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Reservoir heterogeneity, water-oil mobility ratio, cementation degree, and strong injection and production significantly influence long-term waterflooding and polymer flooding processes in oil reservoir development, leading to the formation of low-resistance dominant seepage channels in the lower part of thick oil layers without internal laminations. Understanding the spatial distribution and evolution of dominant seepage channels in oil reservoirs during waterflooding and polymer flooding is crucial for improving reservoir development and recovery rates. It uses a streamlined numerical simulation method to quantitatively show the spatial and temporal distribution of dominant seepage channels in the oil reservoir. A model and chart were created to demonstrate the relationship between permeability and throat radius, capturing changes in reservoir permeabilities over time. The study developed a comprehensive mathematical model to identify dominant seepage channels, considering parameters such as inter-well flow ratio, injection efficiency, permeability change value, and water saturation. Research findings indicate a 14.8 % increase in reservoir permeability after polymer flooding, with slight changes in porosity and a 20.3 % decrease in clay content. The established mathematical model and identification criteria were used to comprehensively quantitatively evaluate flow channels, describing the distribution characteristics and evolution process of dominant seepage channels in the experimental area over four periods: pre-polymer flooding, low water-saturation period during polymer flooding, post-polymer injection, and subsequent 10 years of water flooding. Both polymer flooding and subsequent water flooding have significantly altered the distribution pattern of predominant fluid pathways: 254 well layers now demonstrate robust predominant fluid pathways (19 %); another 272 well layers feature moderately predominant fluid pathways (22 %); while an additional 440 well layers display weaker predominant fluid pathways (approximately 35 %). There has been a noticeable increase in both weak and moderate predominant fluid pathways, which are now more widespread in the area. However, localized occurrences of strong predominant fluid pathways persist with no significant change in their distribution characteristics. Analysis at four different time points shows a clear trend of increasing intensity as we move from polymer to subsequent water flooding in this decade. Additionally, examination along an axis from upper left to lower right reveals a linear progression that indicates clear connections among different categories of dominant seepage channel. The verification results show a strong correlation between the calculated dominant seepage channel distribution and actual water-injection profile test results, indicating that the method effectively identifies dominant seepage channels in oil reservoirs after polymer flooding and has the potential to enhance oil recovery further.

Abstract Ulinastatin, a broad-spectrum inflammatory inhibitor widely employed in the management of severe pancreatitis and sepsis, has not been extensively investigated for its therapeutic potential in bacterial meningitis. This study aims to assess the neuroprotective effects of ulinastatin on bacterial meningitis and elucidate its underlying mechanism. The rat model of bacterial meningitis was established by intracerebral injection of Escherichia coli. 3-week-old SD rats were randomly divided into 5 groups with 8 rats in each group, including control group, E.coli group, E.coli + UTI group (ulinastatin 50000IU/kg), E.coli + UTI + PMA group (ulinastatin 50000IU/kg + PMA 200 ug/kg), and E.coli + PMA group(PMA 200 ug/kg). Behavioral changes were assessed by Loeffler neurobehavioral score. Histomorphologic changes and apoptosis were assessed by hematoxylin and eosin staining, Nissl staining and TUNEL staining. Immunohistochemistry and immunofluorescence and western blotting were used to detect the expression levels of zonula occludens-1 (ZO-1) and phosphorylation protein kinase C (PKCα).It was found that ulinastatin treatment in Escherichia coli meningitis rats improved neurological function, alleviated meningeal inflammatory infiltration, reduced neuronal death, promoted the integrity of the blood–brain barrier structure. Moreover, phorbol myristate acetate (PMA, a protein kinase C activator), blocked the effective action of ulinastatin. These findings suggest that ulinastatin had neuroprotective effects on bacterial meningitis by inhibiting PKCα phosphorylation and reducing ZO-1 degradation, demonstrating that ulinastatin may be a promising strategy in the treatment of bacterial meningitis.

Abstract The aim of this study is to address the issue of TDOA/FDOA measurement accuracy in complex underwater environments, which is affected by multipath effects and variations in water sound velocity induced by the challenging nature of the underwater environment. To this end, a novel cooperative localisation algorithm has been developed, integrating the attention mechanism and convolutional neural network-bidirectional gated recurrent unit (CNN-BiGRU) with TDOA/FDOA and two-step weighted least squares (ImTSWLS). This algorithm is designed to enhance the accuracy of TDOA/FDOA measurements in complex underwater environments. The algorithm initially makes use of the considerable capacity of a convolutional neural network (CNN) to extract profound spatial and frequency domain characteristics from multimodal data. These features are of paramount importance for the characterisation of underwater signal propagation, particularly in complex environments. Subsequently, through the use of a bidirectional gated recurrent unit (BiGRU), the algorithm is able to effectively capture long-term dependencies in time series data. This enables a more comprehensive analysis and understanding of the changing pattern of signals over time. Furthermore, the incorporation of an attention mechanism within the algorithm enables the model to focus more on the signal features that have a significant impact on localisation, while simultaneously suppressing the interference of extraneous information. This further enhances the efficiency of identifying and utilising the key signal features. ImTSWLS is employed to resolve the position and velocity data following the acquisition of the predicted TDOA/FDOA, thereby enabling the accurate estimation of the position and velocity of the mobile radiation source. The algorithm was subjected to a series of tests in a variety of simulated underwater environments, including different sea states, target motion speeds and base station configurations. The experimental results demonstrate that the algorithm exhibits a deviation of only 2.88 m/s in velocity estimation and 2.58 m in position estimation when the noise level is 20 dB. The algorithm presented in this paper demonstrates superior performance in both position and velocity estimation compared to other algorithms.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease caused by mutations in the tumor suppressor genes TSC1 and/or TSC2. Its clinical manifestations include recurrent seizures, intellectual disability, and facial angiofibromas. Herein, we report the case of a patient with TSC who had recurrent seizures since childhood, shark skin nevus on the right occipital region, and multiple purple-red nodules on both cheeks. Computer tomography (CT) revealed multiple small calcifications around the lateral ventricles, pulmonary lymphangioleiomyomatosis, multiple renal angiomyolipomas, and multiple lipomatous lesions on the left ventricular wall. Through this case report, we aimed to improve the understanding of TSC.

Kidney diseases are significant global public health concern, with increasing prevalence and substantial economic impact. Developing novel therapeutic approaches are essential for delaying disease progression and improving patient quality of life. Cell death signifying the termination of cellular life, could facilitate appropriate bodily development and internal homeostasis. Recently, regulated cell death (RCD) forms such as ferroptosis, characterized by iron-dependent lipid peroxidation, has garnered attention in diverse renal diseases and other pathological conditions. This review offers a comprehensive examination of ferroptosis, encompassing an analysis of the involvement of iron and lipid metabolism, the System Xc-/glutathione/glutathione peroxidase 4 signaling, and additional associated pathways. Meanwhile, the review delves into the potential of targeting ferroptosis as a therapeutic approach in the management of acute kidney injury (AKI), chronic kidney disease (CKD), diabetic nephropathy, and renal tumors. Furthermore, it emphasizes the significance of ferroptosis in the transition from AKI to CKD and further accentuates the potential for repurposing drug and utilizing traditional medicine in targeting ferroptosis-related pathways for clinical applications. The integrated review provides valuable insights into the role of ferroptosis in kidney diseases and highlights the potential for targeting ferroptosis as a therapeutic strategy.

