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Abstract Background Extracellular vesicles (EVs) secreted by mesenchymal stromal cells (MSCs) have been shown to provide significant protection against renal ischemia–reperfusion injury (IRI). Hypoxia has emerged as a promising strategy to enhance the tissue repair capabilities of MSCs. However, the specific effects of hypoxia on MSCs and MSC-EVs, as well as their therapeutic potential in renal IRI, remain unclear. In this study, we investigated the alterations occurring in MSCs and the production of MSC-EVs following hypoxia pre-treatment, and further explored the key intrinsic mechanisms underlying the therapeutic effects of hypoxic MSC-EVs in the treatment of renal IRI. Methods Human umbilical cord MSCs were cultured under normoxic and hypoxic conditions. Proliferation and related pathways were measured, and RNA sequencing was used to detect changes in the transcriptional profile. MSC-EVs from both normoxic and hypoxic conditions were isolated and characterized. In vivo, the localization and therapeutic effects of MSC-EVs were assessed in a rat renal IRI model. Histological examinations were conducted to evaluate the structure, proliferation, and apoptosis of IRI kidney tissue respectively. Renal function was assessed by measuring serum creatinine and blood urea nitrogen levels. In vitro, the therapeutic potential of MSC-EVs were measured in renal tubular epithelial cells injured by antimycin A. Protein sequencing analysis of hypoxic MSC-EVs was performed, and the depletion of Glutathione S-Transferase Omega 1 (GSTO1) in hypoxic MSC-EVs was carried out to verify its key role in alleviating renal injury. Results Hypoxia alters MSCs transcriptional profile, promotes their proliferation, and increases the production of EVs. Hypoxia-pretreated MSC-EVs demonstrated a superior ability to mitigate renal IRI, enhancing proliferation and reducing apoptosis of renal tubular epithelial cells both in vivo and in vitro. Protein profiling of the EVs revealed an accumulation of numerous anti-oxidative stress proteins, with GSTO1 being particularly prominent. Knockdown of GSTO1 significantly reduced the antioxidant and therapeutic effects on renal IRI of hypoxic MSC-EVs. Conclusions Hypoxia significantly promotes the generation of MSC-EVs and enhances their therapeutic effects on renal IRI. The antioxidant stress effect induced by GSTO1 is identified as one of the most critical underlying mechanisms. Our findings highlight that hypoxia-pretreated MSC-EVs represent a novel and promising therapeutic strategy for renal IRI. Graphical Abstract

Abstract Although 3D reconstruction has been widely used in many fields as a key component of environment perception, existing technologies still have the potential for further improvement in 3D scene reconstruction. We propose an improved reconstruction algorithm based on the MVSNet network architecture. To glean richer pixel details from images, we suggest deploying a DE module integrated with a residual framework, which supplants the prevailing feature extraction mechanism. The DE module uses ECA-Net and dilated convolution to expand the receptive field range, performing feature splicing and fusion through the residual structure to retain the global information of the original image. Moreover, harnessing attention mechanisms refines the 3D cost volume's regularization process, bolstering the integration of information across multi-scale feature volumes, consequently enhancing depth estimation precision. When assessed our model using the DTU dataset, findings highlight the network's 3D reconstruction scoring a completeness (comp) of 0.411 mm and an overall quality of 0.418 mm. This performance is higher than that of traditional methods and other deep learning-based methods. Additionally, the visual representation of the point cloud model exhibits marked advancements. Trials on the Blended MVS dataset signify that our network exhibits commendable generalization prowess.

Enterovirus 68 (EV-D68) is a non-enveloped virus with a positive-sense single-stranded RNA genome that causes respiratory diseases and acute flaccid myelitis, posing significant threats to human health. However, an effective vaccine remains undeveloped. SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent enzyme, plays a key role in cellular metabolism, but its interaction with NAD+ during viral infections is not well understood. In this study, through a metabolomics analysis, we demonstrate that EV-D68 infection influences cellular metabolism. Additionally, we show that NAD+ inhibits EV-D68 infection both in vivo and in vitro. EV-D68 reduces cellular NAD+ levels by regulating the expression of enzymes involved in NAD+ consumption and synthesis. Moreover, the infection increases the expression of sirtuin 1 (SIRT1), which inhibits EV-D68 replication in turn. Mechanistically, SIRT1 suppresses EV-D68 5′UTR-mediated translation, and the antiviral effect of SIRT1 on EV-D68 replication is enhanced by NAD+. Collectively, our findings highlight the critical role of NAD+ metabolism in EV-D68 infection and reveal the antiviral potential of SIRT1, providing valuable insights for the development of antiviral strategies.

This paper reports on the successful synthesis of a novel alumina powder with a unique rose-like structure composed of alumina platelets, using the molten salt method. The synthesized powder was then utilized to prepare alumina ceramic with impressive mechanical properties. The influences of the synthesizing temperature of alumina powder on the microstructure and mechanical properties of alumina ceramic are investigated in details. The results indicate that the alumina ceramic prepared using the rose-like powder synthesized at 800 °C exhibits a high relative density of 99.5 %, flexural strength of 408.2 ± 18.7 MPa, and fracture toughness of 6.14 ± 0.63 MPa m1/2. The work presented in this paper will provide a useful guideline for the preparation of high-performance alumina ceramic materials in the future.

In the original publication [...]

