarization metasurfaces to break the inherent eigen-polarization constraint over the wavelengths in mid-infrared. This recipe enables to select arbitrary orthogonal polarization basis at individual wavelength independently, therefore alleviating the crosstalk and efficiency degradation. A six-channel all-silicon metasurface is specifically presented to project focused mid-infrared light to distinct positions at three wavelengths, each with a pair of arbitrarily chosen orthogonal polarizations. An isolation ratio of 117 between neighboring polarization channels is experimentally recorded, exhibiting detection sensitivity one order of magnitude higher than existing infrared detectors. Remarkably, the high aspect ratio ~30 of our meta-structures manufactured by deep silicon etching technology at temperature −150 °C guarantees the large and precise phase dispersion control over a broadband from 3 to 4.5 μm. We believe our results would benefit the noise-immune mid-infrared detections in remote sensing and space-to-ground communications.

An important role for liver in the regulation of adipose tissue thermogenesis upon cold exposure has been suggested; however, the underlying mechanisms remain incompletely defined. Here, we identify elevated serum bradykinin levels in response to acute cold exposure in male mice. A bolus of anti-bradykinin antibodies reduces body temperature during acute cold exposure, whereas bradykinin has the opposite effect. We demonstrate that bradykinin induces brown adipose tissue thermogenesis and white adipose tissue browning, and bradykinin increases uncoupling protein 1 (UCP1) expression in adipose tissue. The bradykinin B2 receptor (B2R), adrenergic signaling and nitric oxide signaling are involved in regulating bradykinin-increased UCP1 expression. Moreover, acute cold exposure inhibits hepatic prolyl endopeptidase (PREP) activity, causing reduced liver bradykinin degradation and increased serum bradykinin levels. Finally, by blocking the breakdown of bradykinin, angiotensin-converting enzyme inhibitors (ACEIs) increase serum bradykinin levels and induce brown adipose tissue thermogenesis and white adipose tissue browning via B2R. Collectively, our data provide new insights into the mechanisms underlying organ crosstalk in whole-body physiology control during cold exposure and also suggest bradykinin as a possible anti-obesity target.

Plasma membrane Na+/Ca2+ exchanger 1 (NCX1) is a bidirectional ion transporter to operate in Ca2+ entry and exit modes, and TRPC1 is Ca2+-permeable membrane channels. Both play critical roles in maintaining cytosolic free Ca2+ ([Ca2+]cyt) homeostasis in mammalian cells. Although either TRPC1 channels or Ca2+ entry mode of NCX1 is implicated in several human tumorigenesis, it has not been explored for a coordination of NCX1 and TRPC1 to involve in the pathogenesis of H. pylori-associated gastric cancer (GC). The protein expression of NCX1 was significantly enhanced in human GC specimens, which correlated with tumor progression and poor survival in GC patients. TRPC1 and NCX1 proteins were parallelly enhanced，co-localized and bound in human GC cells. By a functional coupling, TRPC1 drives NCX1 to its Ca2+ entry mode to raise [Ca2+]cyt in GC cells. Moreover, CaCl2, H. pylori and their virulence factors all enhanced expressions and activities of NCX1 and TRPC1, and evoked aberrant Ca2+ entry to promote proliferation, migration, and invasion of GC cells through AKT/b-catenin pathway. Tumor growth and metastasis also depended on the enhanced expression of NCX1 in subcutaneously xenografted GC model of nude mice. Overall, our findings indicate that TRPC1/NCX1 coupling may promote H. pylori-associated GC through the Ca2+/AKT/b-catenin pathway. Since Ca2+ exit mode and Ca2+ entry mode of NCX1 play different roles under mostly physiological and pathological conditions respectively, we propose that targeting TRPC1/NCX1 coupling could be a novel strategy for selectively blocking Ca2+ entry mode to potentially treat digestive cancer.

