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Objective We sought the optimal preprocessing method to improve the long-term transfer efficiency of adeno-associated viral (AAV) vectors of rat bladder urothelium. Methods Rat bladders were pretreated by eight different chemical reagents including PBS, trypsin, poly-L-lysine (PLL), protamine sulfate (PS), sodium dodecyl sulfate (SDS), n-dodecyl-β-d-maltoside (DDM), HCl or NaOH followed by transurethral instillation with AAV2/9-CMV-zsgreen. The transfection efficiency was evaluated by the percentage of urothelium with green fluorescence after 4 weeks. Results We employed eight different chemical components and eleven pretreatment methods. The rat bladder was harvested and evaluated without any mortality at 4 weeks post-infection. Compared with other treatment groups, the rate of urothelium transfection is comparatively high in the groups of rats treated with HCl or NaOH. In addition, rats treated with 0.1N NaOH 4 min showed significantly highest transfection efficiency (about 3%). The histopathologic results showed regular morphology of the bladder treated with HCl or NAOH and no significant damage was observed. Conclusion Pretreatment with 0.1N NaOH 4 min could improve the transfection efficiency of AAV in bladder urothelium and maintain the transfection efficiency for a long time without pathological damage. Importance We found that pretreatment of the bladder with HCl and NaOH can improve the transfection efficiency of AAV for a long time compared to control group. In addition, rats treated with 0.1N NaOH 4 min could have the most significant effect among these strategies, which was discovered for the first time. This could be valuable for future bladder gene therapy.

Two-dimensional (2D) transition metal oxide monolayers are currently attracting great interest in materials research due to their versatility and tunable electronic and magnetic properties. In this study, we report the prediction of magnetic phase changes in H x CrO2 (0 ⩽ x ⩽ 2) monolayer on the basis of first-principles calculations. As the H adsorption concentration x increases from 0 to 0.75, H x CrO2 monolayer transforms from a ferromagnetic (FM) half-metal to a small-gap FM insulator. When x = 1.00 and 1.25, it behaves as a bipolar antiferromagnetic (AFM) insulator, and eventually becomes an AFM insulator as x increases further up to 2.00. The results suggest that the magnetic properties of CrO2 monolayer can be effectively controlled by hydrogenation, and that H x CrO2 monolayers have the potential for realizing tunable 2D magnetic materials. Our results provide a comprehensive understanding of the hydrogenated 2D transition metal CrO2 and provide a research method that can be used as a reference for the hydrogenation of other similar 2D materials.

The prognosis analysis of gastric cancer is critical for selection of treatments and development of advanced therapeutic methods. A prognosis approach that is accurate, fast, convenient, and of low cost for gastric cancers is in high demand. Raman spectroscopy is a label-free and non-destructive technique to provide molecular fingerprints of biological samples, holding promises for cancer prognosis. However, the major challenge of gastric cancer prognosis lies in the widely existing tumor heterogeneity, which leads to unexpected spectral variations within one type of samples. In this work, we have developed the Euclidean distance (ED)-based Raman spectroscopy (EDRS) method for the prognosis analysis of gastric cancer to eliminate the influence of tumor heterogeneity. Raman spectra were first collected on the slices of paraffin-preserved tumor tissues from gastric cancer patients. A standard spectrum to represent the 'worst prognostic tumor cells' was then established. The similarity between each spectrum of tissues and the standard spectrum was assessed by ED, to provide a direct assessment on the prognosis status. We have successfully classified the patients into poor and favorable prognosis groups, either based on the averaged regional ED values (sensitivity of 75 %, specificity of 96.8 %), or based on the minimal ED values at the patient level (sensitivity of 90 %, specificity of 100 %). EDRS was also investigated for survival analysis (AUC = 0.955), much better than the commonly applied post-neoadjuvant therapy (ypTNM) category (AUC = 0.718). Our work highlights EDRS as a rapid, accurate, low-cost and robust tool for heterogeneous cancer-related prognosis assessment and survival prediction, providing new insights for spectroscopic tumor analysis.

Background The fractional order calculus (FROC) model has been developed to describe restrained motion of water molecules as well as microstructural heterogeneity, providing a novel tool for non-invasive tumor grading. Purpose To evaluate the role of the FROC model in characterizing clear cell renal cell carcinoma (ccRCC) grades. Material and Methods A total of 59 patients diagnosed with ccRCC were included in this prospective study. The diffusion metrics derived from the mono-exponential model (apparent diffusion coefficient [ADC]), intra-voxel incoherent motion [IVIM] model [D, D*, f], and FROC model [Dfroc, β, μ]) were calculated and compared between low- and high-grade ccRCCs. Binary logistic regression analysis was performed to establish the diagnostic models. Receiver operating characteristic (ROC) analysis and DeLong test were performed to evaluate and compare the diagnostic performance of metrics in grading ccRCC. Results All the metrics except D* and f exhibited statistical differences between low- and high-grade ccRCCs. ROC analysis showed individual FROC parameters, μ, Dfroc, and β, outperformed ADC and IVIM parameters in grading ccRCC. For single parameter, μ demonstrated the highest AUC value, sensitivity, and diagnostic accuracy in discriminating the two ccRCC groups while β exhibited the optimal specificity. Importantly, the combination of Dfroc, μ, and β could further improve the diagnostic performance. Conclusion The FROC parameters were superior to ADC and IVIM parameters in grading ccRCC, indicating the great potential of the FROC model in distinguishing low- and high-grade ccRCCs.