Haze is a phenomenon caused by excessive PM2.5 (air-borne particulate matter having a diameter of fewer than 2.5 μm) and other pollutants and results from the interaction between specific climatic conditions and human activities. It significantly impacts human health, transportation, and the natural environment and has aroused widespread concern. However, the influence of haze on human mental health, being hidden and indirect, is often overlooked. When haze pollution occurs, people express their feelings and concerns about haze events on media such as Weibo. At present, few studies focus on haze public opinion, as well as the changing trends in people’s discussion of haze since its emergence, which is of great significance for haze response and resource management. Based on the perspective of topic analysis, this study explores the psychological impact of haze on people by exploring the feelings of netizens in haze public opinion and investigates the evolution of people’s concerns based on long-term public opinion data. In this study, seven typical provinces and cities in China with severe haze pollution were selected as the research area. Based on data on the “haze” theme from Weibo from 2013 to 2019, first, the microblog posts were preprocessed, and the keyword co-word network was constructed. Second, the Louvain algorithm was used to detect the topic community. Based on this, the cosine similarity was calculated to realize the temporal evolution analysis of topics. The results show that with the development and change in haze pollution, the content and intensity of the topics netizens pay attention to have changed, including five types: merger, split, survival, transformation, and rebirth/extinction. People’s attention to haze shows obvious spatial differences, and it is related to the degree of haze pollution, which is bipolar. Areas with severe haze tend to pay more attention to haze itself and its influence, while areas with light haze pay more attention to haze control. The research results can provide valuable insights for governments and relevant departments in guiding public opinion and resource allocation.

AbstractTranscatheter arterial chemoembolization (TACE) is usually considered more efficacious in the local treatment of parenchyma-sparing hepatocellular carcinoma (HCC). At present, embolic agents commonly used in TACE, include DC pellets, Hepasphere, Lipiodol, etc. Except that iodine oil is a viscous fluid embolic agent, other solid microsphere particles used clinically range from 70 to 700 µm, among which 100 to 300 µm is the most commonly used. With the technology development of micro-invasive interventional therapy, the specific distal embolization through TACE to occlude tumor arterial blood supply in patients with HCC is also required more accurately. Effective terminal embolization is considered to be a preferred option for TACE therapy due to significantly improving the survival rate of patients and preserving liver function. In this article, we prepared the multifunctional multivesicular liposomes (IVO-DOX-MVLs) (

ABSTRACTThe coronavirus disease 2019 (COVID-19) and its mutant viruses are still wreaking global havoc over the last two years, but the impact of human activity on the transmission of the pandemic is difficult to ascertain. Estimating human dynamic spatiotemporal distribution can help in our understanding of how to mitigate COVID-19 spread, which can help in maintaining urban health within a county and between counties within a country. This distribution can be computed using the Volunteered Geographic Information (VGI) of the citizens in conjunction with other variables, such as climatic conditions, and used to analyze how human’s daily density distribution quantitatively affects COVID-19 transmission. Based on the estimated population density, when the population density increases daily by 1 person/km2 in a county or prefectural-level administrative unit with an average size of 26,000 km2, the county would have an additional 3.6 confirmed cases and 0.054 death cases after 5 days, which is the illness onset time for a new COVID-19 case. After 14 days, which is the maximum incubation period of the COVID-19 virus, there would be 5 new confirmed cases and 0.092 death cases. However, in neighboring regions, there can be 0.96 fewer people infected with COVID-19 on average per day as a result of strong intervention of local and neighboring authorities. The primary innovation and contribution are that this is the first quantitative assessment of the impacts of dynamic population density on the COVID-19 pandemic. Additionally, the direct and indirect effects of the impact are estimated using spatial panel models. The models that control the unobserved factors improve the reliability of the estimation, as validated by random experiments and the use of the Baidu migration dataset.

Acute kidney injury (AKI) is a life-threatening health condition associated with increasing morbidity and mortality. Despite extensive research on the mechanisms underlying AKI, effective clinical tools for prediction and treatment remain scarce. Oxidative stress and mitochondrial damage play a critical role in AKI and dopamine D4 receptor (DRD4) has been confirmed to be associated with oxidative stress. In this study, we hypothesized that DRD4 could attenuate AKI through its antioxidative and antiapoptotic effects. In vivo, DRD4 was remarkably decreased in the kidneys of mice subjected to ischemia/reperfusion injury (IRI) or cisplatin treatment. Notably, DRD4 significantly attenuated nephrotoxicity by suppressing oxidative stress and enhancing mitochondrial bioenergetics through the downregulation of reactive oxygen species (ROS) generation and NADPH oxidase 4 (NOX4) expression. In vitro, DRD4 demonstrated the ability to ameliorate oxidative stress-induced apoptosis in HK-2 cells subjected to hypoxia/reoxygenation- or cisplatin treatment. Transcriptome sequencing revealed that, mechanistically, DRD4 reduced the expression of its downstream target, interferon-stimulated gene 15 (ISG15), suppressing NOX4 ISGylation, enhancing the ubiquitination of NOX4, leading to its degradation, and ultimately counteracting oxidative stress-induced AKI. Altogether, these findings underscore the significance of DRD4 in AKI and elucidate DRD4 as a potential protectant against IRI or cisplatin-induced nephrotoxicity.