AAV-mediated gene therapy typically requires a high dose of viral transduction, risking acute immune responses and patient safety, part of which is due to limited understanding of the host-viral interactions, especially post-transduction viral genome processing. Here, through a genome-wide CRISPR screen, we identified SMCHD1 (Structural Maintenance of Chromosomes Hinge Domain 1), an epigenetic modifier, as a critical broad-spectrum restricting host factor for post-entry AAV transgene expression. SMCHD1 knock-down by RNAi and CRISPRi or knock-out by CRISPR all resulted in significantly enhanced transgene expression across multiple viral serotypes, as well as for both single-strand and self-complementary AAV genome types. Mechanistically, upon viral transduction, SMCHD1 effectively repressed AAV transcription by the formation of an LRIF1-HP1-containing protein complex and directly binding with the AAV genome to maintain a heterochromatin-like state. SMCHD1-KO or LRIF1-KD could disrupt such a complex and thus result in AAV transcriptional activation. Together, our results highlight the host factor-induced chromatin remodeling as a critical inhibitory mechanism for AAV transduction and may shed light on further improvement in AAV-based gene therapy.

Abstract Copy-number variations (CNVs), which refer to deletions and duplications of chromosomal segments, represent a significant source of variation among individuals, contributing to human evolution and being implicated in various diseases ranging from mental illness and developmental disorders to cancer. Despite the development of several methods for detecting copy number variations based on next-generation sequencing (NGS) data, achieving robust detection performance for CNVs with arbitrary coverage and amplitude remains challenging due to the inherent complexity of sequencing samples. In this paper, we propose an alternative method called OTSUCNV for CNV detection on whole genome sequencing (WGS) data. This method utilizes a newly designed adaptive sequence segmentation algorithm and an OTSU-based CNV prediction algorithm, which does not rely on any distribution assumptions or involve complex outlier factor calculations. As a result, the effective detection of CNVs is achieved with lower computational complexity. The experimental results indicate that the proposed method demonstrates outstanding performance, and hence it may be used as an effective tool for CNV detection.

This article studies the mixed noise removal problem for hyperspectral images (HSIs), which often suffer from Gaussian noise and sparse noise. Conventional denoising models mainly employ the $L_{1}$-norm-based regularizers to remove sparse noise and ensure piecewise smoothness. However, the denoising performance is poor for highly structured images with severe noise since the $L_{1}$-norm overpenalizes large entries. To tackle this limitation, we propose a denoising model that combines tensor decomposition with two kinds of $L_{0}$-norm-based regularizers. First, we use low-rank Tucker decomposition with the Stiefel manifold to characterize the global correlation of HSIs. Then, we utilize the $L_{0}$-norm to leverage the intrinsic sparsity information of the corruption domain, thereby enhancing the effectiveness of sparse noise removal. Simultaneously, we introduce a weighted $L_{0}$-norm regularizer on the gradient of each pixel to promote the local spectral-spatial smoothness. To solve the proposed model, we design a hard-thresholding-based alternating direction method of multipliers algorithm. Instead of spending time to find a proper rank in advance, we adopt a rank-increasing scheme to dynamically adjust the tensor rank during the optimization procedure. In this way, our algorithm avoids the rank selection burden and improves computational efficiency. Finally, we test the proposed method on both synthetic and real datasets. Numerical results demonstrate its superiority, especially, the improvements of our method over the best-compared results up to 2.07 dB for mixed noise removal.

As the fleet of high-speed rail vehicles expands, ensuring train safety is of the utmost importance, emphasizing the critical need to enhance the precision of axel temperature warning systems. Yet, the limited availability of data on the unique features of high thermal axis temperature conditions in railway systems hinders the optimal performance of intelligent algorithms in alarm detection models. To address these challenges, this study introduces a novel dynamic principal component analysis preprocessing technique for tolerance temperature data to effectively manage missing data and outliers. Furthermore, a customized generative adversarial network is devised to generate distinct data related to high thermal axis temperature, focusing on optimizing the network’s objective functions and distinctions to bolster the efficiency and diversity of the generated data. Finally, an integrated model with an optimized transformer module is established to accurately classify alarm levels, provide a comprehensive solution to pressing train safety issues, and, in a timely manner, notify drivers and maintenance departments (DEPOs) of high-temperature warnings.

Aiming at the problem that traditional wireless sensor networks produce errors in the positioning and tracking of motorised targets due to noise interference, this paper proposes a motorised target tracking method with a convolutional bi-directional long and short-term memory neural network and extended Kalman filtering, which is trained by using the simulated RSSI value and the actual target value of motorised targets collected from the convolutional bi-directional neural network to the sensor anchor node, so as to obtain a more accurate initial value of the manoeuvre target, and at the same time, the extended Kalman filtering method is used to accurately locate and track the real-time target, so as to obtain the accurate positioning and tracking information of the real-time target. Through experimental simulation, it can be seen that the algorithm proposed in this paper has good tracking effect in both linear manoeuvre target tracking scenarios and non-linear manoeuvre target tracking scenarios.

Abstract Freestanding MXene‐based macroforms have gained significant attention as versatile components in electrochemical energy storage applications owing to their interconnected conductive network, strong mechanical strength, and customizable surface chemistries derived from MXene nanosheets. This comprehensive review article encompasses key aspects related to the synthesis of MXene nanosheets, strategies for structure design and surface medication, surface modification, and the diverse fabrication methods employed to create freestanding MXene‐based macroform architectures. The review also delves into the recent advancements in utilizing freestanding MXene macroforms for electrochemical energy storage applications, offering a detailed discussion on the significant progress achieved thus far. Notably, the correlation between the macroform's structural attributes and its performance characteristics is thoroughly explored, shedding light on the critical factors influencing efficiency and durability. Despite the remarkable development, the review also highlights the existing challenges and presents future perspectives for freestanding MXene‐based macroforms in the realms of high‐performance energy storage devices. By addressing these challenges and leveraging emerging opportunities, the potential of freestanding MXene‐based macroforms can be harnessed to enable groundbreaking advancements in the field of energy storage.

Abstract Intersection markings play a vital role in providing road users with guidance and information. The conditions of intersection markings will be gradually degrading due to vehicular traffic, rain, and/or snowplowing. Degraded markings can confuse drivers, leading to increased risk of traffic crashes. Timely obtaining high-quality information of intersection markings lays a foundation for making informed decisions in safety management and maintenance prioritization. However, current labor-intensive and high-cost data collection practices make it very challenging to gather intersection data on a large scale. This paper develops an automated system to intelligently detect intersection markings and to assess their degradation conditions with existing roadway Geographic information systems (GIS) data and aerial images. The system harnesses emerging artificial intelligence (AI) techniques such as deep learning and multi-task learning to enhance its robustness, accuracy, and computational efficiency. AI models were developed to detect lane-use arrows (85% mean average precision) and crosswalks (89% mean average precision) and to assess the degradation conditions of markings (91% overall accuracy for lane-use arrows and 83% for crosswalks). Data acquisition and computer vision modules developed were integrated and a graphical user interface (GUI) was built for the system. The proposed system can fully automate the processes of marking data collection and condition assessment on a large scale with almost zero cost and short processing time. The developed system has great potential to propel urban science forward by providing fundamental urban infrastructure data for analysis and decision-making across various critical areas such as data-driven safety management and prioritization of infrastructure maintenance.

DNA is highly vulnerable to spontaneous and environmental timely damage in living cells. DNA damage may cause genetic instability and increase cancer risk if the damages are not repaired timely and efficiently. Human cells possess several DNA damage response (DDR) mechanisms to protect the integrity of their genome. Clarification of the mechanisms underlying the DNA damage response following lethal damage will facilitate the identification of therapeutic targets for cancers. Histone post-translational modifications (PTMs) have been indicated to play different roles in the repair of DNA damage. In this context, histone PTMs regulate recruitment of downstream effectors, and facilitate appropriate repair response. This review outlines the current understanding of different histone PTMs in response to DNA damage repair, besides, enumerates the role of new type PTMs such as histone succinylation and crotonylation in regulating DNA damage repair processes.

