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Aim: The aim of this study was to examine the clinical and pathological characteristics as well as the prognosis of immunoglobulin A nephropathy (IgAN) accompanied by renal thrombotic microangiopathy (rTMA) in paediatric patients. Methods: After balancing epidemiological characteristics and pathological types between groups, 427 patients (rTMA group: 23, non‐rTMA group: 46) were included. The clinical and pathological features, prognosis and clinical risk factors of the two groups were analysed. Results: IgAN‐rTMA children showed more severe clinical and pathological manifestations. The findings from the logistic regression analysis indicated that hypercellularity 1 (E1) (HR: 0.805, 95% CI: 0.763 ~ 1.452, P =.016), endocapillary proliferation (HR: 1.214, 95% CI: 0.093 ~ 4.815, P =.025) and C3 staining (HR: 7.554, 95% CI: 2.563 ~ 15.729, P =.037) were the risk factors for rTMA in children with IgAN. The renal survival in rTMA group was lower than non‐rTMA group (χ2 = 18.467, P =.000). Cox regression analysis showed that E1 (HR: 7.441, 95% CI: 1.095 ~ 10.768, P =.037), C3 disposition (HR: 3.414, 95% CI: 0.834 ~ 11.578, P =.027) and rTMA (HR: 8.918, 95% CI: 1.032 ~ 16.754, P =.041) were identified as independent risk factors for the development of end‐stage renal disease (ESRD). Conclusion: The presence of rTMA had a significant impact on the severity and prognosis of IgAN. And rTMA has been identified as an independent risk factor for the development of renal failure in children diagnosed with IgAN. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Despite the well-documented structural and functional brain changes in schizophrenia, the potential role of glymphatic dysfunction remains largely unexplored. This study investigates the glymphatic system's function in schizophrenia, utilizing diffusion tensor imaging (DTI) to analyze water diffusion along the perivascular space (ALPS), and examines its correlation with clinical symptoms. Study Design A cohort consisting of 43 people with schizophrenia and 108 healthy controls was examined. We quantified water diffusion metrics along the x -, y -, and z -axis in both projection and association fibers to derive the DTI-ALPS index, a proxy for glymphatic activity. The differences in the ALPS index between groups were analyzed using a 2-way ANCOVA controlling for age and sex, while partial correlations assessed the association between the ALPS index and clinical variables. Study Results People with schizophrenia showed a significantly reduced DTI-ALPS index across the whole brain and within both hemispheres (F  = 9.001, P  = .011; F  = 10.024, P  = .011; F  = 5.927, P  = .044; false discovery rate corrected), indicating potential glymphatic dysfunction in schizophrenia. The group by cognitive performance interaction effects on the ALPS index were not observed. Moreover, a lower ALPS index was associated with poorer cognitive performance on specific neuropsychological tests in people with schizophrenia. Conclusion Our study highlights a lower ALPS index in schizophrenia, correlated with more pronounced cognitive impairments. This suggests that glymphatic dysfunction may contribute to the pathophysiology of schizophrenia, offering new insights into its underlying mechanisms. [ABSTRACT FROM AUTHOR]

Research Object: Taking the acquisition mechanism of oscillatory flapping-wing wave energy as the research object, the scheme design and dynamic analysis of the acquisition mechanism are studied. Research Methods: According to the working principle of the acquisition mechanism of oscillatory flapping-wing wave energy, the rotation dynamics model of the acquisition mechanism and the corresponding relationship between the model parameters and the design parameters of the mechanism are established. Based on the momentum moment theorem, the differential equation of the dynamics of the acquisition mechanism and the transfer function of the system are established. The dynamic response of the acquisition mechanism is analyzed, the system parameters are optimized, and the scheme design is carried out. The conversion efficiency of the acquisition mechanism and the energy collection efficiency under different sea conditions are calculated. The motion response of the acquisition mechanism is simulated and analyzed by MATLAB and AQWA software. Research Results: The results show that the response of the crank and swing slider acquisition mechanism is fast and stable, and the average conversion efficiency is 34%. The research process provides an effective reference for the development of the acquisition mechanism of oscillatory flapping-wing wave energy. [ABSTRACT FROM AUTHOR]

Learned video compression has drawn great attention and shown promising compression performance recently. In this article, we focus on the two components in the learned video compression framework, the conditional entropy model and quality enhancement module, to improve compression performance. Specifically, we propose an adaptive spatial-temporal entropy model for image, motion, and residual compression, which introduces a temporal prior to reduce temporal redundancy of latents and an additional modulated mask to evaluate the similarity and perform refinement. In addition, a quality enhancement module is proposed for predicted frame and reconstructed frame to improve frame quality and reduce the bitrate cost of residual coding. The module reuses decoded optical flow as a motion prior and utilizes deformable convolution to mine high-quality information from the reference frame in a bit-free manner. The two proposed coding tools are integrated into a pixel-domain residual coding–based compression framework to evaluate their effectiveness. Experimental results demonstrate that our framework achieves competitive compression performance in the low-delay scenario compared with recent learning-based methods and traditional H.265/HEVC in terms of Peak Signal-to-Noise Ratio (PSNR) and Multi-Scale Structural Similarity Index (MS-SSIM). The code is available at OpenLVC. [ABSTRACT FROM AUTHOR]

Objective: Hemifacial spasm (HFS) is a movement disorder characterized by involuntary muscle contractions on one side of the face. It is associated with disturbances in the brain's functional architecture. Despite this, the structural alterations in the brain related to HFS remain poorly understood. In this study, we investigated the cortical morphology changes in patients with HFS compared to healthy controls (HCs). Methods: We analyzed 3D T1-weighted MRI images from 33 patients with left-sided primary HFS and 33 age- and sex-matched HCs. Measurements of cortical thickness (CTh), sulcal depth, local gyrification index (lGI), and fractal dimension were taken using a computational anatomy toolbox. A general linear model, accounting for age, gender, and total brain volume, was applied for statistical analyses. Significant clusters were then assessed for correlations with clinical parameters. Results: The HFS patients displayed several cortical abnormalities when compared to HCs, including reduced CTh in the contralateral precentral gyrus and left orbitofrontal cortex, decreased sulcal depth in the left orbitofrontal cortex, and increased lGI in the right insula and superior temporal cortex. However, fractal dimension did not differ significantly between the groups. Additionally, in HFS patients, a notable negative correlation was found between the sulcal depth in the left orbitofrontal cortex and the Beck Depression Inventory-II scores. Conclusions: Our findings reveal that HFS is associated with specific surface-based morphological changes in the brain. These alterations contribute to a deeper understanding of the neurophysiological mechanisms involved in HFS and may have implications for future research and treatment strategies. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to examine prospective associations of different intensity levels and types of physical activity (PA) in early pregnancy with premature rupture of membranes (PROM) among Chinese pregnant women. Methods: A total of 6284 pregnant women were included from the Tongji-Shuangliu Birth Cohort. Household/caregiving, occupational, sports/exercise and transportation activities during early pregnancy were investigated by the pregnancy physical activity questionnaire (PPAQ), and the diagnosis of PROM was ascertained during the whole pregnancy. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence interval (CI) for the associations between PA and PROM. Results: Among the 6284 pregnant women, 1246 were identified to have PROM (19.8%). Women undertaking the highest level (3 third tertile) of PA during pregnancy appeared to have a lower risk of PROM [OR = 0.68, 95%CI 0.58–0.80) when compared to those at the lowest tertile of PA. Similarly, women with increased levels of light intensity activity, moderate-vigorous intensive, household/caregiving activity and meeting exercise guidelines during pregnancy were associated with reduced risks of PROM (OR = 0.69, 95% CI 0.59–0.81, OR = 0.70, 95% CI 0.60–0.82, OR = 0.62, 95% CI 0.53–0.73 and OR = 0.82, 95% CI 0.70–0.97, respectively). Conclusions: High levels of PA of different intensities and PA of household/caregiving activities and meeting exercise guidelines during the first trimester were associated with a lower incidence of PROM. Trial registration: The data of human participants in this study were conducted in accordance with the Helsinki Declaration. This study has been approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China ([2017] No. S225). All participants provided written informed consent prior to enrollment. A statement to confirm that all methods were carried out in accordance with relevant guidelines and regulations. [ABSTRACT FROM AUTHOR]

