Search

Intensively farmed animals such as pigs inevitably experience a certain degree of psychological stress, which leads to a reduction in production performance. Mental health traits are currently difficult to measure, resulting in a gap in understanding their genetic basis. To address this challenge, we propose a computational framework called mental health of animals (MeHA), capable of revealing genes related to animal mental health traits. Using MeHA, we identified 109 candidate genes associated with pig mental health and discovered their intricate connections with critical functions, such as memory, cognition, and neural development, which are essential components of mental health and cognitive performance. Importantly, our findings provide evidence of the potential impact of these genes on economically important traits, including meat quality and piglet survival. This research underscores the importance of genetic studies in enhancing our understanding of animal behavior and cognition, as well as promoting agricultural practices. By applying our approach to study the genetic basis of mental health in pigs as a case, we confirmed that our framework is an effective way to reveal genetic factors affecting animal mental health traits, which contributes to animal welfare and has potential implications for understanding human mental disorders.

The digital transformation of metrology is one of the most active activities in the field of metrology at present, where the digital calibration certificate (DCC) being developed is the topic receiving the most concern in the current digital transformation. In practical industrial applications, the issue of storage carrier for the DCC plays a crucial role in its promotion and implementation. To address this issue, a DCC meta-model called DCC-Lite schema has been designed along with a corresponding processing method. This solution involves compressing and segmenting the DCC to make it suitable for storage using RFID tags. These RFID tags are affixed to the instruments and accompany them throughout their usage. Additionally, the DCC-RFID processing system has been developed to validate the effectiveness of the DCC meta-model and its corresponding processing method within a wireless temperature acquisition system. Experimental results demonstrate that the system successfully reads and writes the DCC stored within the RFID tag group. Furthermore, it enables automated parsing of the DCC calibration data by the machine and real-time compensation of measurement data to reduce measurement errors.

Asthma is a chronic airway inflammation that is considered a serious public health concern worldwide. Nobiletin (5,6,7,8,3',4'-hexamethyl flavonoid), an important compound isolated from several traditional Chinese medicines, especially Citri Reticulatae Pericarpium, is widely used for a number of indications, including cancer, allergic diseases, and chronic inflammation. However, the mechanism by which nobiletin exerts its anti-asthmatic effect remains unclear. In this research, we comprehensively demonstrated the anti-asthmatic effects of nobiletin in an animal model of asthma. It was found that nobiletin significantly reduced the levels of inflammatory cells and cytokines in mice and alleviated airway hyperresponsiveness. To explore the target of nobiletin, we identified PDE4B as the target of nobiletin through pharmacophore modeling, molecular docking, molecular dynamics simulation, SPR, and enzyme activity assays. Subsequently, it was found that nobiletin could activate the cAMP-PKA-CREB signaling pathway downstream of PDE4B in mouse lung tissues. Additionally, we studied the anti-inflammatory and anti-airway remodeling effects of nobiletin in LPS-induced RAW264.7 cells and TGF-β1-induced ASM cells, confirming the activation of the cAMP-PKA-CREB signaling pathway by nobiletin. Further validation in PDE4B-deficient RAW264.7 cells confirmed that the increase in cAMP levels induced by nobiletin depended on the inhibition of PDE4B. In conclusion, nobiletin exerts anti-asthmatic activity by targeting PDE4B and activating the cAMP-PKA-CREB signaling pathway.

The development of epoxy resins is mainly dependent on non-renewable petroleum resources, commonly diglycidyl ether bisphenol A (DGEBA)-type epoxy monomers. Most raw materials of these thermoset resins are toxic to the health of human beings. To alleviate concerns about the environment and health, the design and synthesis of bio-based epoxy resins using biomass as raw materials have been widely studied in recent decades to replace petroleum-based epoxy resins. With the improvement in the requirements for the performance of bio-based epoxy resins, the design of bio-based epoxy resins with unique functions has attracted a lot of attention, and bio-based epoxy resins with flame-retardant, recyclable/degradable/reprocessable, antibacterial, and other functional bio-based epoxy resins have been developed to expand the applications of epoxy resins and improve their competitiveness. This review summarizes the research progress of functional bio-based epoxy resins in recent years. First, bio-based epoxy resins were classified according to their unique function, and synthesis strategies of functional bio-based epoxy resins were discussed, then the relationship between structure and performance was revealed to guide the synthesis of functional bio-based epoxy resins and stimulate the development of more types of functional bio-based epoxy resins. Finally, the challenges and opportunities in the development of functional bio-based epoxy resins are presented.

To address the path planning problem for automated guided vehicles (AGVs) in challenging and complex industrial environments, a hybrid optimization approach is proposed, integrating a Kalman filter with grey wolf optimization (GWO), as well as incorporating partially matched crossover (PMX) mutation operations and roulette wheel selection. Paths are first optimized using GWO, then refined with Kalman filter corrections every ten iterations. Moreover, roulette wheel selection guides robust parent path selection, while an elite strategy and partially matched crossover (PMX) with mutation generate diverse offspring. Extensive simulations and experiments were carried out under a densely packed goods scenario and complex indoor layout scenario, within a fully automated warehouse environment. The results showed that this hybrid method not only enhanced the various optimization metrics but also ensured more predictable and collision-free navigation paths, particularly in environments with complex obstacles. These improvements lead to increased operational efficiency and safety, highlighting the method's potential in real-world applications.

Background: JianPiYiFei (JPYF) II granules are a Chinese medicine for the treatment of chronic obstructive pulmonary disease (COPD). However, the main components and underlying mechanisms of JPYF II granules are not well understood. This study aimed to elucidate the potential mechanism of JPYF II granules in the treatment of COPD using network pharmacology, molecular docking, and molecular dynamics simulation techniques., Methods: The active compounds and corresponding protein targets of the JPYF II granules were found using the TCMSP, ETCM, and Uniport databases, and a compound-target network was constructed using Cytoscape3.9.1. The COPD targets were searched for in GEO datasets and the OMIM and GeneCards databases. The intersection between the effective compound-related targets and disease-related targets was obtained, PPI networks were constructed, and GO and KEGG enrichment analyses were performed. Then, molecular docking analysis verified the results obtained using network pharmacology. Finally, the protein-compound complexes obtained from the molecular docking analysis were simulated using molecular dynamics (MD) simulations., Results: The network pharmacological results showed that quercetin, kaempferol, and stigmasterol are the main active compounds in JPYF II granules, and AKT1, IL-6, and TNF are key target proteins. The PI3K/AKT signaling pathway is a potential pathway through which the JPYF II granules affect COPD. The results of the molecular docking analysis suggested that quercetin, kaempferol, and stigmasterol have a good binding affinity with AKT1, IL-6, and TNF. The MD simulation results showed that TNF has a good binding affinity with the compounds., Conclusions: This study identified the effective compounds, targets, and related underlying molecular mechanisms of JPYF II granules in the treatment of COPD through network pharmacology, molecular docking, and MD simulation techniques, which provides a reference for subsequent research on the treatment of COPD.

Chip-scale devices harnessing the interaction between hot atomic ensembles and light are pushing the boundaries of precision measurement techniques into unprecedented territory. These advancements enable the realization of super-sensitive, miniaturized sensing instruments for measuring various physical parameters. The evolution of this field is propelled by a suite of sophisticated components, including miniaturized single-mode lasers, microfabricated alkali atom vapor cells, compact coil systems, scaled-down heating systems, and the application of cutting-edge micro-electro-mechanical system (MEMS) technologies. This review delves into the essential technologies needed to develop chip-scale hot atomic devices for quantum metrology, providing a comparative analysis of each technology's features. Concluding with a forward-looking perspective, this review discusses the future potential of chip-scale hot atomic devices and the critical technologies that will drive their advancement.

