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Abstract Exercise training (ExT) is capable of improving the heart function of spontaneously hypertensive rats (SHRs), but the underlying molecular mechanisms remain elusive. This study was aimed to investigate whether inhibition of RhoA/ROCK signaling pathway contributes to the cardiac protection by low-intensity ExT in SHRs. The results demonstrated that, compared with Wistar-Kyoto (WKY) rats, SHRs obviously exhibited higher blood pressure, increased heart weight index and thickness of left ventricular wall, decreased left ventricular function, damaged myocardial construction, and increased collagen fiber of left ventricle (P

Abstract Background Medical evidence from more recent observational studies may significantly alter our understanding of disease incidence and progression, and would require recalibration of existing computational and predictive disease models. However, it is often challenging to perform recalibration when there are a large number of model parameters to be estimated. Moreover, comparing the fitting performances of candidate parameter designs can be difficult due to significant variation in simulated outcomes under limited computational budget and long runtime, even for one simulation replication. Methods We developed a two-phase recalibration procedure. As a proof-of-the-concept study, we verified the procedure in the context of sex-specific colorectal neoplasia development. We considered two individual-based state-transition stochastic simulation models, estimating model parameters that govern colorectal adenoma occurrence and its growth through three preclinical states: non-advanced precancerous polyp, advanced precancerous polyp, and cancerous polyp. For the calibration, we used a weighted-sum-squared error between three prevalence values reported in the literature and the corresponding simulation outcomes. In phase 1 of the calibration procedure, we first extracted the baseline parameter design from relevant studies on the same model. We then performed sampling-based searches within a proper range around the baseline design to identify the initial set of good candidate designs. In phase 2, we performed local search (e.g., the Nelder-Mead algorithm), starting from the candidate designs identified at the end of phase 1. Further, we investigated the efficiency of exploring dimensions of the parameter space sequentially based on our prior knowledge of the system dynamics. Results The efficiency of our two-phase re-calibration procedure was first investigated with CMOST, a relatively inexpensive computational model. It was then further verified with the V/NCS model, which is much more expensive. Overall, our two-phase procedure showed a better goodness-of-fit than the straightforward employment of the Nelder-Mead algorithm, when only a limited number of simulation replications were allowed. In addition, in phase 2, performing local search along parameter space dimensions sequentially was more efficient than performing the search over all dimensions concurrently. Conclusion The proposed two-phase re-calibration procedure is efficient at estimating parameters of computationally expensive stochastic dynamic disease models.

Abstract Remote sensing scene classification aims to automatically assign a specific semantic label to each image. It is challenging to classify remote sensing scene images due to the images' diversity and rich spatial information. Recently, convolutional neural networks have been widely used to overcome these difficulties, such as the famous Visual Geometry Group (VGG) network. However, the VGG network with local receptive fields cannot model the global information of remote sensing images well. It also needs a large number of parameters and floating point operations to achieve satisfactory accuracy. To overcome these challenges, we introduce the self‐attention mechanism to the VGG network. Specifically, we replace the last four convolutional layers in the VGG‐19 network with two cascaded self‐attention blocks, each consisting of two multi‐head self‐attention (MHSA) layers with the residual network structure. The new structure can simultaneously explore the local and global information from remote sensing scenes. Such improvements not only reduce model parameters but also improve the classification performance. The effectiveness of the proposed method is validated through experiments on four public data sets, i.e., NaSC‐TG2, WHU‐RS19, AID and EuroSAT.

Testicular cancer is the most common malignancy in men 20–40 years old and most commonly metastasizes to the lung, liver, and brain. Choroidal metastasis from testicular cancer is exceedingly rare, and only few cases have been described in the literature. We report a patient who presented with painful unilateral vision loss as the initial presenting symptom of metastatic testicular germ cell tumor (GCT). A 22-year-old Latino man presented with a 3-week history of progressive central vision loss and dyschromatopsia, accompanied by intermittent, throbbing ocular, and periocular pain, in the left eye. Associated symptom was remarkable for abdominal pain. Examination of the left eye disclosed light perception vision and a large choroidal mass in the posterior pole involving the optic disk and the macula with associated hemorrhages. Neuroimaging showed a 2.1-cm lesion in the posterior globe of the left eye, and B-scan and A-scan ultrasonography findings were consistent with choroidal metastasis. Systemic workup revealed a mass in the left testicle with metastasis to the retroperitoneum, lungs, and liver. Biopsy of a retroperitoneal lymph node showed a GCT. Visual acuity worsened from light perception to no light perception 5 days following initial presentation. Several cycles of chemotherapy were completed, including salvage therapy; however, these treatments were unsuccessful. While vision loss due to choroidal metastasis as the initial presenting symptom of testicular cancer is rare, clinicians should consider metastatic testicular cancer in the differential diagnoses in patients with choroidal tumors, especially in young men.

Mesenchymal stem cells (MSCs), one of the most common types of stem cells, are involved in the modulation of the tumor microenvironment (TME). With the advancement of nanotechnology, exosomes, especially exosomes secreted by MSCs, have been found to play an important role in the initiation and development of tumors. In recent years, nanobiotechnology and bioengineering technology have been gradually developed to detect and identify exosomes for diagnosis and modify exosomes for tumor treatment. Several novel therapeutic strategies bioengineer exosomes to carry drugs, proteins, and RNAs, and further deliver their encapsulated cargoes to cancer cells through the properties of exosomes. The unique properties of exosomes in cancer treatment include targeting, low immunogenicity, flexibility in modification, and high biological barrier permeability. Nevertheless, the current comprehensive understanding of the roles of MSCs and their secreted exosomes in cancer development remain inadequate. It is necessary to better understand/update the mechanism of action of MSCs-secreted exosomes in cancer development, providing insights for better modification of exosomes through bioengineering technology and nanobiotechnology. Therefore, this review focuses on the role of MSCs-secreted exosomes and bioengineered exosomes in the development, progression, diagnosis, and treatment of cancer.

Abstract Background Circular RNA (circRNA) and N6‐methyladenosine (m6A) play a critical role in tumour occurrence and development, including colorectal cancer (CRC). However, little is known about the interaction between circRNA and m6A in the radiosensitivity of CRC. Here, we investigated the role of a novel m6A‐regulated circRNA in CRC. Methods Differentially expressed circRNAs from radiosensitive and radioresistant CRC tissues were screened. Modifications of the selected circRNAs were examined by methylated RNA immunoprecipitation assay. Finally, the selected circRNAs were subjected to radiosensitivity assay. Results We identified that circAFF2 is closely related to both radiosensitivity and m6A in CRC. CircAFF2 was highly expressed in patients with radiosensitive rectal cancer, and patients with high expression of circAFF2 had a better prognosis. In addition, circAFF2 can enhance the radiosensitivity of CRC cells both in vitro and in vivo. The regulation of circAFF2 involves ALKBH5‐mediated demethylation, followed by its recognition and degradation via YTHDF2. Rescue experiments revealed that circAFF2 could reverse the radiosensitivity induced by ALKBH5 or YTHDF2. Mechanistically, circAFF2 binds with CAND1, promotes the binding of CAND1 to Cullin1 and inhibits its neddylation, subsequently impacting the radiosensitivity of CRC. Conclusion We identified and characterised circAFF2 as a novel m6A‐modified circRNA and validated the ALKBH5/YTHDF2/circAFF2/Cullin‐NEDD8 axis as a potential radiotherapy target for CRC.