Accelerometers are commonly used to measure vibrations for condition monitoring in mechanical and civil structures; however, their high cost and point-based measurement approach present practical limitations. With rapid advancements in computer vision and deep learning, research into tracking the motion of individual pixels with vision cameras has increased. The recently developed CoTracker, a transformer-based model, has demonstrated excellence in motion tracking, yet its performance in measuring structural vibrations has not been fully explored. This paper investigates the efficacy of the CoTracker model in extracting full-field structural vibrations using cameras. It is initially applied to capture the dense point movements in video sequences of a cantilever beam recorded using a high-speed camera. Subsequently, modal analysis using delay-embedding dynamic mode decomposition (DMD) is conducted to extract modal parameters including natural frequencies, damping ratios, and mode shapes. The results, benchmarked against those from a reference accelerometer and the Finite Element Method (FEM) result, demonstrate CoTracker’s high potential for general applicability in structural vibration measurements.

Effects of different ionic strengths (0.2, 0.4, and 0.6 mol/L) and different hydrodynamic cavitation (HC) treatment times (0, 1, 2, 3, and 4 min) on the conformation and gel properties of tilapia myofibrillar proteins (TMP) were investigated. The results showed that the solubility of TMP was significantly enhanced (p < 0.05) with the increase in NaCl concentration, and the gel characteristics were significantly improved. After HC treatment of TMP, the average particle size was significantly reduced (p < 0.05) and solubility was significantly enhanced (p < 0.05) with the increase in treatment time, the internal hydrophobic groups and reactive sulfhydryl groups were exposed. The intrinsic fluorescence spectra showed the unfolding of the spatial tertiary structure of proteins, and the circular dichroism spectroscopy showed the significant reduction in the content of α-helix in the secondary structure of the proteins (p < 0.05). In addition, the WHC and gel strength of the TMP heat-induced gels were enhanced, which improved the microstructure of the gels, and scanning electron microscopy showed that the gel network of the TMP gels became denser and more homogeneous. Dynamic rheology results showed that HC treatment resulted in a significant increase in the final G’ and G” values of TMP. In conclusion, HC treatment was able to improve the physicochemical structure and gel properties of TMP at different ionic strengths. This study presents a novel processing technique for the quality maintenance aspect of salt-reduced surimi gel products.

Objective: The present study aimed to investigate the safety, feasibility, and efficacy of three-dimensional visualization technique (3DVT)-guided hepatectomy in the treatment of complicated hepatolithiasis. Methods: The clinical and follow-up data of 279 patients with complicated hepatolithiasis were retrospectively analyzed. The patients were divided into a 3DVT group (group A, 66 cases) and a non-3DVT group (group B, 213 cases). After baseline data were balanced using propensity score matching (PSM), the clinical characteristics and follow-up data of the two groups were observed. Results: After 1:1 PSM, 58 patients in each group were successfully matched with each other. When the groups were compared, the surgical duration (p = 0.033) and intraoperative blood loss (p = 0.002) of group A were lower than those of group B. The immediate stone clearance rate (91.4% vs. 75.9%, p = 0.024) and quality of life outcome (p = 0.034) of group A were significantly higher than those of group B. Logistic regression analysis showed that history of two or more biliary tract operations (odds ratio [OR] = 6.544, 95% confidence interval [CI] = 1.193–35.890, p = 0.031), bilateral stone distribution (OR = 4.198, 95% CI = 1.186–14.854, p = 0.026), and Geng grade III or IV (OR = 12.262, 95% CI = 2.224–67.617, p = 0.004) were independent risk factors for poor outcomes in patients with complicated hepatolithiasis. Conclusion: Compared to conventional imaging examinations, 3DVT can be used to guide and achieve accurate preoperative diagnosis of complicated hepatolithiasis and has good safety, feasibility, and efficacy.

The position accuracy of the third mirror’s Z axis will directly affect the measurement accuracy of the optical telescope, so it is necessary to improve the position accuracy. In order to improve the control performances of the third mirror’s Z-axis of a large optical telescope, this paper proposes a novel control algorithm based on hyperbolic tangent function (tanh). The proposed algorithm is used to replace the traditional integral separated proportional-integral (IS-PI) controller which is widely used in industry servo control system. Firstly, a mathematical model of the third mirror’s Z-axis is established. Secondly, a controller based on tanh is proposed, and the characteristics and stability of the algorithm are analyzed. Thirdly, the parameters tuning method of the proposed algorithm is given. The simulation results show that the proposed algorithm has higher tracking accuracy than IS-PI controller. Finally, experiments are carried out on a large optical telescope’s Z axis. In the experiments, IS-PI controller and tanh controller are compared, and the results show that the control performances are greatly improved.

Continuous cutting of sponge samples is a key technique for efficient cutting with sponge ring cutters. However, existing methods are not suitable for complex-shaped and large quantities of sponge samples. To address this issue, this paper proposes a S-shaped sequencing algorithm based on region segmentation. Firstly, the algorithm separates the sample set into multiple molecular regions using the inflexion point samples. Then, global and local sorting are performed on each molecular region to determine the optimized search sequence. Next, entry and exit points are defined, and pre-generated processing paths for the samples within the region are created. Path collisions are identified and eliminated, resulting in the optimal cutting sequence for the samples within the molecular region. Experimental results demonstrate that this algorithm effectively reduces the empty travel distance and collision occurrences during the cutting process. Compared to manual methods, this algorithm can reduce the empty travel distance by 14-25%. In the next step, the algorithm will generate processing code to facilitate the practical application of the algorithm.

Abstract Background This study attempted to verify the potential of KCNJ14 as a biomarker in colorectal cancer (CRC). Methods Data on transcriptomics and DNA methylation and the clinical information of CRC patients were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. Biological information analysis methods were conducted to determine the role of KCNJ14 in the prognosis, diagnosis, immune cell infiltration, and regulation mechanism of CRC patients. The effect of KCNJ14 on the proliferation and migration of HCT116 and SW480 CRC cell lines was verified by in vitro experiments (MTT, colony-forming, wound healing, and transwell assays). Western blotting was performed to detect the effect of KCNJ14 on the levels of mTOR signalling pathway-related proteins. Results KCNJ14 expression was remarkably increased in CRC tissues and cell lines, which reduced the overall survival time of patients. KCNJ14 mRNA was negatively regulated by its methylation site cg17660703, which can also endanger the prognosis of patients with CRC. Functional enrichment analysis suggested that KCNJ14 is involved in the mTOR, NOD-like receptor, and VEGF signalling pathways. KCNJ14 expression was positively correlated with the number of CD4 + T cells and negatively correlated with that of CD8 + T cells in the immune microenvironment. KCNJ14 knockdown significantly reduced not only the proliferation and migration of CRC cell lines but also the levels of mTOR signalling pathway-related proteins. Conclusions This study not only increases the molecular understanding of KCNJ14 but also provides a potentially valuable biological target for the treatment of colorectal cancer.

Salinity stress is a great threat to the growth and productivity of crops, and development of salt-tolerant crops is of great necessity to ensure food security. Although a few genes with natural variations that confer salt tolerance at germination and seedling stage in rice have been cloned, effective intragenic markers for these genes are awaited to be developed, which hinder the use of these genes in genetic improvement of salt tolerance in rice. In this study, we first performed haplotype analysis of five rice salt-tolerant–related genes using 38 rice accessions with reference genome and 4,726 rice germplasm accessions with imputed genotypes and classified main haplotype groups and haplotypes. Subsequently, we identified unique variations for elite haplotypes reported in previous studies and developed 11 effective intragenic makers. Finally, we conducted genotyping of 533 of the 4,726 rice accessions from worldwide and 70 approved temperate geng/japonica cultivars in China using the developed markers. These results could provide effective donors and markers of salt-tolerant–related genes and thus could be of great use in genetic improvement of salt tolerance in rice.