Intratumoral hypoxia is associated with tumor progression, aggressiveness, and therapeutic resistance in several cancers. Hypoxia causes cancer cells to experience replication stress, thereby activating DNA damage and repair pathways. MutT homologue-1 (MTH1, also known as NUDT1), a member of the Nudix family, maintains the genomic integrity and viability of tumor cells in the hypoxic tumor microenvironment. Although hypoxia is associated with poor prognosis and can cause therapeutic resistance by regulating the microenvironment, it has not been considered a treatable target in cancer. This study aimed to investigate whether hypoxia-induced MTH1 is a useful target for immunotherapy and whether hypoxic conditions influence the antitumor activity of immune cells. Our results showed that MTH1 expression was elevated under hypoxic conditions in head and neck cancer cell lines. Furthermore, we identified a novel MTH1-targeting epitope peptide that can activate peptide-specific CD4+ helper T cells with cytotoxic activity. The proliferation and cytotoxic activity of T cells were maintained under hypoxic conditions, and PD-1 blockade further augmented the cytotoxicity. These results indicate that MTH1-targeted immunotherapy combined with checkpoint blockade can be an effective strategy for the treatment of hypoxic tumors.

This study aims to extract phenolic-enriched compounds, specifically oleuropein, luteoloside, and hydroxytyrosol, from olive leaves using ball milling-assisted extraction (BMAE). Response surface methodology (RSM) and the Box-Behnken design (BBD) were used to evaluate the effects of the temperature, solvent-to-solid ratio, and milling speed on extraction recovery. The contents of the extract were determined by ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS) and converted to recoveries to evaluate the extraction efficiency. The optimal extraction conditions for oleuropein, luteoloside, and hydroxytyrosol were identified. Oleuropein had a recovery of 79.0% ± 0.9% at a temperature of 56.4 °C, a solvent-to-solid ratio of 39.1 mL/g, and a milling speed of 429 rpm. Luteoloside's recovery was 74.6% ± 1.2% at 58.4 °C, 31.3 mL/g, and 328 rpm. Hydroxytyrosol achieved 43.1% ± 1.3% recovery at 51.5 °C, 32.7 mL/g, and 317 rpm. The reason for the high recoveries might be that high energy ball milling could reduce the sample size further, breaking down the cell walls of olive leaves, to enhance the mass transfer of these components from the cell to solvent. BMAE is displayed to be an efficient approach to extracting oleuropein, luteoloside, and hydroxytyrosol from olive leaves, which is easy to extend to industrial production.

Medical procedures, such as radiation therapy, are a vital element in treating many cancers, significantly contributing to improved survival rates. However, a common long-term complication of such exposure is radiation-induced skin fibrosis (RISF), a complex condition that poses substantial physical and psychological challenges. Notably, about 50% of patients undergoing radiation therapy may achieve long-term remission, resulting in a significant number of survivors managing the aftereffects of their treatment. This article delves into the intricate relationship between RISF, reactive oxygen species (ROS), and angiotensin II (Ang II) signaling. It proposes the underlying mechanisms and examines potential treatments for mitigating skin fibrosis. The primary goal is to offer essential insights in order to better care for and improve the quality of life of cancer survivors who face the risk of developing RISF.

Oncolytic virotherapy is expected to provide a new treatment strategy for cancer. Aphrocallistes vastus lectin (AVL) is a Ca 2+ -dependent lectin receptor containing the conserved domain of C-type lectin and the hydrophobic N-terminal region, which can bind to the bird's nest glycoprotein and D-galactose. Our previous studies suggested that the oncolytic vaccinia virus (oncoVV) armed with the AVL gene exerted remarkable replication and antitumor effects in vitro and in vivo. In this study, we found that oncoVV-AVL may reprogram the metabolism of hepatocellular carcinoma cells to promote ROS, and elevated ROS subsequently promoted viral replication and induced apoptosis. This study will provide a new theoretical basis for the application of oncoVV-AVL in liver cancer.

Metastatic pheochromocytomas and paragangliomas (PPGLs) are rare endocrine malignancies with limited effective treatment options. The association between the tumor microenvironment (TME) with somatostatin receptor 2 (SSTR2) and hypoxia-induced factor-2α (HIF-2α) in PPGLs, critical for optimizing combination therapeutic strategies with immunotherapy, remains largely unexplored. To evaluate the association of SSTR2 and HIF-2α immunoreactivity with the TME in patients with PPGLs, we analyzed the expression of SSTR2A, HIF-2α, and TME components, including tumor-infiltrating lymphocytes (CD4 and CD8), tumor-associated macrophages (CD68 and CD163), and PD-L1, using immunohistochemistry in patients with PPGLs. The primary outcome was to determine the association of the immune profiles with SSTR2A and HIF-2α expression. Among 45 patients with PPGLs, SSTR2A and HIF2α were positively expressed in 21 (46.7%) and 14 (31.1%) patients, respectively. The median PD-L1 immunohistochemical score (IHS) was 2.0 (interquartile range: 0-30.0). Positive correlations were observed between CD4, CD8, CD68, and CD163 levels. A negative correlation was found between the CD163/CD68 ratio (an indicator of M2 polarization) and SSTR2A expression (r = -0.385, p = 0.006). HIF-2α expression showed a positive correlation with PD-L1 IHS (r = 0.348, p = 0.013). The co-expression of PD-L1 (HIS > 10) and HIF-2α was found in seven patients (15.6%). No associations were observed between SDHB staining results and the CD163/CD68 ratio, PD-L1, or SSTR2A expression. Our data suggest the potential of combination therapy with immunotherapy and peptide receptor radionuclide therapy or HIF-2α inhibitors as a treatment option in selected PPGL populations.

Approximately 30% of steroid-resistant nephrotic syndromes are attributed to monogenic disorders that involve 27 genes. Mutations in KANK family members have also been linked to nephrotic syndrome; however, the precise mechanism remains elusive. To investigate this, podocyte-specific Kank1 knockout mice were generated to examine phenotypic changes. In the initial assessment under normal conditions, Kank1 knockout mice showed no significant differences in the urinary albumin-creatinine ratio, blood urea nitrogen, serum creatinine levels, or histological features compared to controls. However, following kidney injury with adriamycin, podocyte-specific Kank1 knockout mice exhibited a significantly higher albumin-creatinine ratio and a significantly greater sclerotic index than control mice. Electron microscopy revealed more extensive foot process effacement in the knockout mice than in control mice. In addition, KANK1 -deficient human podocytes showed increased detachment and apoptosis following adriamycin exposure. These findings suggest that KANK1 may play a protective role in mitigating podocyte damage under pathological conditions.

Tonsillectomy with steroid pulse therapy (SPT) has been established as an effective treatment for immunoglobulin A nephropathy (IgAN) in Japan. However, the underlying mechanisms supporting tonsillectomy remain unclear. This study assessed palatine tonsils from 77 patients with IgAN, including 14 and 63 who received SPT before and after tonsillectomy, respectively. Tonsils from 21 patients with chronic tonsillitis were analyzed as controls. Specific tonsillar lesions were confirmed in patients with IgAN, correlating with active or chronic renal glomerular lesions and SPT. T-nodule and involution of lymphoepithelial symbiosis scores in tonsils correlated with the incidence of active crescents and segmental sclerosis in the glomeruli, respectively. The study revealed an essential role of the tonsil-glomerular axis in early active and late chronic phases. Moreover, the SPT-preceding group demonstrated no changes in the T-nodule score, which correlated with active crescent formation, but exhibited a considerable shrinkage of lymphatic follicles that produced aberrant IgA1. The study underscores the involvement of innate and cellular immunity in IgAN and advocates for tonsillectomy as a necessary treatment alongside SPT for IgAN, based on a stepwise process.