The small-signal S parameters of the fabricated double-finger gate AlGaN/GaN high electron mobility transistors (HEMTs) were measured at various direct current quiescent operating points (DCQOPs). Under active bias conditions, small-signal equivalent circuit (SSEC) parameters such as Rs and Rd, and intrinsic parameters were extracted. Utilizing fT and the SSEC parameters, the effective electron velocity (νe−eff) and intrinsic electron velocity (νe−int) corresponding to each gate bias (VGS) were obtained. Under active bias conditions, the influence mechanism of VGS on νe−eff was systematically studied, and an expression was established that correlates νe−eff, νe−int, and bias-dependent parasitic resistances. Through the analysis of the main scattering mechanisms in AlGaN/GaN HEMTs, it has been discovered that the impact of VGS on νe−eff should be comprehensively analyzed from the aspects of νe−int and parasitic resistances. On the one hand, changes in VGS influence the intensity of polar optical phonon (POP) scattering and polarization Coulomb field (PCF) scattering, which lead to changes in νe−int dependent on VGS. The trend of νe−int with changes in VGS plays a dominant role in determining the trend of νe−eff with changes in VGS. On the other hand, both POP scattering and PCF scattering affect νe−eff through their impact on parasitic resistance. Since there is a difference in the additional scattering potential corresponding to the additional polarization charges (APC) between the gate-source/drain regions and the region under the gate, the mutual effects of PCF scattering on the under-gate electron system and the gate-source/drain electron system should be considered when adjusting the PCF scattering intensity through device structure optimization to improve linearity. This study contributes to a new understanding of the electron transport mechanisms in AlGaN/GaN HEMTs and provides a novel theoretical basis for improving device performance.

Multi-view stereo based on learning is a critical task in three-dimensional reconstruction, enabling the effective inference of depth maps and the reconstruction of fine-grained scene geometry. However, the results obtained by current popular 3D reconstruction methods are not precise, and achieving high-accuracy scene reconstruction remains challenging due to the pervasive impact of feature extraction and the poor correlation between cost and volume. In addressing these issues, we propose a cascade deep residual inference network to enhance the efficiency and accuracy of multi-view stereo depth estimation. This approach builds a cost-volume pyramid from coarse to fine, generating a lightweight, compact network to improve reconstruction results. Specifically, we introduce the omni-dimensional dynamic atrous spatial pyramid pooling (OSPP), a multiscale feature extraction module capable of generating dense feature maps with multiscale contextual information. The feature maps encoded by the OSPP module can generate dense point clouds without consuming significant memory. Furthermore, to alleviate the issue of feature mismatch in cost volume regularization, we propose a normalization-based 3D attention module. The 3D attention module aggregates crucial information within the cost volume across the dimensions of channel, spatial, and depth. Through extensive experiments on benchmark datasets, notably DTU, we found that the OD-MVSNet model outperforms the baseline model by approximately 1.4% in accuracy loss, 0.9% in completeness loss, and 1.2% in overall loss, demonstrating the effectiveness of our module.

High strength and toughness are contradictory in ceramic materials. Improving the toughness of ceramics through the introduction of a ductile phase to dissipate energy is usually at the sacrifice of strength, stiffness, and the ability to operate at high temperature. Here we developed a simple approach to fabricate isotropic alumina monolithic ceramic characterized by a unique combination of high strength (405.4 MPa), high toughness (5.62 MPa m1/2) and thermal shock resistance toughness (746.2 °C), displaying a non-brittle fracture behavior. A clear picture of the toughening mechanism was depicted. This work highlights a practical guideline for development of bioinspired structural alumina ceramic.

Acetate promotes miR-493-3p expression, which in turn suppresses the expression of macrophage migration inhibitory factor, leading to decreased macrophages recruitment and reduced hyperoxaluria-induced renal injury in mice.

IntroductionDeep deterministic policy gradient (DDPG)-based path planning algorithms for intelligent robots struggle to discern the value of experience transitions during training due to their reliance on a random experience replay. This can lead to inappropriate sampling of experience transitions and overemphasis on edge experience transitions. As a result, the algorithm's convergence becomes slower, and the success rate of path planning diminishes.MethodsWe comprehensively examines the impacts of immediate reward, temporal-difference error (TD-error), and Actor network loss function on the training process. It calculates experience transition priorities based on these three factors. Subsequently, using information entropy as a weight, the three calculated priorities are merged to determine the final priority of the experience transition. In addition, we introduce a method for adaptively adjusting the priority of positive experience transitions to focus on positive experience transitions and maintain a balanced distribution. Finally, the sampling probability of each experience transition is derived from its respective priority.ResultsThe experimental results showed that the test time of our method is shorter than that of PER algorithm, and the number of collisions with obstacles is less. It indicated that the determined experience transition priority accurately gauges the significance of distinct experience transitions for path planning algorithm training.DiscussionThis method enhances the utilization rate of transition conversion and the convergence speed of the algorithm and also improves the success rate of path planning.

