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Background Infected pancreatic necrosis (IPN) exacerbates complications in patients with acute pancreatitis (AP), increasing mortality rates if not treated promptly. We aimed to evaluate the predictive value of clinical characteristics within 24 hours of admission for IPN prediction.Methods We conducted a retrospective, multicentre cohort study including 3005 patients with AP from eight hospitals in China. Clinical variables collected within 24 hours after admission were analysed using least absolute shrinkage and selection operator regression (10 cross-validations) for variable selection, followed by multivariate logistic regression to develop an IPN prediction model. Internal cross-validation of the development set and validation of the validation set were performed to ensure robustness. Decision curve analysis was used to evaluate its clinical utility.Results IPN occurred in 176 patients (176/3005, 5.9%). The final model included temperature, respiratory rate, plasma calcium ion concentration, serum urea nitrogen and serum glucose. The area under the receiver operating characteristics curve (AUC) was 0.85 (95% CI 0.81 to 0.89), outperforming widely used severity scoring systems. The model demonstrated robust performance on the internal validation cohort (mean AUC: 0.84) and external validation cohort (AUC: 0.82, 95% CI 0. 77 to 0.87).Conclusion We developed a simple and robust model for predicting IPN in patients with AP, demonstrating strong predictive performance and clinical utility.

This study utilized a modified split Hopkinson pressure bar apparatus to subject polypropylene fiber-reinforced foamed concrete (PPFRFC) to substantial deformation loading at high temperatures and strain rates. Based on experimental results, the study systematically investigated the coupled effects of temperature and strain rate on the dynamic mechanical behavior of PPFRFC across a broad range of strain rates (0.001 s−1 to 1300 s−1) and temperatures (25 °C–600 °C). The findings revealed that elevated temperatures significantly affected various mechanical parameters including peak stress, plateau stress, elastic modulus, densification strain, dynamic increase factor (DIF), and energy absorption. Notably, with increasing temperature, the strain rate amplified the peak stress, plateau stress, and energy absorption, whereas its influence on the elastic modulus diminished. Microstructural examination revealed the absence of notable cracks in the pore walls after high-temperatures exposure. However, degradation of the cement matrix results in a loose skeleton structure within the pore walls, leading to a considerable reduction in material strength. Finally, a constitutive model was developed, considering the coupling effects of temperature and strain rate. This model accurately describes the mechanical response of the PPFRFC across various stages, including the elastic, plateau, and densification stages, as well as the stress drop behavior in the transition stage. Moreover, it effectively reflects the influence of strain rate and temperature coupling effects on the material's mechanical properties.

Abstract Background Inadequate surface matching, variation in the guide design, and soft tissue on the skeletal surface may make it difficult to accurately place the 3D-printed patient-specific instrument (PSI) exactly to the designated site, leading to decreased accuracy, or even errors. Consequently, we developed a novel 3D-printed PSI with fluoroscopy-guided positioning markers to enhance the accuracy of osteotomies in joint-preserving surgery. The current study was to compare whether the fluoroscopically calibrated PSI (FCPSI) can achieve better accuracy compared with freehand resection and conventional PSI (CPSI) resection. Methods Simulated joint-preserving surgery was conducted using nine synthetic left knee bone models. Osteotomies adjacent to the knee joint were designed to evaluate the accuracy at the epiphysis side. The experiment was divided into three groups: free-hand, conventional PSI (CPSI), and fluoroscopically Calibrated PSI (FCPSI). Post-resection CT scans were quantitatively analyzed. Analysis of variance (ANOVA) was used. Result FCPSI improved the resection accuracy significantly. The mean location accuracy is 2.66 mm for FCPSI compared to 6.36 mm (P