Sensor faults are one of the most common faults that cause performance degradation or functional loss in permanent magnet traction drive systems (PMTDSs). To quickly diagnose faulty sensors, this paper proposes a real-time joint diagnosis method for multi-sensor faults based on structural analysis. Firstly, based on limited monitoring signals on board, a structured model of the system was established using the structural analysis method. The isolation and detectability of faulty sensors were analyzed using the Dulmage-Mendelsohn decomposition method. Secondly, the minimum collision set method was used to calculate the minimum overdetermined equation set, transforming the higher-order system model into multiple related subsystem models, thereby reducing modeling complexity and facilitating system implementation. Next, residual vectors were constructed based on multiple subsystem models, and fault detection and isolation strategies were designed using the correlation between each subsystem model and the relevant sensors. The validation results of the physical testing platform based on online fault data recordings showed that the proposed method could achieve rapid fault detection and the localization of multi-sensor faults in PMTDS and had a good application value.

This article primarily focuses on the localization and extraction of multiple moving objects in images taken from a moving camera platform, such as image sequences captured by drones. The positions of moving objects in the images are influenced by both the camera's motion and the movement of the objects themselves, while the background position in the images is related to the camera's motion. The main objective of this article was to extract all moving objects from the background in an image. We first constructed a motion feature space containing motion distance and direction, to map the trajectories of feature points. Subsequently, we employed a clustering algorithm based on trajectory distinctiveness to differentiate between moving objects and the background, as well as feature points corresponding to different moving objects. The pixels between the feature points were then designated as source points. Within local regions, complete moving objects were segmented by identifying these pixels. We validated the algorithm on some sequences in the Video Verification of Identity (VIVID) program database and compared it with relevant algorithms. The experimental results demonstrated that, in the test sequences when the feature point trajectories exceed 10 frames, there was a significant difference in the feature space between the feature points on the moving objects and those on the background. Correctly classified frames with feature points accounted for 67% of the total frames.The positions of the moving objects in the images were accurately localized, with an average IOU value of 0.76 and an average contour accuracy of 0.57. This indicated that our algorithm effectively localized and segmented the moving objects in images captured by moving cameras.

Hereditary hemorrhagic telangiectasia (HHT), also called Rendu-Osler syndrome, is a group of rare genetic diseases characterized by autosomal dominance, multisystemic vascular dysplasia, and age-related penetrance. This includes arteriovenous malformations (AVMs) in the skin, brain, lung, liver, and mucous membranes. The correlations between the phenotype and genotype for HHT are not clear. An HHT Chinese pedigree was recruited. Whole exome sequencing (WES) analysis, Sanger verification, and co-segregation were conducted. Western blotting was performed for monitoring ENG/VEGFα signaling. As a result, a nonsense, heterozygous variant for ENG/CD105: c.G1169A:p. Trp390Ter of the proband with hereditary hemorrhagic telangiectasia type 1 (HHT1) was identified, which co-segregated with the disease in the M666 pedigree. Western blotting found that, compared with the normal levels associated with non-carrier family members, the ENG protein levels in the proband showed approximately a one-half decrease (47.4% decrease), while levels of the VEGFα protein, in the proband, showed approximately a one-quarter decrease (25.6% decrease), implying that ENG haploinsufficiency, displayed in the carrier of this variant, may affect VEGFα expression downregulation. Pearson and Spearman correlation analyses further supported TGFβ/ENG/VEGFα signaling, implying ENG regulation in the blood vessels. Thus, next-generation sequencing including WES should provide an accurate strategy for gene diagnosis, therapy, genetic counseling, and clinical management for rare genetic diseases including that in HHT1 patients.

Fluorescence in situ hybridization (FISH) is a powerful cytogenetic method used to precisely detect and localize nucleic acid sequences. This technique is proving to be an invaluable tool in medical diagnostics and has made significant contributions to biology and the life sciences. However, the number of cells is large and the nucleic acid sequences are disorganized in the FISH images taken using the microscope. Processing and analyzing images is a time-consuming and laborious task for researchers, as it can easily tire the human eyes and lead to errors in judgment. In recent years, deep learning has made significant progress in the field of medical imaging, especially the successful application of introducing the attention mechanism. The attention mechanism, as a key component of deep learning, improves the understanding and interpretation of medical images by giving different weights to different regions of the image, enabling the model to focus more on important features. To address the challenges in FISH image analysis, we combined medical imaging with deep learning to develop the SEAM-Unet++ automated cell contour segmentation algorithm with integrated attention mechanism. The significant advantage of this algorithm is that it improves the accuracy of cell contours in FISH images. Experiments have demonstrated that by introducing the attention mechanism, our method is able to segment cells that are adherent to each other more efficiently.

Autonomous mobile robots have become integral to daily life, providing crucial services across diverse domains. This paper focuses on path following, a fundamental technology and critical element in achieving autonomous mobility. Existing methods predominantly address tracking through steering control, neglecting velocity control or relying on path-specific reference velocities, thereby constraining their generality. In this paper, we propose a novel approach that integrates the conventional pure pursuit algorithm with deep reinforcement learning for a nonholonomic mobile robot. Our methodology employs pure pursuit for steering control and utilizes the soft actor-critic algorithm to train a velocity control strategy within randomly generated path environments. Through simulation and experimental validation, our approach exhibits notable advancements in path convergence and adaptive velocity adjustments to accommodate paths with varying curvatures. Furthermore, this method holds the potential for broader applicability to vehicles adhering to nonholonomic constraints beyond the specific model examined in this paper. In summary, our study contributes to the progression of autonomous mobility by harmonizing conventional algorithms with cutting-edge deep reinforcement learning techniques, enhancing the robustness of path following.

Background: This study aims to present the feasibility of developing a synchrotron-based proton ultra-high dose rate (UHDR) pencil beam scanning (PBS) system., Methods: The RF extraction power in the synchrotron system was increased to generate 142.4 MeV pulsed proton beams for UHDR irradiation at ~100 nA beam current. The charge per spill was measured using a Faraday cup. The spill length and microscopic time structure of each spill was measured with a 2D strip transmission ion chamber. The measured UHDR beam fluence was used to derive the spot dwell time for pencil beam scanning. Absolute dose distributions at various depths and spot spacings were measured using Gafchromic films in a solid-water phantom., Results: For proton UHDR beams at 142.4 MeV, the maximum charge per spill is 4.96 ± 0.10 nC with a maximum spill length of 50 ms. This translates to an average beam current of approximately 100 nA during each spill. Using a 2 × 2 spot delivery pattern, the delivered dose per spill at 5 cm and 13.5 cm depth is 36.3 Gy (726.3 Gy/s) and 56.2 Gy (1124.0 Gy/s), respectively., Conclusions: The synchrotron-based proton therapy system has the capability to deliver pulsed proton UHDR PBS beams. The maximum deliverable dose and field size per pulse are limited by the spill length and extraction charge.