Introduction: Zhixue Zhentong capsules (ZXZTCs) are a Tibetan medicine preparation solely composed of Lamiophlomis rotata (Benth.) Kudo. L. rotata is the only species of the genus Laniophlomis (family Lamiaceae) that has medicinal constituents derived from the grass or root and rhizome. L. rotata is one of the most extensively used folk medicines by Tibetan, Mongolian, Naxi, and other ethnic groups in China and has been listed as a first-class endangered Tibetan medicine. The biological effects of the plant include hemostasis, analgesia, and the removal of blood stasis and swelling.Purpose: This study aimed to profile the overall metabolites of ZXZTCs and those entering the blood. Moreover, the contents of six metabolites were measured and the hemostatic, analgesic, and anti-inflammatory effects of ZXZTCs were explored.Methods: Ultra-performance liquid chromatography–tandem quadrupole time-of-flight high-resolution mass spectrometry (UPLC-Q-TOF-MS) was employed for qualitative analysis of the metabolites of ZXZTCs and those entering the blood. Six metabolites of ZXZTCs were quantitatively determined via high-performance liquid chromatography The hemostatic, analgesic, and anti-inflammatory effects of ZXZTCs were evaluated in various animal models.Results: A total of 36 metabolites of ZXZTCs were identified, including 13 iridoid glycosides, 9 flavonoids, 9 phenylethanol glycosides, 4 phenylpropanoids, and 1 other metabolite. Overall, 11 metabolites of ZXZTCs entered the blood of normal rats. Quantitative analysis of the six main metabolites, shanzhiside methyl ester, chlorogenic acid, 8-O-acetyl shanzhiside methyl ester, forsythin B, luteoloside, and verbascoside, was extensively performed. ZXZTCs exerted hemostatic effects by reducing platelet aggregation and thrombosis and shortening bleeding time. Additionally, ZXZTCs clearly had an analgesic effect, as observed through the prolongation of the latency of writhing, reduction in writhing, and increase in the pain threshold of experimental rats. Furthermore, significant anti-inflammatory effects of ZXZTCs were observed, including a reduction in capillary permeability, the inhibition of foot swelling, and a reduction in the proliferation of granulation tissue.Conclusion: Speculative identification of the overall metabolites of ZXZTCs and those entering the blood can provide a foundation for determining its biologically active constituents. The established method is simple and reproducible and can help improve the quality control level of ZXZTCs as a medicinal product. Evaluating the hemostatic, analgesic, and anti-inflammatory activities of ZXZTCs can help reveal its mechanism.

The chemical ordering and its effect on structure and elastic properties of Mg1-xScx alloys are studied by ab initio method. The MgSc alloys show strong chemical long range ordering tendency as the Sc concentration increase. The predicted martensitic phase of fully disordered alloy is hcp when the transformation occurs through the Burgers path. Chemical long range ordering could lead to a lattice distortion and results in a low symmetric orthorhombic martensitic phase, namely, there is a chemical-structural coupling in MgSc alloys. The chemical long range ordering also has strong hardening effect, the single crystalline elastic moduli C′, C44, Young’s modulus and Shear modulus are increased by 12.6%, 4.2%, 4.4% and 5% for Mg80Sc20 alloy, respectively. Electronic structure analysis showed that the additional s-d and p-d hybridization between near neighboring Mg and Sc ions in ordered phase is accounting for the elastic hardening and chemical-structural coupling in MgSc alloys.

Silicon steel is a widely used soft magnetic material that requires different texture components for different applications, typically classified as grain-oriented or non-oriented. However, the methods of fabricating such types of silicon steel via laser-powder bed fusion (LPBF) have not been fully investigated. In this study, near grain-oriented and near non-oriented Fe-3.5 wt.%Si silicon steel is fabricated using LPBF by controlling processing parameters. Different textures are investigated using electron backscatter diffraction (EBSD), and the morphology of the molten pool is characterized by optical microscopy (OM) and scanning electron microscopy (SEM). Magnetic properties are measured with alternating current (AC) method. The results show that reducing both the linear energy density (LED) and laser power leads to a change in the side morphology of the molten pool from large, flat, and well-overlapped to small, protuberant, and less-overlapped, resulting in an extremely strong θ-fiber texture or a random distribution of grain orientations, respectively. Additionally, reducing both the laser power and scanning speed causes the top morphology of the molten pool to change from teardrop to elliptical shape at the trailing edge, resulting in a shift in the angle between the 〈001〉 of grains in the θ-fiber texture and the scanning direction from 45° to 30°. Samples with fewer defects (i.e., larger grain size and fewer pores) and a larger area fraction of 〈001〉//H exhibit higher permeability, although this superiority is not so significant due to residual stress and high dislocation in the as-built samples. This study provides insight into the relationship between processing parameters, texture evolution, and magnetic properties in LPBFed silicon steel.

BackgroundIntracellular communication within the tumour is complex and extracellular vesicles (EVs) have been identified as major contributing factors for the cell-to-cell communication in the local and distant tumour environments. Here, we examine the differential effects of breast cancer (BC) subtype-specific patient serum and cell-line derived EVs in the regulation of T cell mediated immune responses. MethodsUltracentrifugation was used to isolate EVs from sera of 63 BC patients, 15 healthy volunteers and 4 human breast cancer cell lines. Longitudinal blood draws for EV isolation for patients on neoadjuvant chemotherapy was also performed. Characterization of EVs was performed by Nanoparticle Tracking Analysis (NTA), transmission electron microscopy (TEM) and immunoblotting. CD63 staining was performed on a tissue microarray of 218 BC patients. In-house bioinformatics algorithms were utilized for the computation of EV associated expression scores within The Cancer Genome Atlas (TCGA) and correlated with tumour infiltrating lymphocyte (TIL) scores. In vitro stimulation of PBMCs with EVs from serum and cell-line derived EVs was performed and changes in the immune phenotypes characterized by flow cytometry. Cytokine profiles were assessed using a 105-plex immunoassay or IL10 ELISA. ResultsPatients with triple negative breast cancers (TNBCs) exhibited the lowest number of EVs in the sera; whilst the highest was detected in ER+HER2+ cancers; reflected also in the higher level of CD63+ vesicles found within the ER+HER2+ local tumour microenvironment. Transcriptomic analysis of the TCGA data identified that samples assigned with lower EV scores had significantly higher abundance of CD4+ memory activated T cells, T follicular cells and CD8 T cells, plasma, and memory B cells; whilst samples with high EV scores were more enriched for anti-inflammatory M2 macrophages and mast cells. A negative correlation between EV expression scores and stromal TIL counts was also observed. In vitro experiments confirmed that circulating EVs within breast cancer subtypes have functionally differing immunomodulatory capabilities, with EVs from patients with the most aggressive breast cancer subtype (TNBCs) demonstrating the most immune-suppressive phenotype (decreased CD3+HLA-DR+ but increased CD3+PD-L1 T cells, increased CD4+CD127-CD25hi T regulatory cells with associated increase in IL10 cytokine production). In depth assessment of the cytokine modulation triggered by the serum/cell line derived exosomes confirmed differential inflammatory cytokine profiles across differing breast cancer subtypes. Studies using the MDA-231 TNBC breast cancer cell-line derived EVs provided further support that TNBC EVs induced the most immunosuppressive response within PBMCs.DiscussionOur study supports further investigations into how tumour derived EVs are a mechanism that cancers can exploit to promote immune suppression; and breast cancer subtypes produce EVs with differing immunomodulatory capabilities. Understanding the intracellular/extracellular pathways implicated in alteration from active to suppressed immune state may provide a promising way forward for restoring immune competence in specific breast cancer patient populations.