Because of the recent growth in ground-level ozone and increased emission of volatile organic compounds (VOCs), VOC emission control has become a major concern in China. In response, emission caps to control VOC have been stipulated in recent policies, but few of them were constrained by the co-control target of PM

Diabetic cardiomyopathy (DCM) can develop in diabetes mellitus and is a major cause of morbidity and mortality. Surgical bariatric surgery procedures, such as sleeve gastrectomy (SG), result in remission of type 2 diabetes and have benefits regarding systolic and diastolic myocardial function. The NLR family pyrin domain containing 3 (NLRP3) inflammasome appears to participate in the development of DCM. However, whether SG surgery affects myocardial NLRP3 inflammasome-related pyroptosis to improve cardiac function remains unclear. This study was aimed at investigating the effect of SG surgery on NLRP3-associated pyroptosis in rats with DCM. We also examined cellular phenotypes and molecular mechanisms in high glucose-stimulated myocytes. The rat model of DCM was established by high-fat diet feeding and low-dose streptozotocin injection. We observed a metabolic benefit of SG, including a reduced body weight, food intake, and blood glucose levels and restored glucose tolerance and insulin sensitivity postoperatively. We observed a marked decline in glucose uptake in rats with DCM, and this was restored after SG. Also, SG alleviated the dysfunction of myocardial contraction and diastole, delayed the progression of DCM, and reduced the NLRP3 inflammasome-mediated myocardial pyroptosis in vivo. H9c2 cardiomyocytes showed membrane disruption and DNA damage under a high glucose stimulus, which suggested myocardial pyroptosis. Using a ROS scavenger or chloride channel blocker in vitro restored myocardial NLRP3-mediated pyroptosis. Furthermore, we found that chloride efflux acted downstream of ROS generation. In conclusion, SG may ameliorate or even reverse the progression of DCM. Our study provides evidence that the SG operation alleviates NLRP3 inflammasome dysregulation in DCM. Clearance of ROS overburden and suppression of chloride efflux due to SG might act as the proximal event before inhibition of NLRP3 inflammasome in the myocardium, thus contributing to morphological and functional alleviation of DCM.

Objective. To determine the impact of cardiopulmonary rehabilitation administered through WeChat on exercising resilience and life quality in aged people with heart failure (HF). Methods. We conducted prospective cohort study that included 80 heart failure patients who were admitted to the Second Affiliated Hospital of Wenzhou Medical University from June 2018 to September 2020, 80 patients with heart failure. Patients were grouped according to their use of WeChat for rehabilitation. WeChat cohort provides remote supervision of rehabilitation and nursing guidance through WeChat. Specifically, the findings below were predetermined and compared across treatment groups utilizing analysis of variance corrected for baseline levels of the end measure and location: changes in the length of cardiopulmonary exercise tests, peak VO2, the proportion of predicted maximum VO2, and variation in the distance covered during the 6-minute walk distance (6MWD) assessment. Comparison of negative emotions between two groups, a Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS), and Survey Short Form-36 (SF36) at baseline and at month 2. Results. In contrast with the control cohort, the WeChat cohort did not show any significant differences in general data ( P > 0.05). After the rehabilitation, the WeChat group has a notably higher level in 6MWD than in the control group. Prior to the rehabilitation, there were no statistical gaps between the two cohorts in terms of SAS and SDS scores ( P > 0.05). Even though the two cohorts saw a decline in SAS and SDS scores following nursing, the observation cohort indicated a much relatively low level in contrast with the control cohort ( P P > 0.05). Following nursing, the scores of the two cohorts declined significantly, with the control cohort scoring far lower than the other ( P

Objectives To elaborately decipher the mouse and human bladders at single‐cell levels. Materials and Methods We collected more than 50,000 cells from multiple datasets and created, up to date, the largest integrated bladder datasets. Pseudotime trajectory of urothelium and interstitial cells, as well as dynamic cell‐cell interactions, was investigated. Biological activity scores and different roles of signaling pathways between certain cell clusters were also identified. Results The glucose score was significantly high in most urothelial cells, while the score of H3 acetylation was roughly equally distributed across all cell types. Several genes via a pseudotime pattern in mouse (Car3, Dkk2, Tnc, etc.) and human (FBLN1, S100A10, etc.) were discovered. S100A6, TMSB4X, and typical uroplakin genes seemed as shared pseudotime genes for urothelial cells in both human and mouse datasets. In combinational mouse (n = 16,688) and human (n = 22,080) bladders, we verified 1,330 and 1,449 interactive ligand‐receptor pairs, respectively. The distinct incoming and outgoing signaling was significantly associated with specific cell types. Collagen was the strongest signal from fibroblasts to urothelial basal cells in mouse, while laminin pathway for urothelial basal cells to smooth muscle cells (SMCs) in human. Fibronectin 1 pathway was intensely sent by myofibroblasts, received by urothelial cells, and almost exclusively mediated by SMCs in mouse bladder. Interestingly, the cell cluster of SMCs 2 was the dominant sender and mediator for Notch signaling in the human bladder, while SMCs 1 was not. The expression of integrin superfamily (the most common communicative pairs) was depicted, and their co‐expression patterns were located in certain cell types (eg, Itgb1 and Itgb4 in mouse and human basal cells). Conclusions This study provides a complete interpretation of the normal bladder at single‐cell levels, offering an in‐depth resource and foundation for future research., Multiple scRNA‐seq datasets of normal mouse and human bladder were collected. Through standard workflow of Seurat R package, we identified cell clusters in bladder tissue. After initial exploration of differentially expressed gene and gene set enrichment analysis, we performed trajectory analysis for pan‐fibroblasts and urothelial cells and identified common pseudotime genes across datasets and species. Then, we integrated multiple datasets to create, to date, the largest cell map of mouse and human bladder, respectively. We further explored the details of signaling pathways between certain cell types and the communication networks of specific pathways.

To compare the accuracy of several volume and diameters modified prostate health index (mPHI) models with PHI density (PHID), PHI, and other prostate-specific antigen (PSA) derivatives in detecting PSA grey zone prostate cancer (PCa).Between August 2020 and September 2021, a consecutive cohort of 214 suspected PCa patients with elevated total PSA values ranged from 4.0 to 10.0 ng/mL were prospectively recruited and received PHI detections and transrectal ultrasonography (TRUS) measurements, followed by systematic prostate biopsies confirmation.Among the 214 patients enrolled in the project, a total of 80 were diagnosed with PCa. In univariate analysis for the training cohort, the area under curve (AUC) of mPHI-2 [Formula: see text] was 0.8310, which outperformed PHID in identifying PSA grey zone PCa (P ≤ 0.0001) and showed the best net benefit in decision curve analysis (DCA). By a threshold of 0.2835, the sensitivity and specificity in the prediction of PCa were 78.9% and 90.3%, while the positive predictive value (PPV) and negative predictive value (NPV) were 78.3% and 78.6%, respectively.According to our present single-center experience, the mPHI-2 risk predictor outperformed PHID or other classical parameters alone in the PCa detection with a grey zone PSA level in Asian males.