Traditional low earth orbit (LEO) satellite networks are typically independent of terrestrial networks, which develop relatively slowly due to the on-board capacity limitation. By integrating emerging mobile edge computing (MEC) with LEO satellite networks to form the business-oriented "end-edge-cloud" multi-level computing architecture, some computing-sensitive tasks can be offloaded by ground terminals to satellites, thereby satisfying more tasks in the network. How to make computation offloading and resource allocation decisions in LEO satellite edge networks, nevertheless, indeed poses challenges in tracking network dynamics and handling sophisticated actions. For the discrete-continuous hybrid action space and time-varying networks, this work aims to use the parameterized deep Q-network (P-DQN) for the joint computation offloading and resource allocation. First, the characteristics of time-varying channels are modeled, and then both communication and computation models under three different offloading decisions are constructed. Second, the constraints on task offloading decisions, on remaining available computing resources, and on the power control of LEO satellites as well as the cloud server are formulated, followed by the maximization problem of satisfied task number over the long run. Third, using the parameterized action Markov decision process (PAMDP) and P-DQN, the joint computing offloading, resource allocation, and power control are made in real time, to accommodate dynamics in LEO satellite edge networks and dispose of the discrete-continuous hybrid action space. Simulation results show that the proposed P-DQN method could approach the optimal control, and outperforms other reinforcement learning (RL) methods for merely either discrete or continuous action space, in terms of the long-term rate of satisfied tasks.

Infrared small target detection plays a crucial role in maritime security. However, detecting small targets within heavy sea clutter environments remains challenging. Existing methods often fail to deliver satisfactory performance in the presence of substantial clutter interference. This paper analyzes the spatial-temporal appearance characteristics of small targets and sea clutter. Based on this analysis, we propose a novel detection method based on the appearance stable isotropy measure (ASIM). First, the original images are processed using the Top-Hat transformation to obtain the salient regions. Next, a preliminary threshold operation is employed to extract the candidate targets from these salient regions, forming a candidate target array image. Third, to distinguish between small targets and sea clutter, we introduce two characteristics: the gradient histogram equalization measure (GHEM) and the local optical flow consistency measure (LOFCM). GHEM evaluates the isotropy of the candidate targets by examining their gradient histogram equalization, while LOFCM assesses their appearance stability based on local optical flow consistency. To effectively combine the complementary information provided by GHEM and LOFCM, we propose ASIM as a fusion characteristic, which can effectively enhance the real target. Finally, a threshold operation is applied to determine the final targets. Experimental results demonstrate that our proposed method exhibits superior comprehensive performance compared to baseline methods.

Background and Objectives : The Wakayama prefecture is endemic for two types of tick-borne rickettsioses: Japanese spotted fever (JFS) and scrub typhus (ST). Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne hemorrhagic viral disease with a high mortality rate and is often difficult to differentiate from such rickettsioses. SFTS cases have recently increased in Wakayama prefecture. For early diagnosis, this study aimed to evaluate the clinical characterization of such tick-borne infections in the co-endemic area. Materials and Methods : The study included 64 febrile patients diagnosed with tick-borne infection in Wakayama prefecture between January 2013 and May 2022. Medical records of 19 patients with SFTS and 45 with rickettsiosis (JSF, n = 26; ST, n = 19) were retrospectively examined. The receiver operating curve (ROC) and area under the curve (AUC) were calculated to evaluate potential factors for differentiating SFTS from rickettsiosis. Results : Adults aged ≥70 years were most vulnerable to tick-borne infections (median, 75.5 years; interquartile range, 68.5-84 years). SFTS and rickettsiosis occurred mostly between summer and autumn. However, no significant between-group differences were found in age, sex, and comorbidities; 17 (89%) patients with SFTS, but none of those with rickettsiosis, experienced gastrointestinal symptoms such as vomiting, abdominal pain, and diarrhea. Meanwhile, 43 (96%) patients with rickettsiosis, but none of those with SFTS, developed a skin rash. The AUCs of white blood cells (0.97) and C-reactive protein (CRP) levels (0.98) were very high. Furthermore, the differential diagnosis of SFTS was significantly associated with the presence of gastrointestinal symptoms (AUC 0.95), the absence of a skin rash (AUC 0.98), leukopenia <3.7 × 10 9 /L (AUC 0.95), and low CRP levels < 1.66 mg/dL (AUC 0.98) ( p < 0.001 for each factor). Conclusions : Clinical characteristics and standard laboratory parameters can verify the early diagnosis of SFTS in areas where tick-borne infections are endemic.

Quercetin (Que) is a flavonol compound found in plants, which has a variety of biological activities. Necroptosis, a special form of programmed cell death, plays a vital role in the development of many gastrointestinal diseases. This study aimed to explore whether Que could attenuate the intestinal injury and barrier dysfunction of piglets after deoxynivalenol (DON) exposure through modulating the necroptosis signaling pathway. Firstly, twenty-four weaned piglets were used in a 2 × 2 factorial design and the main factors, including Que (basal diet or diet supplemented with 100 mg/kg Que) and DON exposure (control feed or feed contaminated with 4 mg/kg DON). After feeding for 21 d, piglets were killed for samples. Next, the intestinal porcine epithelial cell line (IPEC-1) was pretreated with or without Que (10 μmol/mL) in the presence or absence of a DON challenge (0.5 μg/mL). Dietary Que increased the body weight, average daily gain, and average daily feed intake ( p < 0.05) through the trial. Que supplementation improved the villus height, and enhanced the intestinal barrier function ( p < 0.05) indicated by the higher protein expression of occludin and claudin-1 ( p < 0.05) in the jejunum of the weaned piglets after DON exposure. Dietary Que also down-regulated the protein abundance of total receptor interacting protein kinase 1 (t-RIP1), phosphorylated RIP1 (p-RIP1), p-RIP3, total mixed lineage kinase domain-like protein (t-MLKL), and p-MLKL ( p < 0.05) in piglets after DON exposure. Moreover, Que pretreatment increased the cell viability and decreased the lactate dehydrogenase (LDH) activity ( p < 0.05) in the supernatant of IPEC-1 cells after DON challenge. Que treatment also improved the epithelial barrier function indicated by a higher transepithelial electrical resistance (TEER) ( p < 0.001), lower fluorescein isothiocyanate-labeled dextran (FD4) flux ( p < 0.001), and better distribution of occludin and claudin-1 ( p < 0.05) after DON challenge. Additionally, pretreatment with Que also inhibited the protein abundance of t-RIP1, p-RIP1, t-RIP3, p-RIP3, t-MLKL, and p-MLKL ( p < 0.05) in IPEC-1 cells after DON challenge. In general, our data suggest that Que can ameliorate DON-induced intestinal injury and barrier dysfunction associated with suppressing the necroptosis signaling pathway.

Corneal wound healing is a complex biological process that integrates a host of different signals to coordinate cell behavior. Upon wounding, there is the generation of an endogenous wound electric field that serves as a powerful cue to guide cell migration. Concurrently, the corneal epithelium reduces sialylated glycoforms, suggesting that sialylation plays an important role during electrotaxis. Here, we show that pretreating human telomerase-immortalized corneal epithelial (hTCEpi) cells with a sialyltransferase inhibitor, P-3FAX-Neu5Ac (3F-Neu5Ac), improves electrotaxis by enhancing directionality, but not speed. This was recapitulated using Kifunensine, which inhibits cleavage of mannoses and therefore precludes sialylation on N-glycans. We also identified that 3F-Neu5Ac enhanced the responsiveness of the hTCEpi cell population to the electric field and that pretreated hTCEpi cells showed increased directionality even at low voltages. Furthermore, when we increased sialylation using N-azidoacetylmannosamine-tetraacylated (Ac4ManNAz), hTCEpi cells showed a decrease in both speed and directionality. Importantly, pretreating enucleated eyes with 3F-Neu5Ac significantly improved re-epithelialization in an ex vivo model of a corneal injury. Finally, we show that in hTCEpi cells, sialylation is increased by growth factor deprivation and reduced by PDGF-BB. Taken together, our results suggest that during corneal wound healing, reduced sialylated glycoforms enhance electrotaxis and re-epithelialization, potentially opening new avenues to promote corneal wound healing.