As an important renewable resource, wood is widely used in various industries. When addressing wood defects that limit the amount of wood used during processing, manual inspection and other technologies are not suitable for automated production scenarios. In this paper, we first establish our own dataset, which includes information about multiple tree species and multiple defects types, to enhance the overall applicability of the proposed model. Second, target detection technology involving deep learning is used for defect detection. The conditional parametric convolution (CondConv), Wise-IoU, and BiFormer modules are used to improve upon the latest YOLOv8 algorithm. Based on the experimental findings, the suggested approach exhibits notable improvements in terms of both the mAP@0.5 index and the mAP@0.5:0.95 index, surpassing the performance of the YOLOv8 algorithm by 3.5% and 5.8%, respectively. It also has advantages over other target detection algorithms. The proposed method can effectively improve wood utilization and automated wood processing technology. [ABSTRACT FROM AUTHOR]

Background/purpose: Patients with alcohol‐associated cirrhosis and acute decompensation are considered critically ill and have a higher risk of short‐term mortality. This study aimed to establish a nomogram to evaluate their 90‐day survival and identify factors that affect disease progression. Methods: We included patients from September 2008 to December 2016 (n = 387 in the derivation group) and from January 2017 to August 2020 (n = 157 in the validation group). LASSO regression and Cox multivariate risk regression were used to analyze the influencing factors of the 90‐day mortality risk, and a nomogram was constructed. The performance of a model was analyzed based on the C‐index, area under the receiver operating curve, calibration curve, and decision curve analysis. Results: Total bilirubin >10 upper limit of normal, high‐density lipoprotein cholesterol, lymphocyte and monocyte ratios ≤2.33, white blood cells, and hemoglobin were identified as independent risk factors affecting the 90‐day mortality risk of patients and the nomogram was developed. A nomogram demonstrated excellent model predictive accuracy in both the derivation and validation cohorts (C‐index: 0.976 and 0.945), which was better than other commonly used liver scoring models (p < 0.05). The nomogram also performed good calibration ability and more clinical net benefit. According to the nomogram score, patients were divided into high‐ and low‐risk groups. Mortality was significantly higher in the high‐risk group than in the low‐risk group (p < 0.0001). Conclusion: The nomogram could accurately predict the 90‐day mortality risk in patients with alcohol‐associated cirrhosis and acute decompensation, helping to identify high‐risk patients and personalize treatment at their first admission. [ABSTRACT FROM AUTHOR]

Monascus pigments (MPs), a class of secondary metabolites produced by Monascus spp., can be classified into yellow, orange, and red MPs according to their differences in the wavelength of the maximum absorption. However, the biosynthetic sequence and cellular biosynthesis mechanism of different MPs components are still not yet completely clear in Monascus spp. In this study, the subcellular localization of five MPs synthases was investigated using fluorescent protein fusion expression. The results revealed that the proteins encoded by the MPs biosynthetic gene cluster were compartmentalized in various subcellular locations, including the mitochondrial polyketide synthase MrPigA, cytosolic enzymes consisting of the ketoreductase MrPigC, the oxidoreductase MrPigE, and the monooxygenase MrPigN, and the cell-wall-bound oxidoreductase MrPigF. Moreover, the correct localization of MrPigF to the cell wall was crucial for the synthesis of orange MPs. Lastly, we discussed the compartmentalized biosynthetic pathway of MPs. This study will not only be helpful in clarifying the biosynthetic sequence and biosynthesis mechanism of different MPs but also provides new insights into the cellular biosynthesis of secondary metabolites in filamentous fungi. [ABSTRACT FROM AUTHOR]

Prinsepia utilis seed oil (PUSO) is a natural medication obtained from Prinsepia utilis Rogle seed, which has been used for the treatment of skin diseases. The study aims to prepare ethosomes with high drug loading as a water-soluble transdermal vehicle to enhance the transdermal delivery of PUSO. PUSO-loaded ethosomes (PEs) were prepared using a cold method, and optimized by an orthogonal experimental design with entrapment efficiency (EE) as the dependent variable. The PEs prepared with the optimized formulation showed good stability, with a spherical shape under transmission electron microscopy (TEM), average particle size of 39.12 ± 0.85 nm, PDI of 0.270 ± 0.01, zeta potential of -11.3 ± 0.24 mV, and EE of 95.93 ± 0.43%. PEs significantly increased the skin deposition of PUSO compared to the PUSO suspension (P < 0.001). Moreover, the optimum formula showed significant ameliorative effects on ultraviolet B (UVB) irradiation-associated macroscopic and histopathological changes in mice skin. Therefore, PEs represent a promising therapeutic approach for the treatment of UVB-induced skin inflammation, with the potential for industrialization. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholangiocarcinoma (ICCA) is a heterogeneous group of malignant tumors characterized by high recurrence rate and poor prognosis. Heterochromatin Protein 1α (HP1α) is one of the most important nonhistone chromosomal proteins involved in transcriptional silencing via heterochromatin formation and structural maintenance. The effect of HP1α on the progression of ICCA remained unclear. Methods: The effect on the proliferation of ICCA was detected by experiments in two cell lines and two ICCA mouse models. The interaction between HP1α and Histone Deacetylase 1 (HDAC1) was determined using Electrospray Ionization Mass Spectrometry (ESI-MS) and the binding mechanism was studied using immunoprecipitation assays (co-IP). The target gene was screened out by RNA sequencing (RNA-seq). The occupation of DNA binding proteins and histone modifications were predicted by bioinformatic methods and evaluated by Cleavage Under Targets and Tagmentation (CUT & Tag) and Chromatin immunoprecipitation (ChIP). Results: HP1α was upregulated in intrahepatic cholangiocarcinoma (ICCA) tissues and regulated the proliferation of ICCA cells by inhibiting the interferon pathway in a Signal Transducer and Activator of Transcription 1 (STAT1)-dependent manner. Mechanistically, STAT1 is transcriptionally regulated by the HP1α-HDAC1 complex directly and epigenetically via promoter binding and changes in different histone modifications, as validated by high-throughput sequencing. Broad-spectrum HDAC inhibitor (HDACi) activates the interferon pathway and inhibits the proliferation of ICCA cells by downregulating HP1α and targeting the heterodimer. Broad-spectrum HDACi plus interferon preparation regimen was found to improve the antiproliferative effects and delay ICCA development in vivo and in vitro, which took advantage of basal activation as well as direct activation of the interferon pathway. HP1α participates in mediating the cellular resistance to both agents. Conclusions: HP1α-HDAC1 complex influences interferon pathway activation by directly and epigenetically regulating STAT1 in transcriptional level. The broad-spectrum HDACi plus interferon preparation regimen inhibits ICCA development, providing feasible strategies for ICCA treatment. Targeting the HP1α-HDAC1-STAT1 axis is a possible strategy for treating ICCA, especially HP1α-positive cases. [ABSTRACT FROM AUTHOR]