Diabetic cardiomyopathy (DCM) is characterized by impaired diastolic and systolic myocardial performance and is a major cause of morbidity and mortality in patients with diabetes. Surgical bariatric procedures, such as sleeve gastrectomy (SG), result in remission of type 2 diabetes (T2DM) and have benefits with myocardial function. Maintaining cardiac mitochondrial homeostasis is a promising therapeutic strategy for DCM. However, whether SG surgery affects mitochondrial function and its underlying mechanism remains unclear. This study aimed to investigate the effect of SG surgery on mitochondrial homeostasis and intracellular oxidative stress in rats with DCM. We also examined cellular phenotypes and molecular mechanisms in high glucose and high fat-stimulated myocytes. The rat model of DCM was established by high-fat diet feeding and low-dose streptozotocin injection. We observed a remarkably metabolic benefit of SG, including a reduced body weight, food intake, blood glucose levels, and restored glucose tolerance and insulin sensitivity post-operatively. Also, SG ameliorated the pathological cardiac hypertrophy, myocardial fibrosis and the dysfunction of myocardial contraction and diastole, consequently delayed the progression of DCM. Also, SG restored the mitochondrial dysfunction and fragmentation through the AMPK signaling activation mediated nuclear receptor subfamily 4 group A member 1 (NR4A1)/DRP1 suppression

The Ca2+ modulated pulsatile secretion of glucagon and insulin by pancreatic α and β cells plays a key role in glucose homeostasis. However, how α and β cells coordinate via paracrine interaction to produce various Ca2+ oscillation patterns is still elusive. Using a microfluidic device and transgenic mice in which α and β cells were labeled with different colors, we were able to record islet Ca2+ signals at single cell level for long times. Upon glucose stimulation, we observed heterogeneous Ca2+ oscillation patterns intrinsic to each islet. After a transient period, the oscillations of α and β cells were globally phase-locked, i.e., the two types of cells in an islet each oscillate synchronously but with a phase shift between the two. While the activation of α cells displayed a fixed time delay of ~20 s to that of β cells, β cells activated with a tunable delay after the α cells. As a result, the tunable phase shift between α and β cells set the islet oscillation period and pattern. Furthermore, we demonstrated that the phase shift can be modulated by glucagon. A mathematical model of islet Ca2+ oscillation taking into consideration of the paracrine interaction was constructed, which quantitatively agreed with the experimental data. Our study highlights the importance of cell-cell interaction to generate stable but tunable islet oscillation patterns.

A $(2+1)$-dimensional gapped quantum many-body system can have a topologically protected energy current at its edge. The magnitude of this current is determined entirely by the temperature and the chiral central charge, a quantity associated with the effective field theory of the edge. We derive a formula for the chiral central charge that, akin to the topological entanglement entropy, is completely determined by the many-body ground state wave function in the bulk. According to our formula, nonzero chiral central charge gives rise to a topological obstruction that prevents the ground state wave function from being real-valued in any local product basis., Comment: 4+6 pages, 6 figures, added references, minor changes

Background: Cardiac hypertrophy as a main pathological manifestation of diabetic cardiomyopathy (DCM), is a significant complication of diabetes. Bariatric surgery has been proven to relieve DCM; however, whether it can alleviate diabetes-induced cardiac hypertrophy is undefined.Methods: Diabetic and obese rats were performed sleeve gastrectomy (SG) after having diabetes for 16weeks. The rats were euthanized 8weeks after SG. Metabolic parameters, heart function parameters, myocardial glucose uptake, morphometric and histological changes, and the expression level of mitogen-activated protein kinases (MAPKs) were determined and compared among the control group (CON group), diabetes mellitus group (DM group), sham operation group (SHAM group), and SG group.Results: Compared with the SHAM group, the blood glucose, body weight, insulin resistance, and other metabolic parameters were significantly improved in the SG group. There was also a marked improvement in myocardial morphometric and histological parameters after SG. Furthermore, the myocardial glucose uptake and heart function were reversed after SG. Additionally, the phosphorylation of MAPKs was inhibited after SG, including p38 MAPKs, c-Jun N-terminal kinases (JNKs), and extracellular signal-regulated kinases 1/2 (ERK1/2). The expression of DUSP6, which dephosphorylates ERK1/2, was upregulated after SG. These findings suggest that SG ameliorated diabetes-induced cardiac hypertrophy correlates with the MAPK signaling pathway.Conclusion: These results showed that diabetes-induced cardiac hypertrophy was ameliorated after SG was closely related to the inhibition of the MAPK signaling pathway and upregulation of DUSP6. Therefore, this study provides a novel strategy for treating diabetes-induced cardiac hypertrophy.

Recently, a topological-to-trivial insulator quantum-phase transition induced by an electric field has been experimentally reported in monolayer (ML) and bilayer (BL) Na

Antiferromagnetism within the two-dimensional (2D) family offers a platform for spintronics. The emergent 2D semiconductor ${\mathrm{Cr}\mathrm{PS}}_{4}$ is proved to be composed of ferromagnetic layers with antiferromagnetic coupling along the stacking direction in the experiment. By using the first-principles quantum-transport simulation, we evaluate the spin-resolved transport in the magnetic tunnel junction built by the 2D ${\mathrm{Cr}\mathrm{PS}}_{4}$ tunnel barrier with large thickness ranges. We find the magnetoresistance generally increases with the number of tunnel layers from 140% (three layers) to a surprising 370 000% (10 layers). An odd-even oscillation magnetoresistance behavior exists in few layers due to the electrode option. Our results will inspire further experimental verification and provide vital insights for 2D spintronics design.

