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Spatialization and analysis of the gross domestic product of second and tertiary industries (GDP23) can effectively depict the socioeconomic status of regional development. However, existing studies mainly conduct GDP spatialization using nighttime light data; few studies specifically concentrated on the spatialization and analysis of GDP23 in a built-up area by combining multi-source remote sensing images. In this study, the NPP-VIIRS-like dataset and Sentinel-2 multi-spectral remote sensing images in six years were combined to precisely spatialize and analyze the variation patterns of the GDP23 in the built-up area of Zibo city, China. Sentinel-2 images and the random forest (RF) classification method based on PIE-Engine cloud platform were employed to extract built-up areas, in which the NPP-VIIRS-like dataset and comprehensive nighttime light index were used to indicate the nighttime light magnitudes to construct models to spatialize GDP23 and analyze their change patterns during the study period. The results found that (1) the RF classification method can accurately extract the built-up area with an overall accuracy higher than 0.90; the change patterns of built-up areas varied among districts and counties, with Yiyuan county being the only administrative region with an annual expansion rate of more than 1%. (2) The comprehensive nighttime light index is a viable indicator of GDP23 in the built-up area; the fitted model exhibited an R2 value of 0.82, and the overall relative errors of simulated GDP23 and statistical GDP23 were below 1%. (3) The year 2018 marked a significant turning point in the trajectory of GDP23 development in the study area; in 2018, Zhoucun district had the largest decrease in GDP23 at −52.36%. (4) GDP23 gradation results found that Zhangdian district exhibited the highest proportion of high GDP23 (>9%), while the proportions of low GDP23 regions in the remaining seven districts and counties all exceeded 60%. The innovation of this study is that the GDP23 in built-up areas were first precisely spatialized and analyzed using the NPP-VIIRS-like dataset and Sentinel-2 images. The findings of this study can serve as references for formulating improved city planning strategies and sustainable development policies. [ABSTRACT FROM AUTHOR]

MXene materials have shown numerous useful mechanical and electronic properties, and have been found to possess nice potential in the field of optical modulation. Here, we fabricated a MXene Cr2C saturable absorber by the liquid-phase exfoliation method, and systemically analyzed the surface morphology and nonlinear properties of the Cr2C sample. Applying the Cr2C saturable absorber as a Q-switch in a thulium-doped yttrium aluminum perovskite (Tm: YAP) laser, the shortest single pulse was obtained with a width of 602 ns under an absorbed pump power of 3.3 W at a repetition rate of 55 kHz with a T = 1% output coupler. The maximum output power was obtained with a T = 5% output coupler at a repetition rate of 58 kHz. The obtained maximum pulse energy and peak power were 3.96 μJ and 4.36 W, separately, which reveal that the MXene Cr2C can be applied as a promising modulation material in the near-infrared pulsed lasers. [ABSTRACT FROM AUTHOR]

Two aplysiatoxin derivatives, neo-debromoaplysiatoxin I (1) and neo-debromoaplysiatoxin J (2), were isolated from marine cyanobacterium Lyngbya sp. collected from the South China Sea. Their structures including absolute configurations were assigned by spectroscopic analysis, in combination with GIAO NMR shift calculation and DP4+ analysis. Structures of neo-debromoaplysiatoxin I and neo-debromoaplysiatoxin J contained a decahydro-5H-pyrano [2,3,4-de] chromen-5-one 6/6/6 ring skeleton and an intriguing peroxide bridge group, respectively, which are unprecedented structure scaffold and motif in aplysiatoxins. Two compounds displayed comparable inhibitory activities against Kv1.5 K+ channel with IC50 values of 2.59 ± 0.37 μM (1) and 1.64 ± 0.15 μM (2); however, they presented differential cytotoxic effects. It is worth noting that neo-debromoaplysiatoxin J, containing a peroxide bridge, showed remarkable cytotoxicity against four cancer cell lines including SW480, SGC7901, LoVo and PC-9 compared to the human normal cell line. [ABSTRACT FROM AUTHOR]

Background: Compared with singleton pregnancy, twin gestation is featured by a greater increase in cardiac output. Therefore, norepinephrine might be more suitable than phenylephrine for maintaining blood pressure during cesarean section for twins, as phenylephrine causes reflex bradycardia and a resultant decrease in cardiac output. This study was to determine whether norepinephrine was superior to phenylephrine in maintaining maternal hemodynamics during cesarean section for twins. Methods: Informed consent was obtained from all the patients before enrollment. In this double-blinded, randomized clinical trial, 100 parturients with twin gestation undergoing cesarean section with spinal anesthesia were randomized to receive prophylactic norepinephrine (3.2 μg/min) or phenylephrine infusion (40 μg/min). The primary outcome was the change of heart rate and blood pressure during the study period. The secondary outcomes were to compare maternal complications, neonatal outcomes, Apgar scores and umbilical blood acid-base status between the two vasopressors. Results: There was no significant difference observed for the change of heart rate between two vasopressors. The mean standardized area under the curve of heart rate was 78 ± 12 with norepinephrine vs. 74 ± 11 beats/min with phenylephrine (mean difference 4.4, 95%CI − 0.1 to 9.0; P =.0567). The mean standardized area under the curve of systolic blood pressure (SBP) was significantly lower in parturients with norepinephrine, as the mean of differences in standardized AUC of SBP was 6 mmHg, with a 95% CI from 2 to 9 mmHg (P =.0013). However, requirements of physician interventions for correcting maternal hemodynamical abnormalities (temporary cessation of vasopressor infusion for reactive hypertension, rescuing vasopressor bolus for hypotension and atropine for heart rate less < 50 beats/min) and neonatal outcomes were also not significantly different between two vasopressors. Conclusion: Infusion of norepinephrine was not associated with less overall decrease in heart rate during cesarean section for twins, compared with phenylephrine. Trial registration: Chinese Clinical Trial Registry (ChiCTR1900021281). [ABSTRACT FROM AUTHOR]