High-speed elevator systems comprise numerous components, and vibration issues are prevalent. The evident non-linear behavior resulting from changes in the wire rope length adds complexity to the investigation of elevator dynamics issues. This paper investigates dynamics modeling and numerical solution methods for longitudinal vibrations in a typical high-speed elevator system. The primary contributions of this paper include constructing a dynamics model for high-speed elevators using a substructure dynamics modeling approach. This model incorporates Newton’s law and the Lagrange equation to comprehensively represent the dynamics of the elevator car, car frame, traction system, and tension system. Additionally, a non-linear dynamics model of the steel wire rope is developed using the centralized mass method. This paper also presents an algorithm to solve the time-domain dynamics based on the variable-step-length Runge–Kutta method. Furthermore, it investigates the non-linear dynamics of elevators considering variations in the elevator’s intrinsic frequency and different elevator control strategies, focusing on the response characteristics of high-speed elevator dynamics. The findings of this thesis hold significant importance in the field of high-speed elevator dynamics. They aid in the design and debugging of high-speed elevator systems and serve as a foundation for future research into the non-linear aspects of elevators.

The torsional stiffness parameter significantly influences the natural frequency of a leaf spring torsional vibration damper and its proper match with a diesel engine, and the nonlinear characteristics of torsional stiffness avoid reduced reliability due to the excessive torsion angle of the damper. An efficient mechanical model for the damper with nonlinear characteristics is established by integrating the Euler–Bernoulli beam theory and accounting for the geometric nonlinearity of leaf spring deformation during operation. The model’s validity is confirmed through finite element analysis. This study then explores the influence of design parameters on the mechanical characteristics of the damper. The results reveal a gradual increase in the torsional stiffness of the damper with the expanding arc radius of the clamping groove. Simultaneously, the torsional stiffness curve exhibits more pronounced nonlinear characteristics. In contrast, an elongation of the leaf spring leads to a sharp decline in torsional stiffness, accompanied by a diminishing prominence of nonlinear traits. Thus, both the arc radius of the clamping groove and the spring length significantly impact the torsional stiffness and nonlinear features of the leaf spring torsional vibration damper. The nonlinear characteristics intensify with an enlarged arc radius of the clamping groove and a reduced leaf spring length. Additionally, the damper’s torsional stiffness is influenced by the leaf spring thickness and the red copper gasket length. Future damper designs should comprehensively consider these relevant parameters.

The layer-by-layer deposition strategy of additive manufacturing makes it ideal to fabricate dissimilar alloy components with varying functionality, which has promising application potential in a large number of industrial areas. In this study, two components composed of ERCuAl-A2 aluminum bronze (CuAl9) and Inconel 718 nickel-based superalloy were fabricated with different deposition orders by wire-arc directed energy deposition. Subject to changes in heat input and thermophysical properties of the substrate, the transition region of the deposited Cu–Ni component with the bottom half of CuAl9 and the top half of Inconel 718 is narrow and serrated. This region features a laminated intermetallic compound layer due to the convection and rapid cooling in the molten pool. In contrast, the Ni–Cu component deposited in the opposite order exhibits a 2 mm gradient transition zone. Within this region, a large number of diverse precipitates were found as well as regional variations in grain size due to the multi-layer partial remelting. Both two components show strong bonds and their tensile specimens tested along the vertical direction always fracture at the softer CuAl9 side. Excellent tensile properties along the horizontal direction were obtained for Cu–Ni (Ultimate tensile strength: 573 MPa, yield stress: 302 MPa, elongation: 22%), while those of Ni–Cu are much lower due to the existence of the solidification cracks in the transition zone. The results from this study provide a reference for the additive manufacturing of Cu/Ni dissimilar alloy components, as well as their microstructure and mechanical properties control.

Two-dimensional (2D) materials, such as tungsten disulfide (WS2), have attracted considerable attention for their potential in gas sensing applications, primarily due to their distinctive electrical properties and layer-dependent characteristics. This research explores the impact of the number of WS2 layers on the ability to detect gases by examining the layer-dependent sensing performance of WS2-based gas sensors. We fabricated gas sensors based on WS2 in both monolayer and multilayer configurations and methodically evaluated their response to various gases, including NO2, CO, NH3, and CH4 at room temperature and 50 degrees Celsius. In contrast to the monolayer counterpart, the multilayer WS2 sensor exhibits enhanced gas sensing performance at higher temperatures. Furthermore, a comprehensive gas monitoring system was constructed employing these WS2-based sensors, integrated with additional electronic components. To facilitate user access to data and receive alerts, sensor data were transmitted to a cloud-based platform for processing and storage. This investigation not only advances our understanding of 2D WS2-based gas sensors but also underscores the importance of layer engineering in tailoring their sensing capabilities for diverse applications. Additionally, the development of a gas monitoring system employing 2D WS2 within this study holds significant promise for future implementation in intelligent, efficient, and cost-effective sensor technologies.

In recent years, quinoa, as a nutritious and sustainable food material, has gained increasing popularity worldwide. To investigate the diversity of nutritional characteristics among different quinoa cultivars and explore their potential health benefits, metabolites of five quinoa cultivars (QL-1, SJ-1, SJ-2, KL-1 and KL-2) were compared by non-targeted metabolomics analysis based on UPLC-ZenoTOF-MS/MS in this study. A total of 248 metabolites across 13 categories were identified. Although the metabolite compositions were generally similar among the different quinoa cultivars, significant variations existed in their respective metabolite contents. Among the identified metabolites, amino acids/peptides, nucleosides, saponins and phenolic acids were the most abundant. Notably, SJ-1 exhibited the most distinct metabolite profile when compared to the other cultivars. Amino acids/peptides and nucleosides were found to be crucial factors contributing to the unique metabolite profile of SJ-1. Collectively, these aforementioned metabolites accounted for a substantial 60% of the total metabolites observed in each quinoa variety. Additionally, a correlation between the DPPH radical scavenging activity and the free phenolic content of quinoa was observed. Variations in phenolic content resulted in different antioxidant capacities among the quinoa cultivars, and SJ-1 exhibited lower phenolic levels and weaker antioxidant activity than the others. These results can provide important information for the development of quinoa resources.

Brown rice, as a kind of whole-grain food, has attracted significant attention due to its health benefits. This paper aimed to investigate the effect of rice bran content and retrograded time on the physicochemical properties and culinary qualities of brown rice noodles (BRNs). The results indicated that the addition of rice bran altered the pasting properties, gel properties, and texture of the brown rice flours (BRFs). The optimal cooking time and water absorption of BRNs were reduced after the incorporation of rice bran to 14.9% and 41.9%, respectively, while the breaking rate increased from 2.2% to 23.3%. The color of BRNs became darker and yellower, and the overall acceptability by the consumer decreased. The addition of rice bran also led to a decrease in hardness, chewiness and crystallinity. The binding water inside the BRNs decreased, while the free water increased, resulting in a looser structure. This study revealed that the retrograded time of the BRNs also affected its quality. When the retrograded time was 7 h, the cooked BRNs had a lower breaking rate, good hardness, cohesiveness, chewiness, and better overall acceptability by consumers. The structure was compact, the internal binding water content of BRN was higher, and the free water content was lower. This study provides insights into developing nutritionally healthy, high-quality novel rice flour products, and offers a theoretical basis for the industrial production of BRNs.

Localized Surface Plasmon Resonance (LSPR) is an optical method for detecting changes in refractive index by the interaction between incident light and delocalized electrons within specific metal thin films’ localized “hot spots”. LSPR-based sensors possess advantages, including their compact size, enhanced sensitivity, cost-effectiveness, and suitability for point-of-care applications. This research focuses on the development of LSPR-based nanohole arrays (NHAs) as a platform for monitoring probe/target binding events in real time without labeling, for low-level biomolecular target detection in biomedical diagnostics. To achieve this objective, this study involves creating a liquid-phase setup for capturing target molecules. Finite-difference time-domain simulations revealed that a 75 nm thickness of gold (Au) is ideal for NHA structures, which were visually examined using scanning electron microscopy. To illustrate the functionality of the liquid-phase sensor, a PDMS microfluidic channel was fabricated using a 3D-printed mold with a glass slide base and a top glass cover slip, enabling reflectance-mode measurements from each of four device sectors. This study shows the design, fabrication, and assessment of NHA-based LSPR sensor platforms within a PDMS microfluidic channel, confirming the sensor’s functionality and reproducibility in a liquid-phase environment.

