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Implementing quantum algorithms on realistic devices requires translating high-level global operations into sequences of hardware-native logic gates, a process known as quantum compiling. Physical limitations, such as constraints in connectivity and gate alphabets, often result in unacceptable implementation costs. To enable successful near-term applications, it is crucial to optimize compilation by exploiting the capabilities of existing hardware. Here we implement a resource-efficient construction for a quantum version of AND logic that can reduce the compilation overhead, enabling the execution of key quantum circuits. On a high-scalability superconducting quantum processor, we demonstrate low-depth synthesis of high-fidelity generalized Toffoli gates with up to 8 qubits and Grover’s search algorithm in a search space of up to 64 entries. Our experimental demonstration illustrates a scalable and widely applicable approach to implementing quantum algorithms, bringing more meaningful quantum applications on noisy devices within reach.

Background: Acute myeloid leukemia (AML), one of the most common malignancies of the hematologic system, has progressively increased in incidence. Aging is present in both normal tissues and the tumor microenvironment. However, the relationship between senescence and AML prognosis is still not elucidated. Methods: In this study, RNA sequencing data of AML were obtained from TCGA, and prognostic prediction models were established by LASSO-Cox analysis. Differences in immune infiltration between the different risk groups were calculated using the CIBERSORT and ESTIMATE scoring methods. The KEGG and GO gene enrichment and GSEA enrichment were also used to enrich for differential pathways between the two groups. Subsequently, this study collected bone marrow samples from patients and healthy individuals to verify the differential expression of uncoupling protein 2 (UCP2) in different populations. Genipin, a UCP2 protein inhibitor, was also used to examine its effects on proliferation, cell cycle, and apoptosis in AML cell lines in vitro. Results: It showed that Aging-related genes (ARGs) expression was correlated with prognosis. And there was a significant difference in the abundance of immune microenvironment cells between the two groups of patients at high risk and low risk. Subsequently, UCP2 expression was found to be elevated in AML patients. Genipin inhibits UCP2 protein and suppresses the proliferation of AML cell lines in vitro. Conclusion: ARGs can be used as a predictor of prognosis in AML patients. Moreover, suppressing UCP2 can reduce the proliferation of AML cell lines, alter their cell cycle and promote apoptosis in vitro.

Background The increasing incidence of osteoporosis in recent years has aroused widespread public concern; however, existing effective treatments are limited. Therefore, new osteoporosis treatment methods, including stem cell transplantation and exosome therapy, have been proposed and are gaining momentum. Exosomes are considered to have greater potential for clinical application owing to their immunocompatibility. This study summarises the latest evidence demonstrating the efficacy of exosomes in improving bone loss in the treatment of osteoporosis. Main text This systematic review and meta-analyses searched PubMed, Embase, and Cochrane Library databases from inception to 26 March 2022 for osteoporosis treatment studies using stem cell-derived exosomes. Six endpoints were selected to determine efficacy: bone mineral density, trabecular bone volume/tissue volume fraction, trabecular number, trabecular separation, trabecular thickness, and cortical thickness. The search generated 366 citations. Eventually, 11 articles that included 15 controlled preclinical trials and 242 experimental animals (rats and mice) were included in the meta-analysis. Conclusion The results were relatively robust and reliable despite some publication biases, suggesting that exosome treatment increased bone mass, improved bone microarchitecture, and enhanced bone strength compared with placebo treatments. Moreover, stem cell-derived exosomes may favour anabolism over catabolism, shifting the dynamic balance towards bone regeneration.

The aim of the present study was to investigate the anti-diabetic effect of CGSGCG and its beneficial effects on gut microbiota in type 2 diabetes (T2D) mice induced by streptozotocin and high sucrose and high fat diet. The results showed that treatment with CGSGCG reduced fasting blood glucose, improved oral glucose tolerance test, protected the liver from injury, and reduced inflammation in T2D mice. The contents of acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid and isovaleric acid in CGSGCG group were 2.49-, 1.74-, 3.31-, 1.93-, 1.36- and 1.30-fold than that of the model group. Moreover, administration of CGSGCG up-regulated the expression of INSR/IRS-1/PI3K/AKT/GLUT4 and mTOR but down-regulated the P38MAPK expression. Furthermore, the abundance of beneficial bacteria such as Verrucomicrobia, Proteobacteria, Osillibacter, Dubosiella and Lactococcus in intestinal tract increased, indicating that CGSCGG regulated and improved the bacterial community structure of T2D mice, which were closely related to glycometabolism.