Reverse top-k keyword-based location query (RTkKL), aims to find the maximum spatial region such that the query object is contained in the result of any top-k spatial keyword query with users' queried keywords and any location in the region as arguments. Existing efforts on RTkKL find the objects in the Euclidean space. In this paper, we study the problem of reverse top-k keyword-based location query on road networks. We propose two methods. One is based on mark vertex, and the other is based on bisector. For the mark vertex based method, we identify the mark vertex according to the definition of RTkKL on road networks. Based on the mark vertex, we will get the mark segments in the result. For the bisector-based method, we find the border points for the query q and some objects. With Dijkstra algorithm, we start from the query point q. For each closed edge, whose two adjacent vertices have been extracted from the min heap, we would search the border points on the edge, and count the border points for the adjacent vertex. For each method, we propose effective pruning strategy to reduce the search range and computation cost. Finally, experiments demonstrate the efficiency of the proposed algorithm. [ABSTRACT FROM AUTHOR]

RNA helicase DDX21 plays vital roles in ribosomal RNA biogenesis, transcription, and the regulation of host innate immunity during virus infection. How DDX21 recognizes and unwinds RNA and how DDX21 interacts with virus remain poorly understood. Here, crystal structures of human DDX21 determined in three distinct states are reported, including the apo‐state, the AMPPNP plus single‐stranded RNA (ssRNA) bound pre‐hydrolysis state, and the ADP‐bound post‐hydrolysis state, revealing an open to closed conformational change upon RNA binding and unwinding. The core of the RNA unwinding machinery of DDX21 includes one wedge helix, one sensor motif V and the DEVD box, which links the binding pockets of ATP and ssRNA. The mutant D339H/E340G dramatically increases RNA binding activity. Moreover, Hill coefficient analysis reveals that DDX21 unwinds double‐stranded RNA (dsRNA) in a cooperative manner. Besides, the nonstructural (NS1) protein of influenza A inhibits the ATPase and unwinding activity of DDX21 via small RNAs, which cooperatively assemble with DDX21 and NS1. The structures illustrate the dynamic process of ATP hydrolysis and RNA unwinding for RNA helicases, and the RNA modulated interaction between NS1 and DDX21 generates a fresh perspective toward the virus–host interface. It would benefit in developing therapeutics to combat the influenza virus infection. [ABSTRACT FROM AUTHOR]

Background. Neutrophil to lymphocyte ratio (NLR) is a new inflammatory marker; the relationship between NLR and adverse cardiovascular (CV) prognosis has been gradually emphasized in the general population. However, their association in peritoneal dialysis (PD) patients remains unclear. Methods. From January 1, 2010, to May 31, 2017, a total of 1652 patients were recruited. NLR was categorized in triplicates: NLR ≤ 2.74 , 2.74 < NLR ≤ 3.96 , and NLR > 3.96. Kaplan-Meier cumulative incidence curve and multivariable COX regression analysis were used to determine the relationship between NLR and the incidence of adverse CV outcome, while a competitive risk model was applied to assess the effects of other outcomes on adverse CV prognosis. Besides, forest plot was investigated to analyze the adverse CV prognosis in different subgroups. Results. During follow-up, 213 new-onset CV events and 153 CV disease (CVD) deaths were recorded. Multivariable COX regression models showed that the highest tertile of NLR level was associated with increased risk of CV events (HR = 1.39 , 95 % CI = 1.01 ‐ 1.93 , P = 0.046) and CVD mortality (HR = 1.81 , 95 % CI = 1.22 ‐ 2.69 , P = 0.003), while compared to the lowest tertile. Competitive risk models showed that the differences in CV event (P < 0.001) and CVD mortality (P = 0.004) among different NLR groups were still significant while excluding the effects of other outcomes. In subgroups, with each 1 increased in the NLR level, adjusted HR of new-onset CV event was 2.02 (95 % CI = 1.26 − 3.23 , P = 0.003) and CVD mortality was 2.98 (95 % CI = 1.58 − 5.62 , P = 0.001) in the younger group (age < 60 years). Conclusions. NLR is an independent risk factor for adverse CV prognosis in PD patients younger than 60 years old. [ABSTRACT FROM AUTHOR]

The existing spatial keyword cover query only considers the relevance of the text and the position, and ignores the temporal information of the geospatial objects. In this paper, we define a new query, time-aware spatial keyword cover query (TSKCQ), which takes into account the textual relevance, positional relevance, and temporal information of the objects. A new cost function is proposed in TSKCQ, which is used to evaluate the user's satisfaction in time and space under the premise of satisfying textual constraints proposed by the user. With this function, an object set with the best cost function value would be returned by TSKCQ. We propose a TR-tree for indexing the temporal and spatial information of objects. Based on this, we propose an exact algorithm to tackle TSKCQ, in which effective pruning strategies are used. Finally, experiments demonstrate the efficiency of the proposed algorithm. [ABSTRACT FROM AUTHOR]