Abstract Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is highly contagious and has resulted in a protracted pandemic. Infections caused by new coronavirus strains, primarily Delta and Omicron and currently highly prevalent globally. In response to the epidemic, countries, and cities implemented isolation and quarantine guidance, such as limiting social contact, which have affected the lifestyles and quality of life of the population. Parental feeding behaviors may vary as a result of factors such as prolonged home isolation of parents and children, lack of supplies during isolation, and stress. This study was designed to assess the available evidence and its implications for parental feeding practices in the context of COVID-19. We screened and reviewed research published in five electronic databases between 2020 and 2022, and eight studies met the selection criteria. Parents were observed to use a variety of feeding practices, including high levels of coercive control and reduction of rules and limits according to Vaughn’s food parenting constructs. The findings suggest that parental feeding practices are changing as a result of the pandemic and that more research is needed to further explore how to provide supportive feeding guidance to parents during emergencies in order to jointly promote child health.

Abstract To achieve scalable quantum information processing, great efforts have been devoted to the creation of large-scale entangled states in various physical systems. Ultracold atom in optical lattice is considered as one of the promising platforms due to its feasible initialization and parallel manipulation. In this work, we propose an efficient scheme to generate and characterize global entanglement in the optical lattice. With only two-layer quantum circuits, the generation utilizes two-qubit entangling gates based on the superexchange interaction in double wells. The parallelism of these operations enables the generation to be fast and scalable. To verify the entanglement of this non-stabilizer state, we mainly design three complementary detection protocols which are less resource-consuming compared to the full tomography. In particular, one just needs two homogenous local measurement settings to identify the entanglement property. Our entanglement generation and verification protocols provide the foundation for the further quantum information processing in optical lattice.

Single image super-resolution (SISR) typically reconstructs higher-resolution (HR) images from the corresponding low-resolution (LR) images in the presence of natural HR images. SISR is highly important in generating high-quality images in forensic scenarios since it facilitates close investigation and examination of captured shoeprints. However, it becomes more challenging when there are no available natural HR ground truth images that correspond to the input LR images. In such cases, HR reconstruction becomes even more crucial for providing HR versions that retain the natural characteristics of shoeprints. For this purpose, we propose IPAS-Net, which utilizes U-Net for feature extraction, shares the learned parameters from LR space in HR space, and innovatively upscales, refines, and enhances the HR space via special treatments. The upsampling-and-refinement block comprises a parallel pipeline composed of attention mechanism block (AMB) and one-step-high-iteration (OSHI). All upsampling solutions are infused so that distinct upscaling can compensate each others’ weaknesses. The generated HR shoeprints are evaluated using blind/non-reference evaluation metrics, and the proposed method outperforms the state of the art (SOTA) deep learning modalities on low-quality shoeprints.

Abstract Background Thyroid hormone responsive protein (THRSP) is a lipogenic nuclear protein that is highly expressed in murine adipose tissue, but its role in humans remains unknown. Methods We characterized the insulin regulation of THRSP in vivo in human adipose tissue biopsies and in vitro in Simpson-Golabi-Behmel syndrome (SGBS) adipocytes. To this end, we measured whole-body insulin sensitivity using the euglycemic insulin clamp technique in 36 subjects [age 40 ± 9 years, body mass index (BMI) 27.3 ± 5.0 kg/m2]. Adipose tissue biopsies were obtained at baseline and after 180 and 360 min of euglycemic hyperinsulinemia for measurement of THRSP mRNA concentrations. To identify functions affected by THRSP, we performed a transcriptomic analysis of THRSP-silenced SGBS adipocytes. Mitochondrial function was assessed by measuring mitochondrial respiration as well as oxidation and uptake of radiolabeled oleate and glucose. Lipid composition in THRSP silencing was studied by lipidomic analysis. Results We found insulin to increase THRSP mRNA expression 5- and 8-fold after 180 and 360 min of in vivo euglycemic hyperinsulinemia. This induction was impaired in insulin-resistant subjects, and THRSP expression was closely correlated with whole-body insulin sensitivity. In vitro, insulin increased both THRSP mRNA and protein concentrations in SGBS adipocytes in a phosphoinositide 3-kinase (PI3K)-dependent manner. A transcriptomic analysis of THRSP-silenced adipocytes showed alterations in mitochondrial functions and pathways of lipid metabolism, which were corroborated by significantly impaired mitochondrial respiration and fatty acid oxidation. A lipidomic analysis revealed decreased hexosylceramide concentrations, supported by the transcript concentrations of enzymes regulating sphingolipid metabolism. Conclusions THRSP is regulated by insulin both in vivo in human adipose tissue and in vitro in adipocytes, and its expression is downregulated by insulin resistance. As THRSP silencing decreases mitochondrial respiration and fatty acid oxidation, its downregulation in human adipose tissue could contribute to mitochondrial dysfunction. Furthermore, disturbed sphingolipid metabolism could add to metabolic dysfunction in obese adipose tissue.

Andersen et al. have demonstrated a new type of beam steering device based on the excitonic response of an atomically thin semiconductor. Using electrostatic gates, the authors achieved tunable steering with switching times on the nanosecond scale.

Abstract Synthetic rocks are used in laboratories to measure the physical and chemical properties of Earth’s constituent minerals in order to understand Earth’s interior. To understand the phenomena in the middle and upper crust, dense aggregates of Na-rich plagioclase are necessary. Therefore, we explored a method of fabricating dense aggregates of albite with low porosities, homogeneous microstructures, the absence of melt and sample sizes larger than a cubic centimetre using hot pressing by solid-state sintering. We conducted multiple experiments in which we varied the particle sizes, the agglomerations of powder, the method of forming, the sintering temperature, and the pressure and duration of the hot pressing. Two particle size fractions of powder, less than two micrometres and less than a few hundred nanometres, were prepared by pulverisation and decantation of natural albite powder. Because fine-grained albite powder seems to agglomerate easily, a technique to dry and disperse the powder was also developed. Hot pressing was carried out at temperatures of 1000‒1150 °C and pressures of 40‒120 MPa. The following were found to be important in obtaining dense aggregates of albite: (1) powders with a particle size less than a few hundred nanometres; (2) powders are adequately dispersed; and (3) preparation of green bodies by slip casting, which makes hot pressing efficient. A dense albite aggregate can then be fabricated using hot pressing at a temperature of 1080 °C and pressure of 100 MPa by solid-state sintering.

BackgroundAtherosclerosis (AS) risk is elevated in diabetic patients, but the underlying mechanism such as involvement of epigenetic control of foam macrophages remains unclear. We have previously shown the importance of immune regulation on endothelial cells to AS development in diabetes. In this study, we examined the hypothesis that diabetes may promote AS through modification of the epigenetic status of macrophages.MethodsWe employed the Laser Capture Microdissection (LCM) method to evaluate the expression levels of key epigenetic regulators in both endothelial cells and macrophages at the AS lesions of patients. We then assessed the correlation between the significantly altered epigenetic regulator and serum levels of low-density Lipoprotein (LDL), triglycerides (TRIG) and high-density Lipoprotein (HDL) in patients. In vitro, the effects of high glucose on glucose utilization, lactate production, succinate levels, oxygen consumption and polarization in either undifferentiated or differentiated bone marrow-derived macrophages (BMDMs) were analyzed. The effects of depleting this significantly altered epigenetic regulator in macrophages on AS development were assessed in AS-prone diabetic mice.ResultsHistone deacetylase 3 (HDAC3) was identified as the most significantly altered epigenetic regulator in macrophages from the AS lesions in human diabetic patients. The levels of HDAC3 positively correlated with high serum LDL and TRIG, as well as low serum HDL. High glucose significantly increased glucose utilization, lactate production, succinate levels and oxygen consumption in cultured macrophages, and induced proinflammatory M1-like polarization. Macrophage depletion of HDAC3 significantly attenuated AS severity in AS-prone diabetic mice.ConclusionEpigenetically altered macrophages promote development of diabetes-associated AS, which could be prevented through HDAC3 depletion.