A detailed morphological description and comparative study were conducted on numerous large-sized hamster remains collected from the late Middle Pleistocene Locality 2 of Shanyangzhai (Syz 2), Hebei Province, China. The comparisons reveal that these fossils are highly similar to the extant Tscherskia triton in size and morphology, including the small degree of alternating between the main opposite cusps on M1-3, the presence of axioloph on M3, and mesolophids on m1-2 that are present but seldom reach the lingual margin of the teeth, among other features. However, minor differences between the two still exist. Consequently, all these fossils are designated as a chronosubspecies of the extant species, T. triton varians comb. nov. The skull and molar morphologies of Cricetinus varians and T. triton were meticulously compared to resolve the long-standing debate regarding the validity of Cricetinus Zdansky, 1928 and C. varians Zdansky, 1928. The findings indicate that the differences between the two are slight; as a result, C. varians can only be considered a chronosubspecies of T. triton, i.e., T. triton varians comb. nov., and Cricetinus should be recognized as a junior synonym of Tscherskia. We tentatively propose that, among the seven species once referred to Cricetinus, C. europaeus, C. gritzai, C. janossyi, and C. koufosi should be reassigned to Tscherskia, while C. beremendensis should be transferred to Allocricetus, and C. mesolophidos to Neocricetodon. Excluding Tscherskia sp. from the Late Pliocene Youhe fauna, there are no reliable Tscherskia fossils in China earlier than the Middle Pleistocene. Based on the current evidence, Tscherskia may have originated from Neocricetodon during the Early Pliocene in Europe and subsequently spread to Asia. T. triton is its sole surviving representative, which now exclusively inhabits East Asia.

Copy number variation (CNV) has been increasingly recognized as a type of genomic/genetic variation that plays a critical role in driving human diseases and genomic diversity. CNV detection and analysis from cancer genomes could provide crucial information for cancer diagnosis and treatment. There still remain considerable challenges in the control-free calling of CNVs accurately in cancer analysis, although advances in next-generation sequencing (NGS) technology have been inspiring the development of various computational methods. Herein, we propose a new read-depth (RD)-based approach, called CNVbd, to explore CNVs from single tumor samples of NGS data. CNVbd assembles three statistics drawn from the density peak clustering algorithm and isolation forest algorithm based on the denoised RD profile and establishes a back propagation neural network model to predict CNV bins. In addition, we designed a revision process and a boundary search algorithm to correct the false-negative predictions and refine the CNV boundaries. The performance of the proposed method is assessed on both simulation data and real sequencing datasets. The analysis shows that CNVbd is a very competitive method and can become a robust and reliable tool for analyzing CNVs in the tumor genome.

Background One key to the development of the tiered diagnosis and treatment system lies in the establishment of a gatekeeping system in primary care supporting the implementation of first contact in primary care and the achievement of orderly healthcare-seeking. And the serving capacities of primary care professionals are essential in implementing first contact in primary care. Objective To understand the overall level of Henan primary care physicians' capabilities of diagnosing and treating common diseases, and to put recommendations for solving the problems. Methods In August 2020, by use of typical sampling method, physicians were selected from all primary care hospitals in four areas of Henan Province (Kaifeng's Xiangfu District and Lankao County, and Jiaozuo's Weidu District and Yanling County) . An online self-administered questionnaire survey was conducted with them for collecting information about their demographics, and capabilities of diagnosing and treating common diseases (involving the identification and diagnosis of common diseases, interpretation of relevant auxiliary examinations, and prescription of common medications) . Results In all, 1 844 cases attended the survey, and 1 669 of them (90.51%) who effectively responded to the survey were included for final analysis. Among the 1 669 respondents, 917 (54.94%) had secondary health school education level or below, 663 (39.72%) had no professional title, 524 (31.40%) had a rural doctor certificate, and 509 (30.50%) had a practicing certificate. Among the 1 117 village doctors, 722 (64.64%) were 45 years old and above, 83 (7.43%) were 60 years old and above, and 848 (75.92%) had secondary health school education level or below. Among 1 631 respondents, 1 564 (95.89%) were basically able to diagnose and identify common diseases, 1 402 (86.00%) could interpret the results of common auxiliary examinations, 1 542 (94.54%) could prescribe common medications, and 1 336 (81.91%) had capabilities to diagnose and treat common diseases. Compared with urban primary care physicians, rural primary care physicians had higher level of capabilities in identifying and diagnosing common diseases as well as prescribing common medications, but lower level of capabilities in interpreting biochemical tests and electrocardiogram results (P

The battery management system (BMS), as an important link between battery pack, vehicle system and motor, is one of the important core technologies of new energy vehicles. The response and treatment of BMS to faults directly affects the safety and reliability of electric vehicles. This paper focuses on the accuracy, timeliness and reliability testing technology of BMS fault response, based on the hardware-in-the-loop simulation environment and the actual test environment. Study different BMS in battery system fault condition (such as over-charge, over-discharge, over-temperature, over-current) under the condition of the response as a result, the analysis of fault report speed, protect reliability key parameters such as response time and response. The test results show that the BMS applied to ternary battery system is obviously faster than the BMS applied to lithium iron phosphate battery system to diagnose faults and alarm time. However, the application range and boundary of lithium iron phosphate battery system are wider, and its battery performance is more stable, which also verifies the rationality of its failure response time setting value and treatment mode. Through constructing BMS fault response test evaluation technology platform, realize the BMS fault response performance of accurate and real evaluation.

Abstract In this study, we examine the cross‐view gait recognition problem. Many existing methods establish global feature representation based on the whole human body shape. However, they ignore some important details of different parts of the human body. In the latest literature, positioning partial regions to learn fine‐grained features has been verified to be effective in human identification. But they only consider coarse fine‐grained features and ignore the relationship between neighboring regions. Taken the above insights together, we propose a novel model called GaitGP, which learns both important details through fine‐grained features and the relationship between neighboring regions through global features. Our GaitGP model mainly consists of the following two aspects. First, we propose a Channel‐Attention Feature Extractor (CAFE) to extract the global features, which aggregates the channel‐level attention to enhance the spatial information in a novel convolutional component. Second, we present the Global and Partial Feature Combiner (GPFC) to learn different fine‐grained features, and combine them with the global features extracted by the CAFE to obtain the relevant information between neighboring regions. Experimental results on the CASIA gait recognition dataset B (CASIA‐B), The OU‐ISIR gait database, multi‐view large population dataset, and The OU‐ISIR gait database gait datasets show that our method is superior to the state‐of‐the‐art cross‐view gait recognition methods.

Up till now, the spatial and temporal dynamics of transverse mode instability (TMI) in fiber laser oscillator have increasingly attracted a worldwide attention. Here, we develop a high-speed modal decomposition (MD) system to analyze the modal coupling for fiber laser oscillator above the TMI threshold. A set of angular-multiplexing transmission functions (TFs) are designed for simultaneous MD and monitoring the far-field beam profile. The TMI threshold of the deployed fiber laser oscillator is 181 W at a co-pumping power (CPP) of 279 W. As the CPP increases from 318 W to 397 W, the power fluctuations of the output laser become more drastic. The changes of the far-field beam profile and the centroid of far-field spot (COFFS) indicate an increased velocity of energy transfer between modes. The high-speed MD verifies above process and analyzes the modal components, indicating that the single cycle of modal coupling decreases from 11 ms to 4 ms. Otherwise, the strong mode coupling occurs between modes with relatively large weights. The high-speed MD provides a powerful tool to research the TMI effect.