Abstract Given a set of spatial objects O , the search radius r and the submodular function f are specified by the user. The best region search (BRS) is to find an optimal area with fixed range size, in which the object set has the maximum submodular function value. The BRS problem has long been studied because of its wide application in spatial data mining, facility locating and so on. However, most of the existing work focus on either Euclidean space or motionless objects, which is not applicable in many real-life cases. In this paper, we propose the best region monitoring problem in the spatial data streams in road networks (MBRS). Many real life applications can obtain benefit from MBRS problem, such as monitoring traffic and tracking in ecology. We first propose an efficient algorithm to the static BRS problem in road networks, and extend the solution to a naive method to solve the MBRS problem. Then, we put forward effective pruning strategies and branch-and-bound algorithm GER on the basis of the preprocessing to monitor best region at different times. Finally, a large number of experiments verify the efficiency of the proposed method. [ABSTRACT FROM AUTHOR]

A large number of studies have shown that proton pump inhibitors (PPIs) are associated with infection events. Therefore, we retrospectively evaluated the association of PPI therapy with the occurrence of first pneumonia and peritoneal dialysis(PD)-related peritonitis events in the maintenance PD patients. We collected PD patients in two large hospitals from January 1, 2012 to December 31, 2016, and divided them into the PPI group and the non-PPI group. Multivariate Cox proportional hazards models were applied to evaluate the cumulative incidence and hazard ratios (HRs). Inverse probability of treatment weight (IPTW) method was used to adjust for covariate imbalance between the two groups and further confirm our findings. Finally, 656 PD patients were included for data analysis, and the results showed that PPI usage was associated with an increased risk of pneumonia [HR 1.71; 95% CI 1.06-2.76; p = 0.027] and peritonitis [HR 1.73; 95% CI 1.24-2.40; p = 0.001]. IPTW-adjusted HRs for the association of PPIs with pneumonia and peritonitis were 1.58 (95% CI:1.18-2.12; p = 0.002) and 2.33 (95% CI:1.91-2.85; p < 0.001), respectively. Moreover, the competitive risk model proved that under the conditions of competition for other events(including transfer to hemodialysis therapy, kidney transplant, transfer from our research center, loss to follow-up, and death), the differences in endpoints events between the two groups were still statistically significant (p = 0.009, p < 0.001, respectively). PPIs was associated with an increased risk of first pneumonia and PD-related peritonitis events in PD patients, which reminds clinicians to be cautious when prescribing acid-suppressing drugs for PD patients. [ABSTRACT FROM AUTHOR]

The development of fifth‐generation technology has resulted in increased demand for materials with low dielectric losses and superior thermal and mechanical properties. However, ensuring the widespread use of such materials by investigating their aging mechanisms and operating lifetimes remains challenging. In this study, a glass‐fiber (GF)‐reinforced acrylate‐styrene‐acrylonitrile/polycarbonate (ASA/GF/PC) composite is designed and comprehensively investigated its aging behavior, mechanism, and service lifetime under long‐term hygrothermal conditions. Based on the general Peck model, the composite maintains a high level of quality for over 10 years, including under harsh conditions of 40 °C and 80% relative humidity. The aging mechanism is primarily ascribed to cracking between the GF fibers and matrix, the breaking of chemical bonds, the generation of new cross‐linked domains, and physical aging. These findings provide valuable insights into the long‐term utilization of ASA/GF/PC composites in harsh environments. [ABSTRACT FROM AUTHOR]

In the process of block compressed sensing (CS) applied to the rolling bearing fault signal, the reconstruction accuracy of the signal is low due to the large difference in sparsity between blocks and the unreasonable components of reconstruction support set, which affects the overall reconstruction effect of the signal. To improve the signal reconstruction results, forward and backward stagewise orthogonal matching pursuit (FBStOMP) based on the adaptive block method is proposed. First, to equalize the sparsity of each block signal, the fault signal is divided into blocks according to the adaptive block length, which is obtained by the short-time autocorrelation algorithm. Then, the K-singular value decomposition algorithm is used to train the sparse dictionary to obtain a better sparse effect. Finally, the FBStOMP algorithm is proposed. The atom backtracking and screening process is added in the reconstruction process to improve the possibility that all the effective atoms can be selected into the support set. The experimental analysis of the simulation signal and bearing fault signal show that, compared with the traditional CS reconstruction algorithm, the adaptive block-FBStOMP algorithm proposed in the paper can effectively improve the reconstruction accuracy of the bearing fault signal. [ABSTRACT FROM AUTHOR]