Graph neural networks have been clearly proven to be powerful in recommendation tasks since they can capture high-order user-item interactions and integrate them with rich attributes. However, they are still limited by the cold-start problem and data sparsity. Using social relationships to assist recommendation is an effective practice, but it can only moderately alleviate these problems. In addition, rich attributes are often unavailable, which prevents graph neural networks from being fully effective. Hence, we propose to enrich the model by mining multiple implicit feedback and constructing a triple GCN component. We have noticed that users may be influenced not only by their trusted friends but also by the ratings that already exist. The implicit influence spreads among the item's previous and potential raters, and makes a difference on future ratings. The implicit influence is analyzed on the mechanism of information propagation, and fused with the user's binary implicit attitude, since negative influence propagates as well as the positive one. Furthermore, we leverage explicit feedback, social relationships, and multiple implicit feedback in the triple GCN component. Abundant experiments on real-world datasets reveal that our model has improved significantly in the rating prediction task compared with other state-of-the-art methods. [ABSTRACT FROM AUTHOR]

With the increasing demand for energy and the depletion of traditional resources, the development of alternative energy sources has become a critical issue. Shale gas, as an abundant and widely distributed resource, has great potential as a substitute for conventional natural gas. However, due to the low permeability of shale-gas reservoirs, efficient extraction poses significant challenges. The application of hydraulic fracturing technology has been proven to effectively enhance rock permeability, but the influence of environmental factors on its efficiency remains unclear. In this study, we investigate the impact of gas fracturing on shale-gas extraction efficiency under varying environmental conditions using numerical simulations. Our simulations provide a comprehensive analysis of the physical changes that occur during the fracturing process, allowing us to evaluate the effects of gas fracturing on rock mechanics and permeability. We find that gas fracturing can effectively induce internal fractures within the rock, and the magnitude of tensile stress decreases gradually during the process. The boundary pressure of the rock mass is an important factor affecting the effectiveness of gas fracturing, as it exhibits an inverse relationship with the gas content present within the rock specimen. Furthermore, the VL constant demonstrates a direct correlation with gas content, while the permeability and PL constant exhibit an inverse relationship with it. Our simulation results provide insights into the optimization of gas fracturing technology under different geological parameter conditions, offering significant guidance for its practical applications. [ABSTRACT FROM AUTHOR]

The article focuses on community-preserving social recommendation using cyclic transfer learning. Topics include mitigating data sparsity in user-item interactions, incorporating social influence from direct connections between users, and addressing structural discrepancies among communities to improve prediction performance in recommender systems.

Objective: Radiation therapy (RT) may increase the risk of second cancer. This study aimed to determine the association between exposure to radiotherapy for the treatment of thoracic cancer (TC) and subsequent secondary lung cancer (SLC). Materials and Methods: The Surveillance, Epidemiology, and End Results (SEER) database (from 1975 to 2015) was queried for TC. Univariate Cox regression analyses and multiple primary standardized incidence ratios (SIRs) were used to assess the risk of SLC. Subgroup analyses of patients stratified by latency time since TC diagnosis, age at TC diagnosis, and calendar year of TC diagnosis stage were also performed. Overall survival and SLC‐related death were compared among the RT and no radiation therapy (NRT) groups by using Kaplan–Meier analysis and competitive risk analysis. Results: In a total of 329 129 observations, 147 847 of whom had been treated with RT. And 6799 patients developed SLC. Receiving radiotherapy was related to a higher risk of developing SLC for TC patients (adjusted HR, 1.25; 95% CI, 1.19–1.32; P < 0.001). The cumulative incidence of developing SLC in TC patients with RT (3.8%) was higher than the cumulative incidence (2.9%) in TC patients with NRT(P). The incidence risk of SLC in TC patients who received radiotherapy was significantly higher than the US general population (SIR, 1.19; 95% CI, 1.14–1.23; P < 0.050). Conclusions: Radiotherapy for TC was associated with higher risks of developing SLC compared with patients unexposed to radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Cyprinidae, the largest fish family, encompasses approximately 367 genera and 3006 species. While they exhibit remarkable adaptability to diverse aquatic environments, it is exceptionally rare to find them in seawater, with the Far Eastern daces being of few exceptions. Therefore, the Far Eastern daces serve as a valuable model for studying the genetic mechanisms underlying seawater adaptation in Cyprinidae. Results: Here, we sequenced the chromosome-level genomes of two Far Eastern daces (Pseudaspius brandtii and P. hakonensis), the two known cyprinid fishes found in seawater, and performed comparative genomic analyses to investigate their genetic mechanism of seawater adaptation. Demographic history reconstruction of the two species reveals that their population dynamics are correlated with the glacial-interglacial cycles and sea level changes. Genomic analyses identified Pseudaspius-specific genetic innovations related to seawater adaptation, including positively selected genes, rapidly evolving genes, and conserved non-coding elements (CNEs). Functional assays of Pseudaspius-specific variants of the prolactin (prl) gene showed enhanced cell adaptation to greater osmolarity. Functional assays of Pseudaspius specific CNEs near atg7 and usp45 genes suggest that they exhibit higher promoter activity and significantly induced at high osmolarity. Conclusions: Our results reveal the genome-wide evidence for the evolutionary adaptation of cyprinid fishes to seawater, offering valuable insights into the molecular mechanisms supporting the survival of migratory fish in marine environments. These findings are significant as they contribute to our understanding of how cyprinid fishes navigate and thrive in diverse aquatic habitats, providing useful implications for the conservation and management of marine ecosystems. [ABSTRACT FROM AUTHOR]

Background and Purpose: Kaempferol‐3‐O‐sophoroside (PCS‐1) is the main component in Crocus sativus (Saffron), a herb with mood‐enhancing properties. AMP‐activated protein kinase (AMPK) is a potential therapeutic target for depression. This study explores the antidepressive‐like properties of PCS‐1 and its AMPK activation to confirm AMPK as a target for antidepression. Experimental Approach: Corticosterone (CORT)‐induced PC12 cell injury served as an in vitro model to evaluate the neuroprotective effect of PCS‐1. Neuro‐2a cells and primary neurons were utilized to evaluate the synaptogenesis role of PCS‐1. CORT‐induced mouse depression model and chronic unpredictable mild stress (CUMS) model were used to assess the antidepressive‐like properties of PCS‐1 through behavioural tests, magnetic resonance imaging, and biochemical index measurements. Western blot and immunofluorescence assays were used to study the mechanisms of PCS‐1. Cellular thermal shift assay was used to confirm the binding target. Key Results: PCS‐1 (12.5–50 μM) ameliorated CORT‐induced PC12 cell damage, oxidative stress and inflammation. PCS‐1 alone promoted an increase in synapses in Neuro‐2a cells and primary neurons. Oral administration of PCS‐1 (10 and 20 mg·kg−1) ameliorated weight loss, dyskinesia, and hippocampal volume reduction induced by CORT and CUMS. PCS‐1 bound to AMPK to improve the expression of brain‐derived neurotrophic factor (BDNF) and induce autophagy. Conclusion and Implications: PCS‐1 binds to AMPK to promote BDNF production and autophagy enhancement, ultimately achieving antidepressant effects. This study provides support for the clinical application of saffron petals and provides further evidence for AMPK as a potential target for antidepression. [ABSTRACT FROM AUTHOR]