Objective To identify the risk factors of refractory peritoneal dialysis related peritonitis (PDRP) and construct a nomogram to predict the occurrence of refractory PDRP.Methods Refractory peritonitis was defined as the peritonitis episode with persistently cloudy bags or persistent dialysis effluent leukocyte count >100 × 109/L after 5 days of appropriate antibiotic therapy. The study dataset was randomly divided into a 70% training set and a 30% validation set. Univariate logistic analysis, LASSO regression analysis, and random forest algorithms were utilized to identify the potential risk factors for refractory peritonitis. Independent risk factors identified using multivariate logistic analysis were used to construct a nomogram. The discriminative ability, calibrating ability, and clinical practicality of the nomogram were evaluated using the receiver operating characteristic curve, Hosmer–Lemeshow test, calibration curve, and decision curve analysis.Results A total of 294 peritonitis episodes in 178 patients treated with peritoneal dialysis (PD) were enrolled, of which 93 were refractory peritonitis. C-reactive protein, serum albumin, diabetes mellitus, PD duration, and type of causative organisms were independent risk factors for refractory peritonitis. The nomogram model exhibited excellent discrimination with an area under the curve (AUC) of 0.781 (95% CI: 0.716–0.847) in the training set and 0.741 (95% CI: 0.627–0.855) in the validation set. The Hosmer–Lemeshow test and calibration curve indicated satisfactory calibration ability of the predictive model. Decision curve analysis revealed that the nomogram model had good clinical utility in predicting refractory peritonitis.Conclusion This nomogram can accurately predict refractory peritonitis in patients treated with PD.

The Double U-pipe ground heat exchanger, known for its simple process, cost-effectiveness, high heat exchange efficiency, and low thermal resistance, remains the predominant type of ground heat exchanger in today’s shallow geothermal energy development and utilization. In recent years, significant research has focused on the factors influencing heat transfer and the heat exchange performance of Double U-pipe ground heat exchangers through experimental testing methods. However, studies that integrate numerical simulation with in situ testing have been less common. Utilizing the cylindrical heat source model theory and the results of regional in situ thermal response tests, this paper develops a Double U-pipe ground heat transfer model by establishing physical, mathematical, and heat transfer geometric models. It evaluates the effects of varying inlet temperatures, flow rates, and initial ground temperatures on heat exchange efficiency under heating conditions. The results confirm the accuracy of the Double U-pipe ground heat exchanger model based on in situ testing. They indicate that increasing the temperature differential between the inlet and initial temperatures, raising the initial ground temperature, and moderately enhancing the flow rate can improve the system’s heat exchange efficiency.

To enhance the strength and toughness of metallic materials simultaneously over a wide range of temperatures and strain rates, a eutectic high-entropy FCC/Laves composite with a heterogeneous initial microstructure was fabricated by powder plasma arc additive manufacturing. The mechanical behavior of the composite over a wide range of temperatures and strain rates was tested with the aid of an electronic universal testing machine and an improved Split Hopkinson pressure bar. The high-entropy FCC/Laves composite possesses a unique combination of strength and ductility over the selected temperature and strain rate ranges due to the in situ composite nature with both soft high-entropy FCC phase and hard high-entropy Laves phase. Complicated thermal viscoplastic behavior is presented. To reveal the mechanisms of the complicated thermal viscoplastic behavior, microstructure evolution was characterized. The high-entropy Laves phase, as a kind of multi-component intermetallic, defies convention by displaying plastic deformation at room temperature and different strain rates. Superior damage tolerance of the high-entropy FCC/Laves composite can be achieved over the selected temperature and strain rate ranges with the contribution of deformation twin in FCC phase, as well as dynamic recrystallization over high temperature range. Finally, a constitutive description was developed, which is shown to be able to accurately describe the complicated plastic behavior over a wide range of temperatures and strain rates. These findings suggest promising prospects for advanced material design, opening a new avenue to achieve a fine balance between strength and ductility across different conditions.