Background: RNA modifications, especially N6-methyladenosine, N1-methyladenosine and 5–methylcytosine, play an important role in the progression of cardiovascular disease. However, its regulatory function in dilated cardiomyopathy (DCM) remains to be undefined. Methods: In the study, key RNA modification regulators (RMRs) were screened by three machine learning models. Subsequently, a risk prediction model for DCM was developed and validated based on these important genes, and the diagnostic efficiency of these genes was assessed. Meanwhile, the relevance of these genes to clinical traits was explored. In both animal models and human subjects, the gene with the strongest connection was confirmed. The expression patterns of important genes were investigated using single-cell analysis. Results: A total of 4 key RMRs were identified. The risk prediction models were constructed basing on these genes which showed a good accuracy and sensitivity in both the training and test set. Correlation analysis showed that insulin-like growth factor binding protein 2 (IGFBP2) had the highest correlation with left ventricular ejection fraction (LVEF) (R = -0.49, P = 0.00039). Further validation expression level of IGFBP2 indicated that this gene was significantly upregulated in DCM animal models and patients, and correlation analysis validation showed a significant negative correlation between IGFBP2 and LVEF (R = -0.87; P = 6*10–5). Single-cell analysis revealed that this gene was mainly expressed in endothelial cells. Conclusion: In conclusion, IGFBP2 is an important biomarker of left ventricular dysfunction in DCM. Future clinical applications could possibly use it as a possible therapeutic target. [ABSTRACT FROM AUTHOR]

Background: Stabilization and increased activity of hypoxia-inducible factor 1-α (HIF-1α) can directly increase cancellous bone formation and play an essential role in bone modeling and remodeling. However, whether an increased HIF-1α expression in adipose-derived stem cells (ADSCs) increases osteogenic capacity and promotes bone regeneration is not known. Results: In this study, ADSCs transfected with small interfering RNA and HIF-1α overexpression plasmid were established to investigate the proliferation, migration, adhesion, and osteogenic capacity of ADSCs and the angiogenic ability of human umbilical vein endothelial cells (HUVECs). Overexpression of HIF-1α could promote the biological functions of ADSCs, and the angiogenic ability of HUVECs. Western blotting showed that the protein levels of osteogenesis-related factors were increased when HIF-1α was overexpressed. Furthermore, the influence of upregulation of HIF-1α in ADSC sheets on osseointegration was evaluated using a Sprague–Dawley (SD) rats implant model, in which the bone mass and osteoid mineralization speed were evaluated by radiological and histological analysis. The overexpression of HIF-1α in ADSCs enhanced bone remodeling and osseointegration around titanium implants. However, transfecting the small interfering RNA (siRNA) of HIF-1α in ADSCs attenuated their osteogenic and angiogenic capacity. Finally, it was confirmed in vitro that HIF-1α promotes osteogenic differentiation and the biological functions in ADSCs via the VEGF/AKT/mTOR pathway. Conclusions: This study demonstrates that HIF-1α has a critical ability to promote osteogenic differentiation in ADSCs by coupling osteogenesis and angiogenesis via the VEGF/AKT/mTOR signaling pathway, which in turn increases osteointegration and bone formation around titanium implants. [ABSTRACT FROM AUTHOR]

Summary During social transmission of food preference (STFP), mice form long-term memory of food odors presented by a social partner. How does the brain associate a social context with odor signals to promote memory encoding? Here we show that odor exposure during STFP, but not unconditioned odor exposure, induces glomerulus-specific long-term potentiation (LTP) of synaptic strength selectively at the GABAergic component of dendrodendritic synapses of granule and mitral cells in the olfactory bulb. Conditional deletion of synaptotagmin-10, the Ca 2+ sensor for IGF1 secretion from mitral cells, or deletion of IGF1 receptor in the olfactory bulb prevented the socially relevant GABAergic LTP and impaired memory formation after STFP. Conversely, the addition of IGF1 to acute olfactory bulb slices elicited the GABAergic LTP in mitral cells by enhancing postsynaptic GABA receptor responses. Thus, our data reveal a synaptic substrate for a socially conditioned long-term memory that operates at the level of the initial processing of sensory information. [ABSTRACT FROM AUTHOR]

Objective: To investigate the diagnostic role of heart rate variability in breast cancer and its relationship with Carcinoembryonic antigen (CEA) in peripheral serum. Methods: We reviewed the electronic medical records of patients who attended Zhujiang Hospital of Southern Medical University between October 2016 and May 2019. The patients were grouped based on breast cancer history and were divided into two groups: breast cancer group(n = 19) and control group(n = 18). All women were invited for risk factor screening, including 24-hour ambulatory ECG monitoring and blood biochemistry after admission. The difference and correlation between the breast cancer group and control group were performed by comparing the heart rate variability and serum CEA levels. Additionally, diagnostic efficacy analysis of breast cancer was calculated by combining heart rate variability and serum CEA. Results: In total, 37 patients were eligible for analysis, with 19 and 18 patients in the breast cancer group and control groups, respectively. Women with breast cancer had a significantly lower level of total LF, awake TP, and awake LF, and a significantly higher level of serum CEA compared with women with no breast cancer. Total LF, awake TP, and awake LF were negatively correlated with the CEA index (P < 0.05). The receiver operating characteristic (ROC) curves indicated the highest area under the curve (AUC) scores and specificity of the combination of awake TP, awake LF, and serum CEA (P < 0.05), while sensitivity was highest for total LF, awake TP, and awake LF (P < 0.05). Conclusions: Women with history of breast cancer had abnormalities in autonomic function. The combined analysis of heart rate variability and serum CEA analysis may have a predictive effect on the development of breast cancer and provide more basis for clinical diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Actinomycin is a family of chromogenic lactone peptides that differ in their peptide portions of the molecule. An antimicrobial peptide, actinomycin X2 (Ac.X2), was produced through the fermentation of a Streptomyces cyaneofuscatus strain. Immobilization of Ac.X2 onto a prepared silk fibroin (SF) film was done through a carbodiimide reaction. The physical properties of immobilized Ac.X2 (antimicrobial films, AMFs) were analyzed by ATR-FTIR, SEM, AFM, and WCA. The findings from an in vitro study showed that AMFs had a more broad-spectrum antibacterial activity against both S. aureus and E. coli compared with free Ac.X2, which showed no apparent strong effect against E. coli. These AMFs showed a suitable degradation rate, good hemocompatibility, and reduced cytotoxicity in the biocompatibility assay. The results of in vivo bacterially infected wound healing experiments indicated that wound inflammation was prevented by AMFs, which promoted wound repair and improved the wound microenvironment. This study revealed that Ac.X2 transformation is a potential candidate for skin wound healing. [ABSTRACT FROM AUTHOR]