In order to improve the filtration performance, silicon carbide porous ceramics with network cell wall were fabricated via the polyurethane foaming method using silicon carbide powder, alumina powder, polyether polyol, polymethylene polyphenyl polyisocyanate, dibutyltin dilaurate, triethylenediamine and silicone oil (foam stabilizer) as raw materials. The effects of the solid loadings of the slurry (45%, 50%, 55% and 60%, by mass) on the microstructure, physical properties and their filtration properties towards particu-late matters were studied. The result shows that: (1) with the increasing solid loading, the bulk density and cold compressive strength gradually increase, and the apparent porosity decreases; (2) the micropores generated during the polyurethane foaming process are distributed on the ceramic pore wall to form a network cell wall structure, which increases the collision probability between particles and the wall pores and improves the filtration efficiency; meanwhile, the network cell wall structure also improves the pore interconnectivity and reduces the press drop; (3) when the solid loading is 55%, the silicon carbide based porous ceramics have the bulk density of 0.57 g · cm-3, apparent porosity of 79.2%, cold compressive strength of 3.7 MPa, and the filtering efficiency of the paniculate matter of 91.2%, achieving good regeneration performance. [ABSTRACT FROM AUTHOR]

Purpose: Uncontrolled intra-alveolar inflammation is a central pathogenic feature, and its severity translates into a valid prognostic indicator of acute lung injury (ALI). Unfortunately, current clinical imaging approaches are unsuitable for visualizing and quantifying intra-alveolar inflammation. This study aimed to construct a small-sized vascular cell adhesion molecule-1 (VCAM-1)-targeted magnetic particle imaging (MPI) nanoprobe (ESPVPN) to visualize and accurately quantify intra-alveolar inflammation at the molecular level. Methods: ESPVPN was engineered by conjugating a peptide (VHPKQHRGGSK(Cy7)GC) onto a polydopamine-functionalized superparamagnetic iron oxide core. The MPI performance, targeting, and biosafety of the ESPVPN were characterized. VCAM-1 expression in HUVECs and mouse models was evaluated by western blot. The degree of inflammation and distribution of VCAM-1 in the lungs were assessed using histopathology. The expression of pro-inflammatory markers and VCAM-1 in lung tissue lysates was measured using ELISA. After intravenous administration of ESPVPN, MPI and CT imaging were used to analyze the distribution of ESPVPN in the lungs of the LPS-induced ALI models. Results: The small-sized (~10 nm) ESPVPN exhibited superior MPI performance compared to commercial MagImaging® and Vivotrax, and ESPVPN had effective targeting and biosafety. VCAM-1 was highly expressed in LPS-induced ALI mice. VCAM-1 expression was positively correlated with the LPS-induced dose (R = 0.9381). The in vivo MPI signal showed positive correlations with both VCAM-1 expression (R = 0.9186) and representative pro-inflammatory markers (MPO, TNF-α, IL-6, IL-8, and IL-1β, R > 0.7). Conclusion: ESPVPN effectively targeted inflammatory lungs and combined the advantages of MPI quantitative imaging to visualize and evaluate the degree of ALI inflammation. [ABSTRACT FROM AUTHOR]

In the fringe projection profilometry (FPP), the traditional phase-shifting (TPS) algorithm and the Fourier transform (FT) algorithm are beset with a conundrum where measurement efficiency and conflicts with measurement accuracy, thereby limiting their application in dynamic three-dimensional (3D) measurements. Here, we propose a phase shift generation (PSG) method, which acquires the sinusoidal fringes by sparse sampling and reconstructs the complete phase-shifting sequence by generating the missing fringes with superimposed coupling of adjacent fringes. According to our proposed PSG method in which the sinusoidal fringe sequence size is about half of the TPS method, meaning that the PSG method will be timesaving in the phase-shifting sequence sampling process. Moreover, because of the utilization of multiframe fringes, our PSG method allows for a more accurate measurement than the FT method. Both simulation and experimental results demonstrate that our proposed PSG method can well balance the measurement accuracy and efficiency with a lower sampling rate, bearing a great potential to be applied in both scientific and industrial areas. [ABSTRACT FROM AUTHOR]

Aims: To investigate the sex‐specific associations between predicted skeletal muscle mass index (pSMI) and incident type 2 diabetes in a retrospective longitudinal cohort of Chinese men and women. Materials and Methods: We enrolled Chinese adults without diabetes at baseline from WATCH (West chinA adulT health CoHort), a large health check‐up‐based database. We calculated pSMI to estimate skeletal muscular mass, and measured blood glucose variables and assessed self‐reported history to identify new‐onset diabetes. The nonlinear association between pSMI and incident type 2 diabetes was modelled using the penalized spline method. The piecewise association was estimated using segmented linear splines in weighted Cox proportional hazards regression models. Results: Of 47 885 adults (53.2% women) with a median age of 40 years, 1836 developed type 2 diabetes after a 5‐year median follow‐up. In women, higher pSMI was associated with a lower risk of incident type 2 diabetes (Pnonlinearity = 0.09, hazard ratio [HR] per standard deviation increment in pSMI: 0.79 [95% confidence interval {CI} 0.68, 0.91]). A nonlinear association of pSMI with incident type 2 diabetes was detected in men (Pnonlinearity < 0.001). In men with pSMI lower than 8.1, higher pSMI was associated with a lower risk of incident type 2 diabetes (HR 0.58 [95% CI 0.40, 0.84]), whereas pSMI was not significantly associated with incident diabetes in men with pSMI equal to or greater than 8.1 (HR 1.08 [95% CI 0.93, 1.25]). Conclusions: In females, a larger muscular mass is associated with a lower risk of type 2 diabetes. For males, this association is significant only among those with diminished muscle mass. [ABSTRACT FROM AUTHOR]

Owing to the diverse connection configurations of dual active bridge converters, a multiplicity of low-voltage DC port structures are anticipated to emerge in the independent DC bus structure multiport power electronic transformer (IDBS-MPET). An inadequate low-voltage DC port structure exacerbates the power imbalance in IDBS-MPET, presenting a risk of overmodulation even when transmitting relatively low levels of power. To overcome this limitation, a design scheme of IDBS-MPET topology based on the maximum power transmission capability of the low-voltage DC ports is proposed in this paper. Three topology design rules are derived from the maximum power transmission capability results of more than 80 typical IDBS-MPET topologies. The symmetrical triple cross-phase connection structure, the symmetrical double cross-phase connection structure and the single-phase connection structure are sequentially identified as the three most optimal structures of low-voltage DC ports. By employing the proposed design methodology, each low-voltage DC port achieves its maximum power transfer capability relative to other configurations. The effectiveness of the proposed design scheme is validated by an optimal designed IDBS-MPET topology with six low-voltage DC ports. [ABSTRACT FROM AUTHOR]