IntroductionWe aimed to investigate the feasibility of metabolomics to explain the underlying biological implications of radiomics features obtained from magnetic resonance imaging (MRI) preceding carbon ion radiotherapy (CIRT) in patients with prostate cancer and to further explore the clinical significance of radiomics features on the prognosis of patients, based on their biochemical recurrence (BCR) status.MethodsMetabolomic results obtained using high-performance liquid chromatography coupled with tandem mass spectrometry of urine samples, combined with pre-RT radiomic features extracted from MRI images, were evaluated to investigate their biological significance. Receiver operating characteristic (ROC) curve analysis was subsequently conducted to examine the correlation between these biological implications and clinical BCR status. Statistical and metabolic pathway analyses were performed using MetaboAnalyst and R software.ResultsCorrelation analysis revealed that methionine alteration extent was significantly related to four radiomic features (Contrast, Difference Variance, Small Dependence High Gray Level Emphasis, and Mean Absolute Deviation), which were significantly correlated with BCR status. The area under the curve (AUC) for BCR prediction of these four radiomic features ranged from 0.704 to 0.769, suggesting that the higher the value of these four radiomic features, the greater the decrease in methionine levels after CIRT and the lower the probability of BCR. Pre-CIRT MRI radiomic features were associated with CIRT-suppressed metabolites.DiscussionThese radiomic features can be used to predict the alteration in the amplitude of methionine after CIRT and the BCR status, which may contribute to the optimization of the CIRT strategy and deepen the understanding of PCa.

Objectives Coagulation factors participates in the inflammatory cascade, known to play a crucial role in the development of acute kidney injury (AKI). Thus, it’s likely that some factors may be associated with AKI. Among them, low levels of fibrinogen and antithrombin III (ATIII) activity have been proved to increase mortality in patients with sepsis. Moreover, they are also reported to be associated with higher incidence of AKI. However, the association between coagulation parameters, especially fibrinogen and ATIII, and prognosis of AKI has not been examined.Methods Data were acquired from Multiparameter Intelligent Monitoring in Intensive Care Database IV (MIMIC-IV) version 1.0. Cox proportional hazards regression model was used to estimate the relationship between coagulation parameters and in-hospital mortality in critically ill patients with AKI. Subgroup analysis was also conducted to assess the robustness of the association. Restricted cubic spline (RCS) curve was utilized to examine the nonlinear relationships between fibrinogen or ATIII and in-hospital mortality. Kaplan–Meier method was used to estimate cumulative incidence of mortality by fibrinogen or ATIII levels. Receiver-operating characteristic (ROC) curve was plotted and area under curve was calculated to evaluate predictive ability of fibrinogen or ATIII.Results A total of 5914 eligible patients were enrolled in fibrinogen cohort study and 115 patients were eligible for ATIII cohort study. The baseline of low fibrinogen (

Abstract Background Severe respiratory and neurological diseases caused by human enterovirus D68 (EV-D68) pose a serious threat to public health, and there are currently no effective drugs and vaccines. Adenosine deaminase acting on RNA1 (ADAR1) has diverse biological functions in various viral infections, but its role in EV-D68 infections remains undetermined. Methods Rhabdomyosarcoma (RD) and human embryonic kidney 293 T (293 T) cells, and HeLa cells were used to evaluate the expression level of ADAR1 upon EV-D68 (Fermon strain) and human parainfluenza virus type 3 (HPIV3; NIH47885) infection, respectively. Knockdown through silencing RNA (siRNA) and overexpression of either ADAR1p110 or ADAR1p150 in cells were used to determine the function of the two proteins after viral infection. ADAR1p110 double-stranded RNA binding domains (dsRBDs) deletion mutation was generated using a seamless clone kit. The expression of ADAR1, EV-D68 VP1, and HPIV3 hemagglutinin–neuraminidase (HN) proteins was identified using western blotting. The median tissue culture infectious dose (TCID50) was applied to detect viral titers. The transcription level of EV-D68 mRNA was analyzed using reverse transcription-quantitative PCR (RT-qPCR) and the viral 5′-untranslated region (5′-UTR)-mediated translation was analyzed using a dual luciferase reporter system. Conclusion We found that the transcription and expression of ADAR1 was inhibited upon EV-D68 infection. RNA interference of endogenous ADAR1 decreased VP1 protein expression and viral titers, while overexpression of ADAR1p110, but not ADAR1p150, facilitated viral replication. Immunofluorescence assays showed that ADAR1p110 migrated from the nucleus to the cytoplasm after EV-D68 infection. Further, ADAR1p110 lost its pro-viral ability after mutations of the active sites in the deaminase domain, and 5′-UTR sequencing of the viral genome revealed that ADAR1p110 likely plays a role in EV-D68 RNA editing. In addition, after ADAR1 knockdown, the levels of both phosphorylated double-stranded RNA dependent protein kinase (p-PKR) and phosphorylated eukaryotic initiation factor 2α (p-eIF2α) increased. Attenuated translation activity of the viral genome 5′-UTR was also observed in the dual-luciferase reporter assay. Lastly, the deletion of ADAR1p110 dsRBDs increased the level of p-PKR, which correlated with a decreased VP1 expression, indicating that the promotion of EV-D68 replication by ADAR1p110 is also related to the inhibition of PKR activation by its dsRBDs. Our study illustrates that ADAR1p110 is a novel pro-viral factor of EV-D68 replication and provides a theoretical basis for EV-D68 antiviral research.