The growth and maturation of the ventricular chamber require spatiotemporally precise synergy between diverse cell types. Alternative splicing deeply affects the processes. However, the functional properties of alternative splicing in cardiac development are largely unknown. Our study reveals that an alternative splicing factor polypyrimidine tract-binding protein 1 (PTBP1) plays a key role in ventricular chamber morphogenesis. During heart development, PTBP1 colocalizes with endothelial cells but is almost undetectable in cardiomyocytes. The endothelial-specific knockout of Ptbp1, in either endocardial cells or pan-endothelial cells, leads to a typical phenotype of left ventricular noncompaction (LVNC). Mechanistically, the deletion of Ptbp1 reduces the migration of endothelial cells, disrupting cardiomyocyte proliferation and ultimately leading to the LVNC. Further study shows that Ptbp1 deficiency changes the alternative splicing of β-arrestin-1 (Arrb1), which affects endothelial cell migration. In conclusion, as an alternative splicing factor, PTBP1 is essential during ventricular chamber development, and its deficiency can lead to congenital heart disease.

Purpose Retinol-binding protein 4 (RBP4) has been considered to be related to metabolic related diseases, such as hyperuricemia, obesity, and diabetes mellitus. However, whether nonalcoholic fatty liver disease (NAFLD) is related to RBP4 is unclear. Previous studies on the relationship between NAFLD and RBP4 levels have yielded inconsistent results. Hence, this meta-analysis was aimed to clarify whether circulating RBP4 levels are in relation to the risk of NAFLD. Methods A meta-analysis was performed by applying observational studies to evaluate circulating RBP4 levels and NAFLD. Eligible studies published up to September 23, 2022, were searched in Embase, PubMed, and Cochrane databases. Results In this study, 17 cross-sectional studies involving 8423 participants were included. Results from a random effects model showed that circulating RBP4 levels were higher in NAFLD patients than non-NAFLD (standardized mean difference (SMD) 0.28; 95% confidence intervals (CI): 0.11–0.46, I2: 89.8%). This association was confirmed in the Yellow race. However, no significant association was noted in the Caucasian race. After excluding the morbidly obese Population from the weight loss study (n = 2), the results of the comparison remained largely unchanged (SMD 0.28; 95% CI: 0.10–0.47, I2: 90.8%). Remarkable publication bias was not found. Although considerable heterogeneity was observed among the studies, no potential sources of heterogeneity were found in the subgroup analysis. Diagnostic methods for NAFLD were determined to be a potential source of statistical heterogeneity in meta-regression. Conclusion The findings provide evidence that NAFLD patients exhibit higher levels of circulating RBP4 compared with controls, but high heterogeneity was observed. Thus, a high RBP4 level is probably a potential risk factor for NAFLD. To confirm the causal link between NAFLD and RBP4 level of causality, further prospective cohort studies are needed.

Currently, convolutional neural networks (CNNs) have made remarkable achievements in skin lesion classification because of their end-to-end feature representation abilities. However, precise skin lesion classification is still challenging because of the following three issues: (1) insufficient training samples, (2) inter-class similarities and intra-class variations, and (3) lack of the ability to focus on discriminative skin lesion parts. To address these issues, we propose a deep metric attention learning CNN (DeMAL-CNN) for skin lesion classification. In DeMAL-CNN, a triplet-based network (TPN) is first designed based on deep metric learning, which consists of three weight-shared embedding extraction networks. TPN adopts a triplet of samples as input and uses the triplet loss to optimize the embeddings, which can not only increase the number of training samples, but also learn the embeddings robust to inter-class similarities and intra-class variations. In addition, a mixed attention mechanism considering both the spatial-wise and channel-wise attention information is designed and integrated into the construction of each embedding extraction network, which can further strengthen the skin lesion localization ability of DeMAL-CNN. After extracting the embeddings, three weight-shared classification layers are used to generate the final predictions. In the training procedure, we combine the triplet loss with the classification loss as a hybrid loss to train DeMAL-CNN. We compare DeMAL-CNN with the baseline method, attention methods, advanced challenge methods, and state-of-the-art skin lesion classification methods on the ISIC 2016 and ISIC 2017 datasets, and test its generalization ability on the PH2 dataset. The results demonstrate its effectiveness.