Gas fracturing technology for enhancing rock permeability is an area with considerable potential for development. However, the complexity and variability of underground conditions mean that a variety of rock physical parameters can affect the outcome of gas fracturing, with temperature being a critical factor that cannot be overlooked. The presence of a temperature field adds further complexity to the process of gas-induced rock fracturing. To explore the effects of temperature fields on gas fracturing technology, this paper employs numerical simulation software to model the extraction of shale gas under different temperature conditions using gas fracturing techniques. The computer simulations monitor variations in the mechanical characteristics of rocks during the process of gas fracturing. This analysis is performed both prior to and following the implementation of a temperature field. The results demonstrate that gas fracturing technology significantly improves rock permeability; temperature has an impact on the effectiveness of gas fracturing, with appropriately high temperatures capable of enhancing the fracturing effect. The temperature distribution plays a crucial role in influencing the results of gas fracturing. When the temperature is low, the fracturing effect is diminished, resulting in a lower efficiency of shale gas extraction. Conversely, when the temperature is high, the fracturing effect is more pronounced, leading to a higher shale gas production efficiency. Optimal temperatures can enhance the efficacy of gas fracturing and consequently boost the efficiency of shale gas extraction. Changes in the parameters of the rock have a substantial impact on the efficiency of gas extraction, and selecting suitable rock parameters can enhance the recovery rate of shale gas. This paper, through numerical simulation, investigates the influence of temperature on gas fracturing technology, with the aim of contributing to its improved application in engineering practices. [ABSTRACT FROM AUTHOR]

Objectives: 2D real-time (RT) phase-contrast (PC) MRI is a promising alternative to conventional PC MRI, which overcomes problems due to irregular heartbeats or poor respiratory control. This study aims to evaluate a prototype compressed sensing (CS)-accelerated 2D RT-PC MRI technique with shared velocity encoding (SVE) for accurate beat-to-beat flow measurements. Methods: The CS RT-PC technique was implemented using a single-shot fast RF-spoiled gradient echo with SVE by symmetric velocity encoding, and acquired with a temporal resolution of 51–56.5 ms in 1–5 heartbeats. Both aortic dissection phantom (n = 8) and volunteer (n = 7) studies were conducted using the prototype CS RT (CS, R = 8), the conventional (GRAPPA, R = 2), and the fully sampled PC sequences on a 3T clinical system. Flow parameters including peak velocity, peak flow rate, net flow rate, and maximum velocity were calculated to compare the performance between different methods using linear regression, intraclass correlation (ICC), and Bland–Altman analyses. Results: Comparisons of the flow measurements at all locations in the phantoms demonstrated an excellent correlation (all R2 ≥ 0.93) and agreement (all ICC ≥ 0.97) with negligible means of differences. In healthy volunteers, a similarly good correlation (all R2 ≥ 0.80) and agreement (all ICC ≥ 0.90) were observed; however, CS RT slightly underestimated the maximum velocities and flow rates (~ 12%). Conclusion: The highly accelerated CS RT-PC technique is feasible for the evaluation of flow patterns without requiring breath-holding, and it allows for rapid flow assessment in patients with arrhythmia or poor breath-hold capacity. Clinical relevance statement: The free-breathing real-time flow MRI technique offers improved spatial and temporal resolutions, as well as the ability to image individual cardiac cycles, resulting in superior image quality compared to the conventional PC technique when imaging patients with arrhythmias, especially those with atrial fibrillation. Key Points: • The highly accelerated prototype CS RT-PC MRI technique with improved temporal resolution by the concept of SVE is feasible for beat-to-beat flow evaluation without requiring breath-holding. • The results of the phantom and in vivo quantitative flow evaluation show the ability of the prototype CS RT-PC technique to obtain reliable flow measurements similarly to the conventional PC MRI. • With less than 12% underestimation, excellent agreements between the two techniques were shown for the measurements of peak velocities and flow rates. [ABSTRACT FROM AUTHOR]

Field experiments were conducted to investigate the effects of different application rates of potassium chloride (KCl) on biomass, seed yield, and nutrient accumulation and distribution in oilseed rape at both the seedling and maturity stages. The study was carried out in Jiangxia District, Wuhan City, Hubei Province, located in the middle reaches of the Yangtze River from 2021 to 2022. This research aims to provide a theoretical foundation for the optimal application of potassium (K) fertilizer in oilseed rape cultivation. Six treatments were applied, including K0 (K2O 0 kg/hm²), K30 (K2O 30 kg/hm²), K60 (K2O 60 kg/hm²), K90 (K2O 90 kg/hm²), K120 (K2O 120 kg/ hm²) and K150 (K2O 150 kg/hm²). The results indicated that the biomass of all oilseed rape organs at both seedling and maturity stages, as well as seed yield, significantly increased within a certain range of increasing levels of K fertilizer. The maximum increase in seed yield was observed to be up to 1199.6 kg/hm² with an increase ratio of up to 57.20%. When the application rate of K exceeded 120 kg/hm², there was no significant increase in shoot biomass and seed yield. With increasing K fertilizer application, there was a significant increase in K content across all organs. However, N content did not show significant changes at both the seedling and maturity stages. Notably, P content in seeds at the maturity stage exhibited a significant increase. The partial factor productivity of K fertilizer significantly decreased with increasing K fertilizer application. However, the agronomic efficiency, physiological efficiency, apparent recovery efficiency and harvest index of K fertilizer all reached their maximum at an application rate of 90 kg/hm². Subsequently, these efficiencies gradually decreased with further increases in K fertilizer. Economic analysis revealed that the output-input ratio and net income were optimized at a K application rate of 120 kg/ hm². Further increases in K fertilizer would lead to reduced economic efficiency. In addition, the optimal application rate of K fertilizer for maximizing economic efficiency in this region is determined to be 114.6 kg/hm² based on a combination of linear and platform fitting results. Consequently, rational utilization of K fertilizer can significantly enhance shoot biomass and promote the accumulation of essential nutrients (N, P, and K), thereby resulting in increased plant height, primary branch count, pod number, and ultimately achieving higher yields while ensuring maximum economic efficiency. [ABSTRACT FROM AUTHOR]