Purpose: Radiopharmaceuticals targeting poly(ADP-ribose) polymerase (PARP) have emerged as promising agents for cancer diagnosis and therapy. PARP enzymes are expressed in both cancerous and normal tissue. Hence, the injected mass, molar activity and potential pharmacological effects are important considerations for the use of radiolabelled PARP inhibitors for diagnostic and radionuclide therapeutic applications. Here, we performed a systematic evaluation by varying the molar activity of [18F]olaparib and the injected mass of [TotalF]olaparib to investigate the effects on tumour and normal tissue uptake in two subcutaneous human glioblastoma xenograft models. Methods: [18F]Olaparib uptake was evaluated in the human glioblastoma models: in vitro on U251MG and U87MG cell lines, and in vivo on tumour xenograft-bearing mice, after administration of [TotalF]olaparib (varying injected mass: 0.04–8.0 µg, and molar activity: 1–320 GBq/μmol). Results: Selective uptake of [18F]olaparib was demonstrated in both models. Tumour uptake was found to be dependent on the injected mass of [TotalF]olaparib (µg) but not the molar activity. An injected mass of 1 μg resulted in the highest tumour uptake (up to 6.9 ± 1.3%ID/g), independent of the molar activity. In comparison, both the lower and higher injected masses of [TotalF]olaparib resulted in lower relative tumour uptake (%ID/g; P < 0.05). Ex vivo analysis of U87MG xenograft sections showed that the heterogeneity in [18F]olaparib intratumoural uptake correlated with PARP1 expression. Substantial upregulation of PARP1-3 expression was observed after administration of [TotalF]olaparib (> 0.5 µg). Conclusion: Our findings show that the injected mass of [TotalF]olaparib has significant effects on tumour uptake. Moderate injected masses of PARP inhibitor-derived radiopharmaceuticals may lead to improved relative tumour uptake and tumour-to-background ratio for cancer diagnosis and radionuclide therapy. [ABSTRACT FROM AUTHOR]

The successful implementation of the low-carbonization strategy is heavily reliant on the development of low-loss and high-efficiency green antenna technology. However, long-term exposure to high heat and oxygen leads to the degradation of antenna materials and the release of harmful substances. Studies on the aging behavior and mechanism of the antenna materials are of essence to realize the low-carbonization strategy. To address this issue, an unplasticized polyvinyl chloride filled with calcium carbonate (uPVC/CaCO 3) has been successfully prepared using the injection molding technique. After that, the aging behavior, mechanism, and working lifetime were comprehensively explored under thermal and oxidative conditions. It is found that the composite maintains a high level of functionality for up to 24 years at 60 ℃ and 4.5 years at 70 ℃ on the impact strength failure criterion. The simultaneous oxidation and dehydrochlorination reaction, cross-linking reaction, and deterioration of the interaction between components are responsible for the aging of the uPVC/CaCO 3 composite. These findings provide valuable insights into the development of radome materials for achieving low-loss and high-efficiency green antenna technology. [ABSTRACT FROM AUTHOR]

Background: The effect of time delay from diagnosis to surgery on the prognosis of elderly patients with liver cancer is not well known. We investigated the effect of surgical timing on the prognosis of elderly hepatocellular carcinoma patients undergoing surgical resection and constructed a Nomogram model to predict the overall survival of patients.Methods: A retrospective analysis was performed on elderly patients with primary liver cancer after hepatectomy from 2012 to 2018. The effect of surgical timing on the prognosis of elderly patients with liver cancer was analyzed using the cut-off times of 18 days, 30 days, and 60 days. Cox was used to analyze the independent influencing factors of overall survival in patients, and a prognostic model was constructed.Results: A total of 232 elderly hepatocellular carcinoma patients who underwent hepatectomy were enrolled in this study. The cut-off times of 18, 30, and 60 days were used. The duration of surgery had no significant effect on overall survival. Body Mass Index, Child-Pugh classification, Tumor size Max, and Length of stay were independent influencing factors for overall survival in the elderly Liver cancer patients after surgery. These factors combined with Liver cirrhosis and Venous tumor emboli were incorporated into a Nomogram. The nomogram was validated using the clinical data of the study patients, and exhibited better prediction for 1-year, 3-year, and 5-year overall survival.Conclusions: We demonstrated that the operative time has no significant effect on delayed operation in the elderly patients with hepatocellular carcinoma, and a moderate delay may benefit some patients. The constructed Nomogram model is a good predictor of overall survival in elderly patients with hepatectomy. [ABSTRACT FROM AUTHOR]