Surgery is the standard treatment for stage I non-small cell lung cancer (NSCLC); however, no clear randomized trial demonstrates its superiority to stereotactic body radiotherapy (SBRT) regarding survival. We aimed to retrospectively evaluate the treatment outcomes of SBRT in operable patients with stage I NSCLC using a large Japanese multi-institutional database to show real-world outcome. Exactly 399 patients (median age 75 years; 262 males and 137 females) with stage I (IA 292, IB 107) histologically proven NSCLC (adenocarcinoma 267, squamous cell carcinoma 96, others 36) treated at 20 institutions were reviewed. SBRT was prescribed at a total dose of 48-70 Gy in 4-10 fractions. The median follow-up period was 38 months. Local progression-free survival rates were 84.2% in all patients and 86.1% in the T1, 78.6% in T2, 89.2% in adenocarcinoma, and 70.5% in squamous cell subgroups. Overall 3-year survival rates were 77.0% in all patients: 90.7% in females, 69.6% in males, and 41.2% in patients with pulmonary interstitial changes. Fatal radiation pneumonitis was observed in two patients, all of whom had pulmonary interstitial changes. This real-world evidence will be useful in shared decision-making for optimal treatment, including SBRT for operable stage I NSCLC, particularly in older patients.

There is an ongoing need for patient-specific chemotherapy for pancreatic cancer. Tumour cells isolated from human tissues can be used to predict patients' response to chemotherapy. However, the isolation and maintenance of pancreatic cancer cells is challenging because these cells become highly vulnerable after losing the tumour microenvironment. Therefore, we investigated whether the cells retained their original characteristics after lentiviral transfection and expansion. Three human primary pancreatic cancer cell lines were lentivirally transduced to create expandable (Ex) cells which were then compared with primary (Pri) cells. No obvious differences in the morphology or epithelial-mesenchymal transition (EMT) were observed between the primary and expandable cell lines. The two expandable cell lines showed higher proliferation rates in the 2D and 3D models. All three expandable cell lines showed attenuated migratory ability. Differences in gene expression between primary and expandable cell lines were then compared using RNA-Seq data. Potential target drugs were predicted by differentially expressed genes (DEGs), and differentially expressed pathways (DEPs) related to tumour-specific characteristics such as proliferation, migration, EMT, drug resistance, and reactive oxygen species (ROS) were investigated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We found that the two expandable cell lines expressed similar chemosensitivity and redox-regulatory capability to gemcitabine and oxaliplatin in the 2D model as compared to their counterparts. In conclusion, we successfully generated expandable primary pancreatic cancer cell lines using lentiviral transduction. These expandable cells not only retain some tumour-specific biological traits of primary cells but also show an ongoing proliferative capacity, thereby yielding sufficient material for drug response assays, which may provide a patient-specific platform for chemotherapy drug screening.

Sclerotinia sclerotiorum is a devastating fungal pathogen that causes severe crop losses worldwide. It is of vital importance to understand its pathogenic mechanism for disease control. Through a forward genetic screen combined with next-generation sequencing, a putative protein kinase, Ss Cak1, was found to be involved in the growth and pathogenicity of S. sclerotiorum . Knockout and complementation experiments confirmed that deletions in SsCak1 caused defects in mycelium and sclerotia development, as well as appressoria formation and host penetration, leading to complete loss of virulence. These findings suggest that Ss Cak1 is essential for the growth, development, and pathogenicity of S. sclerotiorum . Therefore, Ss Cak1 could serve as a potential target for the control of S. sclerotiorum infection through host-induced gene silencing (HIGS), which could increase crop resistance to the pathogen.

This study aimed to clarify the effects of ipriflavone, which effectively reduces KIAA1199 activity, on osteoarthritis (OA) development and progression in an in vivo OA mouse model. The OA model mice were divided into the ipriflavone (200 mg/kg/day) group and the control group. OA onset and progression were evaluated with the Mankin score, and KIAA1199 expression and hyaluronan (HA) accumulation were analyzed by immunostaining. The molecular weight of HA in the cartilage tissue and serum HA concentration were analyzed by chromatography and competitive HA enzyme-linked immunoassay. The effects of ipriflavone on the bovine cartilage explant culture under the influence of IL-1β were also investigated. In the ipriflavone group, Safranin-O stainability was well-preserved, resulting in significant reduction of the Mankin score ( p = 0.027). KIAA1199 staining positivity decreased and HA stainability was preserved in the ipriflavone group. The serum HA concentration decreased, and the molecular weight of HA in the cartilage tissue increased in the ipriflavone group. The results of the cartilage explant culture indicated that ipriflavone could reduce GAG losses and increase the molecular weight of HA. Thus, ipriflavone may have an inhibitory effect on OA development/progression. Ipriflavone could be a therapeutic drug for OA by targeting KIAA1199 activity.

Tomato mottle mosaic virus (ToMMV) is an emerging seed-transmissible tobamovirus that infects tomato and pepper. Since the first report in 2013 in Mexico, ToMMV has spread worldwide, posing a serious threat to the production of both crops. To prevent the spread of this virus, early and accurate detection of infection is required. In this study, we developed a detection method for ToMMV based on reverse-transcription loop-mediated isothermal amplification (RT-LAMP). A LAMP primer set was designed to target the genomic region spanning the movement protein and coat protein genes, which is a highly conserved sequence unique to ToMMV. This RT-LAMP detection method achieved 10-fold higher sensitivity than conventional RT-polymerase chain reaction methods and obtained high specificity without false positives for closely related tobamoviruses or healthy tomato plants. This method can detect ToMMV within 30 min of direct sampling of an infected tomato leaf using a toothpick and therefore does not require RNA purification. Given its high sensitivity, specificity, simplicity, and rapidity, the RT-LAMP method developed in this study is expected to be valuable for point-of-care testing in field surveys and for large-scale testing.

MAX phases have exhibited diverse physical properties, inspiring their promising applications in several important research fields. The introduction of a chalcogen atom into a phase of MAX has further facilitated the modulation of their physical properties and the extension of MAX family diversity. The physical characteristics of the novel chalcogen-containing MAX 211 phase Zr 2 SeB and Zr 2 SeN have been systematically investigated. The present investigation is conducted from a multi-faceted perspective that encompasses the stability, electronic structure, and mechanical properties of the system, via the employment of the first-principles density functional theory methodology. By replacing C with B/N in the chalcogen-containing MAX phase, it has been shown that their corresponding mechanical properties are appropriately tuned, which may offer a way to design novel MAX phase materials with enriched properties. In order to assess the dynamical and mechanical stability of the systems under investigation, a thorough evaluation has been carried out based on the analysis of phonon dispersions and elastic constants conditions. The predicted results reveal a strong interaction between zirconium and boron or nitrogen within the structures of Zr 2 SeB and Zr 2 SeN. The calculated band structures and electronic density of states for Zr 2 SeB and Zr 2 SeN demonstrate their metallic nature and anisotropic conductivity. The theoretically estimated Pugh and Poisson ratios imply that these phases are characterized by brittleness.