In this study, the interfacial reaction method was used to modify the laponite particles using 3-glycidoxypropyltrimethoxysilane and octadecylamine, and the structure, morphology, and displacement performance tests of the modified particles were carried out. Elemental analysis, Fourier-transform infrared spectrometer, thermogravimetric analysis, and transmission electron microscopy are used to characterize the structure and morphology of the modified particles, and the results showed that laponite particles had been successfully modified. Results of the study indicated that Laponite®-based amphiphilic janus nanosheets (LAS) can accumulate at the interface, reduce the interfacial tension from 14.9 to 9.6 mN/m, and have a good emulsification effect for a long time. Second, the wettability alteration exhibited by LAS can change the wettability of the rock from oil-wet to water-wet. In addition, oil displacement experiments showed that LAS nanofluids can extract 11.6% at low concentration, which has a certain application potential.

In recent years, transverse mode instability (TMI) has been widely observed in fiber laser amplifier systems. The transverse mode instability phenomenon in fiber laser oscillators is less studied. Here, we focus on the dynamical output properties, i.e., its temporal signal and modal characteristics in a 30-μm-core-diameter ytterbium (Yb)-doped fiber laser oscillator. The TMI occurs at a pumping power around 310 W. Different from amplifiers, the basic oscillation frequency is quite low, at around 100 Hz, changing with time and pump power. When the fiber laser oscillator operates beyond TMI threshold at 357 W or 377 W for a while, the temporal fluctuation slowly disappears together with a decreased oscillation frequency, and appears again later. Based on the mode decomposition technique, we find that during the period of fluctuation disappearance at 357 W, the power output stays low and the output beam is still a mixture of fundamental mode and higher-order modes. The fundamental mode content is calculated to be averagely higher when temporal fluctuation disappears, increasing from ∼57% to ∼63%. Our results indicate complex interaction between the fiber laser oscillation and the TMI effect, and calls for more attention into understanding TMI in fiber laser oscillators.

BackgroundKeloids are benign skin hyperplasias but have a tumor-like appearance. Clinical management of keloids remains challenging.AimsWe retrospectively evaluated the safety and efficacy of internal mammary artery perforator propeller flaps combined with timely radiotherapy in the treatment of large chest keloids.MethodsFrom June 2017 to May 2020, 25 patients with large chest keloids (average size 4.82 cm ± 2.53 cm × 9.04 cm ± 4.86 cm) who received both radiotherapy and internal mammary artery perforator flaps transplantation in our department were included. After surgical removal of the keloids, various propeller flaps based on the unilateral internal mammary artery were designed and applied to repair the defects. Timely and full-dose radiotherapy was performed for these patients after the operation.ResultsAfter keloid resection, the dimensions of the defect area were 3 cm–15 cm × 4 cm–25 cm, and the sizes of the flaps were 3 cm–16 cm × 4 cm–27 cm. For all 25 patients, the flaps survived, and the incisions healed in one stage. During the follow-up (median 18 months), no local recurrence was observed, and the itching and pain symptoms in the scar area were significantly relieved. Both physicians and patients were satisfied with the results.ConclusionsThe application of internal mammary artery perforator propeller flaps combined with radiotherapy in the treatment of chest keloids can effectively reduce the recurrence of keloids and relieve the related symptoms. It also has advantages including minimized donor site damage, short operation time and speedy postoperative recovery, suggesting its great clinical value.

Abstract Background A large body of evidence supports a link between type 2 diabetes mellitus (T2DM) and cognitive function, including dementia. However, longitudinal studies on the association between T2DM and decline of cognitive function are scarce and reported mixed results, and we hence set out to investigate the cross-sectional and longitudinal association between T2DM and global as well as domain-specific cognitive performance. Methods We used multivariable regression models to assess associations of T2DM with cognitive performance and cognitive decline in a subsample of a population-based prospective cohort study (ESTHER). This subsample (n = 732) was aged 70 years and older and had participated in telephone-based cognitive function assessment (COGTEL) measuring global and domain-specific cognitive performance during the 5- and 8-year follow-up. Results Total COGTEL scores of patients with prevalent T2DM were 27.4 ± 8.3 and 29.4 ± 8.7 at the 5- and 8-year measurements, respectively, and were roughly two points lower than those of T2DM-free participants after adjustment for age and sex. In cross-sectional models, after adjustment for several potential confounders, performance in verbal short-term and long-term memory tasks was statistically significantly lower in participants with T2DM, but the association was attenuated after further adjustment for vascular risk factors. The difference in total COGTEL scores reflecting global cognitive function by T2DM status after full adjustment for confounders and vascular risk factors was equivalent to a decrement in global cognitive function associated with a four-year age difference. In longitudinal models, a statistically significantly stronger cognitive decline in patients with T2DM was observed for working memory. Conclusions In this sample of older individuals, T2DM was associated with worse performance and stronger decline in a cognitive function test. Memory-related domains were found to be particularly sensitive to T2DM. Further large-scale prospective studies are needed to clarify potential T2DM-related predictors of cognitive decline and possible consequences on the abilities to perform patient self-management tasks in diabetes care.

Sky radiative cooling is a kind of passive cooling technology that uses the “atmospheric window” to emit the object’s own heat to the low temperature of outer space; this technology has low energy consumption, no pollution, and other useful characteristics, so in recent years it has attracted widespread attention. The cooling effect of the sky radiative cooler is mainly affected by the constantly changing outdoor ambient temperature. In addition, the structure of the radiative cooler itself also means that its radiative cooling power undergoes obvious changes. Here, we utilized COMSOL simulation software to establish a numerical heat transfer model for radiative cooling, aimed at investigating the influencing factors on the sky radiative cooler and methods to enhance the structure of the radiative cooling. This study discusses outdoor ambient wind speed, the inlet flow rate of the cooler, installation angle of the cooler, and different cooler structures. Based on simulation results, it is observed that, for varying wind speeds, when the ambient radiation temperature is higher than the surface temperature of the cooler, a larger ambient wind speed leads to a poorer refrigeration effect. The maximum temperature difference in surface temperature at wind speeds of 0 m/s and 4 m/s is 0.59 °C. When the ambient temperature is lower than the surface temperature of the cooler, a smaller wind speed results in a greater net refrigeration power. The maximum temperature difference in this scenario is 0.32 °C. The net refrigeration power of the radiative cooler increases with an increase in water flow rate. As the water flow rate increases from 0 L/min to 5 L/min, the net refrigeration power increases from 25 W/m2 to 200 W/m2 and gradually stabilizes. Considering the radiative impact of the cooler on the surrounding environment, as the installation angle increases from 0° to 90°, the surface temperature of the cooler first increases and then decreases, reaching its highest temperature of 29.26 °C at 45°. The surface temperature of the cooler varies with the thickness of the air sandwich, increasing from 1 cm to 12 cm, and then decreasing. The lowest temperature of 23.4 °C is achieved at a thickness of 8 cm. The increase in the fin structure on the surface of the radiative cooler leads to a decrease in its refrigeration performance, and the difference between the inlet and outlet temperatures of the radiative cooler with a flat plate structure is always greater than that of the finned plate, and the difference in the average radiance is 23.52 W/m2. Finally, the energy-saving effect of the sky radiative cooling composite system is analyzed. Taking a typical small office building as an example, an energy consumption analysis model is set up, and the energy consumption of the composite system is simulated in four cities with different climates, using EnergyPlus software (version 8.6); the system’s power consumption is the largest in hot and humid climates. Compared with the traditional vapor-compression refrigeration system, the composite system reduces air conditioning power consumption by 25.7%, 32.5%, 37.1%, and 44.8% in Guangzhou, Shanghai, Jinan, and Shenyang, respectively. The main innovations of this paper include analyzing and studying the influence of the tilt angle change of the radiative plate on the refrigeration performance of the cooler and the relationship between the surrounding buildings, adding air sandwiches and ribs to the radiative cooler to analyze the influence of convective heat transfer on the refrigeration effect, which plays a guiding role in the design and research of the sky radiative cooler.