Multi-view subspace clustering has been an important and powerful tool for partitioning multi-view data, especially multi-view high-dimensional data. Despite great success, most of the existing multi-view subspace clustering methods still suffer from three limitations. First, they often recover the subspace structure in the original space, which can not guarantee the robustness when handling multi-view data with nonlinear structure. Second, these methods mostly regard subspace clustering and affinity matrix learning as two independent steps, which may not well discover the latent relationships among data samples. Third, many of them ignore the different importance of multiple views, whose performance may be badly affected by the low-quality views in multi-view data. To overcome these three limitations, this paper develops a novel subspace clustering method for multi-view data, termed Kernelized Multi-view Subspace Clustering via Auto-weighted Graph Learning (KMSC-AGL). Specifically, the proposed method implicitly maps the multi-view data from linear space into nonlinear space via kernel-induced functions, so as to exploit the nonlinear structure hidden in data. Furthermore, our method aims to enhance the clustering performance by learning a set of view-specific representations and their affinity matrix in a general framework. By integrating the view weighting strategy into this framework, our method can automatically assign the weights to different views, while learning an optimal affinity matrix that is well-adapted to the subsequent spectral clustering. Extensive experiments are conducted on a variety of multi-view data sets, which have demonstrated the superiority of the proposed method.

As an excitatory transmitter system, the glutamatergic transmitter system controls excitability and conductivity of neurons. Since both cardiomyocytes and neurons are excitable cells, we hypothesized that cardiomyocytes may also be regulated by a similar system. Here, we have demonstrated that atrial cardiomyocytes have an intrinsic glutamatergic transmitter system, which regulates the generation and propagation of action potentials. First, there are abundant vesicles containing glutamate beneath the plasma membrane of rat atrial cardiomyocytes. Second, rat atrial cardiomyocytes express key elements of the glutamatergic transmitter system, such as the glutamate metabolic enzyme, ionotropic glutamate receptors (iGluRs), and glutamate transporters. Third, iGluR agonists evoke iGluR-gated currents and decrease the threshold of electrical excitability in rat atrial cardiomyocytes. Fourth, iGluR antagonists strikingly attenuate the conduction velocity of electrical impulses in rat atrial myocardium both in vitro and in vivo. Knockdown of GRIA3 or GRIN1, two highly expressed iGluR subtypes in atria, drastically decreased the excitatory firing rate and slowed down the electrical conduction velocity in cultured human induced pluripotent stem cell (iPSC)-derived atrial cardiomyocyte monolayers. Finally, iGluR antagonists effectively prevent and terminate atrial fibrillation in a rat isolated heart model. In addition, the key elements of the glutamatergic transmitter system are also present and show electrophysiological functions in human atrial cardiomyocytes. In conclusion, our data reveal an intrinsic glutamatergic transmitter system directly modulating excitability and conductivity of atrial cardiomyocytes through controlling iGluR-gated currents. Manipulation of this system may open potential new avenues for therapeutic intervention of cardiac arrhythmias.

Landscape plants have both ecological and aesthetic value and may also represent ideal candidates for phytoremediation. In the present study, one round of hydroponic culture for 14 days with different cadmium (Cd) concentrations (0, 0.5, 1, and 2 mg L-1 Cd) was carried out to test whether Hydrocotyle vulgaris L. is a Cd-tolerant plant. Furthermore, physiological parameters, including pigment concentrations, photosynthesis, antioxidant enzyme activities (AEAs), and nutrient uptake, were also examined to determine the tolerance of H. vulgaris to Cd exposure. The results showed that H. vulgaris could grow normally under all Cd supply levels. The Cd removal efficiency reached 100% at Cd concentrations ≤1.0 mg L-1. The concentrations of Cd in roots and shoots increased (P < 0.05) with Cd supplementation. The maximum concentrations of Cd reached 26.4 and 118 mg kg-1 in shoots and roots, respectively. The translocation factor values were similar under all Cd treatments. The highest mean daily increase in biomass (MDIB) was obtained under 1 mg L-1 Cd exposure, which increased by 69.86% compared to that in the control, which may be due to the increased photosynthetic pigments, photosynthetic rate, and the consistent nutrient concentrations under this Cd level, as there were positive relationships between these parameters and MDIB. Moreover, the activities of AEA also generally explicated highest among all Cd levels. All these results indicate that the above physiological parameters play a positive role in promoting plant growth and alleviating Cd stress. In summary, H. vulgaris was verified as a potential Cd-tolerant plant, providing new information for Cd phytoremediation. Furthermore, given its extensive habitat distribution, this species might be tested for phytoremediation of contaminated soils in future work.