This paper presents our study of the deformation and failure characteristics surrounding rock in roadways with super-large sections during the integrated coal pillar excavation, filling and retention process between coalfaces. Based on the theory of complex variable function, the mapping accuracy of conformal transformation is improved, and an analytical solution for surrounding rock stress in super-large sections of roadway is derived. The stress distribution law of the surrounding rock of rectangular roadways is analyzed, and numerical simulation software is used for supplementary analysis and verification. According to the research findings, the compressive stresses on two sides and the tensile stress on the roof of a rectangular roadway with super-large sections decreased with the increase in the side-pressure coefficient; however, when the side-pressure coefficient increased to a certain point, those two sides changed from a pressure-bearing status to a tensile force-bearing status, while the roof changed from a tensile force-bearing status to a pressure-bearing status. In these stress changes, all the stresses upon the surrounding rock of roadways were compressive stresses and the two critical side-pressure coefficient values were λup and λdown. As the aspect ratio of the roadway increased from 1 to 9, its λup increased from 1.823 to 5.865 and its λdown increased from 0.549 to 0.888. When those side-pressure coefficients in the environment where a roadway is located exceed their critical values, tensile stress will take place on the roadway boundary and result in tensile failure, thus leading to instability in the roadway super-large section. The impact of the side-pressure coefficient upon the plastic zone range of roadway surrounding rock is greater than the impact of the roadway width. In order to secure stability in the surrounding rock of roadways with super-large sections during the excavation process, the side-pressure coefficient should remain around 1; in this situation, the plastic zone covers the smallest range and the relevant support work is the easiest. These research findings provide theoretical references for the excavation and support of roadways with super-large sections.

Astragalin (AG), a typical flavonoid found in Thesium chinense Turcz (T. chinense), is abundant in various edible plants and possesses high nutritional value, as well as antioxidant and antibacterial effects. In this study, we initially predicted the mechanism of action of AG with two anti-aging and antioxidant-related protein targets (CD38 and IGFR) by molecular docking and molecular dynamics simulation techniques. Subsequently, we examined the anti-aging effects of AG in Caenorhabditis elegans (C. elegans), the antioxidant effects in zebrafish, and verified the related molecular mechanisms. In C. elegans, AG synergistically extended the lifespan of C. elegans by up-regulating the expression of daf-16 through inhibiting the expression of daf-2/IGFR and also activating the AMPK and MAPK pathways to up-regulate the expression of sir-2.1, sir-2.4, and skn-1. In oxidatively damaged zebrafish embryos, AG demonstrated a synergistic effect in augmenting the resistance of zebrafish embryos to oxidative stress by up-regulating the expression levels of SIRT1 and SIRT6 within the zebrafish embryos system via the suppression of CD38 enzymatic activity and then inhibiting the expression of IGFR through high levels of SIRT6. These findings highlight the antioxidant and anti-aging properties of AG and indicate its potential application as a supplementary ingredient in aquaculture for enhancing fish health and growth.

Blindly developing shallow geothermal energy (SGE) may lead to difficulties in reinjection, a low coefficient of performance (COP), and the waste of funds. In order to avoid these problems and improve development efficiency, it is necessary to scientifically conduct a development suitability evaluation and classify the suitability levels before development. This article takes Chengde City, Hebei Province, China as an example and constructs an evaluation index system based on the analysis of regional basic conditions. The Analytic Hierarchy Process (AHP) was used to calculate the constant weight. A Fuzzy C-means Clustering (FCM) analysis was used to determine the critical value of evaluation index classification and the interval threshold of variable weights. The parameters of the variable-weight model were calculated using the method of model backcalculation. Based on the constructed variable-weight model, the suitability of SGE development for groundwater sources in the study area was evaluated, and it was divided into five levels: most suitable area, suitable area, relatively suitable area, less suitable area, and unsuitable area. Through a verification analysis of engineering examples and a comparison with the evaluation results under traditional constant-weight models, it was found that the evaluation results based on variable weight theory have better data discreteness and a higher accuracy. Research has shown that variable-weight models can adjust the weight of each index based on its state value. Through this study, the accuracy of the suitability evaluation for regional SGE development can be improved. This can provide a certain reference for the suitability evaluation of SGE development in other regions.