(1) Background: despite the fact that nowadays the genus Vulpes Frisch, 1775, is the most diverse among extant Canidae, its fossil record is utterly scarce, especially in the Asian Pliocene. The sparse nature of this record further complicates the reconstruction of the evolutionary scenario to fit these taxa with extant species. The situation seems to change slightly in the Early Pleistocene when two species are recorded: Vulpes alopecoides (Del Campana, 1913) in Europe and Vulpes chikushanensis, Young, 1930, in Asian localities. Unlike the former, which has an extensive record, the remains of the Chinese V. chikushanensis are sporadic and the validity of the taxon has also been questioned. (2) Methods: the study of the specimens from the Early Pleistocene site of Bajiazui (1.8–1.2 Ma, Qingyang, Gansu) in comparison to an extensive sample of Vulpes spp. The Pliocene–Early Pleistocene is relevant for the delimitation of fossil foxes variability; (3) Results: morphologically and morphometrically, the specimens of Bajiazui fit with the specimens of V. chikushanensis from other Chinese localities of the Early Pleistocene, e.g., Longdan (Gansu) and Huiyu (Fangshang), highlighting some difference with the latest Early Pleistocene forms of Jigushan fox; (4) Conclusions: the revision of the Asian fossil record of Vulpes is crucial in our attempt to understand and reconstruct the evolution of carnivoran guild during the late Early Pleistocene (1.8–0.8 Ma). The fox remains from Bajiazui, although fragmentary, add a valuable piece to our knowledge of V. chikushanensis, a species possibly strongly related to the extant Vulpes corsac (Linnaeus, 1768).

There have been some studies conducted about the single factor viscoelasticity of polymer solution or wettability effect on the micro-flow mechanism of polymer flooding. In this paper, the flow mechanism of polymer solution in dual heterogeneous reservoir considering the wettability and gravity was studied. The influences of wettability and rock particle shape on flow characteristics were studied based on the characteristics of saturation and pressure distribution. Compared with the simulation results of polymer flooding in three different rock particle shapes porous media, the oil displacement efficiency of the circular particle model is the highest at 91.57%, which is 3.34% and 11.48% higher than that in the hexagonal and diamond models, respectively. The influence of wettability was studied by the circular particle model. The oil displacement efficiency under water-wet conditions was higher than that under oil-wet conditions. The displacement process considering gravity was affected by the crossflow caused by gravity and viscous force, and the micro-oil displacement efficiency was 9.87% lower than that of non-gravity. Considering the wettability, vertical crossflow will be formed. The oil displacement efficiency under water-wet conditions was 3.9% higher than in oil-wet conditions. The research results can not only expand and enrich the micro-flow mechanism of viscoelastic polymer solution, but also provide reference and guidance for polymer flooding scheme design.

Digital transformation plays an important role in reshaping the core competitiveness of enterprises and achieving high-quality development. Based on panel data of Chinese A-share listed companies in Shanghai and Shenzhen from 2009 to 2019, this study examines the impact of digital transformation on corporate internals from the perspective of corporate tax avoidance. It finds that digital transformation significantly inhibits corporate tax avoidance by improving the quality of corporate internal controls; its inhibitory effect on corporate tax avoidance shows significant heterogeneity when firms are in different tax collection intensities and receive different amounts of government subsidies; and the inhibition of corporate tax avoidance significantly improves the efficiency of corporate investment. The research in this study expands the theoretical understanding of digital transformation and corporate tax avoidance and provides relevant insights for the government to promote the deep integration of the digital economy with the real economy.

The purpose of this research was to explore the different hydrodynamic cavitation (HC) times (0, 5, 10, 15, 20 min; power 550 W, pressure 0.14 MPa) on the emulsifying properties of tilapia myofibrillar protein (TMP). Results of pH, particle size, turbidity, solubility, surface hydrophobicity, and reactive sulfhydryl (SH) group indicated that HC changed the structure of TMP, as confirmed by the findings of intrinsic fluorescence and circular dichroism (CD) spectra. Furthermore, HC increased the emulsifying activity index (EAI) significantly (P < 0.05) and changed the emulsifying stability index (ESI), droplet size, and rheology of TMP emulsions. Notably, compared with control group, the 10-min HC significantly decreased particle size and turbidity but increased solubility (P < 0.05), resulting in accelerated diffusion of TMP in the emulsion. The prepared TMP emulsion showed the highest ESI (from 71.28 ± 5.50 to 91.73 ± 5.56 min), the smallest droplet size (from 2,754 ± 110 to 2,138 ± 182 nm) and the best rheological properties, as demonstrated by the microstructure photographs. Overall, by showing the effect of HC in improving the emulsifying properties of TMP, the study demonstrated HC as a potential technique for meat protein processing.

Fournier gangrene (FG) is a life-threatening disease affecting the soft tissues of the genital, perineal, and perianal regions. This retrospective study aimed to summarize the characteristics of FG and evaluate the effects of negative-pressure wound therapy (NPWT). We analyzed clinical data of 36 patients with FG admitted to our department. Thirty-four cases had perianal and external genital infections, and the other two had secondary infection of the urinary fistula after trauma and retroperitoneal abscess, respectively. Monomicrobial, polymicrobial, culture-negative, and fungal infections were identified in 16, 17, 2, and 1 cases, respectively. Escherichia coli, Enterococcus faecalis, Enterococcus faecium, Klebsiella pneumoniae, and Staphylococcus haemolyticus were the most common pathogens. The mortality rate was 8%. Twenty-seven and nine patients were treated with NPWT (group A) and conventional dressing (group B), respectively. The length of stay was 38.0 ± 16.1 and 51.0 ± 17.3 days, number of operations were 3 (3,6) and 13 (4,17), and wound healing times were 39.2 ± 18.1 and 66.5 ± 17.1 days in groups A and B, respectively. Taken together, clinicians should always consider the possibility of perianal or external genital infections progressing to FG in the daily work, especially for patients with diabetes mellitus. Enterobacteriaceae, Enterococcus, and Staphylococcus haemolyticus are the most common causative pathogens, and NPWT is an effective adjuvant therapy for wound management with fewer operations and a shorter wound healing time.

Purpose: Radiotherapy is a promising treatment option for lung cancer, but patients’ responses vary. The purpose of the study was to investigate the potential of radiomics and clinical signature for predicting the radiotherapy sensitivity and overall survival of inoperable stage III and IV non-small-cell lung cancer (NSCLC) patients. Materials: This retrospective study collected 104 inoperable stage III and IV NSCLC patients at the Yunnan Cancer Hospital from October 2016 to September 2020. They were divided into radiation-sensitive and non-sensitive groups. We used analysis of variance (ANOVA) to select features and support vector machine (SVM) to build the radiomic model. Furthermore, the logistic regression method was used to screen out clinically relevant predictive factors and construct the combined model of radiomics–clinical features. Finally, survival was estimated using the Kaplan–Meier method. Results: There were 40 patients in the radiation-sensitive group and 64 in the non-sensitive group. These patients were divided into training set (73 cases) and testing set (31 cases) according to the ratio of 7:3. Nine radiomics features and one clinical feature were significantly associated with radiotherapy sensitivity. Both the radiomics model and combined model have good predictive performance (the areas under the curve (AUC) values of the testing set were 0.864 (95% confidence interval [CI]: 0.683-0.996) and 0.868 (95% CI: 0.689-1.000), respectively). Only platelet level status was associated with overall survival. Conclusion: The combined model constructed based on radiomics and clinical features can effectively identify the radiation-sensitive population and provide valuable clinical information. Patients with higher platelet levels may have a poor prognosis.