IntroductionLaboratory teaching of medical microbiology involves highly pathogenic microorganisms, thus posing potential biosafety risks to the students and the teacher. To address these risks, non/low-pathogenic microorganisms were modified to mimic highly pathogenic ones or highly pathogenic microorganisms were attenuated directly using the CRISPR/Cas9 technology. This study describes the modification of Escherichia coli DH5α to mimic Shigella and its evaluation as a safe alternative for medical laboratory teaching.MethodsTo generate E. coli DH5α△FliC△tnaA2a, the tnaA and FliC genes in E. coli DH5α were knocked out using CRISPR/Cas9 technology; a plasmid bearing the O-antigen determinant of S. flexneri 2a was then constructed and transformed. Acid tolerance assays and guinea pig eye tests were used to assess the viability and pathogenicity, respectively. Questionnaires were used to analyze teaching effectiveness and the opinions of teachers and students.ResultsThe survey revealed that most teachers and students were inclined towards real-time laboratory classes than virtual classes or observation of plastic specimens. However, many students did not abide by the safety regulations, and most encountered potential biosafety hazards in the laboratory. E. coli DH5α△FliC△tnaA2a was biochemically and antigenically analogous to S. flexneri 2a and had lower resistance to acid than E. coli. There was no toxicity observed in guinea pigs. Most of teachers and students were unable to distinguish E. coli DH5α△FliC△tnaA2a from pure S. flexneri 2a in class. Students who used E. coli DH5α△FliC△tnaA2a in their practice had similar performance in simulated examinations compared to students who used real S. flexneri 2a, but significantly higher than the virtual experimental group.DiscussionThis approach can be applied to other high-risk pathogenic microorganisms to reduce the potential biosafety risks in medical laboratory-based teaching and provide a new strategy for the development of experimental materials.

In order to ameliorate the combustion properties of 1,3,5,7-tetranitro-1,3,5,7-tetrazacyclooctane (HMX) based composite modified double base (CMDB) propellants, HMX particles with many gullies are first prepared, and then 2,4-dihydroxybenzoic acid (DHBA) and 1,2,4-triazol-5-one (NTO) are used to react with lead via in situ deposition to coat HMX for preparing HMX@DHBA-Pb and HMX@NTO-Pb composites. The structures and properties of HMX@DHBA-Pb and HMX@NTO-Pb composites are characterized in detail. The characterization results show that DHBA-Pb and NTO-Pb shells are uniformly coated on HMX surfaces. The chemical structure of HMX maintains constant during in situ deposition coating process. The mechanical and thermal safeties of HMX are enhanced after coating with DHBA-Pb and NTO-Pb shells. The introduce of DHBA-Pb and NTO-Pb can catalyze the decomposition and combustion of HMX core, and the catalytic effects of in situ coating are better than that of physical mixing.

In recent years, the emergence of dockless bike-sharing has brought new ways of transportation, while also providing support for observing urban dynamics at a finer granularity. This study uses dockless bike-sharing data, combined with point of interest (POI) data, to explore intra-urban human mobility and daily activity patterns, using Beijing as a case study. Here, we employ spatial statistics and graph network to quantify the characteristics of travel behavior. Firstly, spatiotemporal statistics analysis was conducted to investigate the travel patterns and spatiotemporal differences of bike-sharing in Beijing. It was found that bike trips have clear peak hours and highly overlap with the subway lines, indicating that the bike-sharing system effectively completes the ‘last mile’ of travel in Beijing. Secondly, graph networks were used to reveal the core patterns and community structures of human mobility in Beijing and their connections to daily activities. Our findings indicate that there are different core structures of human mobility in Beijing, some dominated by a single core node, while others are formed by the aggregation of multiple cores. Finally, POI data was used to analyze human daily activity patterns. We analyzed the temporal characteristics and the hotspot areas of each daily activity in Beijing and found that transferring to other transportation modes is the most popular activity for people riding bikes, followed by shopping, working, and eating out. These findings provide a reference for understanding urban human dynamics and urban structure from the perspective of dockless bike-sharing.

Abstract There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole‐exome sequencing on normal‐tumor‐thrombus‐metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs). A total of 706 nonmetastatic ccRCC patients with VTT from three independent cohorts were included in this study. C‐index analysis revealed that pathological grading of VTT outperformed other indicators in risk assessment (OS: 0.663 versus 0.501–0.610, 0.667 versus 0.544–0.651, and 0.719 versus 0.511–0.700 for Training, China‐Validation, and Poland‐Validation cohorts, respectively). We constructed a risk predicting model, TT‐GPS score, based on four independent variables: VTT height, VTT grading, perinephric fat invasion, and sarcomatoid differentiation in PT. The TT‐GPS score displayed better discriminatory ability (OS, c‐index: 0.706–0.840, AUC: 0.788–0.874; DFS, c‐index: 0.691–0.717, AUC: 0.771–0.789) than previously reported models in risk assessment. In conclusion, we identified for the first‐time pathological grading of VTT as an unheeded prognostic factor. By incorporating VTT grading, the TT‐GPS score is a promising prognostic tool in predicting the survival of nonmetastatic ccRCC patients with VTT.