Abstract Ferroptosis, a novel mode of cell death dependent on iron and reactive oxygen species, has been extensively explored during malignant tumors metastasis. Ferroptosis can interact with multiple components of the tumor microenvironment to regulate metastasis. These interactions generally include the following aspects: (1) Epithelial-mesenchymal transformation, which can help cancer cells increase their sensitivity to ferroptosis while they have multiple mechanisms to fight against it; (2) Disorder of iron metabolism in cancer stem cells which maintains their stem characteristics; (3) Polarization of M0 macrophages to M2. (4) The paradoxical effects of iron metabolism and CD8 + T cells induced by ferroptosis (5) Regulation of angiogenesis. In addition, ferroptosis can be regulated by miRNAs through the reprogramming of various intracellular metabolism processes, including the regulation of the glutathione- glutathione peroxidase 4 pathway, glutamic acid/cystine transport, iron metabolism, lipid metabolism, and oxidative stress. Therefore, there are many potential interactions between ferroptosis-related miRNAs and tumor metastasis, including interaction with cancer cells and immune cells, regulating cytokines, and angiogenesis. This review focuses on the role of ferroptosis-related miRNA in tumor metastasis, aiming to help readers understand their relationship and provide a new perspective on the potential treatment strategies of malignant tumors.

Abstract The rapid development of 2D magnetic materials has opened new possibilities in the field of spintronics. CrTe2, a 2D material with perpendicular magnetic anisotropy (PMA) and ferromagnetic transient temperature near room temperature, holds promise for various applications. However, the underlying mechanism responsible for its global magnetism remains unclear. This work focuses on investigating the magneto‐transport properties of ultra‐thin CrTe2 Field Effect Transistor (FET) under the influence of top gate biases. The application of gate voltage ranging from 25 to −15 V tunes its coercivity (HC) and Curie temperature (TC) (from 152 to 191 K). Notably, a linear correlation is observed between the TC and the hole concentration (np1/3) in the CrTe2 film, indicating the involvement of the Ruderman–Kittel–Kasuya–Yosida interaction. This experimental analysis sheds light on the mechanism of the CrTe2’s ferromagnetism and paves the way for future advancements and applications in this material.

Based on the paraxial wave equation, this study extends the theory of small-scale self-focusing (SSSF) from coherent beams to spatially partially coherent beams (PCBs) and derives a general theoretical equation that reveals the underlying physics of the reduction in the B-integral of spatially PCBs. From the analysis of the simulations, the formula for the modulational instability (MI) gain coefficient of the SSSF of spatially PCBs is obtained by introducing a decrease factor into the formula of the MI gain coefficient of the SSSF of coherent beams. This decrease can be equated to a drop in the injected light intensity or an increase in the critical power. According to this formula, the reference value of the spatial coherence of spatially PCBs is given, offering guidance to overcome the output power limitation of the high-power laser driver due to SSSF.

PurposeTo establish a model combining radiomic and clinicopathological factors based on magnetic resonance imaging to predict pathological complete response (pCR) after neoadjuvant chemotherapy in breast cancer patients.MethodMRI images and clinicopathologic data of 329 eligible breast cancer patients from the Affiliated Hospital of Qingdao University from August 2018 to August 2022 were included in this study. All patients received neoadjuvant chemotherapy (NAC), and imaging examinations were performed before and after NAC. A total of 329 patients were randomly allocated to a training set and a test set at a ratio of 7:3. We mainly studied the following three types of prediction models: radiomic models, clinical models, and clinical-radiomic models. All models were evaluated using subject operating characteristic curve analysis and area under the curve (AUC), decision curve analysis (DCA) and calibration curves.ResultsThe AUCs of the clinical prediction model, independent imaging model and clinical combined imaging model in the training set were 0.864 0.968 and 0.984, and those in the test set were 0.724, 0.754 and 0.877, respectively. According to DCA and calibration curves, the clinical-radiomic model showed good predictive performance in both the training set and the test set, and we found that we had developed a more concise clinical-radiomic nomogram.ConclusionWe have developed a clinical-radiomic model by integrating radiomic features and clinical factors to predict pCR after NAC in breast cancer patients, thereby contributing to the personalized treatment of patients.