The spectrum of information related to precision medicine in diabetes generally includes clinical data, genetics, and omics-based biomarkers that can guide personalized decisions on diabetes care. Given the remarkable progress in patient risk characterization, there is particular interest in using molecular biomarkers to guide diabetes management. Metabolomics is an emerging molecular approach that helps better understand the etiology and promises the identification of novel biomarkers for complex diseases. Both targeted or untargeted metabolites extracted from cells, biofluids, or tissues can be investigated by established high-throughput platforms, like nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques. Metabolomics is proposed as a valuable tool in precision diabetes medicine to discover biomarkers for diagnosis, prognosis, and management of the progress of diabetes through personalized phenotyping and individualized drug-response monitoring. This review offers an overview of metabolomics knowledge as potential biomarkers in type 2 diabetes mellitus (T2D) diagnosis and the response to glucose-lowering medications.

This cross-sectional study aimed to investigate the association between non-alcoholic fatty liver disease (NAFLD) and atherosclerotic cardiovascular disease (ASCVD), a global public health concern. A total of 9044 out of 10,104 adults from Guangzhou, China, were included in the analysis. We utilized the fatty liver index (FLI), a noninvasive indicator of NAFLD, and the pooled cohort equations (PCE) based on the 2013 ACC/AHA Guideline, the China-PAR model, and the Framingham Risk Score to assess the 10-year ASCVD risk. The results demonstrated a significant association between FLI and 10-year ASCVD risk ( p < 0.001). Adjusted for age, individuals with high FLI (≥60) had an odds ratio of 3.91 (95% CI 2.52-6.08) compared to those with low FLI (<30). These findings persisted after adjusting for metabolic indicators. Notably, this association was consistently observed across all three risk prediction models: the PCE model, the China-PAR model, and the Framingham Risk Score. In conclusion, our study provides evidence supporting FLI as a reliable indicator of increased 10-year ASCVD risk in Chinese NAFLD patients. FLI serves as a valuable marker for early detection of ASCVD, highlighting its potential in clinical practice for risk assessment and prevention strategies.

Aspirin, also known as acetylsalicylic acid, is widely consumed as a pain reliever and an anti-inflammatory as well as anti-platelet agent. Recently, our studies using the animal model of Drosophila demonstrated that the dietary supplementation of aspirin renovates age-onset intestinal dysfunction and delays organismal aging. Nevertheless, it remains probable that aspirin plays functional roles in other biological activities, for instance antiviral defense reactions. Intriguingly, we observed that the replications of several types of viruses were drastically antagonized in Drosophila macrophage-like S2 cells with the addition of aspirin. Further in vivo experimental approaches illustrate that adult flies consuming aspirin harbor higher resistances to viral infections with respect to flies without aspirin treatment. Mechanistically, aspirin positively contributes to the Drosophila antiviral defense largely through mediating the STING (stimulator of interferon genes) but not the IMD (immune deficiency) signaling pathway. Collectively, our studies uncover a novel biological function of aspirin in modulating Drosophila antiviral immunity and provide theoretical bases for exploring new antiviral treatments in clinical trials.

Necroptosis, an actively researched form of programmed cell death closely related to the inflammatory response, is important in a variety of disorders and diseases. However, the relationship between necroptosis and muscle protein degradation in cachexia is rarely reported. This study aimed to elucidate whether necroptosis played a crucial role in muscle protein degradation in a cachexia model of weaned piglets induced by lipopolysaccharide (LPS). In Experiment 1, the piglets were intraperitoneally injected with LPS to construct the cachexia model, and sacrificed at different time points after LPS injection (1, 2, 4, 8, 12, and 24 h). In Experiment 2, necrostatin-1 (Nec-1), a necroptosis blocker, was pretreated in piglets before the injection of LPS to inhibit the occurrence of necroptosis. Blood and longissimus dorsi muscle samples were collected for further analysis. In the piglet model with LPS-induced cachexia, the morphological and ultrastructural damage, and the release of pro-inflammatory cytokines including tumor necrosis factor ( TNF ) -α , interleukin ( IL ) -1β , and IL-6 were dynamically elicited in longissimus dorsi muscle. Further, protein concentration and protein/DNA ratio were dynamically decreased, and protein degradation signaling pathway, containing serine/threonine kinase ( Akt ), Forkhead box O ( FOXO ), muscular atrophy F-box ( MAFbx ), and muscle ring finger protein 1 (MuRF1), was dynamically activated in piglets after LPS challenge. Moreover, mRNA and protein expression of necroptosis signals including receptor-interacting protein kinase ( RIP ) 1 , RIP3 , and mixed lineage kinase domain-like pseudokinase ( MLKL ), were time-independently upregulated. Subsequently, when Nec-1 was used to inhibit necroptosis, the morphological damage, the increase in expression of pro-inflammatory cytokines, the reduction in protein content and protein/DNA ratio, and the activation of the protein degradation signaling pathway were alleviated. These results provide the first evidence that necroptosis mediates muscle protein degradation in cachexia by LPS challenge.

In this work, a novel bio-based high-performance bisbenzoxazine resin was synthesized from daidzein, 2-thiophenemethylamine and paraformaldehyde. The chemical structure was confirmed using nuclear magnetic resonance spectroscopy (NMR) and Fourier-transform infrared spectroscopy (FT-IR). The polymerization process was systematically studied using differential scanning calorimetry (DSC) and in situ FT-IR spectra. It can be polymerized through multiple polymerization behaviors under the synergistic reaction of thiophene rings with benzopyrone rather than a single polymerization mechanism of traditional benzoxazines, as reported. In addition, thermogravimetric analysis (TGA) and a microscale combustion calorimeter (MCC) were used to study the thermal stability and flame retardancy of the resulting polybenzoxazine. The thermosetting material showed a high carbon residue rate of 62.8% and a low heat release capacity (HRC) value of 33 J/gK without adding any flame retardants. Based on its outstanding capability of carbon formation, this newly obtained benzoxazine resin was carbonized and activated to obtain a porous carbon material doped with both sulfur and nitrogen. The CO 2 absorption of the carbon material at 0 °C and 25 °C at 1 bar was 3.64 mmol/g and 3.26 mmol/g, respectively. The above excellent comprehensive properties prove its potential applications in many advanced fields., Competing Interests: The authors declare no conflict of interest.

Smart dental materials are designed to intelligently respond to physiological changes and local environmental stimuli to protect the teeth and promote oral health. Dental plaque, or biofilms, can substantially reduce the local pH, causing demineralization that can then progress to tooth caries. Progress has been made recently in developing smart dental materials that possess antibacterial and remineralizing capabilities in response to local oral pH in order to suppress caries, promote mineralization, and protect tooth structures. This article reviews cutting-edge research on smart dental materials, their novel microstructural and chemical designs, physical and biological properties, antibiofilm and remineralizing capabilities, and mechanisms of being smart to respond to pH. In addition, this article discusses exciting and new developments, methods to further improve the smart materials, and potential clinical applications.

Increasing evidence has demonstrated that ischemic preconditioning (IPC) increases cerebral tolerance to subsequent prolonged ischemic insults. However, the exact mechanisms underlying the process have not been fully explored. In the current study, we aim to investigate whether NLRP3 inflammasome and cell pyroptosis are involved in the neuroprotective mechanism of IPC after ischemic stroke. In vitro, IPC was set up by exposing BV-2 cells to 10 min of oxygen-glucose deprivation (OGD). In vivo, IPC was performed by a transient cerebral ischemia of 10 min occlusion of the middle cerebral artery (MCA) in mice. We found that the NLRP3 inflammasome was activated and cell pyroptosis was induced at 6 h and 24 h post-stroke in an ischemic brain. IPC treatment increased cell viability under OGD state, reduced the infarct size, and attenuated the neurological deficits of mice. However, the effects NLRP3 inflammasome activation and pyroptosis after stroke were attenuated by IPC, which decreased the expression of NLRP3, ASC, cleaved caspase 1, and GSDMD-N and reduced the production of IL-1β and IL-18. In addition, confocal immunofluorescence staining of Annexin V-mCherry and SYTOX green was inhibited by IPC. These findings suggest a more enhanced link between IPC and inflammatory signature and cell death, highlighting that the NLRP3 inflammasome may act as a promising target for the prevention and treatment of ischemic stroke.