Plant diseases and pests have always been major contributors to losses that occur in agriculture. Currently, the use of deep learning-based convolutional neural network models allows for the accurate identification of different types of plant diseases and pests. To enable more efficient identification of plant diseases and pests, we design a novel network architecture called Dise-Efficient based on the EfficientNetV2 model. Our experiments demonstrate that training this model using a dynamic learning rate decay strategy can improve the accuracy of plant disease and pest identification. Furthermore, to improve the model’s generalization ability, transfer learning is incorporated into the training process. Experimental results indicate that the Dise-Efficient model boasts a compact size of 13.3 MB. After being trained using the dynamic learning rate decay strategy, the model achieves an accuracy of 99.80% on the Plant Village plant disease and pest dataset. Moreover, through transfer learning on the IP102 dataset, which represents real-world environmental conditions, the Dise-Efficient model achieves a recognition accuracy of 64.40% for plant disease and pest identification. In light of these results, the proposed Dise-Efficient model holds great potential as a valuable reference for the deployment of automatic plant disease and pest identification applications on mobile and embedded devices in the future.

Since the emergence of new coronaviruses and their variant virus, a large number of medical resources around the world have been put into treatment. In this case, the purpose of this article is to develop a handback intravenous intelligence injection robot, which reduces the direct contact between medical staff and patients and reduces the risk of infection. The core technology of hand back intravenous intelligent robot is a handlet venous vessel detection and segmentation and the position of the needle point position decision. In this paper, an image processing algorithm based on U-Net improvement mechanism (AT-U-Net) is proposed for core technology. It is investigated using a self-built dorsal hand vein database and the results show that it performs well, with an F1-score of 93.91%. After the detection of a dorsal hand vein, this paper proposes a location decision method for the needle entry point based on an improved pruning algorithm (PT-Pruning). The extraction of the trunk line of the dorsal hand vein is realized through this algorithm. Considering the vascular cross-sectional area and bending of each vein injection point area, the optimal injection point of the dorsal hand vein is obtained via a comprehensive decision-making process. Using the self-built dorsal hand vein injection point database, the accuracy of the detection of the effective injection area reaches 96.73%. The accuracy for the detection of the injection area at the optimal needle entry point is 96.50%, which lays a foundation for subsequent mechanical automatic injection.

Radiative neutron capture cross-section and the resonance parameter are very important nuclear data in the field of the R&D of accelerator driven systems, the transmutation of nuclear waste and nuclear astrophysics. In the recent years, radiative neutron capture crosssections of important nuclides were mostly measured based on the white neutron source facilities, such as the CERN n_TOF, GELINA, LANSCE and so on. The back streaming white neutron beam line (Backn) of China Spallation Neutron Source (CSNS) is the first white neutron facility in China, which can provide pulsed neutron beam with 25 Hz frequency in the energy region from thermal neutron to hundreds MeV. The main application of Backn is to perform nuclear data measurement, such as crosssection, reaction yield, nuclear structure, and so on. The C6D6 liquid scintillation detector is widely used for radiative neutron capture crosssection measurements on timeofflight facilities, because of its low neutron sensitivity and good time response. A C6D6 detection system with four detectors was installed at Backn to perform radiative neutron capture crosssection measurement, especially in the resonance energy region. In this work, the measurement of 169Tm(n,γ)170Tm reaction was performed with the C6D6 detection system at the Backn. The stable isotope of thulium, 169Tm, is one of the fission product poisons, which makes the accurate neutron radiative capture crosssection of 169Tm be of major significance for fission and fusion reactor design. Besides, the radioactivity induced by the reactions of 169Tm(n,γ)170Tm and 170Tm(n,γ) 171Tm makes the 169Tm to be an ideal spectrumsensitive activation detector for the neutron intensity diagnosis, in which the precise neutron capture crosssection is of critical importance. In the present measurement, the pulse height weighting technique was used to make detection efficiency be proportional to the excitation energy of the compound nucleus. The black filter method was used to determine the experimental background due to scattered neutron and inbeam gamma ray. The saturated resonance method was used to normalize the capture yield. The Rmatrix code SAMMY was used to fit the capture yield of 169Tm to obtain the resonance parameters, such as resonance energy, neutron width, radiative capture width, and so on. Then the radiative capture crosssection was calculated with the measured resonance parameters and ReichMoore approximation. For most energy region between 1 eV and 100 eV, the present measurement result is consistent with the recommended value of ENDF/BⅧ.0, but there were still some discrepancies between the measured crosssection and the evaluated data. According to the current results, the measurement and data analysis methods used in this work are suitable for the measurement of radiative capture crosssection and resonance parameter. However, in order to perform high precision measurement of radiative capture crosssection at Backn, the neutron flux and the energy resolution function still need to be determined more accurately.