The multistep-ahead prediction of chlorophyll provides an effective means for early warning of red tide. However, since multistep-ahead forecasting presents challenges, such as vague interactive relationships among ocean factors, long-term dependence modeling, and accumulative errors, existing methods mostly concentrate on the current time or one-step-ahead forecasting. In this paper, a hierarchical multistep-ahead forecasting model spatial-temporal attention network(STAN), which integrates the spatial context extractor network(SCE-net), long short-term memory network(LSTM), and the temporal attention mechanism, is proposed for the prediction of chlorophyll. In STAN, the input layer utilizes SCE-net to excavate relationships among ocean factors and generate high-level semantic via embedding factors into a continuous low-dimensional space. The middle layer applies LSTM to build the long-term dependencies of corresponding semantic representations. The output layer uses another LSTM with temporal attention to reduce accumulative errors and maintain temporal continuity. The attention can assign different weights to the middle layer’s hidden state and generate a context vector. Then the context vector and the final predicted value are considered as the current input for better forecasting. The buoy observation data of the Xiamen coastal area monitored in 2009–2011 is used to verify the efficiency of STAN. Experimental results prove that STAN outperforms the state-of-the-art methods of multistep-ahead prediction. When using 7 observation steps to forecast 15 steps, the MAPE of STAN is 0.3209, and the MAE is 0.1 lower than the values of the baselines approaches.

The adult mammalian heart is thought to be a terminally differentiated organ given the postmitotic nature of cardiomyocytes. Consequently, the potential for cardiac repair through cardiomyocyte proliferation is extremely limited. Low-density lipoprotein receptor-related protein 6 (LRP6) is a Wnt co-receptor that is required for embryonic heart development. In this study we investigated the role of LRP6 in heart repair through regulation of cardiomyocyte proliferation. Lrp6 deficiency increased cardiomyocyte cell cycle activity in neonatal, juvenile and adult mice. Cardiomyocyte-specific deletion of Lrp6 in the mouse heart induced a robust regenerative response after myocardial infarction (MI), led to reduced MI area and improvement in left ventricular systolic function. In vivo genetic lineage tracing revealed that the newly formed cardiomyocytes in Lrp6-deficient mouse hearts after MI were mainly derived from resident cardiomyocytes. Furthermore, we found that the pro-proliferative effect of Lrp6 deficiency was mediated by the ING5/P21 signaling pathway. Gene therapy using the adeno-associated virus (AAV)9 miRNAi-Lrp6 construct promoted the repair of heart injury in mice. Lrp6 deficiency also induced the proliferation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Our study identifies LRP6 as a critical regulator of cardiomyocyte proliferation, which may lead to the development of a novel molecular strategy to promote myocardial regeneration and repair.

As the electronic technology becomes increasingly integrated and miniaturized, thermal management has become a major challenge for electronic device applications. A heat pipe is a highly efficient two-phase heat transfer device. Due to its simple structure, high thermal conductivity and good temperature uniformity, it has been used in many different industrial fields. A novel aluminum flat heat pipe, with micro-grooves, has in the present work been designed and fabricated by using a 3D printing technology. Aluminum powder was used as a raw material, which was selectively melted and solidified to form the shape of the heat pipe. The sintered aluminum powder increased the roughness of the inner surface of the heat pipe, and the designed micro-grooves further enhanced the capillary forces induced by the wick structure. The wettability, for the working fluid (acetone), was excellent and the capillary forces were sufficient for the working fluid to flow back in the pipe. The effects of working fluid filling ratio, on the heat transfer performance of the heat pipe, was also investigated. It was shown that a filling ratio of 10% gave the best heat transfer performance with the lowest thermal resistance. The 3D-printed flat heat pipe was, therefore, also tested for the thermal management of a LED. The temperature of the LED could be kept within 40 °C and its service life became prolonged.