There is an urgency to produce novel high-performance resins to support the rapid development of the aerospace field and the electronic industry. In the present work, we designed and consequently synthesized a benzoxazine monomer ( o HPNI-fa ) bearing both norbornene and furan groups through the flexible benzoxazine structural design capability. The molecular structure of o HPNI-fa was verified by the combination characterization of nuclear magnetic resonance spectrum, FT-IR technology, and high-resolution mass spectrum. The thermally activated terpolymerization was monitored by in situ FT-IR as well as differential scanning calorimetry (DSC). Moreover, the low-temperature-curing characteristics of o HPNI-fa have also been revealed and discussed in the current study. Furthermore, the curing kinetics of the o HPNI-fa were investigated by the Kissinger and Ozawa methods. The resulting highly cross-linked thermoset based on o HPNI-fa showed excellent thermal stability as well as flame retardancy (T d10 of 425 °C, THR of 4.9 KJg -1 ). The strategy for molecular design utilized in the current work gives a guide to the development of high-performance resins which can potentially be applied in the aerospace and electronics industries.

Cerebrospinal fluid (CSF) plays an important role in the homeostasis of the brain. We previously reported that CSF major glycoproteins are biosynthesized in the brain, i.e., lipocalin-type prostaglandin D2 synthase (L-PGDS) and transferrin isoforms carrying unique glycans. Although these glycoproteins are secreted from distinct cell types, their CSF levels have been found to be highly correlated with each other in cases of neurodegenerative disorders. The aim of this study was to examine these marker levels and their correlations in other neurological diseases, such as depression and schizophrenia, and disorders featuring abnormal CSF metabolism, including spontaneous intracranial hypotension (SIH) and idiopathic normal pressure hydrocephalus (iNPH). Brain-derived marker levels were found to be highly correlated with each other in the CSF of depression and schizophrenia patients. SIH is caused by CSF leakage, which is suspected to induce hypovolemia and a compensatory increase in CSF production. In SIH, the brain-derived markers were 2-3-fold higher than in other diseases, and, regardless of their diverse levels, they were found to be correlated with each other. Another abnormality of the CSF metabolism, iNPH, is possibly caused by the reduced absorption of CSF, which secondarily induces CSF accumulation in the ventricle; the excess CSF compresses the brain's parenchyma to induce dementia. One potential treatment is a "shunt operation" to bypass excess CSF from the ventricles to the peritoneal cavity, leading to the attenuation of dementia. After the shunt operation, marker levels began to increase within a week and then further increased by 2-2.5-fold at three, six, and twelve months post-operation, at which point symptoms had gradually attenuated. Notably, the marker levels were found to be correlated with each other in the post-operative period. In conclusion, the brain-derived major glycoprotein markers were highly correlated in the CSF of patients with different neurological diseases, and their correlations were maintained even after surgical intervention. These results suggest that brain-derived proteins could be biomarkers of CSF production.

Three-axis atomic magnetometers have great advantages for interpreting information conveyed by magnetic fields. Here, we demonstrate a compact construction of a three-axis vector atomic magnetometer. The magnetometer is operated with a single laser beam and with a specially designed triangular 87Rb vapor cell (side length is 5 mm). The ability of three-axis measurement is realized by reflecting the light beam in the cell chamber under high pressure, so that the atoms before and after reflection are polarized along two different directions. It achieves a sensitivity of 40 fT/Hz in x-axis, 20 fT/Hz in y-axis, and 30 fT/Hz in z-axis under spin-exchange relaxation-free regime. The crosstalk effect between different axes is proven to be little in this configuration. The sensor configuration here is expected to form further values, especially for vector biomagnetism measurement, clinical diagnosis, and field source reconstruction.

The Chemokine-like factor ( CKLF )-like MARVEL transmembrane domain-containing ( CMTM ) family, comprising nine members, is involved in the tumorigenesis and progression of various cancers. However, the expression profiles and clinical significance of CMTM family members in hepatocellular carcinoma (HCC) are not fully clarified. In this study, the RNA-sequencing and clinical data were downloaded from The Cancer Genome Atlas (TCGA) databases. The Kaplan-Meier method and the Cox proportional hazards regression analysis were used to evaluate the prognostic significance of CMTM family members. Single-sample gene set enrichment analysis (ssGSEA) and ESTIMATE algorithms were employed to explore the relationship between CMTM family genes and the tumor microenvironment in HCC. Finally, the prognostic CMTM family gene expression was further validated by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical (IHC) staining in clinical HCC tissue specimens. The results indicated that, compared with normal tissues, the expression of CKLF , CMTM1 , CMTM3 , CMTM4 , CMTM7 , and CMTM8 were significantly upregulated in HCC, while the expression of CMTM2 , CMTM5 , and CMTM6 were significantly downregulated in HCC. Univariate and multivariate Cox regression analysis demonstrated that CKLF was an independent prognostic biomarker for the overall survival (OS) of HCC patients. In HCC, the expression of CKLF was found to be correlated with immune cell infiltration, immune-related functions, and immune checkpoint genes. The qRT-PCR and IHC confirmed that CKLF was highly expressed in HCC. Overall, this research suggested that CKLF is involved in immune cell infiltration and may serve as a critical prognostic biomarker, which provides new light on the therapeutics for HCC.

Heavy metal pollution in lakes is an issue that endangers ecosystems worldwide; however, the vertical properties of heavy metals in the water columns and sediment cores of lakes have been rarely evaluated simultaneously. This study revealed the pollution, risks, and sources of heavy metals from surface water to deep sediments in four typical shallow lakes located in central China. The results showed that the concentrations of heavy metals, except Hg, had insignificant stratification in the water column. Heavy metals had three vertical profiles in sediment cores, i.e., the concentrations of As, Hg, Cd, Pb, and Mn in the surface sediment (0-9 cm) were higher than that in the bottom sediment (9-45 cm) ( p < 0.05), the concentrations of Cr, Co, Fe, and Ni in the bottom sediment were higher than the surface sediment ( p < 0.05), and the concentrations of Cu and Zn had no significant stratification. The Nemerow pollution index showed that heavy metal pollution dominated by Hg reached slight-moderate levels, and had higher levels in surface water than that in bottom water ( p < 0.05). The Nemerow integrated risk index showed that the heavy metals had moderate-extreme potential ecological risks (Cd contributed 43.4%) in the sediments, and the ecological risk in surface sediment was significantly higher than that in bottom sediment ( p < 0.01). Principal component analysis revealed that agriculture, transportation, and chemical industry were the major sources of heavy metals in water and surface sediments, while agriculture and steel-making were the primary sources in bottom sediments. This study provides valuable data and insight for the control of heavy metal pollution in lakes with high human activity loads.