Glaesserella parasuis is a gram-negative bacterium that causes fibrotic polyserositis and arthritis in pig, significantly affecting the pig industry. The pan-genome of G. parasuis is open. As the number of genes increases, the core and accessory genomes may show more pronounced differences. The genes associated with virulence and biofilm formation are also still unclear due to the diversity of G. parasuis. Therefore, we have applied a pan-genome-wide association study (Pan-GWAS) to 121 strains G. parasuis. Our analysis revealed that the core genome consists of 1,133 genes associated with the cytoskeleton, virulence, and basic biological processes. The accessory genome is highly variable and is a major cause of genetic diversity in G. parasuis. Furthermore, two biologically important traits (virulence, biofilm formation) of G. parasuis were studied via pan-GWAS to search for genes associated with the traits. A total of 142 genes were associated with strong virulence traits. By affecting metabolic pathways and capturing the host nutrients, these genes are involved in signal pathways and virulence factors, which are beneficial for bacterial survival and biofilm formation. This research lays the foundation for further studies on virulence and biofilm formation and provides potential new drug and vaccine targets against G. parasuis.

BackgroundThe joint association of hyperuricemia and chronic kidney disease (CKD) with mortality in patients with chronic heart failure (CHF) is not conclusive.MethodsThis retrospective cohort study was conducted in Chinese People's Liberation Army General Hospital, Beijing, China. We included 9,367 patients with CHF, who were hospitalized between January 2011 and June 2019. The definitions of hyperuricemia and CKD were based on laboratory test, medication use, and medical record. We categorized patients with CHF into 4 groups according to the absence (-) or presence (+) of hyperuricemia and CKD. The primary outcomes included in-hospital mortality and long-term mortality. We used multivariate logistic regression and Cox proportional hazards regression to estimate the mortality risk according to the hyperuricemia/CKD groups.ResultsWe identified 275 cases of in-hospital mortality and 2,883 cases of long-term mortality in a mean follow-up of 4.81 years. After adjusting for potential confounders, we found that compared with the hyperuricemia-/CKD- group, the risks of in-hospital mortality were higher in the hyperuricemia+/CKD- group (odds ratio [OR], 95% confidence interval [CI]: 1.58 [1.01-2.46]), hyperuricemia-/CKD+ group (OR, 95% CI: 1.67 [1.10-2.55]), and hyperuricemia+/CKD+ group (OR, 95% CI: 2.12 [1.46-3.08]). Similar results were also found in long-term mortality analysis. Compared with the hyperuricemia-/CKD- group, the adjusted hazard ratios and 95% CI for long-term mortality were 1.25 (1.11-1.41) for hyperuricemia+/CKD- group, 1.37 (1.22-1.53) for hyperuricemia-/CKD+ group, and 1.59 (1.43-1.76) for hyperuricemia+/CKD+ group. The results remained robust in the sensitivity analysis.ConclusionsHyperuricemia and CKD, both individually and cumulatively, are associated with increased mortality risk in patients with CHF. These results highlighted the importance of the combined control of hyperuricemia and CKD in the management of heart failure.

BackgroundObesity is an increasingly severe global public health issue. This study aims to estimate the cross-sectional association between bone mineral density (BMD) and hyperuricemia (HU) in obesity.MethodA total of 275 obese subjects (126 men and 149 women) participated in this cross-sectional study. Obesity was diagnosed as body mass index (BMI) ≥28 kg/m2, whereas HU was defined as the blood uric acid level of 416 μmol/L in men and 360 μmol/L in women. The BMD of the lumbar spine and right hip was measured by dual-energy X-ray absorptiometry (DXA). The multivariable logistic regressions were employed to examine the relationship between BMD and HU in obesity, with the adjustment of gender, age, fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, creatinine, blood urea nitrogen, high-sensitivity C-reactive protein (hs-CRP), cigarette smoking, and alcohol drinking status.ResultThe overall prevalence of HU was 66.9% in this obese population. The mean age and BMI of this population were 27.9 ± 9.9 years and 35.2 ± 5.2 kg/m2, respectively. The multivariable-adjusted OR (the highest vs. lowest BMD quartile) demonstrated a negative relationship between BMD and HU in total (OR = 0.415, 95%CI: 0.182–0.946; p = 0.036), L1 (OR = 0.305, 95%CI: 0.127–0.730; p = 0.008), L2 (OR = 0.405, 95%CI: 0.177–0.925; p = 0.032), and L3 (OR = 0.368, 95%CI: 0.159–0.851; p = 0.020) lumbar vertebrae. In the subgroup analysis for the male population, the BMD was also negatively associated with HU in total (OR = 0.077, 95%CI: 0.014–0.427; p = 0.003), L1 (OR = 0.019, 95%CI: 0.002–0.206; p = 0.001), L2 (OR = 0.161, 95%CI: 0.034–0.767; p = 0.022), L3 (OR = 0.186, 95%CI: 0.041–0.858; p = 0.031), and L4 (OR = 0.231, 95%CI: 0.056–0.948; p = 0.042) lumbar vertebrae. However, such findings did not exist in women. In addition, there was no significant relationship between hip BMD and HU in obesity.ConclusionOur results showed that the lumbar BMD was negatively associated with HU in obesity. However, such findings only existed in men, rather than women. In addition, no significant relationship between hip BMD and HU existed in obesity. Due to the limited sample size and nature of the cross-sectional design, further large prospective studies are still needed to clarify the issues.

Abstract Pinolenic acid (PNLA), an omega-6 polyunsaturated fatty acid from pine nuts, has anti-inflammatory and anti-atherogenic effects. We aimed to investigate the direct anti-inflammatory effect and anti-atherogenic effects of PNLA on activated purified CD14 monocytes from peripheral blood of patients with rheumatoid arthritis (RA) in vitro. Flow cytometry was used to assess the proportions of CD14 monocytes expressing TNF-α, IL-6, IL-1β, and IL-8 in purified monocytes from patients with RA after lipopolysaccharide (LPS) stimulation with/without PNLA pre-treatment. The whole genomic transcriptome (WGT) profile of PNLA-treated, and LPS-activated monocytes from patients with active RA was investigated by RNA-sequencing. PNLA reduced percentage of monocytes expressing cytokines: TNF-α by 23% (p = 0.048), IL-6 by 25% (p = 0.011), IL-1β by 23% (p = 0.050), IL-8 by 20% (p = 0.066). Pathway analysis identified upstream activation of peroxisome proliferator-activated receptors (PPARs), sirtuin3, and let7 miRNA, and KLF15, which are anti-inflammatory and antioxidative. In contrast, DAP3, LIF and STAT3, which are involved in TNF-α, and IL-6 signal transduction, were inhibited. Canonical Pathway analysis showed that PNLA inhibited oxidative phosphorylation (p = 9.14E−09) and mitochondrial dysfunction (p = 4.18E−08), while the sirtuin (SIRTs) signalling pathway was activated (p = 8.89E−06) which interfere with the pathophysiological process of atherosclerosis. Many miRNAs were modulated by PNLA suggesting potential post-transcriptional regulation of metabolic and immune response that has not been described previously. Multiple miRNAs target pyruvate dehydrogenase kinase-4 (PDK4), single-immunoglobulin interleukin-1 receptor molecule (SIGIRR), mitochondrially encoded ATP synthase membrane subunit 6 (MT-ATP6) and acetyl-CoA acyltranferase2 (ACAA2); genes implicated in regulation of lipid and cell metabolism, inflammation, and mitochondrial dysfunction. PNLA has potential anti-atherogenic and immune-metabolic effects on monocytes that are pathogenic in RA and atherosclerosis. Dietary PNLA supplementation regulates key miRNAs that are involved in metabolic, mitochondrial, and inflammatory pathways.