Summary: Background: Interleukin-17C (IL-17C), a member of the IL-17 cytokine family, plays a pathogenic role in kidney diseases. Our previous studies have shown that pre-administration of IL-17C neutralizing antibody attenuated acute kidney injury (AKI, a common acute inflammation associated renal disease). In this study, we explored whether post-ischemia reperfusion (IR) of IL-17C blockade has therapeutic effects on AKI and whether IL-17C is involved in the pathogenesis of diabetic nephropathy (DN), a major type of chronic inflammation-associated kidney disease. Methods: 12-week-old male C57BL/6JGpt mice were treated with IL-17C neutralizing antibody or normal IgG control antibody at 3 h after reperfusion. Renal injury, inflammation, and oxidative stress were assessed. Additionally, we examined renal IL-17C expression in patients with DN and db/db mice and evaluated albuminuria, mesangial matrix accumulation and podocyte loss in db/db mice with IL-17C neutralization. Knockdown of NF-κB p65 using siRNA, and blocking Hypoxia-inducible factor-1α (HIF-1α) using YC-1 in mice and HIF-1α Decoy in HK2 cells were investigated to explore the possible signaling pathway involved in IL-17C regulation. Findings: We found that delayed IL-17C neutralization had similar reno-protective effects on renal ischemia-reperfusion injury (IRI). Additionally, renal IL-17C expression was increased in patients with DN and db/db mice, while IL-17C blockade significantly attenuated DN, accompanied with blunted albuminuria, mesangial matrix accumulation, and podocyte loss. Moreover, IL-17C neutralization significantly repressed the expression of downstream pro-inflammatory cytokines, inflammatory cell infiltration, and Th17/IL-17A activation both in mice with renal IRI and DN. Mechanistical studies demonstrated that hypoxia or high glucose-induced IL-17C up-regulation was predominantly mediated by NF-κB pathway. Interpretation: IL-17C participates in the pathogenesis of AKI and DN and inhibition of IL-17C shows potential as a therapeutic strategy for AKI and DN. Funding: The National Natural Science Foundation of China (81770741, 81700601 and 81870504).

Background Tumor-associated macrophages are mainly polarized into the M2 phenotype, remodeling the tumor microenvironment and promoting tumor progression by secreting various cytokines.Methods Tissue microarray consisting of prostate cancer (PCa), normal prostate, and lymph node metastatic samples from patients with PCa were stained with Yin Yang 1 (YY1) and CD163. Transgenic mice overexpressing YY1 were constructed to observe PCa tumorigenesis. Furthermore, in vivo and in vitro experiments, including CRISPR-Cas9 knock-out, RNA sequencing, chromatin immunoprecipitation (ChIP) sequencing, and liquid–liquid phase separation (LLPS) assays, were performed to investigate the role and mechanism of YY1 in M2 macrophages and PCa tumor microenvironment.Results YY1 was highly expressed in M2 macrophages in PCa and was associated with poorer clinical outcomes. The proportion of tumor-infiltrated M2 macrophages increased in transgenic mice overexpressing YY1. In contrast, the proliferation and activity of anti-tumoral T lymphocytes were suppressed. Treatment targeting YY1 on M2 macrophages using an M2-targeting peptide-modified liposome carrier suppressed PCa cell lung metastasis and generated synergistic anti-tumoral effects with PD-1 blockade. IL-4/STAT6 pathway regulated YY1, and YY1 increased the macrophage-induced PCa progression by upregulating IL-6. Furthermore, by conducting H3K27ac-ChIP-seq in M2 macrophages and THP-1, we found that thousands of enhancers were gained during M2 macrophage polarization, and these M2-specific enhancers were enriched in YY1 ChIP-seq signals. In addition, an M2-specific IL-6 enhancer upregulated IL-6 expression through long-range chromatin interaction with IL-6 promoter in M2 macrophages. During M2 macrophage polarization, YY1 formed an LLPS, in which p300, p65, and CEBPB acted as transcriptional cofactors.Conclusions Phase separation of the YY1 complex in M2 macrophages upregulated IL-6 by promoting IL-6 enhancer–promoter interactions, thereby increasing PCa progression.

In order to ameliorate the sensitivities, thermal and combustion properties of cyclotrimethylenetrinitramine (RDX), tannic acid (TA) is used to react with lead and copper via in situ self-assembly to coat RDX for preparing RDX@TA-Pb/Cu microcapsules. The structures of RDX@TA-Pb/Cu microcapsules are characterized by X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and Fourier-transform infrared spectra (FT-IR). The surface topography of RDX@TA-Pb/Cu microcapsules are characterized by scanning electron microscope (SEM) and energy dispersive spectroscopy (EDS). The mechanical sensitivities and explosion points of RDX@TA-Pb/Cu microcapsules are measured to study the influence of TA-Pb/Cu shells on mechanical and thermal safeties of RDX. The non-isothermal properties of RDX@TA-Pb/Cu microcapsules are characterized by differential scanning calorimetry (DSC). The catalytic effects of TA-Pb/Cu shells on RDX are characterized by accelerating rate calorimeter (ARC). The residues of RDX@TA-Pb/Cu microcapsules after combustion in air are collected and characterized by SEM and XRD to further study the catalytic effect of TA-Pb/Cu shells. The study results show that a 150 nm TA-Pb/Cu shells are uniformly coated on RDX surfaces. The chemical structure of RDX maintains constant during in situ self-assembly coating process. The mechanical and thermal safeties of RDX are enhanced after coating with TA-Pb/Cu shells. The decomposition and combustion property of RDX can be catalyzed by TA-Pb/Cu, and the catalytic effects of in situ self-assembly coating are better than that of physical mixing. The RDX@TA-Pb/Cu microcapsules can be used in RDX based composite modified double base (CMDB) propellants.