Deep and ultra-deep reservoirs have gradually become the primary focus of hydrocarbon exploration as a result of a series of significant discoveries in deep hydrocarbon exploration worldwide. These reservoirs present unique challenges due to their deep burial depth (4500e8882 m), low matrix permeability, complex crustal stress conditions, high temperature and pressure (HTHP, 150e200 °C, 105e155 MPa), coupled with high salinity of formation water. Consequently, the costs associated with their exploitation and development are exceptionally high. In deep and ultra-deep reservoirs, hydraulic fracturing is commonly used to achieve high and stable production. During hydraulic fracturing, a substantial volume of fluid is injected into the reservoir. However, statistical analysis reveals that the flowback rate is typically less than 30%, leaving the majority of the fluid trapped within the reservoir. Therefore, hydraulic fracturing in deep reservoirs not only enhances the reservoir permeability by creating artificial fractures but also damages reservoirs due to the fracturing fluids involved. The challenging "three-high" environment of a deep reservoir, characterized by high temperature, high pressure, and high salinity, exacerbates conventional forms of damage, including water sensitivity, retention of fracturing fluids, rock creep, and proppant breakage. In addition, specific damage mechanisms come into play, such as fracturing fluid decomposition at elevated temperatures and proppant diagenetic reactions at HTHP conditions. Presently, the foremost concern in deep oil and gas development lies in effectively assessing the damage inflicted on these reservoirs by hydraulic fracturing, comprehending the underlying mechanisms, and selecting appropriate solutions. It's noteworthy that the majority of existing studies on reservoir damage primarily focus on conventional reservoirs, with limited attention given to deep reservoirs and a lack of systematic summaries. In light of this, our approach entails initially summarizing the current knowledge pertaining to the types of fracturing fluids employed in deep and ultra-deep reservoirs. Subsequently, we delve into a systematic examination of the damage processes and mechanisms caused by fracturing fluids within the context of hydraulic fracturing in deep reservoirs, taking into account the unique reservoir characteristics of high temperature, high pressure, and high in-situ stress. In addition, we provide an overview of research progress related to high-temperature deep reservoir fracturing fluid and the damage of aqueous fracturing fluids to rock matrix, both artificial and natural fractures, and sand-packed fractures. We conclude by offering a summary of current research advancements and future directions, which hold significant potential for facilitating the efficient development of deep oil and gas reservoirs while effectively mitigating reservoir damage. [ABSTRACT FROM AUTHOR]

IL-33 has been associated with pro- and anticancer functions in cancer. However, its role in pancreatic cancer metastasis remains unknown. This study aimed to explore the role of miR-548t-5p/IL-33 axis in the metastasis of pancreatic cancer. Luciferase activity assay, qRT-PCR, Western blot and ELISA were performed to prove whether IL-33 is the target of miR-548t-5p. In vivo metastasis assay and cellular transwell assay were performed to explore the role of miR-548t-5p/IL-33 axis in the invasion and metastasis of pancreatic cancer. Co-culture experiments and immunohistochemistry were performed to observe whether IL-33 affects cell invasion and metastasis dependent on the involvement of M2 macrophages. THP-1 cell induction experiment and flow cytometry were performed to explore the effect of IL-33 on macrophage polarization. CCK-8, colony formation, cell apoptosis, cell cycle, cell wound healing and transwell assay were performed to investigate the effect of IL-33 induced M2 macrophages on cell malignant biological behavior by coculturing pancreatic cancer cells with the conditioned medium (CM) from macrophages. We found that miR-548t-5p regulated the expression and secretion of IL-33 in pancreatic cancer cells by directly targeting IL-33 mRNA. IL-33 secreted by cancer cells promoted the recruitment and activation of macrophages to a M2-like phenotype. In turn, IL-33 induced M2 macrophages promoted the migration and invasion of cancer cells. Moreover, IL-33 affected pancreatic cancer cell invasion dependent on the involvement of M2 macrophages in the co-culture system. Thus, our study suggested that manipulation of this IL-33-dependent crosstalk has a therapeutic potential for the treatment of pancreatic cancer metastasis. [ABSTRACT FROM AUTHOR]

Designing ultra‐light, green, and flexible films for efficient electromagnetic interference (EMI) shielding is crucial yet challenging. Herein, laminated Ti3C2Tx MXene nanosheets are prepared and impregnated into a delignified wood matrix to fabricate composite films. Through a facile drop‐casting and densification strategy, highly aligned cellulose fibers are used for regulating the stacking behavior of MXenes, and the MXenes are encapsulated and attached tightly to the cellulose chains through hydrogen bonds. A high MXene loading up to 32.5 wt.% can be realized, and the resultant MXene/wood film exhibits a tensile strength of 260.7 MPa. The EMI shielding effectiveness is calculated to be 55.5 dB (X‐band, 8.2–12.4 GHz), with a normalized surface‐specific shielding effectiveness of 2673.4 B cm2 g−1. Moreover, the superior electrical conductivity and structural robustness of the composite film give it pressure‐sensing properties and show high sensitivity for monitoring diverse human physiological movements. [ABSTRACT FROM AUTHOR]

Aims: To examine the prospective association between fibroblast growth factor 21 (FGF21) and risk of gestational diabetes mellitus (GDM) and the modifying effect of overweight/obesity for this association. Methods: Serum FGF21 levels were measured at 6–15 weeks of gestation among 332 GDM cases and 664 matched controls. Conditional logistic regression was used to evaluate its association with GDM risk. Interaction analyses on multiplicative and additive scales were conducted to investigate the modifying effect of overweight/obesity. Results: Elevated FGF21 levels were associated with a higher risk of GDM in multivariable models, but the positive association was attenuated after further adjustment for pre‐pregnancy body mass index (BMI). A significant multiplicative interaction was noted between FGF21 (both continuous and dichotomous) and pre‐pregnancy BMI (p for interaction = 0.049 and 0.03), and the association was only significant in participants with pre‐pregnancy BMI ≥24 kg/m2. When participants were grouped based on pre‐pregnancy BMI (≥24 and <24 kg/m2) and FGF21 levels (≥median and

Designing ultra‐light, green, and flexible films for efficient electromagnetic interference (EMI) shielding is crucial yet challenging. Herein, laminated Ti3C2Tx MXene nanosheets are prepared and impregnated into a delignified wood matrix to fabricate composite films. Through a facile drop‐casting and densification strategy, highly aligned cellulose fibers are used for regulating the stacking behavior of MXenes, and the MXenes are encapsulated and attached tightly to the cellulose chains through hydrogen bonds. A high MXene loading up to 32.5 wt.% can be realized, and the resultant MXene/wood film exhibits a tensile strength of 260.7 MPa. The EMI shielding effectiveness is calculated to be 55.5 dB (X‐band, 8.2–12.4 GHz), with a normalized surface‐specific shielding effectiveness of 2673.4 B cm2 g−1. Moreover, the superior electrical conductivity and structural robustness of the composite film give it pressure‐sensing properties and show high sensitivity for monitoring diverse human physiological movements. [ABSTRACT FROM AUTHOR]

The Dendrolimus houi, a phytophagous pest, displays a broad range of adaptations and often inflicts localized damage to its hosts. Cupressus funebris, an indigenous timber species in China, is significantly impacted by D. houi. Investigating the suitable habitat distribution and changes in D. houi and its host plant, C. funebris, within the context of climate warming, is essential for understanding D. houi's development and providing novel insights for managing D. houi and conserving C. funebris resources. In this study, MaxEnt was employed to simulate the distribution of D. houi and its host plant, C. funebris, in their suitable habitats, evaluating the influence of environmental factors on their distribution and determining changes under a warming scenario. MaxEnt model parameters were adjusted using the Kuenm data package based on available distribution and climatic data. The minimum temperature of the coldest month emerged as the primary environmental factor influencing the distribution of a suitable habitat for D. houi and C. funebris, with a percentage contribution of environmental factors over 60%. There was a substantial similarity in the suitable habitat distributions of D. houi and C. funebris, with varying degrees of expansion in the total habitat area under different temporal and climatic scenarios. Intersection analysis results indicated that the 2041–2060 period, especially under low (SSP1-2.6) and high (SSP5-8.5) emission scenarios, is a critical phase for D. houi control. The habitat expansion of D. houi and C. funebris due to climate change was observed, with the distribution center of D. houi shifting northeast and that of C. funebris shifting northwest. [ABSTRACT FROM AUTHOR]