Semiconductor photocatalysis has attracted considerable attention because it is a promising way to deal with the global energy scarcity and environmental degradation. Over the past few decades, numerous strategies have been put forward to improve the visible-light absorption and decrease the electron–hole recombination of semiconductor photocatalysts. This review mainly focuses on the recent progress in morphology and the structure design of heterostructure-based semiconductor photocatalysts. In addition, the photocatalytic performance of semiconductor systems discussed mainly involves the environmental and energy application, including the degradation of pollutants, hydrogen generation and reduction of CO2 to form hydrocarbon fuel. Finally, the challenges and perspectives for future development of photocatalysts are also addressed.

In the present work, a systematic analysis of the microscopic plastic deformation mechanism and mechanical properties of interstitial impurities (H, O, N, S, and P) and Ni doped, or not doped, with Cr, was conducted based on generalized stacking fault energy curves generated via first-principles calculations. Focus has been put on the effects of Cr on plastic deformation for Ni doped interstitial impurities, upon the GPFE curve, with the aim to investigate the effects of Cr on the deformation mode and mechanical properties for doped Ni systems. It is found that a solid solution of Cr caused the tendency of partial dislocation in Ni. The evaluation of the Rice criterion reveals that Cr tends to decrease the ductility in Ni, and it cannot reverse interstitial H promoting the probability of cleavage fracture in Ni, while increases the ductility of O, P and S doped Ni, particular in O doped Ni, due to increasing the value of ductility D remarkably, so possibly changes the tendency of cleavage fracture. Besides, the solid solution of Cr is beneficial in promoting the dissociation of dislocation into fragments more easily in Ni, and enhances dislocation nucleation, while O, N, and S impurities have a slower rate of partial dislocation emission in Ni when interacting with Cr. Furthermore, Cr promotes the probability of twinning in Ni, and probably switches the deformation mechanism of H doped Ni from dislocation mediated slipping to twinning. Our study provides important insights toward the understanding and control of dislocation dynamics in doped Ni.

BackgroundLong non-coding RNAs (lncRNAs) have been identified as important epigenetic regulators that play critical roles in human cancers. However, the regulatory functions of lncRNAs in tumorigenesis remains to be elucidated. Here, we aimed to investigate the molecular mechanisms and potential clinical application of a novel lncRNA, retinoblastoma associated transcript-1 (RBAT1), in tumorigenesis.MethodsRBAT1 expression was determined by real-time PCR in both retinoblastoma (Rb) and bladder cancer (BCa) cell lines and clinical tissues. Chromatin isolation using RNA purification (ChIRP) assays were performed to identify RBAT1-interacting proteins. Patient-derived xenograft (PDX) retinoblastoma models were established to test the therapeutic potential of RBAT1-targeting GapmeRs.ResultsHere, we found that RBAT1 expression was significantly higher in Rb and BCa tissues than that in adjacent tissues. Functional assays revealed that RBAT1 accelerated tumorigenesis both in vitro and in vivo.Mechanistically, RBAT1 recruited HNRNPL protein to E2F3 promoter, thereby activating E2F3 transcription. Therapeutically, GapmeR-mediated RBAT1 silencing significantly inhibited tumorigenesis in orthotopic xenograft retinoblastoma models derived from Rb cell lines and Rb primary cells.ConclusionsRBAT1 overexpression upregulates a known oncogene, E2F3, via directly recruiting HNPNPL to its promoter and cis-activating its expression. Our finding provides a novel mechanism of lncRNA biology and provides potential targets for diagnosis and treatment of Rb and BCa.