The combination of gemcitabine-based chemotherapy and immune checkpoint inhibitors has a good efficacy in advanced biliary tract cancer (BTC). The multi-target TKI lenvatinib and NGS-guided targeted therapy are also promising in BTC treatment. This study aimed to explore the performance of GemOX plus sintilimab and TKI (either lenvatinib or by NGS-guided targeted therapy) for local advanced or metastatic BTCs.This prospective single-arm study included patients with local advanced or metastatic BTCs and applied intravenous infusion of standard GemOX plus sintilimab and lenvatinib (no targetable gene alterations) or targeted therapy based on NGS (olaparib for BRCA1/2 mutation, dasatinib for IDH1/2 mutation, afatinib for EGFR amplification, lenvatinib for PDGFR and KIT mutation, and lenvatinib for FGFR/KIT mutation).From November 2020 to December 2021, 22 patients BTCs (6 GBC, 14 iCCA, 1 pCCA and 1 dCCA cases) were enrolled, with an average age of 58.4 years. Partial response (PR) was achieved in 10 cases, stable disease (SD) in 9 cases and progression disease (PD) in 3 cases (13.6%). The objective response rate (ORR) was 45.5%, and the disease control rate (DCR) was 86.4%. During the treatment, the incidence of adverse reactions was 81.8%, and the incidence of grade 3/4 adverse events was 9.09%. For 14 patients with NGS, 5 patients were treated by targeted therapy and there were 1 SD and 4 PR cases. For four patients with positive PD-L1 expression, the ORR was 100%. While among the three patients with super-progression markers such as RET, MDM2 and FGF14/STK24, there were two SD and one PD cases.In patients with advanced BTCs, the combination of GemOX plus sintilimab and lenvatinib or NGS-guided targeted therapy showed promising ORR and DCR, especially for the patients with positive PD-L1 expression and targetable gene alterations.

Generation of construction and demolition waste (CDW) is a challenge for sustainable development. Recycling is required in response to energy consumption and natural resource depletion caused by CDW. Public-private partnership (PPP) mode provides a strategy for CDW recycling. This study aims to investigate the decision-making behaviours of the government and recyclers and propose management mechanisms to improve CDW recycling. Based on evolutionary game model, the influencing factors of stakeholders' behavioural strategies were identified, including the government supervision costs, penalty, subsidy, the benefits and costs of recyclers' cooperation and opportunism and consumers' purchase intention. The results revealed how the initial strategy proportions, penalties, subsidies and consumers' purchase intentions affect the evolutionary paths of stakeholders' decision-making behaviours in CDW recycling PPP projects. The larger the initial strategy value, the faster the evolutionary trajectory reaches ESS (0, 1). The penalty can restrain speculative behaviours of recyclers, whilst the subsidy has no significant effect. Consumer purchase intention can reduce the cost of government supervision and improve the cooperation efficiency of recyclers. These findings may contribute to enriching the body of knowledge in CDW and providing management mechanisms for CDW recycling practice. Appropriate penalty, subsidy and financial support policies should be formulated to promote the development of CDW recycling PPP projects.

CD2 is a costimulatory protein expressed in all mature T/NK-cells, in particular memory T-cells. CD58 (or LFA-3) is the receptor for CD2 and is ubiquitously expressed. CD2-CD58 interaction has key functions in T-cell activation and organization of the immunological synapse between T- and antigen-presenting cells. Cancer cells have developed multiple mechanisms to evade immune surveillance. Loss of CD58 expression is one frequently reported in diffuse large B-cell lymphomas (DLBCL). On the other hand, in non-hematological neoplasms, tumor infiltrating lymphocytes (TILs) with reduced expression of CD2 have been associated with defective cytotoxicity and T-cell exhaustion. Here, we reported a case of DLBCL involving the jejunal mucosa associated with a rim of cytotoxic reactive T-cells with features of immune evasion (CD2- and TCR-) and T-cell exhaustion (PD1 + high). This case likely exemplifies a previously unrecognized immune evasion mechanism in lymphoma involving a decreased CD2 expression in the lymphoma-associated T-cells.