Purpose: Spinocerebellar ataxia type 2 (SCA2) is a progressive neurodegenerative disorder characterized by cerebellar atrophy. However, studies to elucidate the longitudinal progression of the neuropathology are limited. We sought to identify brain macrostructural and microstructural alterations in patients with SCA2 using fixel-based analysis (FBA) to better understand its distribution patterns and progression. Methods: We enrolled 9 patients with SCA2 and 16 age- and gender-matched controls. Longitudinal clinical and imaging data were collected at baseline, and 3.5 years later. Fiber density (FD), fiber-bundle cross-section (FC), and a combination of FD and FC (FDC) were calculated. The paired t-test was used to examine longitudinal differences. The associations between fixel-based metrics and clinical variables were explored in SCA2 patients. Results: At baseline, patients with SCA2 displayed multiple white matter tracts with significantly decreased FD, FC, and FDC in the corticospinal tract, cerebellar peduncles, brainstem, corpus callosum, thalamus, striatum, and prefrontal cortex, compared to controls. Over time, many of these macrostructural and microstructural alterations progressed, manifesting lower FD, FC, and FDC in corticospinal tract, middle cerebellar peduncle, brainstem, striatum, fornix, and cingulum. No significant brain white matter alterations were found in the healthy controls over time. There was no association between the FBA-derived metrics and clinical variables in SCA2. Conclusion: This study provides evidence of brain macrostructural and microstructural alterations and of progression over time in SCA2. The FBA-derived metrics may serve as potential biomarkers of SCA2 progression. [ABSTRACT FROM AUTHOR]

Featured Application: The results of this work can be included in the design stage of interior permanent-magnet synchronous motors for aircraft drive applications. The torque performance of the interior permanent-magnet synchronous motor (IPMSM) must be further improved to satisfy the growing demand of aircraft drive application. To this end, this article focuses on the design optimization of the IPMSM structure in the aircraft drive systems to improve the torque density and reduce the torque ripple. A special fractional-slot winding and ∇-type magnetic-pole rotor topology are proposed as the optimized IPMSM structure compared with the structure of an existing motor. The simulations of the original and optimized structures at different current values reveal the variance of the torque in the average and ripple, mechanical and external characteristics, efficiency and steady-state temperature. The performance of an optimized prototype is analyzed by experimental testing, and the results show that an optimized motor has a higher torque density and lower torque ripple than the original one at the same speed and rated power, but it also has a higher temperature rise. However, the temperature rise value is acceptable in the experimental testing condition, so the validity of the design optimization method for the proposed structure is verified. [ABSTRACT FROM AUTHOR]

Ceria nanoparticles (CeO2NPs) exhibit great potential in cardiovascular disease and nonalcoholic fatty liver disease due to its excellent antioxidant capacity. However, the profitable effect of CeO2NPs on many diseases is almost all attributed to the regulation of ROS. Apart from the general antioxidant function, there seems to be no more distinct mechanism to reflect its unique multi-disease improvement effect. Here, we for the first time reveal a new discovery of CeO2NPs in mimicking nitric oxide synthase (NOS) by catalyzing L-arginine (L-Arg) to produce nitric oxide (NO) or the derivatives. NOS-like activity of CeO2NPs is original and associated with multiple factors like substrate concentration, pH, temperature and time, etc. where oxygen vacancy ratio plays a more critical role. Meanwhile, NOS-like activity of CeO2NPs successfully elevates NO secretion in endothelial cells and macrophages without expanding eNOS/iNOS expression. Importantly, NOS-like activity of CeO2NPs and the responsive endogenous NO promote the re-distribution of blood lipids and stabilize eNOS expression but suppress iNOS, thus collectively alleviate the accumulation of vascular plaque. Altogether, we provide a new angle of view to survey the outstanding potential of CeO2NPs, apart from the inevitable antioxidant capacity, the covert but possible and more critical NOS-like enzymatic activity is more noteworthy. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, as a new type of hypoglycemic drug, can prevent proximal renal tubule injury related to glucose toxicity and play a renoprotective role. Canagliflozin, a recognized SGLT-2 inhibitor, has been proved to have potential protection in diabetic nephropathy (DN), but its mechanism has not been fully elucidated. In this study, the protective effect of canagliflozin against high glucose (HG)-induced renal tubular epithelial cell (NRK-52E) injury in vitro was assessed. Methods: The viability and apoptosis of NRK-52E cells were detected using cell counting kit-8 (CCK-8) assay and flow cytometry analysis, respectively. The expression levels of cleaved caspase-3, oxidative stress-related proteins (NOX4 and Nrf2), autophagy marker light chain 3 (LC3) I/II, and adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway-related proteins were evaluated by Western blot. Reactive oxygen species (ROS) level was evaluated by dihydroethidium (DHE) reactive oxygen species assay, the activities of SOD, CAT, GSH-Px and MDA were analyzed using kits. The changes of morphology and red fluorescent protein (RFP)-LC3 fluorescence were observed under microscopy. Results: Canagliflozin significantly ameliorated HG-induced NRK-52E cell apoptosis and caspase-3 cleavage. Furthermore, canagliflozin markedly ameliorated HG-induced NRK-52E cell oxidative stress. Moreover, canagliflozin significantly increased LC3-II levels and induced RFP-LC3-containing punctate structures in NRK-52E cells. Finally, canagliflozin increased the phosphorylation of AMPK and suppressed the phosphorylation of mTOR. The AMPK inhibitor compound C abolished canagliflozin-induced autophagy activation, as well as the anti-apoptotic effect of canagliflozin. Conclusion: Canagliflozin effectively ameliorate HG-induced apoptosis of NRK-52E cells in vitro that involved its antioxidant effect and induction of autophagy through the AMPK/mTOR pathway. [ABSTRACT FROM AUTHOR]