Background: Perioperative neurocognitive disorders (PND) occur frequently and refer to alterations in cognitive function after surgery, especially in elderly patients. PND is characterized as abnormalities of learning, memory, language, and emotions. Cucurbitacin E has been reported to possess various pharmacological properties, including anticancer, antiviral, and anti-inflammatory effects. In this study, we investigated whether cucurbitacin E could alleviate sevoflurane-induced cognitive dysfunction in rats. Methods: Sprague-Dawley male rats (~6 weeks old) were randomly assigned to three groups: the control group, the Sevoflurane group, and the Sevoflurane + Cucurbitacin E group. Subsequently, the cognitive dysfunction of the rats was evaluated through the morris water maze test. Hematoxylin and eosin (HE) staining was used to measure the pathological change in brain tissues. Enzyme-linked immunosorbent assay (ELISA) kits were used for determinations of S-100 calcium binding protein B (S-100β) and neuron-specific enolase (NSE) and cytokine. Cell apoptosis was analyzed by TdT-Mediated Nick-End Labeling (TUNEL) staining. Protein levels were confirmed by Western blotting. Results: Cucurbitacin E relieved brain injury in rats induced by sevoflurane. Cucurbitacin E alleviated sevoflurane-induced S-100β and NSE levels. Additionally, the Morris water maze task revealed that cucurbitacin E attenuated cognition impairment in sevoflurane-induced rats. Sevoflurane increased levels of IL-6, TNF-α and IL-1β levels, and decreased the level of IL-10. However, cucurbitacin E exhibited opposite effects on these cytokines, which were induced by sevoflurane. Furthermore, cucurbitacin E inhibited sevoflurane-induced neuron apoptosis and NF-κB pathway in rats. Conclusion: These findings indicate that cucurbitacin E can improve sevoflurane-induced cognitive dysfunction in rats by regulating NF-κB pathway, which provided a new strategy for PND treatment.

Antarctic krill has been widely studied because of its abundant biomass, rich nutritional value, and great production potential. Notably, krill oil (KO) is rich in phospholipids (PLs), polyunsaturated fatty acids (PUFAs), and astaxanthin. A method based on a green switchable hydrophilicity solvent N,N-dimethylcyclohexylamine (DMCHA), which can reversibly change from oil soluble to water soluble in the presence of CO2 was used to extract KO from frozen Antarctic krill as it consumes less energy than traditional methods. We showed that DMCHA destroyed the surface structure of Antarctic krill and accelerated the dissolution of KO. In addition, this method enabled the PL extraction to reach up to 80.2% of total PLs, among which PC accounted for the highest proportion, up to 90.91% in PL. In fact, the astaxanthin extraction reached up to 81.44% of total astaxanthin while the fatty acid (FA) extraction up to 84.35%. The KO extracted through DMCHA was rich in PUFA, up to 47.74%, and the content of EPA + DHA reached 42.16% of total FA content. Furthermore, the amount of residual solvent in the lipid phase was just 0.23% of the DMCHA used for the extraction and the recovery rate of solvent was up to 93.2%. Our results demonstrated the high efficiency of oil extraction and the environmental friendliness of this method.

Ferromagnetic order in two-dimensional (2D) van der Waals crystals has been attracting much attention recently. Remarkably, room temperature metallic ferromagnetism is realized in 2D Fe3GeTe2. Here we design a monolayer (ML) Fe3GeTe2 spin-valve device by attaching two ends to ferromagnetic electrodes and applying a magnetic field to these ferromagnetic electrodes. We investigate the spin-involved transport characteristics of such a spin valve by using ab initio quantum transport simulation. A high magnetoresistance of ∼390% is obtained and significantly increased to 450–510% after the gates are introduced. The magnetoresistance of the ML Fe3GeTe2 spin valve is insensitive to the strain modulation. Our study provides a potential option for magnetic storage applications and will motivate further studies in spintronics based on this class of materials.

Monolayer (ML) MoS2 is one of the most extensively studied two-dimensional (2D) semiconductors. However, it suffers from low carrier mobility and pervasive Schottky contact with metal electrodes. 2D semiconductor Bi2O2S, a sulfur analogue of 2D Bi2O2Se, has been prepared recently. ML fully hydrogen-passivated Bi2O2S2 (Bi2O2S2H2) posseses a comparable band gap (1.92 eV) with ML MoS2 (1.8 eV), but probably has a better device performance than ML MoS2. Based on the density functional theory, the electron and hole mobilities of ML Bi2O2S2H2 at 300 K are calculated to be 16 447–26 699 and 264–968 cm2 V−1 s−1, respectively. Then we firstly characterize the contact properties of ML half hydrogen-passivated Bi2O2S2 (Bi2O2S2H) with four bulk metal electrodes (Ti, Sc, Pd, and Pt) based on ab initio quantum transport simulation. In the lateral direction, a p-type Schottky contact is found in Pd and Pt electrodes, and the corresponding hole Schottky barrier heights (SBHs) are 0.54 and 0.99 eV, respectively. Remarkably, a coveted n-type Ohmic contact appears in Sc and Ti electrodes. Finally, the current on–off ratio of the ML hydrogen-passivated Bi2O2S2 field effect transistor with a Ti electrode reaches 105. Hence, the good intrinsic properties, contact properties, and large switching ability put ML hydrogen-passivated Bi2O2S2 in the rank of potential channel candidates for post-silicon era field effect transistors.

Two-dimensional (2D) semiconductors are expected to be suitable channel materials for next-generation transistors because of their ultrathin thickness and smooth surface. Monolayer (ML) BiH (bismut...

Two-dimensional (2D) semiconducting InSe has received great attention due to its high mobility. Compared with its monolayer, bilayer (BL) InSe has a more appropriate band gap as the channel of fiel...