The authors demonstrate compact spectral light-field imaging by using a transversely dispersive metalens array and a monochrome imaging sensor. They show that 4D images can be obtained in a single shot, and demonstrate discrimination of visually indistinguishable objects.

As one of the greatest inventions of human beings, the electric machine (EM) has realized the mutual conversion between electrical energy and mechanical energy, which has essentially led humanity into the age of electrification and greatly promoted the progress and development of human society. This paper will briefly review the development of EMs in the past two centuries, highlighting the historical milestones and investigating the driving force behind it. With the innovation of theory, the progress of materials and the breakthrough of computer science and power electronic devices, the mainstream EM types has been continuously changing since its appearance. This paper will not only summarize the basic operation principle and performance characteristics of traditional EMs, but also that of the emerging types of EMs. Meanwhile, control and drive system, as a non-negligible part of EM system, will be complementarily introduced. Finally, due to the background of global emission reduction, industrial intelligentization and transportation electrification, EM industry will usher again in a golden period of development. Accordingly, several foreseeable future developing trends will be analyzed and summarized.

Abstract Background The present study aimed 1) to examine the effects of epidemic-related job stressors, perceived social support and organizational support on the burnout and well-being of Chinese healthcare workers in the period of COVID-19 regular epidemic prevention and control and 2) to investigate the moderating effects of social support and organizational support on the relationship between job stressors and burnout and well-being within the theoretical framework of the Job Demands-Resources (JD-R) model. Methods A sample of healthcare workers (N = 3477) from 22 hospitals in Beijing, China participated in the cross-sectional investigation in October 2020 and reported epidemic-related job stressors, perceived social support, organizational support, burnout, anxiety and depression symptoms. Results 1) Medical doctors, females, people aged from 30 to 50, and those who worked in the second line during the pandemic reported higher scores of psychological symptoms and burnout in the period of regular epidemic prevention and control; 2) Epidemic-related job stressors positively predicted burnout, anxiety, and depression among healthcare workers; 3) Perceived social support and organizational support were negatively related to reported burnout, anxiety and depression symptoms; 4) Social support reduced the adverse effects of epidemic-related job stressors on anxiety and depression but enhanced the association between stressors and burnout; 5) Organizational support mitigated the adverse effects of epidemic-related job stressors on depression. Conclusion The results shed light on preventing burnout and enhancing the psychological well-being of healthcare workers under epidemic prevention and control measures by reducing epidemic-related job stressors and strengthening personal and organizational support systems.

Abstract Background The indications and efficacy after arthroscopic partial meniscectomy (APM) for degenerative medial meniscus lesions (DMMLs) have been controversial. The purpose of this study was to identify predictors of unfavorable clinical and radiologic outcomes after APM for DMMLs and to choose appropriate indications and improve treatment efficacy. Methods A total of 86 patients with DMMLs undergoing APM were retrospectively reviewed. The mean follow-up time was 32.1 months. Clinical outcomes (including Lysholm score) and radiographic results (including Kellgren-Lawrence grade (K–L grade: 0/1/2/3/4) were evaluated at preoperative and final follow-up. Preoperative prognostic factors, including gender, age, Body Mass Index (BMI), Hip–Knee–Ankle (HKA), Medial Posterior Tibial Slope (MPTS), Medial Meniscus Extrusion (MME), K–L grade, occupational kneeling, and cartilaginous condition (Outerbridge grade ≤ 2, VS ≥ 3), for relatively unfavorable (fair or poor grade) Lysholm and progression of K–L grade, were investigated by multivariate logistic regression analysis. Receiver operating characteristic curve was used to identify a cutoff point for the extent of medial meniscal extrusion that was associated with the final Lysholm score. Results A significantly improved postoperative Lysholm score (84.5 ± 9.7) compared with the preoperative score (63.8 ± 9.3) (P

Gefitinib (GEF) is a clinical medication for the treatment of lung cancer targeting the epidermal growth factor receptor (EGFR). However, its efficacy is remarkably limited by low solubility and dissolution rates. In this study, two cocrystals of GEF with co-formers were successfully synthesized using the recrystallization method characterized via Powder X-ray Diffraction, Fourier Transform Infrared Spectroscopy, and 2D Nuclear Overhauser Effect Spectroscopy. The solubility and dissolution rates of cocrystals were found to be two times higher than those of free GEF. In vitro cytotoxicity studies revealed that the cocrystals enhanced the inhibition of cell proliferation and apoptosis in A549 and H1299 cells compared to free GEF. In mouse models, GEF@TSBO demonstrated targeted, safe, and effective antitumor activity with only one-dose administration. Mechanistically, the GEF cocrystals were shown to increase the cellular levels of damaged DNA, while potentially downregulating PARP, thereby impairing the DNA repair machinery and leading to an imbalance between DNA damage and restoration. These findings suggest that the cocrystallization of GEF could serve as a promising adjunct to significantly enhance the physicochemical and biopharmaceutical performance for lung cancer treatment, providing a facial strategy to improve GEF anticancer efficiency with high bioavailability that can be orally administrated with only one dose.

The complement system mediates diverse regulatory immunological functions. C5aR2, an enigmatic receptor for anaphylatoxin C5a, has been shown to modulate PRR-dependent pro-inflammatory cytokine secretion in human macrophages. However, the specific downstream targets and underlying molecular mechanisms are less clear. In this study, CRISPR-Cas9 was used to generate macrophage models lacking C5aR2, which were used to probe the role of C5aR2 in the context of PRR stimulation. cGAS and STING-induced IFN-β secretion was significantly increased in C5aR2 KO THP-1 cells and C5aR2-edited primary human monocyte-derived macrophages, and STING and IRF3 expression were increased, albeit not significantly, in C5aR2 KO cell lines implicating C5aR2 as a regulator of the IFN-β response to cGAS-STING pathway activation. Transcriptomic analysis by RNAseq revealed that nucleic acid sensing and antiviral signalling pathways were significantly up-regulated in C5aR2 KO THP-1 cells. Altogether, these data suggest a link between C5aR2 and nucleic acid sensing in human macrophages. With further characterisation, this relationship may yield therapeutic options in interferon-related pathologies.

This study proposes Stamp-MLP, an enhanced seal impression representation learning technique based on MLP-Mixer. Instead of using the patch linear mapping preprocessing method, this technique uses circular seal remapping, which reserves the seals’ underlying pixel-level information. In the proposed Stamp-MLP, the average pooling is replaced by a global pooling of attention to extract the information more comprehensively. There were three classification tasks in our proposed method: categorizing the seal surface, identifying the product type, and distinguishing individual seals. The three tasks shared an identical dataset comprising 81 seals, encompassing 16 distinct seal surfaces, with each surface featuring six diverse product types. The experiment results showed that, in comparison to MLP-Mixer, VGG16, and ResNet50, the proposed Stamp-MLP achieved the highest classification accuracy (89.61%) in seal surface classification tasks with fewer training samples. Meanwhile, Stamp-MLP outperformed the others with accuracy rates of 90.68% and 91.96% in the product type and seal impression classification tasks, respectively. Moreover, Stamp-MLP had the fewest model parameters (2.67 M).