Background and Purpose: Psoriasis is a chronic immune‐mediated inflammatory skin disease that easily recurs and is difficult to cure. DGT is a novel synthetic heterocyclic diterpenoid, whose structure has not been previously reported. We have investigated the action of DGT against psoriasis, specifically the hyperproliferation of epidermal keratinocytes, angiogenesis and pathogenic inflammatory responses. Experimental Approach We investigated its pharmacokinetics in skin after topical administration. We characterized its pharmacological actions in vitro and in vivo using cell proliferation assay, cell apoptosis assay, diethylstilbestrol‐induced mouse vaginal epithelial cell mitosis model, tube formation assay, cell migration assay, chick embryonic chorioallantoic membrane (CAM) assay, histological, flow cytometric analysis and imiquimod (IMQ)‐induced psoriasis‐like model. Key Results: DGT was found to be mainly distributed in the epidermis and dermis, which indicated that DGT was suitable as a topical treatment. DGT inhibited cell proliferation and induced apoptotic cell death of keratinocytes in vitro and in vivo. Moreover, DGT inhibited endothelial cell proliferation, tube formation and migration of in vitro angiogenesis, as well as in vivo CAM angiogenesis. In an IMQ‐induced psoriasis‐like skin inflammation murine model, topical application of DGT ameliorated keratinocyte proliferation and inflammatory response, especially in IL‐17‐related psoriasiform dermatitis. Furthermore, our results demonstrated that DGT prevented these pathological processes of psoriasis through suppression of STAT3 phosphorylation. Conclusion and Implications: DGT has great potential as a novel therapeutic agent for the treatment of psoriatic skin disease. [ABSTRACT FROM AUTHOR]

Disrupting memories that associate environmental cues with drug experiences holds promise for treating addiction, yet accessing the distributed neural network that stores such memories is challenging. Here, we show that the paraventricular nucleus of the thalamus (PVT) orchestrates the acquisition and maintenance of opiate-associated memories via projections to the central nucleus of the amygdala (CeA) and nucleus accumbens (NAc). PVT→CeA activity associates morphine reward to the environment, whereas transient inhibition of the PVT→NAc pathway during retrieval causes enduring protection against opiate-primed relapse. Using brain-wide activity mapping, we revealed distributed network activities that are altered in non-relapsing mice, which enabled us to find that activating the downstream NAc→lateral hypothalamus (LH) pathway also prevents relapse. These findings establish the PVT as a key node in the opiate-associated memory network and demonstrate the potential of targeting the PVT→NAc→LH pathway for treating opioid addiction. • The PVT→CeA pathway associates opiate reward to the environment • Manipulation of the PVT→NAc or NAc→LH pathway prevents opiate-primed relapse • Repeated opiate use enhances feedforward inhibition from PVT to the NAc→LH pathway • iDISCO+ mapping reveals brain-wide networks for storing opiate-associated memories Keyes et al. establish the PVT as a key node in the opiate-associated memory network. The PVT→CeA pathway associates opiate reward to the environment, whereas transient manipulation of the PVT→NAc pathway or its downstream NAc→LH pathway during retrieval erases opiate-associated memory and causes enduring protection against relapse to opioid use. [ABSTRACT FROM AUTHOR]

Thus, we speculate that carvedilol may trigger phosphorylation of AMPK, which would enhance autophagy through mTOR signaling pathway, thus showing cardioprotective effects during ischemia and reperfusion injury. In conclusion, cardioprotective effects of carvedilol on ischemia and reperfusion injury may be related to the up-regulation of AMPK-mTOR-dependent autophagy signaling pathway. [Extracted from the article]

Background: Esterases and lipases hydrolyze short-chain esters and long-chain triglycerides, respectively, and therefore play essential roles in the synthesis and decomposition of ester bonds in the pharmaceutical and food industries. Many SGNH family esterases share high similarity in sequences. However, they have distinct enzymatic activities toward the same substrates. Due to a lack of structural information, the detailed catalytic mechanisms of these esterases remain barely investigated. Results: In this study, we identified two SGNH family esterases, CrmE10 and AlinE4, from marine bacteria with significantly different preferences for pH, temperature, metal ion, and organic solvent tolerance despite high sequence similarity. The crystal structures of these two esterases, including wild type and mutants, were determined to high resolutions ranging from 1.18 Å to 2.24 Å. Both CrmE10 and AlinE4 were composed of five β-strands and nine α-helices, which formed one compact N-terminal α/β globular domain and one extended C-terminal domain. The aspartic residues (D178 in CrmE10/D162 in AlinE4) destabilized the conformations of the catalytic triad (Ser-Asp-His) in both esterases, and the metal ion Cd2+ might reduce enzymatic activity by blocking proton transfer or substrate binding. CrmE10 and AlinE4 showed distinctly different electrostatic surface potentials, despite the similar atomic architectures and a similar swap catalytic mechanism. When five negatively charged residues (Asp or Glu) were mutated to residue Lys, CrmE10 obtained elevated alkaline adaptability and significantly increased the enzymatic activity from 0 to 20% at pH 10.5. Also, CrmE10 mutants exhibited dramatic change for enzymatic properties when compared with the wide-type enzyme. Conclusions: These findings offer a perspective for understanding the catalytic mechanism of different esterases and might facilitate the industrial biocatalytic applications. [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to explore the prognostic value of phospholipase C delta (PLCD) genes in early stage pancreatic ductal adenocarcinoma (PDAC) and its potential molecular mechanisms. The prognostic value of PLCD genes in early stage PDAC was assessed using the Kaplan‐Meier method and multivariate Cox proportional hazards regression model. Genome‐wide correlation analysis was performed on PLCD3 to identify the highly correlated genes in the transcriptome. Then, PLCD3 and these correlated genes together underwent a bioinformatics analysis to elucidate the potential molecular biological functions of PLCD3 in PDAC. PLCD1 and PLCD3 are significantly overexpressed in PDAC. In PDAC patients, PLCD3 is overexpressed in certain groups of people with a history of alcoholism (P =.032). High expression of PLCD3 was found to be associated with lower overall survival (OS) of patients with early stage PDAC (P =.020; adjusted P =.016). A combination of PLCD3 and clinical variables was able to better predict the outcome of patients with early stage PDAC. These clinical variables are histological grade (P =.001; adjusted P =.001), targeted molecular therapy (P <.001; adjusted P <.001), radiation therapy (P =.002; adjusted P =.039), and residual resection (P =.001; adjusted P =.002). The bioinformatics analysis revealed that PLCD3 is associated with angiogenesis, intracellular signal transduction, and regulation of cell proliferation. In conclusion, PLCD3 may be a potential prognostic biomarker for early stage PDAC. [ABSTRACT FROM AUTHOR]