Oncolytic viruses are being developed as novel strategies for cancer therapy. Our previous studies have shown that vaccinia viruses armed with marine lectins improved the antitumor efficacy in diverse cancer types. The objective of this study was to assess the cytotoxic effects of oncoVV harboring Tachypleus tridentatus lectin (oncoVV-TTL), Aphrocallistes vastus lectin (oncoVV-AVL), white-spotted charr lectin (oncoVV-WCL), and Asterina pectinifera lectin (oncoVV-APL) on HCC. Our data revealed that the effects of recombinant viruses on Hep-3B cells were oncoVV-AVL > oncoVV-APL > oncoVV-TTL > oncoVV-WCL; oncoVV-AVL showed stronger cytotoxicity than oncoVV-APL, while oncoVV-TTL/WCL had no effect on cell killing in Huh7 cells, and PLC/PRF/5 cells exhibited sensitivity to oncoVV-AVL/TTL but not to oncoVV-APL/WCL. The cytotoxicity of oncoVV-lectins could be enhanced by apoptosis and replication in a cell-type-dependent manner. Further research revealed that AVL may mediate various pathways, including MAPK, Hippo, PI3K, lipid metabolism, and androgen pathways through AMPK crosstalk, to promote oncoVV replication in HCC in a cell-dependent manner. OncoVV-APL replication could be affected by AMPK/Hippo/lipid metabolism pathways in Hep-3B cells, AMPK/Hippo/PI3K/androgen pathways in Huh7 cells, and AMPK/Hippo pathways in PLC/PRF/5 cells. OncoVV-WCL replication was also multi-mechanistic, which could be affected by AMPK/JNK/lipid metabolism pathways in Hep-3B cells, AMPK/Hippo/androgen pathways in Huh7 cells, and AMPK/JNK/Hippo pathways in PLC/PRF/5 cells. In addition, AMPK and lipid metabolism pathways may play critical roles in oncoVV-TTL replication in Hep-3B cells, and oncoVV-TTL replication in Huh7 cells may depend on AMPK/PI3K/androgen pathways. This study provides evidence for the application of oncolytic vaccinia viruses in hepatocellular carcinoma.

Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by bilateral kidney cysts that ultimately lead to end-stage kidney disease. While the major causative genes of ADPKD are PKD1 and PKD2 , other genes are also thought to be involved. Fifty ADPKD patients were analyzed by exome sequencing or multiplex ligation-dependent probe amplification (MLPA), followed by long polymerase chain reaction and Sanger sequencing. Variants in PKD1 or PKD2 or GANAB were detected in 35 patients (70%). Exome sequencing identified 24, 7, and 1 variants in PKD1 , PKD2 , and GANAB , respectively, in 30 patients. MLPA analyses identified large deletions in PKD1 in three patients and PKD2 in two patients. We searched 90 cyst-associated genes in 15 patients who were negative by exome sequencing and MLPA analyses, and identified 17 rare variants. Four of them were considered "likely pathogenic" or "pathogenic" variants according to the American College of Medical Genetics and Genomics guidelines. Of the 11 patients without a family history, four, two, and four variants were found in PKD1 , PKD2 , and other genes, respectively, while no causative gene was identified in one patient. While the pathogenicity of each variant in these genes should be carefully assessed, a comprehensive genetic analysis may be useful in cases of atypical ADPKD.

Background: While type 2 diabetes (T2D) is a major risk for ischemic stroke, the associated vessel wall characteristics remain essentially unknown. This study aimed to clarify intracranial vascular changes on three-dimensional vessel wall imaging (3D-VWI) using fast spin echo by employing 7Tesla (7T) magnetic resonance imaging (MRI) in T2D patients without advanced atherosclerosis as compared to healthy controls., Methods: In 48 T2D patients and 35 healthy controls, the prevalence of cerebral small vessel diseases and intracranial plaques were evaluated by 3D-VWI with 7T MRI., Results: The prevalence rate of lacunar infarction was significantly higher in T2D than in controls ( n = 8 in T2D vs. n = 0 in control, p = 0.011). The mean number of intracranial plaques in both anterior and posterior circulation of each subject was significantly larger in T2D than in controls (2.23 in T2D vs. 0.94 in control, p < 0.01). In T2D patients, gender was associated with the presence of intracranial plaques., Conclusion: This is the first study to demonstrate the high prevalence of intracranial plaque in T2D patients with neither confirmed atherosclerotic disease nor symptoms by performing intracranial 3D-VWI employing 7TMRI. Investigation of intracranial VWI with 7T MRI is expected to provide novel insights allowing early intensive risk management for prevention of ischemic stroke in T2D patients.

Classification of airborne laser scanning (ALS) point clouds of power lines is of great importance to their reconstruction. However, it is still a difficult task to efficiently and accurately classify the ground, vegetation, power lines and power pylons from ALS point clouds. Therefore, in this paper, a method is proposed to improve the accuracy and efficiency of the classification of point clouds of transmission lines, which is based on improved Random Forest and multi-scale features. The point clouds are filtered by the optimized progressive TIN densification filtering algorithm, then the elevations of the filtered point cloud are normalized. The features of the point cloud at different scales are calculated according to the basic features of the point cloud and the characteristics of transmission lines. The Relief F and Sequential Backward Selection algorithm are used to select the best subset of features to estimate the parameters of the learning model, then an Improved Random Forest classification model is built to classify the point clouds. The proposed method is verified by using three different samples from the study area and the results show that, compared with the methods based on Support Vector Machines, AdaBoost or Random Forest, our method can reduce feature redundancy and has higher classification accuracy and efficiency.

Our previous studies demonstrated that arming vaccinia viruses with marine lectins enhanced the antitumor efficacy in several cancer cells. This study aims to compare the efficacy of oncolytic vaccinia viruses harboring Tachypleus tridentatus lectin (oncoVV-TTL), Aphrocallistes vastus lectin (oncoVV-AVL), white-spotted charr lectin (oncoVV-WCL), and Asterina pectinifera lectin (oncoVV-APL) in breast cancer cells (BC). These results indicated that oncoVV-AVL elicited the highest anti-tumor effect, followed by oncoVV-APL, while oncoVV-TTL and oncoVV-WCL had lower effects in BC. Further studies showed that apoptosis and replication may work together to enhance the cytotoxicity of oncoVV-lectins in a cell-type dependent manner. TTL/AVL/APL/WCL may mediate multiple pathways, including ERK, JNK, Hippo, and PI3K pathways, to promote oncoVV replication in MDA-MB-231 cells. In contrast, these pathways did not affect oncoVV-TTL/AVL/APL/WCL replication in MCF-7 cells, suggesting that the mechanisms of recombinant viruses in MCF-7 (ER + , PR + ) and MDA-MB-231 (TNBC) cells were significantly different. Based on this study, we hypothesized that ER or PR may be responsible for the differences in promoting viral replication and inducing apoptosis between MCF-7 and MDA-MB-231 cells, but the specific mechanism needs to be further explored. In addition, small-molecule drugs targeting key cellular signaling pathways, including MAPK, PI3K/Akt, and Hippo, could be conjunction with oncoVV-AVL to promote breast cancer therapy, and key pathway factors in the JNK and PI3K pathways may be related to the efficacy of oncoVV-APL/TTL/WCL. This study provides a basis for applying oncolytic vaccinia virus in breast carcinoma.

An indole-related molecules have been considered as the potential fluorescent probes for biological and electrochemical sensing. However, most of the indole probes have been usually used in a single detection mode. Indolium probes that enable accurate detection in complex environments are rarely reported. Here, four novel indole derivatives including the phenyl group substituted with different functional moieties were designed on the basis of the donor-π-acceptor (D-π-A) concept. These derivatives exhibit positive solvatochromism owing to their varied molecular conformations upon contacting to various solvents and the different HOMO-LUMO gaps caused by the difference in electronic push-pull capability of the substituents. Their solid-state fluorescence emissions and multiple chromisms are observed due to the inherent twisted geometries and aggregation modes. In addition, these derivatives show dramatic color and fluorescence responses due to the protonation of the nitrogen and oxygen containing groups, and thus novel colorimetric pH sensors, fluorescent papers and logic gates have been designed.