Intelligent transportation systems (ITS) have been developed rapidly over the last few decades because of global urbanization and industrialization. ITS involve a wide range of different technologies and applications such as automatic road enforcement, dynamic traffic light sequence, and as a result, a significant number of scientific papers have been published in the field of ITS. In this paper, we present a useful insight into the development of ITS area by systematically analyzing the publications over the period of 20 years. First, we identify the most cited papers and most impactful authors in the field. Second, in the aspect of topic analysis, we identify some active keywords. To do so, we develop a keyword co-occurrence network to find topics in the ITS field. Finally, for the collaboration pattern analysis, we construct two networks to interpret collaboration patterns, including a co-authorship network, and an author co-keyword network to show the development and research tendency of ITS. Some most interesting findings from our investigation include the following: 1) Besides the USA, China and Europe have begun to play an increasingly significant role in this field and 2) GPS , traffic control , and road safety show an upward trend from the analysis of the evolution of ITS research topics, given the rise of new research areas such as autonomous vehicles. Our first-hand investigation and analysis of the literature provides a valuable reference to research activities in the development of ITS field and presents worthy insights on the current status and future technical trends.

Owing to its promising electronic application of monolayer (ML) MoS2, ML MoS2–metal contacts have been widely explored. The experiments reveal a very strong Fermi level pinning, and the correspondi...

Due to their outstanding gate electrostatics, two-dimensional (2D) semiconducting materials are regarded as promising channel materials used in the next-generation field-effect transistors (FETs). ...

The present study examined optimism, as measured by the Life Orientation Test-Revised, and coping behaviors, as measured by the COPE scale, as predictors of hedonic well-being (viz., life satisfaction, positive affect, and subjective happiness) in a sample of 462 Asian Indians (237 women and 225 men). We hypothesized that optimism would remain an important predictor of well-being even after accounting for coping behaviors. Results of conducting hierarchical regression analyses indicated that coping behaviors, as a set, accounted for a significant amount of unique variance in each of the three measures of hedonic well-being (f2 range = .16 to .39), after controlling for key demographic and socioeconomic factors (e.g., age, sex, parent education level, and family income). Noteworthy, the use of humor was found to be the only consistent coping predictor across the three indices of hedonic well-being. Importantly, when optimism was included in the prediction model, it was consistently found to account for additional variance in hedonic well-being (f2 range = .11 to .15), beyond coping behaviors. These findings are the first to affirm the centrality of optimism in predicting hedonic well-being in Asian Indians. Accordingly, efforts to foster hedonic well-being in Asian Indians might benefit from not only changing coping behaviors, but also from building greater optimism.

Significant photoconductive effects are reported in emergent two-dimensional (2D) ${\mathrm{Bi}}_{2}{\mathrm{O}}_{2}\mathrm{Se}$. In this work, we investigate the layer-dependent photoresponse properties and photovoltaic effects of 2D ${\mathrm{Bi}}_{2}{\mathrm{O}}_{2}X$ (X = $\mathrm{S}$, $\mathrm{Se}$, and $\mathrm{Te}$) by first-principles calculations and quantum-transport simulation. The absorbance per layer increases with the decreasing layer number for high-frequency light, so the absorbance density of 2D ${\mathrm{Bi}}_{2}{\mathrm{O}}_{2}X$ can be elevated by decreasing the layer number. An outstanding open-circuit voltage (1.08 V) among 2D materials is found for the monolayer (ML) ${\mathrm{Bi}}_{2}{\mathrm{O}}_{2}\mathrm{Se}$ p-n junction. The computed responsivities of ML black phosphorous, ${\mathrm{Mo}\mathrm{S}}_{2}$, and ${\mathrm{W}\mathrm{Se}}_{2}$ p-n junctions through our methods are in good agreement with experiments. The ML ${\mathrm{Bi}}_{2}{\mathrm{O}}_{2}\mathrm{Se}$ and ${\mathrm{Bi}}_{2}{\mathrm{O}}_{2}\mathrm{Te}$ p-n junctions show responsivities of 16.8 and 13.6 mA/W, respectively, under AM1.5 sunlight; these values are higher than those of their extensively studied ML ${\mathrm{Mo}\mathrm{S}}_{2}$ (8.6) and ${\mathrm{W}\mathrm{Se}}_{2}$ (8.8) counterparts. The ${\mathrm{Bi}}_{2}{\mathrm{O}}_{2}\mathrm{Se}$ film and ${\mathrm{Bi}}_{2}{\mathrm{O}}_{2}\mathrm{S}$ p-n junctions also show higher responsivities than those of commercial $\mathrm{Si}$ and $\mathrm{Ga}\mathrm{As}$. Therefore, the 2D ${\mathrm{Bi}}_{2}{\mathrm{O}}_{2}X$ p-n junctions have prospective applications in photovoltaic devices.

Fingerspelling, in which words are signed letter by letter, is an important component of American Sign Language. Most previous work on automatic fingerspelling recognition has assumed that the boundaries of fingerspelling regions in signing videos are known beforehand. In this paper, we consider the task of fingerspelling detection in raw, untrimmed sign language videos. This is an important step towards building real-world fingerspelling recognition systems. We propose a benchmark and a suite of evaluation metrics, some of which reflect the effect of detection on the downstream fingerspelling recognition task. In addition, we propose a new model that learns to detect fingerspelling via multi-task training, incorporating pose estimation and fingerspelling recognition (transcription) along with detection, and compare this model to several alternatives. The model outperforms all alternative approaches across all metrics, establishing a state of the art on the benchmark., Comment: CVPR 2021

BackgroundLung cancer is the leading cause of death from cancer, and lung adenocarcinoma (LUAD) is the most common form. Despite the great advances that has been made in the diagnosis and treatment for LUAD, the pathogenesis of LUAD remains unclear. In this study, we aimed to identify the function of circKEAP1 derived from the exon of KEAP1 in LUAD.MethodsThe expression profiles of circRNAs in LUAD tissues and adjacent non-tumor tissues were analyzed by Agilent Arraystar Human CircRNA microarray. The levels and prognostic values of circKEAP1 in tissues and cancer cell lines were determined by quantitative real-time PCR (qRT-PCR). Subsequently, the effects of circKEAP1 on tumor growth were investigated by functional experiments in vitro and in vivo. Mechanistically, the dual luciferase reporter assay, RNA pull-down, and RNA immunoprecipitation experiments were performed to confirm the interaction between circKEAP1 and miR-141-3p in LUAD.ResultsWe found circKEAP1 was significantly downregulated in LUAD tissues and repressed tumor growth both in vitro and in vivo. Mechanistically, circKEAP1 competitively binds to miR-141-3p and relive miR-141-3p repression for its host gene, which activated the KEAP1/NRF2 signal pathway, and finally suppresses the tumor progress. Our findings suggest that circKEAP1 inhibits LUAD progression through circKEAP1/miR-141-3p/KEAP1 axis and it may serve as a novel method for the treatment of LUAD.