Post-translational attachment of a small ubiquitin-like modifier (SUMO) to the lysine (K) residue(s) of target proteins (SUMOylation) is an evolutionary conserved regulatory mechanism. This modification has previously been demonstrated to be implicated in the control of a remarkably versatile regulatory mechanism of cellular processes. However, the exact regulatory role and biological actions of the E2 SUMO-conjugating enzyme (UBC9)-mediated SUMOylation function in pancreatic beta cells has remained elusive. Inducible beta cell-specific Ubc9 (also known as Ube2i) knockout (KO; Ubc9Δbeta) and transgenic (Ubc9Tg) mice were employed to address the impact of SUMOylation on beta cell viability and functionality. Ubc9 deficiency or overexpression was induced at 8 weeks of age using tamoxifen. To study the mechanism involved, we closely examined the regulation of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) through SUMOylation in beta cells. Upon induction of Ubc9 deficiency, Ubc9Δbeta islets exhibited a 3.5-fold higher accumulation of reactive oxygen species (ROS) than Ubc9f/f control islets. Islets from Ubc9Δbeta mice also had decreased insulin content and loss of beta cell mass after tamoxifen treatment. Specifically, at day 45 after Ubc9 deletion only 40% of beta cell mass remained in Ubc9Δbeta mice, while 90% of beta cell mass was lost by day 75. Diabetes onset was noted in some Ubc9Δbeta mice 8 weeks after induction of Ubc9 deficiency and all mice developed diabetes by 10 weeks following tamoxifen treatment. In contrast, Ubc9Tg beta cells displayed an increased antioxidant ability but impaired insulin secretion. Unlike Ubc9Δbeta mice, which spontaneously developed diabetes, Ubc9Tg mice preserved normal non-fasting blood glucose levels without developing diabetes. It was noted that SUMOylation of NRF2 promoted its nuclear expression along with enhanced transcriptional activity, thereby preventing ROS accumulation in beta cells. SUMOylation function is required to protect against oxidative stress in beta cells; this mechanism is, at least in part, carried out by the regulation of NRF2 activity to enhance ROS detoxification. Homeostatic SUMOylation is also likely to be essential for maintaining beta cell functionality.

According to diagnostic criteria, skin tumors can be divided into three categories: benign, low degree and high degree malignancy. For high degree malignant skin tumors, if not detected in time, they can do serious harm to patients' health. However, in clinical practice, identifying malignant degree requires biopsy and pathological examination which is time costly. Furthermore, in many areas, due to the severe shortage of dermatologists, it's inconvenient for patients to go to hospital for examination. Therefore, an easy to access screening method of malignant skin tumors is needed urgently. Firstly, we spend 5 years to build a dataset which includes 4,500 images of 10 kinds of skin tumors. All instances are verified pathologically thus trustworthy; Secondly, we label each instance to be either low-risk, high-risk or dangerous in which Junctional nevus, Intradermal nevus, Dermatofibroma, Lipoma and Seborrheic keratosis are low-risk, Basal cell carcinoma, Bowen's disease and Actinic keratosis are high-risk, Squamous cell carcinoma and Malignant melanoma are dangerous; Thirdly, we apply the Xception architecture to build the risk degree classifier. The area under the curve (AUC) for three risk degrees reach 0.959, 0.919 and 0.947 respectively. To further evaluate the validity of the proposed risk degree classifier, we conduct a competition with 20 professional dermatologists. The results showed the proposed classifier outperforms dermatologists. Our system is helpful to patients in preliminary screening. It can identify the patients who are at risk and alert them to go to hospital for further examination.

The objectives of this epidemiological study were to evaluate the prevalence of farmer's lung disease (FLD) and to explore the potential risk factors for FLD among Chinese greenhouse farmers. A total of 835 plastic film greenhouses, including 5,880 active farmers who engaged in crop cultivation or poultry farming, were randomly selected from the rural regions of Northeastern China. These farmers participated in the study by answering a medical questionnaire. 5,420 greenhouse farmers accepted and answered questionnaires in full (response rate, 92.18 %). Prevalence of FLD among these farmers was 5.7 % (308/5,420). Besides, a number of classic risk factors for FLD were identified, such as years of age, shorter time interval for re-entry greenhouse, ventilation frequency of greenhouse more than once per 4 h, the area of greenhouses greater than 30 m(2) but without a ventilation facility, ventilation duration less than 30 min every time, greenhouse with height less than 1.8 m, greenhouse with humidity greater than 65 %, frequent exposure to moldy materials in greenhouse, living inside greenhouse, and et al. FLD is and will continue to be a real health problem for Chinese farmers. If these preventive measures are implemented, the prevalence of FLD in Chinese greenhouse farmers might be greatly reduced.