The capability of nanolasers to generate coherent light in small volume resonators has made them attractive to be implemented in future ultra-compact photonic integrated circuits. However, compared to conventional lasers, nanolasers are also known for their broader spectral linewidths, that are usually on the order of 1 nm. While it is well known that the broad linewidths in light emitters originate from various noise sources, there has been no rigorous study on evaluating the origins of the linewidth broadening for nanolasers to date to the best of our knowledge. In this manuscript, we investigate the impact of fundamental thermal fluctuations on the nanolaser linewidth. We show that such thermal fluctuations are one of the intrinsic noise sources in a sub-wavelength metal-clad nanolaser inducing significant linewidth broadening. We further show that with the reduction of the nanolaser’s dimensions, i.e., mode volume, and the increase of the ambient temperature, such linewidth broadening is enhanced, due to the effect of more pronounced fundamental thermal fluctuation. Specifically, we show that the finite linewidths induced by the thermal fluctuations at room temperature are 1.14nm and 0.16nm, for nanolasers with core radii of 250nm and 750nm, respectively. Although our study was performed on a metallo-dielectric nanolaser, it is reasonable to assume that, in general, other nanolaser architectures are also more prone to thermal fluctuations, and hence exhibit larger finite linewidths than conventional large mode volume lasers. [ABSTRACT FROM AUTHOR]

In this paper, a normally off Al2O3/AlN/GaN MISFET on Si substrate for achieving high threshold voltage stability and uniformity is obtained based on selective area growth. A thin AlN space layer (SL, ~1 nm) is adopted to GaN-based template, and the AlGaN/GaN het-erostructureis selectivelygrownon the template to naturally form a recessed structure. By insertion of the AlN SL, the Al2O3/AlN/GaN interface trapping and scattering effects are effectively suppressed. As a result, a low threshold voltage hysteresis ( \Delta V\mathrm{ th} , 80 mV at maximum gate sweep voltage of 10 V by dc I – V measurement and smaller than 200 mV in linear region by pulse I – V measurement) and a high peak field-effect mobility ( \mu \sf FE) of 192 cm2/ \textV\cdot \texts are obtained in Al2O3/AlN/GaN MISFET. It is a significant improvement compared with Al2O3/GaN MISFET without AlN SL. The Al2O3/AlN/GaN MISFET also exhibits a maximum drain current ( Id,max) of 620 mA/mm, a low on-resistance ( Rds, \mathrm\scriptscriptstyle ON) of $9.6~\Omega \cdot $ mm, and a high uniformity of {V}_{\mathrm{ th}} (2.5 ± 0.1 V). [ABSTRACT FROM PUBLISHER]

Summary Histone chaperones are critical for guiding specific post-transcriptional modifications of histones, safeguarding the histone deposition (or disassociation) of nucleosome (dis)assembly, and regulating chromatin structures to change gene activities. HAT1-interacting factor 1 (Hif1) has been reported to be an H3-H4 chaperone and to be involved in telomeric silencing and nucleosome (dis)assembly. However, the structural basis for the interaction of Hif1 with histones remains unknown. Here, we report the complex structure of Hif1 binding to H2A-H2B for uncovering the chaperone specificities of Hif1 on binding to both the H2A-H2B dimer and the H3-H4 tetramer. Our findings reveal that Hif1 interacts with the H2A-H2B dimer and the H3-H4 tetramer via distinct mechanisms, suggesting that Hif1 is a pivotal scaffold on alternate binding of H2A-H2B and H3-H4. These specificities are conserved features of the Sim3-Hif1-NASP interrupted tetratricopeptide repeat proteins, which provide clues for investigating their potential roles in nucleosome (dis)assembly. [ABSTRACT FROM AUTHOR]