Anticancer peptides (ACPs) have been proven to possess potent anticancer activities. Although computational methods have emerged for rapid ACPs identification, their accuracy still needs improvement. In this study, we propose a model called ACP-BC, a three-channel end-to-end model that utilizes various combinations of data augmentation techniques. In the first channel, features are extracted from the raw sequence using a bidirectional long short-term memory network. In the second channel, the entire sequence is converted into a chemical molecular formula, which is further simplified using Simplified Molecular Input Line Entry System notation to obtain deep abstract features through a bidirectional encoder representation transformer (BERT). In the third channel, we manually selected four effective features according to dipeptide composition, binary profile feature, k-mer sparse matrix, and pseudo amino acid composition. Notably, the application of chemical BERT in predicting ACPs is novel and successfully integrated into our model. To validate the performance of our model, we selected two benchmark datasets, ACPs740 and ACPs240. ACP-BC achieved prediction accuracy with 87% and 90% on these two datasets, respectively, representing improvements of 1.3% and 7% compared to existing state-of-the-art methods on these datasets. Therefore, systematic comparative experiments have shown that the ACP-BC can effectively identify anticancer peptides.

Seismic data processing plays a key role in the field of geophysics. The collected seismic data are inevitably contaminated by various types of noise, which makes the effective signals difficult to be accurately discriminated. A fundamental issue is how to improve the signal-to-noise ratio of seismic data. Due to the complex characteristics of noise and signals, it is a challenge for the denoising model to suppress noise and recover weak signals. To suppress random noise in seismic data, we propose a multi-scale deformable convolution neural network denoising model based on U-Net, named MSDC-Unet. The MSDC-Unet mainly contains modules of deformable convolution and dilated convolution. The deformable convolution can change the shape of the convolution kernel to adjust the shape of seismic signals to fit different features, while the dilated convolution with different dilation rates is used to extract feature information at different scales. Furthermore, we combine Charbonnier loss and structure similarity index measure (SSIM) to better characterize geological structures of seismic data. Several examples of synthetic and field seismic data demonstrate that the proposed method is effective in the comprehensive results in terms of quantitative metrics and visual effect of denoising, compared with two traditional denoising methods and two deep convolutional neural network denoising models.

Abstract Gastric cancer (GC) is the fifth most common tumor and the third most deadly cancer worldwide. N6-methyladenosine (m6A) modification has been reported to play a regulatory role in human cancers. However, the exact role of m6A in GC remains largely unknown, and the dysregulation of m6A on mitochondrial metabolism has never been studied. In the present study, we demonstrated that FTO, a key demethylase for RNA m6A modification, was up-regulated in GC tissues, especially in tissues with liver metastasis. Functionally, FTO acted as a promoter for the proliferation and metastasis in GC. Moreover, FTO enhanced the degradation of caveolin-1 mRNA via its demethylation, which regulated the mitochondrial fission/fusion and metabolism. Collectively, our current findings provided some valuable insights into FTO-mediated m6A demethylation modification and could be used as a new strategy for more careful surveillance and aggressive therapeutic intervention.

Though Two-stage video object detectors cannot perform detection in real time, the accuracy of them is normally higher than that of one-stage video object detectors. One essence is that two-stage video detectors can easily use feature information from adjacent frames to augment key frame features. How to extract and exploit temporal features in the video stream for one-stage detectors needs further exploration. CenterNet is an anchor-free one-stage object detector that regress bounding boxes from heatmap peaks. We propose to use detected peaks and regressed boxes which encompass peak points to determine the heatmap ROIs as the extracted object heatmap features. A new relation module is designed to evaluate the similarity of heatmap ROI features and output the relation features which can effectively augment the heatmap ROI features. In the video sequence the heatmap ROIs of multiple adjacent frames are aggregated to a heatmap ROI of the key frame. Compared to CenterNet and other CenterNet-based video object detectors, our method achieves improved online real-time performance on ImageNet VID dataset with 78.8% mAP at 36 FPS.

This paper analyzes and evaluates various topologies of yokeless rotary-linear (RL) machine with permanent-magnet (PM) mover targeting for the achieving high dynamic performance. For the conventional yokeless RL machines, the single-stator topology features limited slot area for armature winding excited for both motions, and the coupled magnetic fields of both motions requires complex control strategy. In order to mitigate these issues, a double-stator RL machine with hybrid PMs array, which adopts the PMs with six magnetization directions, is proposed in this paper. An improved PMs array is introduced for the double-stator topology to achieve decoupled control for both motions. In addition, an analytical model of the radial flux density is derived to reveal the characteristics of the magnetic fields in different topologies. The parametric studies towards key dimensions are conducted to provide design guidelines and obtain the optimal design. Finally, the electromagnetic performances of the proposed design are compared systematically with the conventional single-stator counterparts. It is revealed that the proposed topology can enhance the performances in both motions, namely rotary and linear motions.

ObjectiveTuberculosis diagnosis requires rapid, simple and highly sensitive methods. Clustered regularly interspaced short palindromic repeats (CRISPRs) and associated protein (Cas) systems are increasingly being used for clinical diagnostic applications, due to their high flexibility, sensitivity and specificity. We developed a sensitive Mycobacterium tuberculosis (MTB) complex polymerase chain reaction (PCR)-CRISPR/Cas13a detection method (CRISPR-MTB) and then evaluated its performance in detecting MTB in clinical specimens.MethodsThe conserved MTB IS1081 sequence was used to design CRISPR-derived RNAs (crRNAs) and T7 promoter sequencing-containing PCR primers for use in the CRISPR-MTB assay, then assay performance was evaluated using 401 clinical specimens.ResultsThe CRISPR-MTB assay provided a low limit of detection of 1 target sequence copy/μL and excellent specificity. Furthermore, use of the assay to detect MTB in bronchoalveolar lavage fluid (BALF), sputum and pus samples provided superior sensitivity (261/268, 97.4%) as compared to sensitivities of acid-fast bacilli (130/268, 48.5%) and mycobacterial culture (192/268, 71.6%) assays, and comparable or greater sensitivity to that of GeneXpert MTB/RIF (260/268, 97.0%).ConclusionThe CRISPR-MTB assay, which provides excellent sensitivity and specificity for MTB detection in sputum, BALF and pus samples, is a viable alternative to conventional tests used to diagnose TB in resource-limited settings.

Programmable illumination control is essential for many computational microscopy techniques. Conventional light source array is often arranged on a fixed grid of a planar surface for providing programmable sample illumination. Here, we report the development of a freeform illuminator that can be arranged at arbitrary 2-dimensional or 3-dimensional (3D) surface structures for computational microscopy. The freeform illuminator can be designed in a small form factor with a dense light source arrangement in 3D. It can be placed closer to the sample for providing angle-varied illumination with higher optical flux and smaller angular increment. With the freeform illuminators, we develop a calibration process using a low-cost Raspberry-Pi image sensor coated with a monolayer of blood cells. By tracking the positional shift of the blood-cell diffraction patterns at 2 distinct regions of the coded sensor, we can infer the 3D positions of the light source elements in a way similar to the stereo vision reconstruction approach. To demonstrate the applications for computational microscopy, we validate the freeform illuminators for Fourier ptychographic microscopy, 3D tomographic imaging, and on-chip microscopy. We also present a longitudinal study by tracking the growth of live bacterial cultures over a large field of view. The reported freeform illuminators and the related calibration process offer flexibilities and extended scope for imaging innovations in computational microscopy.