Background Despite the survival benefits observed with immune checkpoint blockade (ICB) treatment—programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1), many patients with cancer have not benefited from these agents because of impaired antigen presentation and other resistance mechanisms. To overcome resistance to checkpoint therapy, we designed bispecific antibodies (BsAbs) targeting CD89 and tumor antigens. We demonstrated their immunomodulatory efficacy as a separate treatment strategy or combined with immune checkpoint inhibitors.Methods We have previously generated a heterodimeric one-arm IgG1 Fc-based bispecific antibody. For animal efficacy studies, murine tumors in a humanized transgenic mice model were used to determine the effects of CD89-bispecific antibodies on antigen presentation and immune cell recruitment. The efficacy of the CD89 bispecific antibody against tumors resistant to pembrolizumab was evaluated in double-transgenic mice.Results BsAbs targeting CD89 on tumor-associated macrophages (TAMs) increased the ratio of M1:M2 and activated the antigen presentation, leading to increased cytotoxic T cell-mediated tumor regression. CD89-BsAbs also potentiated a combinational antitumor effect with PD-1/PD-L1 inhibitors and overcame the ICB resistance by augmenting cytotoxic T-cell infiltration and reshaping tumor immune microenvironment. In an hCD89/hPD-1 double transgenic mouse model engrafted with pembrolizumab-resistant B16-HER2 tumor cells, the HER2-CD89 bispecific antibody potently inhibited tumor growth.Conclusions CD89 BsAbs targeting tumor antigens and TAMs controlled tumor growth in animal models by improving antigen presentation and T-cell infiltration. Our results suggest a general strategy for overcoming resistance to ICB.

The advantages of hybrid ships in energy conservation and emission reduction are increasingly prominent in the context of countries around the world paying increasing attention to such matters. Energy management is the key to achieving energy conservation and emission reduction on the premise of ensuring power performance. This paper summarizes the research progress and status of hybrid ship energy management. First, the energy management objectives are summarized in the three aspects of reliability objectives, economy objectives and environmental protection objectives. Second, the energy management strategies are compared and analyzed from the perspectives of rules and optimization, and the advantages, disadvantages and application conditions of the existing energy management strategies are summarized and analyzed deeply and comprehensively. Finally, according to the gaps in the existing research, the future research directions of hybrid ship energy management are predicted.

Abstract Background Hypertension is highly prevalent and is one of the modifiable risk factors for cardiovascular outcomes. Isolated diastolic hypertension (IDH), however, tends to be ignored due to insufficient recognition. We sought to depict the clinical manifestation of IDH and isolated systolic hypertension (ISH) to find a more efficient way to improve the management. Methods Patients with primary hypertension aged over 18 years were investigated from all over the country using convenience sampling during 2017–2019. IDH was defined as systolic blood pressure (SBP)

Modulation of brain arteriole diameter is critical for maintaining cerebral blood pressure and controlling regional hyperemia during neural activity. However, studies of hemodynamic function in health and disease have lacked a method to control arteriole diameter independently with high spatiotemporal resolution. Here, we describe an all-optical approach to manipulate and monitor brain arteriole contractility in mice in three dimensions using combined in vivo two-photon optogenetics and imaging. The expression of the red-shifted excitatory opsin, ReaChR, in vascular smooth muscle cells enabled rapid and repeated vasoconstriction controlled by brief light pulses. Two-photon activation of ReaChR using a spatial light modulator produced highly localized constrictions when targeted to individual arterioles within the neocortex. We demonstrate the utility of this method for examining arteriole contractile dynamics and creating transient focal blood flow reductions. Additionally, we show that optogenetic constriction can be used to reshape vasodilatory responses to sensory stimulation, providing a valuable tool to dissociate blood flow changes from neural activity.

Male infertility is a global issue that seriously affects reproductive health. This study aimed to understand the underlying causes of idiopathic non-obstructive azoospermia (iNOA), which is a type of male infertility with unknown origins that accounts for 10–15% of cases. By using single-cell analysis techniques, we aimed to uncover the mechanisms of iNOA and gain insight into the cellular and molecular changes in the testicular environment. In this study, we performed bioinformatics analysis using scRNA-seq and microarray data obtained from the GEO database. The analysis included techniques such as pseudotime analysis, cell–cell communication, and hdWGCNA. Our study showed a significant difference between the iNOA and the normal groups, indicating a disorder in the spermatogenic microenvironment in iNOA. We observed a reduction in the proportion of Sertoli cells and blocked germ cell differentiation. Additionally, we found evidence of testicular inflammation related to macrophages and identified ODF2 and CABYR as potential biomarkers for iNOA.

Taking reservoir rocks and fluids of the Daqing, Dagang and Changqing oilfields as research objects, the EOR mechanisms and technical approach of polymer flooding were discussed. By comparing the displacement performances of ordinary polymer, glycerol, polymer in “sheet-net” structure and heterogeneous weak gel at the same viscosity and concentration, the relationship between the viscosity of polymer displacement agents and displacement performance was demonstrated, and the method of improving polymer flooding effect was worked out. The main mechanism of polymer flooding to increase oil recovery is the swept volume expansion of water injection due to polymer retention in porous media. The viscosity of polymer agents has no positive correlation with polymer flooding effect. Although polymer of “sheet-net” structure has strong capacity in increasing viscosity, it has poor compatibility with pore throat structure of reservoir rock, low injectivity and low shear resistance. Heterogeneous weak gel system has higher adsorption and capture capacity in porous media, which is easy to retain in porous media, and can effectively establish seepage resistance in high permeability layers (zones). Compared with polymer solutions with the same viscosity or concentration, it has stronger ability to expand swept volume. Long term injection of polymer flooding agents will inevitably lead to fluid entry profile reversal, and thus worsening of polymer flooding effect. Alternate injection of high retention and low or non-retention displacement agents can further improve the displacement effect of polymer flooding agents.

Objectives: We aimed to examine the protective effects of dapagliflozin (dapa) on thoracic aortic constriction (TAC)-induced heart failure in a nondiabetic mouse model. More specifically, we determined the effects of dapa on uncoupling protein 3 (UCP3) activation and subsequent metabolic remodeling. Methods: Sixty C57BL/6J mice were divided into six groups for TAC surgery and received different doses of dapa via gavage for 4 weeks. Echocardiography was performed to evaluate cardiac structure and function. Histological and molecular markers of cardiac remodeling and metabolic changes were assessed through staining assays, RT-PCR, western blot, and ELISA. HL-1 cells were used to explore the role of UCP3 in metabolic remodeling through transfection with UCP3 siRNA. Results: Mice that received TAC exhibited elevated heart weight/body weight ratios (HW/BW), left ventricular (LV) hypertrophy, impaired LV ejection fraction, and increased rates of fibrosis and apoptosis, unlike mice that received sham operation. Treatment with dapa after TAC restored HW/BW, improved LV parameters, and reduced fibrosis and apoptosis. dapa changed the expression levels of enzymes involved in glucose and fatty acid (FA) metabolism, such as pyruvate dehydrogenase lipoamide kinase isozyme 4, glucose transporter 4, carnitine palmitoyltransferase-1α, carnitine O-acetyltransferase, carnitine O-octanoyltransferase, acyl-CoA thioesterase 1, acyl-CoA thioesterase 2, peroxisome proliferator-activated receptors α and β, proliferator-activated receptor-gamma coactivator-1α, and UCP3, relative to the levels in mice in the TAC group. UCP3 siRNA reduced the expression of AMP-activated protein kinase and of factors involved in FA oxidation in vitro. Conclusions: Dapa exhibits cardioprotective effects in the model and augments expression of UCP3, which may be involved in metabolic remodeling in the failing heart.