The global prevalence of inflammatory bowel disease (IBD) is increasing, and mucosal healing is the preferred treatment target of IBD. Sodium (aS,9 R)− 3-hydroxy-16,17-dimethoxy-15-oxidotricyclo[12.3.1.12,6]nonadeca-1(18),2,4,6(19),14,16-hexene-9-yl sulfate hydrate (SDH) is a novel diarylheptane compound, which is designed to treat IBD. Hence, we investigated the potent therapeutic activity of SDH against IBD and explored the underlying mechanisms, and determined if SDH is a safe and well-tolerated oral therapeutic for IBD treatment. We characterized its therapeutic properties in vitro and in vivo using Caco-2 cell monolayer and dextran sodium sulfate (DSS)- or 2,4,6-trinitro-benzene sulfonic acid (TNBS)-induced colitis models. We conducted nonclinical toxicology and safety pharmacology research, including general toxicity, toxicokinetics, pharmacokinetics, metabolism and plasma protein binding, cardiovascular safety pharmacology, central nervous system safety pharmacology, respiratory safety pharmacology, fertility and early embryonic development toxicity, reverse mutation assay, chromosomal aberration assay and micronucleus test. The results showed that SDH promoted expression of tight junction proteins, and protected the integrity and permeability of the epithelial barrier in both cell and animal models. Moreover, lower doses of SDH showed the similar or better efficacy than cyclosporine A (CsA) and mesalazine in DSS- or TNBS-induced colitis animals. Furthermore, our results identified that SDH has satisfactory safety in these studies we tested. In summary, SDH restored the epithelial barrier through tight junction proteins and was expected to be a novel therapeutic agent for the treatment of IBD. [Display omitted] • SDH strengthens tight junction by promoting expression of tight junction proteins. • SDH is an effective and safe compound for treating inflammatory bowel disease. • SDH is a novel therapeutic approach by restoring epithelial barrier function. [ABSTRACT FROM AUTHOR]

In previous studies phospholipids have been proved to be involved in biochemical, physiological, and pathological processes. As a special class of phospholipids, peroxisome-derived lipids (PDLs) have been proved to be potential ligands of invariant natural killer T (iNKT) cells in recent studies. Here, on the basis of phospholipidomics, we focused on the relative quantity of PDLs extracted from mammalian thymus or bone marrow using electrospray ionization mass spectrometry (MS). In phospholipid analysis, we identified 12 classes of phospholipids and accounted for their relative quantities by comparing their relative abundances in the MS map. Our results show that PDLs are present in mammalian thymus as well as mouse spleen and liver. Interestingly, the relative quantity of PDLs extracted from human acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) bone marrows is higher than that extracted from bone marrow of healthy donors. Our results may help to explain the close correlation between PDLs and iNKT cell function in thymus, spleen, liver, and especially in leukemia patients. We think that our phospholipidomics work may reveal a function of iNKT cells. [ABSTRACT FROM AUTHOR]

Background: Common single nucleotide polymorphisms (SNPs) in proprotein convertase subtilisin/kexin type 1 with modest effects on PC1/3 in vitro have been associated with obesity in five genome-wide association studies and with diabetes in one genome-wide association study. We here present a novel SNP and compare its biosynthesis, secretion and catalytic activity to wild-type enzyme and to SNPs that have been linked to obesity. Methodology/Principal Findings: A novel PC1/3 variant introducing an Arg to Gln amino acid substitution at residue 80 (within the secondary cleavage site of the prodomain) (rs1 799904) was studied. This novel variant was selected for analysis from the 1000 Genomes sequencing project based on its predicted deleterious effect on enzyme function and its comparatively more frequent allele frequency. The actual existence of the R80Q (rs1 799904) variant was verified by Sanger sequencing. The effects of this novel variant on the biosynthesis, secretion, and catalytic activity were determined; the previously-described obesity risk SNPs N221D (rs6232), Q665E/S690T (rs6234/rs6235), and the Q665E and S690T SNPs (analyzed separately) were included for comparative purposes. The novel R80Q (rs1 799904) variant described in this study resulted in significantly detrimental effects on both the maturation and in vitro catalytic activity of PC1/3. Conclusion/Significance: Our findings that this novel R80Q (rs1799904) variant both exhibits adverse effects on PC1/3 activity and is prevalent in the population suggests that further biochemical and genetic analysis to assess its contribution to the risk of metabolic disease within the general population is warranted. [ABSTRACT FROM AUTHOR]

Glycosphingolipids (GSLs) are information-bearing biomolecules that play critical roles in embryonic development, signal transduction and carcinogenesis. Previous studies indicate that certain GSLs are associated with differentiation in acute myeloid leukemia (AML) cells. In this study, we collected bone marrow samples from healthy donors and AML patients and analyzed the GSL expression profiles comprehensively using electrospray ionization linear ion-trap mass spectrometry. The results showed that AML patients had higher expression of the GSL lactotriaosylceramide (Lc3), GM3 and neolactotetraosylceramide (nLc4) in their bone marrow than did the healthy donors (P < 0.05), especially the M1 subtype of AML. To further explore the molecular mechanisms of Lc3, we examined the expression of the Lc3 synthase β1,3-N-acetylglucosaminyltransferase5 (β3Gn-T5) and found that the bone marrow samples of AML patients had 16-fold higher expression of β3Gn-T5 than those of healthy donors (P < 0.05). Our results suggest that AML-associated GSLs Lc3, GM3 and nLc4 are possibly involved in initiation and differentiation of AML. [ABSTRACT FROM PUBLISHER]