Background/Aim. Thyroid hormone receptor-β (THR-β) agonists play crucial roles in dyslipidemia and metabolic associated fatty liver disease (MAFLD). We developed a novel oral and liver-targeted THR-β agonist, CS27109, and evaluated its efficacy in the treatment of metabolic disorders. Materials and Methods. We evaluated in vitro and in vivo efficacy and/or safety of CS27109 along with MGL3196 (a phase III THR-β agonist). Results. CS27109 showed pronounced activity and selectivity to THR-β and favorable PK properties, which was equivalent to MGL3196. In the hamster model, animals treated with a high dose of CS27109 showed equivalent reductions in serum TC and LDL-c with groups treated with MGL3196. In the rat model, CS27109 and MGL3196 reduced serum ALT, TC, TG, LDL-c, liver weight ratio, and liver steatosis. CS27109 simultaneously decreased liver TG and TC, and MGL3196 additionally reduced AST. In the mouse model, CS27109 dose-dependently reduced serum AST, ALT, liver inflammation, and NAS score, and also downregulated TC, LDL-c, liver steatosis, and fibrosis, but not in a dose-dependent manner. MGL3196 revealed an equivalent effect with CS27109 in that model. CS27109 also exhibited tolerable toxicity to the heart. Conclusions. CS27109 shows comparative in vitro and in vivo efficacy with MGL3196, suggesting its potential therapeutic application in the treatment of MAFLD such as dyslipidemia and steatohepatitis.

IntroductionThyroid hormone receptor β (THR-β) plays a critical role in metabolism regulation and has become an attractive target for treating lipid metabolism disorders in recent years. Thus, in this study, we discovered CS271011, a novel THR-β agonist, and assessed the safety and efficiency of CS271011 compared to MGL-3196 in vitro and in vivo. MethodsWe conducted luciferase reporter gene assays to assess the activation of THR-β and α in vitro. C57BL/6J mice were fed a high-fat diet for 12 weeks, CS271011 was administered by gavage at the dose of 1 mg/kg and 3 mg/kg, and MGL-3196 was administered at the dose of 3 mg/kg for 10 weeks. Body weight, food intake, serum and hepatic parameters, histological analysis, pharmacokinetic studies, RNA sequencing of the liver and heart, and expression of hepatic lipid-metabolic genes were determined to evaluate the safety and efficiency of CS271011. ResultsCompared with MGL-3196, CS271011 showed higher THR-β activation in vitro. In the diet-induced obesity mice model, CS271011 demonstrated favourable pharmacokinetic properties in mice and was enriched in the liver. Finally, CS271011 improved dyslipidaemia and reduced liver steatosis in the diet-induced obesity murine model. Mechanistically, CS271011 and MGL-3196 showed potent regulation of lipid metabolism-related genes. ConclusionsCS271011 is a potent and liver-targeted THR-β agonist for treating lipid metabolism disorders.

BackgroundPancreatic cancer (PC) is a highly malignant tumor of the digestive system. As clinical trials involving PC are increasingly being conducted, the transparency of the generated data has become an important issue of concern. In other areas of medicine, clinical trial transparency presents a worrying state of affairs. However, at present, there has been no study examining the transparency of data derived from PC clinical trials.MethodsA comprehensive search was conducted in the ClinicalTrial.gov database for clinical trials investigating pancreatic cancer as of June 2022. We examined the availability of clinical trial results and recorded the characteristics of the trials.ResultsA total of 856 trials were included in this study, of which 668 were completed and 188 were terminated or suspended. The results of 626 trials (73.13%) were available, of these 230 trials (26.87%) did not disclose any information on the trial data in any form. The publication rate for trials with available results was 86.10%, but the report rate on ClinicalTrial.gov was only 39.78%.ConclusionAlthough approximately 90% of clinical trial investigating interventions on patients with PC have published study results, 30% of trials did not report any findings, and the disclosure of trial results from ClinicalTrial.gov was unsatisfactory. In general, there is still room for improvement in the transparency of PC clinical trials.

Abstract Olfactory dysfunction is an early pre-motor symptom of Parkinson’s disease (PD) but the neural mechanisms underlying this dysfunction remain largely unknown. Aggregation of α-synuclein is observed in the olfactory bulb (OB) during the early stages of PD, indicating a relationship between α-synuclein pathology and hyposmia. Here we investigate whether and how α-synuclein aggregates modulate neural activity in the OB at the single-cell and synaptic levels. We induced α-synuclein aggregation specifically in the OB via overexpression of double-mutant human α-synuclein by an adeno-associated viral (AAV) vector. We found that α-synuclein aggregation in the OB decreased the ability of mice to detect odors and to perceive attractive odors. The spontaneous activity and odor-evoked firing rates of single mitral/tufted cells (M/Ts) were increased by α-synuclein aggregates with the amplitude of odor-evoked high-gamma oscillations increased. Furthermore, the decreased activity in granule cells (GCs) and impaired inhibitory synaptic function were responsible for the observed hyperactivity of M/Ts induced by α-synuclein aggregates. These results provide direct evidences of the role of α-synuclein aggregates on PD-related olfactory dysfunction and reveal the neural circuit mechanisms by which olfaction is modulated by α-synuclein pathology.

Turbine blade is one of the key components of turbomachinery, and the machining quality of its airfoil surface has an important impact on the operating efficiency, service life, and safety of the turbine. Robotic abrasive belt grinding has become an important means of blade airfoil surface machining. Based on the self-developed robot grinding system, this paper proposes a scanner-based system calibration method to determine the relationships among coordinate systems of measurement, robot base, tool, and workpiece. An accurate and efficent calibration method of workpiece coordinate system based on rapid surface segmentation of point cloud using CAD model is established. An blade error surface is constructed by B-spline interpolation to compensate system errors such as absolute positioning error of robot, calibration error, and blade shape error. The calibration process is illustrated at the end of this paper. The effectiveness of the calibration and error compensation methods proposed in this paper are verified by the simulation results.

Gout is a common inflammatory disease. The activation of NLRP3 inflammasome induced by monosodium urate (MSU) crystals has a critical role in gout, and its prevention is beneficial for patients. Lipoxin A4 (LXA4) is an endogenous lipoxygenase-derived eicosanoid mediator with powerful anti-inflammatory properties. However, whether LXA4 can suppress NLRP3 inflammasome activation induced by MSU crystals remains unclear. This study aimed to investigate the protective effect of LXA4 on MSU-crystal-induced NLRP3 inflammasome activation and its underlying molecular mechanisms. We found that LXA4 inhibited MSU-crystal-induced NLRP3 inflammasome activation, interleukin (IL)-1β maturation, and pyroptosis. More specifically, LXA4 suppressed the assembly of the NLRP3 inflammasome, including oligomerization and speck formation of ASC, and ASC-NLRP3 interaction. Furthermore, LXA4 suppressed oxidative stress, the upstream events for NLRP3 inflammasome activation, as evidenced by the fact that LXA4 eliminated total reactive oxygen species (ROS) generation and alleviated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and mitochondrial dysfunction. However, LXA4 also depressed the Nrf2 activation, a critical molecule in the antioxidant pathway, and then exerted an inhibitory impact on Klf9 expression and promotional impact on TXNRD2 expression, two molecules located downstream of Nrf2 in sequence. Knockdown of TXNRD2 reversed the LXA4-induced depression of ROS and NLRP3 inflammasome. Moreover, LXA4 alleviated joint inflammation and decreased the production of cleaved caspase-1 and matured IL-1β in gouty arthritis rats. Taken together, our findings demonstrate that LXA4 can attenuate MSU-crystal-induced NLRP3 inflammasome activation, probably through suppressing Nrf2 activation to increase TXNRD2 expression. The present study highlights the potential of LXA4 as an attractive new gout treatment candidate.