We study the ground-state entanglement of gapped domain walls between topologically ordered systems in two spatial dimensions. We derive a universal correction to the ground-state entanglement entropy, which is equal to the logarithm of the total quantum dimension of a set of superselection sectors localized on the domain wall. This expression is derived from the recently proposed entanglement bootstrap method., Comment: 5 pages, 5 figures

Gastric cancer (GC), characterized by uncontrolled growth, is a common malignant tumor of the digestive system. The Wnt signaling pathway plays an important role in the tumorigenesis and proliferation of GC. Many studies on this signaling pathway have focused on its intracellular regulatory mechanism, whereas little attention has been given to extracellular regulatory factors. Dickkopf-1 (Dkk1) is a secretory glycoprotein, and it can bind inhibit activation of the Wnt pathway. However, the regulation and mechanism of DKK1 in the proliferation of GC remain unclear. FOXC1 plays an important role in organ development and tumor growth, but its role in GC tumor growth remains unknown. In this study, we found that the FOXC1 is highly expressed in patients with GC and high expression of FOXC1 correlates to poor prognosis. In addition, we found that the Wnt signaling pathway in GC cells with high FOXC1 expression was strongly activated. FOXC1 negatively regulates DKK1 expression by binding to its promoter region, thereby promoting the activation of Wnt pathway. FOXC1 can also form a complex with unphosphorylated β-catenin protein in the cytoplasm and then dissociates from β-catenin in the nucleus, thereby promoting the entry of β-catenin into the nucleus and regulating expression of c-MYC, which promotes the proliferation of GC cells. Our study not only reveals the function and mechanism of FOXC1 in GC, but also provides a potential target for clinic GC treatment.

Fin field-effect transistors (FinFETs) dominate the present Si FETs. However, when the gate length is scaled down to the sub-10 nm region, the experimental Si FinFETs suffer from poor performance due to a large fin width (the minimum value is 3 nm). In this paper, an ultra-thin Si FinFET with a width of 0.8 nm is investigated for the first time by utilizing ab initio quantum transport simulations. Remarkably, even with the gate length down to 5 nm, the on-state current, delay time, power dissipation, and energy-delay product of the optimized perfect ultra-thin Si FinFET still meet the high-performance applications' requirements of the International Technology Roadmap for Semiconductors in the next decade. The overall performance of the simulated ultra-thin Si FinFET is even comparable with that of the typical two-dimensional FETs. Such a good performance can be significantly degraded by the defect. Hence, Si FinFETs have the potential to be scaled down to the sub-10 nm gate length as long as the width is scaled down while keeping a perfect structure.

BackgroundThe neutrophil to lymphocyte ratio (NLR) has been reported as an indicator for poor prognosis in many cancers including esophageal cancer. However, the relationship between the NLR and postoperative complications after esophageal cancer resection remains unclear. At present, enhanced recovery after surgery (ERAS) lacks an inclusion criteria. The aim of this study is to determine whether the preoperative NLR (preNLR) can predict complications after esophageal cancer resection, which could represent the criteria for ERAS. MethodsThis was a retrospective study on 171 patients who underwent esophagectomy at Hospital between November 2019 and November 2020(68 patients from Changhai Hospital, 65 patients from Shanghai General Hospital and 38 patients from Affiliated Hospital of Qingdao University). Univariate and multivariate logistic regression analyses were performed to demonstrate that the preNLR could predict complications after esophagectomy. ResultsA preNLR cutoff value of 2.30 was identified as having the greatest ability to predict complications with a sensitivity of 76% and specificity of 65%. Moreover, the Chi-squared test results showed that the preNLR was significantly associated with complications (x2=13.641, p

Volatile organic compounds (VOCs) source profiles can be used for a number of purposes, such as creating speciated air pollutant emission inventories and providing inputs to receptor and air quality models. In this study, we first collected and schematically evaluated more than 500 Chinese domestic source profiles from literature and field measurements, and then established a most up-to-date dataset of VOCs source profiles in China by integrating 363 selective VOCs profiles into 101 sector-based source profiles. The profile dataset covers eight major source categories and contains 447 VOCs species including non-methane hydrocarbons (NMHCs) species and oxygenated VOCs (OVOCs) species. The results shown that (1) VOCs composition characteristics exhibit variations for most Level-II source sectors and Level-III sub-sectors even under the same Level-I source category; (2) OVOCs, which were significantly missing in previous profiles, account for more than 95% in cooking and 20- 40% in non-road mobile, biomass burning and solvent use sources; (3) aromatics account for 20%-40% in most emission sources except cooking source, alkenes and alkynes account for ~20% in combustion sources (stationary combustion, mobile source and biomass burning), alkanes are abundant in gasoline-related emission sources(on-road mobile source and fuel oil storage and transportation); (4) missing OVOCs species could bring 30%-50% to ozone formation potentials in most emission sources; and (5) there are considerable differences in VOCs chemical groups and individual species for most emission sources between this dataset and the widely used U.S. SPECIATE database, indicating the importance of developing domestic VOCs source profiles. The dataset developed in this study can help support reactive VOCs species-based ozone control strategy and provide domestic profile data for source apportionment and air quality modeling in China and other countries or regions with similar emission source characteristics.

Ferromagnetic order in two-dimensional (2D) van der Waals crystals has been attracting much attention recently. Remarkably, room temperature metallic ferromagnetism is realized in 2D Fe3GeTe2. Here we design a monolayer (ML) Fe3GeTe2 spin-valve device by attaching two ends to ferromagnetic electrodes and applying a magnetic field to these ferromagnetic electrodes. We investigate the spin-involved transport characteristics of such a spin valve by using ab initio quantum transport simulation. A high magnetoresistance of ∼390% is obtained and significantly increased to 450-510% after the gates are introduced. The magnetoresistance of the ML Fe3GeTe2 spin valve is insensitive to the strain modulation. Our study provides a potential option for magnetic storage applications and will motivate further studies in spintronics based on this class of materials.