The aim of this study was to evaluate the correlation between tibial tuberosity-trochlear groove distance (TT-TG) and body height or knee size, and to find height-related pathologic thresholds of increased TT-TG.One-hundred and fifty-three patients with recurrent patellar instability and 151 controls were included. The TT-TG was measured on axial computed tomography (CT) images. Femora width and tibial width were selected to represent knee size. The correlation of TT-TG and gender, body height, femora width, and tibial width was evaluated. The height-related pathologic threshold of increased TT-TG was produced according to Dejour's method. To combine TT-TG with body height and knee size, three new indexes were introduced, ratio of TT-TG to body height (RTH), ratio of TT-TG to femoral width (RTF), and ratio of TT-TG to tibial width (RTT). The ability to predict patellar instability was assessed by the receiver-operating characteristic (ROC) curve, odds ratios (ORs), sensitivity, and specificity.In patients with patellar instability, TT-TG showed significantly correlation with patient height, femoral width, and tibial width respectively (range r = 0.266-0.283). This correlation was not found in the control group. The pathologic threshold of TT-TG was 18 mm in patients 169 cm (53%), and the mean TT-TG was 21 mm in patients ≥ 169 cm (54%). There was significant difference in RTH, RTF, and RTT between the two groups. RTH, RTF and RTT have similar large area under the curve (AUC) with TT-TG.TT-TG showed significant correlation with body height and knee size, respectively. The pathologic threshold of increased TT-TG was suggested to be 21 mm for patients [Formula: see text] 169 cm and 18 mm for patients [Formula: see text] 169 cm. Body height-related pathologic threshold provided a supplement for indications of tibial tuberosity medialization.IV.

Inflammasome contributes to the pathogenesis of various inflammatory diseases, but the epigenetic mechanism controlling its activation remains elusive. Here, we found that the histone methyltransferase Ezh2 mediates the activation of multiple types of inflammasomes in macrophages/microglia independent of its methyltransferase activity and thus promotes inflammasome-related pathologies. Mechanistically, Ezh2 functions through its SANT2 domain to maintain the enrichment of H3K27 acetylation in the promoter region of the long noncoding RNA (lncRNA) Neat1, thereby promoting chromatin accessibility and facilitating p65-mediated transcription of Neat1, which is a critical mediator of inflammasome assembly and activation. In addition, the tumour suppressor protein p53 competes with Ezh2 for the same binding region in the Neat1 promoter and thus antagonises Ezh2-induced Neat1 transcription and inflammasome activation. Therefore, loss of Ezh2 strongly promotes the binding of p53, which recruits the deacetylase SIRT1 for H3K27 deacetylation of the Neat1 promoter and thus suppresses Neat1 transcription and inflammasome activation. Overall, our study demonstrates an epigenetic mechanism involved in modulating inflammasome activation through an Ezh2/p53 competition model and highlights a novel function of Ezh2 in maintaining H3K27 acetylation to support lncRNA Neat1 transcription.

Hepatocellular carcinoma (HCC) is a malignancy worldwide with one of the worst prognoses. Emerging studies have revealed that long noncoding RNAs (lncRNAs) contribute to HCC progression. This research probes the expression and regulatory effect of lncRNA SATB2-AS1 on HCC development. Reverse transcription-polymerase chain reaction (RT-PCR) was applied to measure the SATB2-AS1 profile in HCC tissues and adjacent non-tumor tissues. The impact of SATB2-AS1, miR-3678-3p, or GRIM-19 on HCC cell proliferation, growth, migration, invasion, and apoptosis was determined by gain- and loss-of-function experiments. The results revealed that SATB2-AS1 was downregulated in HCC tissues, and its lower levels were related to higher tumor staging and poorer prognosis of HCC patients. SATB2-AS1 overexpression repressed HCC cell proliferation, induced G1 arrest, and apoptosis, and inhibited migration, invasion, and epithelial-mesenchymal transition (EMT). Mechanistically, SATB2-AS1 inactivated STAT3/HIF-1α and strengthened GRIM-19 expression. After knocking down GRIM-19 with small interfering RNA (siRNA), the malignant phenotypes of HCC cells were enhanced. Further bioinformatics analysis showed that miR-3678-3p was targeted by SATB2-AS1. The dual-luciferase reporter assay, RNA immunoprecipitation (RIP) experiment, and Fluorescence in situ Hybridization (FISH) test confirmed that SATB2-AS1 sponged miR-3678-3p and the latter targeted GRIM-19. The rescue experiments showed that miR-3678-3p aggravated the malignant behaviors of HCC cells, whereas SATB2-AS1 overexpression reversed miR-3678-3p-mediated effects. Inhibition STAT3 promoted SATB2-AS1 and GRIM-19 expression, and reduced miR-3678-3p level. Activation STAT3 exerted opposite effects. Overall, this study confirmed that SATB2-AS1 is a potential prognostic biomarker for HCC and regulates HCC devolvement by regulating the miR-3678-3p/GRIM-19/STAT3/HIF-1α pathway.