This study proposes a novel Bayesian hierarchical approach for online bus speed prediction by explicitly accounting for the spatiotemporal interaction (STI) of speed observations. The use of Laplace approximation can expedite the estimation of Bayesian models and enable the implementation of online prediction. Large numbers of trials are carried out to identify significant predictors and the optimal length of the look-back time window to achieve the highest prediction accuracy. The spatiotemporal interacting patterns are also explored, and results show that the Type IV model assuming the structured spatial effect interacts with the structured temporal effect can best accommodate the bus speed data. Besides, prediction errors of the Type IV model randomly distribute over time and space. The proposed model can achieve high prediction accuracy and computational efficiency without compromising the interpretability of the contributing factors and the unobserved spatiotemporal heterogeneity. The proposed model can be used to assist public transit operation and management, such as bus scheduling, congestion warning, and the development of proactive measures to mitigate bus delays.

Polyploidy, or whole-genome duplication (WGD), often induces dramatic changes in gene expression due to “transcriptome shock. ” However, questions remain about how allopolyploidy (the merging of multiple nuclear genomes in the same nucleus) affects gene expression within and across multiple tissues and developmental stages during the initial foundation of allopolyploid plants. Here, we systematically investigated the immediate effect of allopolyploidy on gene expression variation in an artificial allopolyploidy system consisting of a constructed allotetraploid wheat (AADD genome, accession AT2) and its diploid progenitors Triticum urartu and Aegilops tauschii. We performed comprehensive RNA sequencing of 81 samples from different genotypes, tissues, and developmental stages. First, we found that intrinsic interspecific differences between the diploid parents played a major role in establishing the expression architecture of the allopolyploid. Nonetheless, allopolyploidy per se also induced dramatic and asymmetric patterns of differential gene expression between the subgenomes, and genes from the D subgenome exhibited a more drastic response. Second, analysis of homoeolog expression bias (HEB) revealed that the D subgenome exhibited significant expression bias and that de novo-generated HEB was attributed mainly to asymmetrical differential gene expression. Homoeolog-specific expression (HSE) analyses showed that the cis-only regulatory pattern was predominant in AT2, reflecting significant divergence between the parents. Co-expression network analysis revealed that homoeolog expression connectivity (HEC) was significantly correlated with sequence divergence in cis elements between subgenomes. Interestingly, allopolyploidy-induced reconstruction of network modules was also associated with different HSE patterns. Finally, a transcriptome atlas of spike development demonstrated that the phenotypic similarity of AT2 to T. urartu may be attributed to the combination of relatively stable expression of A-subgenome genes and drastic downregulation of their D-subgenome homoeologs. These findings provide a broad, multidimensional characterization of allopolyploidy-induced transcriptomic responses and suggest that allopolyploidy can have immediate and complex regulatory effects on the expression of nuclear genes.

The number of co-infections with multiple porcine diarrhea viruses has increased in recent years. Inducing mucosal immunity through oral immunization is an effective approach for controlling these pathogens. To generate a multi-pathogen vaccine against viral co-infection, we employed the Lactobacillus vector platform, which was previously used to generate potent candidate vaccines against various diseases. Two strategies were used to test the protective efficiency of recombinant Lactobacillus against multiple diarrhea viruses. First, we used a mixture of recombinant Lactobacillus separately expressing antigens of transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and porcine rotavirus (PoRV). Next, we used a recombinant Lactobacillus expressing an antigen fusion protein of the above viruses. Twenty-four newborn piglets were divided into three groups and orally immunized with a mixture of recombinant Lactobacillus, recombinant Lactobacillus expressing the antigen fusion protein, or sterile phosphate-buffered saline daily for seven consecutive days after birth. After immunization, the piglets were randomly selected from each group for oral administration of PEDV, and these piglets were then cohabited with piglets without PEDV infection for 7 days. The protective effect against PEDV was evaluated based on clinical symptoms, viral shedding, and intestinal pathological damage. Piglets immunized with recombinant Lactobacillus showed specific mucosal and humoral immune responses to the three viruses and were protected against severe diarrhea and intestinal pathology. Our results highlight the potential of an oral multi-pathogen vaccine based on Lactobacillus to prevent transmission and limit the severity of viral co-infection.

ABSTRACT: This study aimed to investigate the subclinical symptom and histological lesions of 21-day-old and 42-day-old broilers exposure to low concentration aflatoxin B1 (AFB1), and the preventive effect with adsorbent (Toxo-MX) supplementation. A total of 576 one-day-old Arbor Acres broilers were randomly allotted into 6 treatments 8 replicates and 12 birds per cage, fed with 0 ppb, 60 ppb and 120 ppb AFB1 contamination diet with or without Toxo-MX supplementation. Results showed both 60 ppb and 120 ppb AFB1 contamination significantly reduced growth performance in 21-day-old broilers (P < 0.05), but not in 42-day-old broilers (P > 0.05), however, AFB1 contamination in diet caused a higher feed to gain ratio (P < 0.05). Broilers of 21-day-old exposure to 60 ppb and 120 ppb AFB1 increased mRNA expression of hepatic inflammatory cytokines, and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity (P < 0.05), 42-day-old broilers showed a same change in 120 ppb but not in 60 ppb of AFB1 contamination (P < 0.05). mRNA expressions of clauding-1, Zonula occludens-1 (ZO-1), and occludin decreased, but Bax, Bcl-2, and caspase-3 increased in 21-day-old broilers exposure to 60 ppb and 120 ppb AFB1 (P < 0.05), broilers of 42-day-old resisted on intestinal aflatoxicosis impairment against 60 ppb AFB1 contamination (P < 0.05), but not in 120 ppb (P < 0.05). Toxo-MX supplementation significantly reversed the detrimental effects on growth performance in both age broilers and reduced the accelerated feed to gain ratio caused by AFB1 (P < 0.05). Intestinal mRNA expression of tight junction and apoptotic genes in both age broilers were recovered by Toxo-MX supplementation (P < 0.05). However, Toxo-MX did not restore the accelerated expression of hepatic inflammation cytokines and SOD, GSH-Px in 120ppb AFB1 group (P < 0.05). The data demonstrated that diet supplementation with Toxo-MX reversed the detrimental effect on growth performance and intestine in broilers exposure to 60 ppb and 120 ppb AFB1. However, did not completely recovered hepatic inflammation induced by AFB1.

The relevance. Compared with conventional reservoir, offshore heavy oil reservoir faced the problem of lower water flooding recovery. It is helpful to improve the water flooding recovery of heavy oil reservoir if we have more knowledge about seepage characteristics of water and oil. The main aim of the research is to investigate the change rule of seepage characteristics of water phase and oil phase in offshore heavy oil reservoir, which is helpful to the decision of field construction and can provide guidance for numerical simulation. Methods. The reservoir geological characteristics, fluid properties and field construction technology of the destination offshore heavy oil reservoir in Bohai Oilfield were taken into consideration. The impact of core permeability, injection water washout and crude oil viscosity on relative permeability curve and displacement efficiency of water flooding were studied, through core displacement experiment using displacement method of unsteady state. The change of core inside structure is presented by core CT scanning and mercury pressure test. Results. With the increase of core permeability, water phase relative permeability increases, the swept volume of water phase becomes bigger, two-phase flow span gets wider, and ultimate recovery enhances. The function of «cleaning» and «erosion» that water washout exerts on core pore structure would enlarge the pore throat radius, increasing core permeability, and its influence on relative permeability curve and displacement efficiency is the same as the influence of permeability increase. With the crude oil viscosity increasing, mobility control ability of water gets weaker in the process of water flooding, displacement phase viscous fingering phenomenon aggravates, the swept volume of water phase becomes smaller, two-phase flow span gets narrower, and ultimate recovery decreases.