BackgroundClonorchis sinensis (C. sinensis) is a epidemiologically significant food-borne parasite, causing several hepatobiliary diseases. Biliary microbiota community structure might be influenced by infection with pathogens. However, the biliary microbiome of biliary obstruction patients infected with C. sinensis is still an unexplored aspect.MethodsA total of 50 biliary obstruction patients were enrolled, including 24 infected with C. sinensis and 26 non-infected subjects. The bile samples were collected by Endoscopic Retrograde Cholangiopancretography. Biliary microbiota alteration was analyzed through high-throughput 16S ribosomal RNA (rRNA) gene sequencing.ResultsOur findings revealed that there was significant increase in both richness and diversity, as well as changes in the taxonomic composition of the biliary microbiota of C. sinensis infected patients. At the phylum level, C. sinensis infection induced Proteobacteria increased and Firmicutes reduced. At the genus level, the relative abundance of Pseudomonas and Staphylococcus increased significantly, while Enterococcus decreased prominently in infected groups (P < 0.05). The PICRUSt analysis further showed remarkably different metabolic pathways between the two groups.ConclusionC. sinensis infection could modify the biliary microbiota, increasing the abundance and changing the phylogenetic composition of bacterial in biliary obstruction patients. This study may help deepen the understanding of the host-biliary microbiota interplay with C. sinensis infection on the background of biliary obstruction and provide new insights into understanding the pathogenesis of clonorchiasis.

Objective The serum triglyceride-glucose (TyG) index is a marker of inflammation. However, the relationship between TyG index and peritoneal dialysis-related peritonitis (PDRP) is unclear. This study aimed to investigate the potential relationship between the baseline TyG index and the initial episode of PDRP.Methods A total of 208 peritoneal dialysis (PD) patients were enrolled from January 1, 2012, to December 31, 2019 and followed up until December 31, 2022. They were divided into 2 groups according to the median TyG. The primary outcome was the occurrence of the initial episode of PDRP while on PD therapy. Kaplan-Meier curves and Cox regression analyses were used to examine the association between them.Results Eighty-five initial episodes of PDRP were identified. The risk of PDRP was higher in the high-TyG index group (p = 0.030). Multivariate Cox regression analysis showed a higher risk of PDRP in patients with a high TyG index (HR = 1.800, 95% CI 1.511–2.815, p = 0.010).Conclusion The baseline serum TyG index was an independent risk factor for the initial episode of PDRP in chronic PD patients.

The Sverdrup Basin is one of the important petroliferous basins in the Arctic. It has abundant oil and gas resources, but the exploration degree is relatively low. Based on the IHS database and literatures in the public domain, this paper documented the geological characteristics and distribution of oil and gas in the Sverdrup Basin, and classified the petroleum systems and hydrocarbon plays in the basin. The undiscovered hydrocarbons were eventually assessed by Monte Carlo simulation and the favorable exploration areas were predicted. The investigation results show that the discovered oil and gas accumulations are mainly distributed in the western area of the basin, which consists of Sabin and Edinburgh sub-basins. Oil and gas are mainly reserved in the Jurassic and Triassic clastic reservoirs. Two petroleum systems, which are the Paleozoic and Mesozoic systems, were identified in the basin. The Mesozoic petroleum system has a far greater exploration potential. Undiscovered recoverable reserves (mean value) in the Mesozoic petroleum system are 474.81 MMbbl (1 MMbbl=1×106 bbl, 1 bbl=0.137 t) of oil, 13 620.82 Bcf (1 Bcf=1×109 ft3, 1 ft3=0.028 3 m3) of natural gas and 63.66 MMbbl of condensate, amounting to 2 808.61 MMboe (3.85×108 t), of which the natural gas accounts for 80.82%. The Lower Jurassic structural hydrocarbon play in the western area of the basin, the Upper Triassic-Lower Jurassic structural hydrocarbon play in the Edinburgh sub-basin and the Upper Jurassic structural hydrocarbon play in the Sabine sub-basin are the most promising exploration areas.