One ubiquitous environmental issue with the abandoned gassy coal mine is the potential of changes in water quality due to water–rock–gas action caused by high residual gas content. Therefore, a better understanding of how to accurately characterize the new multiphase system in the closed gassy coal mine is required. The gas in closed coal mine mainly includes CH $$_{4}$$ , CO $$_{2,}$$ N $$_{2}$$ , H $$_{2}$$ S, CO, etc., existing in the adsorbed, dissolved and free phases, which also leads to complex gas–water–rock interactions in the underground flooded pool. The recovery of the water level caused by the closure of the coal mine varied dramatically in hydrogeochemical conditions as well as gas flow performance in the flooded mine. Based on the nationwide investigation and case studies of high residual coal mine gas in abandoned coal mines in China, some sealed gassy coal mines have been experiencing the CO $$_{2}$$ inrush problems. Modeling experiments of mine water–rock (coal)–gas(CO $$_{2}$$ /N $$_{2}$$ ) reaction were conducted in closed coal mines. The results show that with the increasing reaction time, pH value increases gradually, and the relationship between Eh and pH is negative, by taking CO $$_{2}$$ /N $$_{2}$$ as gas phases in the water–rock reaction. The concentration of HCO $$_{3}^{-}$$ , SO $$_{4}^{2-}$$ , Ca $$^{2+}$$ , Mg $$^{2+, }$$ and SiO $$_{2}$$ increases with a different magnitude, and the level of total Fe decreases gradually, while the TDS of the solution increases. The reaction between typical minerals in coal and high SO $$_{4}^{2-}$$ and Fe $$^{3+}$$ mine water is simulated. The chemical composition of mine water and coal mineral compositions are modified in order to obtain the influence of particular reactions. The results show that in the mine water–rock–gas reaction with CO $$_{2}$$ as gas phase, the pH value of the solution increases, and the Eh decreases. The dissolution of mineral phases leads to an increasing trend in the content of HCO $$_{3}^{-}$$ , SO $$_{4}^{2-}$$ , Ca $$^{2+}$$ , Mg $$^{2+}$$ , and soluble SiO $$_{2}$$ in the water. The concentration of the total Fe in the solution gradually decreases, and the mineralization of the solution gradually increases. Each mineral has individual distinct dissolution reaction rate. The dissolution of kaolinite promotes the dissolution of quartz, while calcite dissolves along with the regeneration of new carbonate minerals. Pyrite dissolves accompanied by chlorite formation. For the N $$_{2}$$ gas phase, changes in hydrochemistry and mineral phases are mainly controlled by water–rock interaction.

An accurate characterization of spatial-temporal emission patterns and speciation of volatile organic compounds (VOCs) for multiple chemical mechanisms is important to improving the air quality ensemble modeling. In this study, we developed a 2017-based high-resolution (3 km × 3 km) model-ready emission inventory for Guangdong Province (GD) by updating estimation methods, emission factors, activity data, and allocation profiles. In particular, a full-localized speciation profile dataset mapped to five chemical mechanisms was developed to promote the determination of VOC speciation, and two dynamic approaches based on big data were used to improve the estimation of ship emissions and open fire biomass burning (OFBB). Compared with previous emissions, more VOC emissions were classified as oxygenated volatile organic compound (OVOC) species, and their contributions to the total ozone formation potential (OFP) in the Pearl River Delta (PRD) region increased by 17%. Formaldehyde became the largest OFP species in GD, accounting for 11.6% of the total OFP, indicating that the model-ready emission inventory developed in this study is more reactive. The high spatial-temporal variability of ship sources and OFBB, which were previously underestimated, was also captured by using big data. Ship emissions during typhoon days and holidays decreased by 23–55%. 95% of OFBB emissions were concentrated in 9% of the GD area and 31% of the days in 2017, demonstrating their strong spatial-temporal variability. In addition, this study revealed that GD emissions have changed rapidly in recent years due to the leap-forward control measures implemented, and thus, they needed to be updated regularly. All of these updates led to a 5–17% decrease in the emission uncertainty for most pollutants. The results of this study provide a reference for how to reduce uncertainties in developing model-ready emission inventories.

The advancement of artificial intelligence and wearable computing triggers the radical innovation of cognitive applications. In this work, we propose VIMES, an augmented reality-based memory assistance system that helps recall declarative memory, such as whom the user meets and what they chat. Through a collaborative method with 20 participants, we design VIMES, a system that runs on smartglasses, takes the first-person audio and video as input, and extracts personal profiles and event information to display on the embedded display or a smartphone. We perform an extensive evaluation with 50 participants to show the effectiveness of VIMES for memory recall. VIMES outperforms (90% memory accuracy) other traditional methods such as self-recall (34%) while offering the best memory experience (Vividness, Coherence, and Visual Perspective all score over 4/5). The user study results show that most participants find VIMES useful (3.75/5) and easy to use (3.46/5).

BackgroundCircular RNAs (circRNAs) are widely expressed noncoding RNAs, and plays a key role in the biological function of competitive endogenous RNA (ceRNA) network in various human diseases, especially in cancer. However, the regulatory roles of circRNAs in lung adenocarcinoma (LUAD) remains largely unknown. MethodsThe expression profiles of circRNAs in LUAD tissues and adjacent non-tumor tissues were analyzed by Agilent Arraystar Human CircRNA microarray. The level and prognostic values of circKEAP1 in tissues and cancer cell lines were determined by quantitative real-time PCR. Then, the effects of circKEAP1 on tumor growth were investigated by functional experiments in vitro and in vivo. Mechanistically, dual luciferase reporter assay, RNA pull-down and RNA immunoprecipitation experiments were performed to confirm the interaction between circKEAP1 and miR-141-3p in LUAD.ResultsWe found circKEAP1 was significantly downregulated in LUAD tissues, and repressed tumor growth both in vitro and in vivo. Mechanistically, circKEAP1 competitively binds to miR-141-3p and relive miR-141-3p repression for its target gene KEAP1, which activated the KEAP1/NRF2 signal pathway, and finally suppress the cell proliferation.ConclusionsOur findings suggest that circKEAP1 inhibits LUAD progression through circKEAP1/miR-141-3p/KEAP1 axis and it may serve as a new target for treatment of LUAD patients.