Background: Cholangiocarcinoma (CCA) refers to a collection of malignancies that are associated with a dismal prognosis. Currently, surgical resection is the only way to cure patients with CCA. Available systemic therapy is limited to gemcitabine plus cisplatin; however, this treatment is palliative in nature. Therefore, there is still a need to explore new effective therapeutic targets to intervene against CCA. Methods: We analyzed the expression of EZH2 and the prognosis of patients in CCA. The proliferation, migration and invasion of CCA cells after gene knockdown and overexpression were examined and validated by a xenograft model and a primary CCA mouse model with corresponding gene intervention. Targeting DNA methylation, and RNA‐sequencing‐based transcriptomic analysis in EZH2 and SUZ12 knockout CCA cells was performed. Bisulfite sequencing polymerase chain reaction (PCR), chromatin immunoprecipitation‐quantitative PCR (ChIP‐qPCR) and reverse‐ChIP assays were performed for research purposes. Results: Increased expression of EZH2 in CCA exhibited a significantly poorer prognosis. DNA hypomethylation of the promoter and increased mRNA levels of secreted frizzled‐related protein 1 (SFRP1) were observed in CCA cells following the inhibition of polycomb repressor complex 2 (PRC2), which was achieved through a knockout of EZH2, SUZ12 and EED, respectively, or treatment with GSK126 and GSK343. Targeting the SFRP1 promoter DNA hypermethylation with dCas9‐DNMT3a decreased the mRNA level of SFRP1. The expression of SFRP1 is regulated by both H3K27me3 and DNA methylation and H3K27me3 plays a crucial role in promoting SFRP1 promotor DNA methylation. GSK343 is a small molecule inhibitor that targets the catalytic activity of EZH2. It effectively inhibits the progression and development of subcutaneous xenografts and primary CCA mouse models. Conclusion: Overall, our data strongly suggested that targeting PRC2 promotes the expression of SFRP1, thereby inhibiting the progression of CCA. Key Points/Headlights: Cholangiocarcinoma (CCA) exhibits elevated expression of EZH2, SUZ12 and EED, resulting in increased levels of H3K27me3.Targeting polycomb repressor complex 2 (PRC2) leads to the removal of H3K27me3 from the secreted frizzled‐related protein 1 (SFRP1) promoter and DNA hypomethylation, thereby activating the transcription of SFRP1.Inhibiting PRC2, including the use of EZH2 inhibitors, holds promise as a potential strategy for developing anti‐cancer drugs for CCA. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chemical fungicides are the mainstay of plant disease control in agricultural production, but there are a very limited number of drugs that can effectively control plant diseases. Two series of secondary amine derivatives were synthesized using the diamine skeleton combined with saturated aromatic and aliphatic aldehydes, and their antibacterial and antifungal activities against plant pathogens were determined. In addition, the antimicrobial mechanism of the highly active compound A26 was preliminarily examined against Xanthomonas oryzae (Xoo). RESULTS: Compound A26 exhibited the highest antibacterial potency among all the target compounds, with MIC values of 3.12, 3.12 and 12.5 μg mL−1 against Xoo, Xanthomonas axonopodis pv. Citri and Pseudomonas sollamacearum, respectively. In addition, compound A26 had powerful curative and protective effects against Xoo at 200 μg mL−1, and was better than the control agent Xinjunan. Preliminary mechanistic studies showed that compound A26 reduced the bacterial pathogenicity by targeting cell membranes and inhibiting the secretion of extracellular polysaccharides. Meanwhile, the toxicity of compound A26 to Human Embryonic Kidney 293 cells and Human Liver‐7702 was similar to that of Xinjunan, and it had moderate toxicity according to the World Health Organization classification standard of oral exogenous toxicity, with an LD50 of 245.47 mg kg−1. CONCLUSION: Secondary amines have efficient and broad‐spectrum antibacterial activity against plant pathogenic bacteria and are expected to be a new class of candidate compounds for antibacterial drugs. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Context: Chronic low-grade inflammation may play a crucial role in the pathogenesis of gestational diabetes mellitus (GDM). However, prospective studies on the relations of inflammatory blood cell parameters during pregnancy with GDM are lacking. Objective: To prospectively investigate the associations of inflammatory blood cell parameters in both early and middle pregnancy, and their change patterns from early to middle pregnancy, with GDM risk. Methods: We used data from the Tongji-Shuangliu Birth Cohort. Inflammatory blood cell parameters (white blood cells [WBC], neutrophils, lymphocytes, monocytes, neutrophil to lymphocyte ratio [NLR], and platelets) were assayed before 15 weeks and between 16 and 28 weeks of gestational age. Logistic regression was used to evaluate the associations between inflammatory blood cell parameters and GDM. Results: Of the 6354 pregnant women, 445 were diagnosed with GDM. After adjustment for potential confounders, WBC, neutrophils, lymphocytes, monocytes, and NLR in early pregnancy were positively associated with GDM risk (odds ratios [95% CI] for extreme-quartile comparison were 2.38 [1.76-3.20], 2.47 [1.82-3.36], 1.40 [1.06-1.85], 1.69 [1.27-2.24], and 1.51 [1.12-2.02], respectively, all P for trend ≤ .010). Similarly, higher levels of WBC, neutrophils, monocytes, and NLR in middle pregnancy were associated with increased risk of GDM (all P for trend ≤ .014). Stable high levels (≥ median in both early and middle pregnancy) of WBC, neutrophils, monocytes, and NLR were positively associated with GDM risk (all P≤ .001). Conclusion: Increased WBC, neutrophils, monocytes, and NLR in both early and middle pregnancy and their stable high levels from early to middle pregnancy were associated with higher GDM risk, highlighting that they might be clinically relevant for identifying individuals at high risk for GDM. [ABSTRACT FROM AUTHOR]

Purpose: The glymphatic system is a fluid exchange pathway that clears waste products that is crucial for the maintenance of brain homeostasis. However, the exact role it plays in the emergence of fibromyalgia (FM) is still not fully understood. Here, we explored the changes in non-invasive MRI proxy probably related to the glymphatic function in FM patients, and explored brain-behavior relationships. Methods: A total of 40 participants, consisting of 20 individuals with FM and 20 healthy controls (HCs), were included in the study. The participants underwent structural T1-weighted MRI, diffusion tensor imaging (DTI), and clinical assessment. The data was obtained from an open access dataset. The study compared non-invasive MRI indices, including choroid plexus (CP) volume and DTI analysis along the perivascular space (ALPS), between the FM and HC groups. Furthermore, correlation analysis was conducted to determine the correlation between clinical parameters and both CP volume and DTI-ALPS index. Results: Patients with FM had significantly higher CP volume and a lower DTI-ALPS index than HCs adjusting for age and intracranial volume. Higher CP volume was associated with lower DTI-ALPS index, and longer disease duration. Conclusion: Our findings demonstrate aberrant glymphatic function in FM, and that dysfunction in the brain glymphatic system may play a role in the neural mechanisms underlying FM. [ABSTRACT FROM AUTHOR]

Purpose: Neuroimaging studies employing analyses dependent on regional assumptions and specific neuronal circuits could miss characteristics of whole-brain structural connectivity critical to the pathophysiology of fibromyalgia (FM). This study applied the whole-brain graph-theoretical approach to identify whole-brain structural connectivity disturbances in FM. Methods: This cross-sectional study used probabilistic diffusion tractography and graph theory analysis to evaluate the topological organization of brain white matter networks in 20 patients with FM and 20 healthy controls (HCs). The relationship between brain network metrics and clinical variables was evaluated. Results: Compared with HCs, FM patients had lower clustering coefficient, local efficiency, hierarchy, synchronization, and higher normalized characteristic path length. Regionally, patients demonstrated a significant reduction in nodal efficiency and centrality; these regions were mainly located in the prefrontal, temporal cortex, and basal ganglia. The network-based statistical analysis (NBS) identified decreased structural connectivity in a subnetwork of prefrontal cortex, basal ganglia, and thalamus in FM. There was no correlation between network metrics and clinical variables (false discovery rate corrected). Conclusions : The current research demonstrated disrupted topological architecture of white matter networks in FM. Our results suggested compromised neural integration and segregation and reduced structural connectivity in FM. [ABSTRACT FROM AUTHOR]