IntroductionThe development of urban resilience, which is fundamentally a balance between the supply capacity of primary care resources and the demand from urban residents, includes an appropriate architecture of primary care facilities. Resilient city construction in highland areas is hampered by the physical environment and transportation constraints and frequently encounters issues like poor accessibility and unequal distribution of primary care facilities.MethodsTo optimize the supply and demand of primary care resources in highland cities and effectively improve the resilience of urban public health, this paper assesses the distribution of primary care facilities within the built-up area of Lhasa (China) through a spatial network analysis method based on GIS, combined with population distribution data, and employs a location-allocation model to optimize the distribution.ResultsFirstly, the overall supply of primary care exceeds the overall demand, but the facilities' service area can only accommodate 59% of the residences. Secondly, there is a clear spatial variation in the accessibility of primary care facilities, and the time cost of healthcare is too high in some residences. Thirdly, the supply-demand relationship of primary care facilities is unbalanced, with both over-saturated and over-deficient areas.DiscussionAfter distribution optimization, the coverage and accessibility of primary care facilities have increased significantly, and the spatial imbalance of supply and demand has been alleviated. This paper proposes a research method to evaluate and optimize the spatial distribution of primary care facilities from multiple perspectives based on the resilience theory. The results of the study and visualization analysis methods can be used as an invaluable reference for planning the distribution of urban healthcare facilities and urban resilience construction in highland areas and other underdeveloped areas.

The goal of this paper is to explore a method for virus inactivation based on ultrasonic treatment, and on this basis, to explore the synergistic effect of methylene blue as a sonosensitizer in virus inactivation. The titer of human parainfluenza virus type 3 (HPIV3), Autographacaliforinica nuclear polyhedrosis virus carried a green fluorescent reporter gene (AcNPV-GFP) and Enterovirus group D 68 (EV-D68) were determined by plaque assays or TCID50 methods after treatment by MB combined with illumination (MB photochemical, MBP) or ultrasonic excitation. Different ultrasonic power and time, MB concentration gradient were set to determine the best anti-viral combination. For the enveloped virus HPIV3 and AcNPV-GFP, pure ultrasonic or MBP treatment could reduce viral titer more than 104，and ultrasonic combined with MB could completely inactivate HPIV3 and AcNPV-GFP in 5min while traditional MBP methods could only reduce viral titer about 10X. For the non-enveloped virus EV-D68, pure ultrasonic or MBP treatment only reduced the viral titer about 102, but ultrasonic combined with MB treatment could reduce the viral titer about 103 in 5min and completely inactive EV-D68 in 10min (reduced 105). Compared with MBP method and pure ultrasonic inactivation, ultrasonic combined with MB has better inactivation effect on either enveloped or non-enveloped viruses, and the appropriate combination of parameters is expected to be a new blood transfusion transmitted virus inactivation method.

Abstract Cervical cancer metastasis is an important cause of death in cervical cancer. Previous studies have shown that epithelial–mesenchymal transition (EMT) of tumors promotes its invasive and metastatic capacity. Alterations in the extracellular matrix (ECM) and mechanical signaling are closely associated with cancer cell metastasis. However, it is unclear how matrix stiffness as an independent cue triggers EMT and promotes cervical cancer metastasis. Using collagen‐coated polyacrylamide hydrogel models and animal models, we investigated the effect of matrix stiffness on EMT and metastasis in cervical cancer. Our data showed that high matrix stiffness promotes EMT and migration of cervical cancer hela cell lines in vitro and in vivo. Notably, we found that matrix stiffness regulates yes‐associated protein (YAP) activity via PPIase non‐mitotic a‐interaction 1 (Pin1) with a non‐Hippo mechanism. These data indicate that matrix stiffness of the tumor microenvironment positively regulates EMT in cervical cancer through the Pin1/YAP pathway, and this study deepens our understanding of cervical cancer biomechanics and may provide new ideas for the treatment of cervical cancer.

Introduction. Sepsis is a common syndrome in critically ill patients. Fibrinogen was reported to be associated with the prognosis of sepsis patients. Materials and Methods. Data was acquired from Multiparameter Intelligent Monitoring in Intensive Care Database IV (MIMIC-IV) version 1.0. Cox proportional hazards regression was utilized to estimate the relationship between fibrinogen and inhospital mortality. The cumulative incidence of mortality by fibrinogen level was estimated through the Kaplan-Meier curve. Restricted cubic spline (RCS) was used to assess nonlinear relationship. Subgroup analysis was also conducted to evaluate the robustness of the association between fibrinogen and inhospital mortality. Propensity score matching (PSM) was applied to adjust for confounding factors. Results. A total of 3365 patients, including 2031 survivors and 1334 nonsurvivors, were enrolled in our study. The survivors had a significantly elevated levels of fibrinogen compared with the deceased. The elevated level of fibrinogen was significantly associated with a decrease in mortality in multivariate Cox regression before and after PSM (HR 0.66, P

Source counting is the key procedure of autonomous detection for underwater unmanned platforms. A source counting method with local-confidence-level-enhanced density clustering using a single acoustic vector sensor (AVS) is proposed in this paper. The short-time Fourier transforms (STFT) of the sound pressure and vibration velocity measured by the AVS are first calculated, and a data set is established with the direction of arrivals (DOAs) estimated from all of the time–frequency points. Then, the density clustering algorithm is used to classify the DOAs in the data set, with which the number of the clusters and the cluster centers are obtained as the source number and the DOA estimations, respectively. In particular, the local confidence level is adopted to weigh the density of each DOA data point to highlight samples with the dominant sources and downplay those without, so that the differences in densities for the cluster centers and sidelobes are increased. Therefore, the performance of the density clustering algorithm is improved, leading to an improved source counting accuracy. Experimental results reveal that the enhanced source counting method achieves a better source counting performance than that of basic density clustering.