Existing deep learning based methods for 3D human pose estimation cannot be deployed on resource-constrained devices. In this paper, we propose a Tiny-HourglassNet for 3D human pose estimation that improves the efficiency of Stacked Hourglass Networks with a guarantee of estimation performance. To be concrete, we develop an efficient Tiny-Hourglass backbone with two different types of ShuffleNet V2 blocks. At the meantime, we present a Simple Estimation Head (SEH) to reduce the resource utility for depth prediction. Furthermore, we develop two feature enhancement modules, namely Feature Enhancement Module (FEM) and Intermediate Enhancement Module (IEM), to improve the feature representation ability of Tiny-HourglassNet without evident increment of resource usage and computational complexity. Experimental results demonstrate that Tiny-HourglassNet achieves equivalent accuracy with a reduction of 80% complexity (FLOPs) in comparison to the baselines.

SUMMARYThe Ca2+ modulated pulsatile secretion of glucagon and insulin by pancreatic α and β cells plays a key role in glucose homeostasis. However, how α and β cells coordinate via paracrine interaction to produce various Ca2+ oscillation patterns is still elusive. Using a microfluidic device and transgenic mice in which α and β cells were labeled with different colors, we were able to record islet Ca2+ signals at single cell level for long times. Upon glucose stimulation, we observed heterogeneous Ca2+ oscillation patterns intrinsic to each islet. After a transient period, the oscillations of α and β cells were globally phase-locked, i.e., the two types of cells in an islet each oscillate synchronously but with a phase shift between the two. While the activation of α cells displayed a fixed time delay of ~20 s to that of β cells, β cells activated with a tunable delay after the α cells. As a result, the tunable phase shift between α and β cells set the islet oscillation period and pattern. Furthermore, we demonstrated that the phase shift can be modulated by glucagon. A mathematical model of islet Ca2+ oscillation taking into consideration of the paracrine interaction was constructed, which quantitatively agreed with the experimental data. Our study highlights the importance of cell-cell interaction to generate stable but tunable islet oscillation patterns.

Background Hexokinase domain component 1 (HKDC1) plays an oncogenic role in certain types of cancer, such as lymphoma, liver cancer, and breast cancer. Previous bioinformatics study revealed that HKDC1 was significantly upregulated in lung adenocarcinoma (LUAD). However, its biological functions and potential mechanism in LUAD have not been studied. Methods We performed bioinformatics analysis, quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, immunohistochemistry, and a series of functional assays in vitro and in vivo to investigate the roles of HKDC1 in LUAD. Results We discovered that HKDC1 was highly expressed in LUAD tissues and cell lines, and the positive expression of HKDC1 was correlated with aberrant clinicopathological characteristics in LUAD patients. Furthermore, HKDC1 could serve as a prognostic predictor for LUAD patients. Overexpression of HKDC1 promoted proliferation, migration, invasion, glycolysis, EMT and tumorigenicity, whereas knockdown of HKDC1 produced the opposite functional effects. Mechanistically, HKDC1 could regulate the AMPK/mTOR signaling pathway to perform its biological function. Conclusions Our findings suggest that HKDC1 plays an oncogenic role in LUAD. Targeting this gene may provide a promising therapeutic target to delay LUAD progression.

Background: Large-scale loss-of-function screening database such as Cancer Dependency Map (Depmap) provide abundant resources. Investigation of these potential dependency genes from human cancer cell lines in the real-world patients cohort would evaluate their prognostic value thus facilitate their clinical application and guide drug development. Methods: A few genes were selected from top clear cell renal cell carcinoma (ccRCC) lineage preferential dependency candidates from Depmap. Their characteristic including expression levels both in normal and tumor tissues and correlations with methylation or copy number, genetic alterations, functional enrichment, immune-associated interactions, prognostic value were evaluated in KIRC cohort from TCGA, GTEx, and multiple other open databases and platforms. Results: 16 genes were collected from 106 ccRCC preferential candidates and further analyzed including B4GALT4, BCL2L1, CDH2, COPG1, CRB3, FERMT2, GET4, GPX4, HNF1B, ITGAV, MDM2, NFE2L2, PAX8, RUVBL1, TFRC, and TNFSF10. The normalized gene effect scores of these genes varied from different ccRCC cell lines and principal component analysis (PCA) showed their tissue specificity expression profiles. Genetic alteration rates of them were low to moderate (0.7%-13%) in KIRC cohort. CDH2, MDM2, TNFSF10 showed a statistically significant higher level in tumors than normal tissues while PAX8 and FERMT2 were significantly downregulated. Moderate positive or negative correlations were observed in several genes between their expression and relative gene copy number or methylation levels, respectively. Based on the multivariable COX regression model adjusted by critical clinical variables revealed the expression of GET4 (p=0.002, HR=1.023 95%CI 1.009-1.038) and CRB3 (p

As one of the thinnest forms of semiconducting silicon, monolayer (ML) silicane has not only excellent gate electrostatics and carrier transport ability, but also compatibility with well-established silicon-based technology. We explore the device performance limits of sub-5-nm ML silicane metal-oxide-semiconductor field-effect transistors (MOSFETs) by applying ab initio quantum transport simulations. The on-state current, effective delay time, and power-delay product of the optimized n-type and p-type ML silicane MOSFETs can well or nearly meet the high-performance device requirements of the International Technology Roadmap for Semiconductors (ITRS) at a gate length of 5 nm. Those of the optimized n-type ML silicane MOSFETs at a gate length of 3 nm and the p-type ML silicane MOSFETs at a gate length of 5 nm can meet the low-power-device demands of the ITRS. Thus, ML silicane as channel materials can scale the Moore's law down to 5 nm.