The investigation and mapping of ground substrate is a whole new field of natural resources survey and monitoring system in the current situation, which has not been evolved into a unified guideline on action. In this paper, based on the summarization of the current situation of the Earth’s critical zone theory and ground substrate survey, fully drawing on the investigation methods and map expression styles of regional geology, engineering geology, Quaternary geology, hydrogeology, environmental geology, etc., and taking Ruyi River Basin in Bashang Plateau of Chengde City as the research area, we establish the method of the investigation and mapping of ground substrate based on the theory of the Earth’s critical zone. Based on the field investigation results, the ground substrate in Ruyi River Basin can be divided into nine types as follows: basalt, andesite, tuff, rhyolite, alluvial-proluvial gravel, eluvial-proluvial gravel, aeolian sand, lacustrine silt and marsh silt. The distribution characteristics as well as the investigation and monitoring indicators in different types of ground substrates are also studied. The spatial distribution map of aeolian sand thickness, coupling relationship profile between the ground substrate and the ground covered layer, and ground substrate map are drew. The spatial distribution map of ground substrate thickness can show the spatial distribution characteristics of the thickness of different types of surface substrate layers. The coupling relationship profile of ground substrate and surface covered layer can directly describe the constraint of the profile structural characteristics and physical and chemical properties of ground substrate on the ecological elements of the covered layer. The ground substrate map can systematically reflect the structure, distribution, characteristics and coupling relationship between ground substrate and ground covered layer. The series maps of ground substrate are the reflection of the interaction of multiple cycles in the Earth’s critical zone, such as the rock, the soil, the water, and the organism. The results of this study can provide references for the nationwide investigation and mapping of the ground substrate.

Heterostructured composites with the coexistence of hard and soft phases can achieve a superior strength-ductility synergy. However, the deformation and fracture mechanisms of these composites under impact loading has not been comprehensively understood. In this work, an in-situ TiB2/2024 Al composite was adopted to investigate the role of heterogeneous structures on the tensile mechanical responses at different strain rates and temperatures. Surprisingly, a simultaneously enhancement of strength and ductility was found in the composite under impact loading. To explore the underlying mechanisms responsible for the observed mechanical behavior, microstructural analyses were performed on the samples before and after deformation. Results reveal that the composite has obvious heterogeneous structure consist of particle-rich regions (regard as hard phase) and particle-lean regions (soft phase). The interaction between the two phases can affect the strain hardening behavior of the composites at different plastic deformation stages. Compared with the strain rate insensitive matrix, the particle-induced constraint makes the flow stress of the composite increases substantially with an increase in strain rate. Meanwhile, the tortuous crack propagation paths induced by the cooperation of hard and soft phases contribute to the improved ductility at high strain rates.

Iridoid components have been reported to have significant neuroprotective effects. However, it is not yet clear whether the efficacy and mechanisms of iridoid components with similar structures are also similar. This study aimed to compare the neuroprotective effects and mechanisms of eight iridoid components (catalpol (CAT), genipin (GE), geniposide (GEN), geniposidic acid (GPA), aucubin (AU), ajugol (AJU), rehmannioside C (RC), and rehmannioside D (RD)) based on corticosterone (CORT)-induced injury in PC12 cells. PC12 cells were randomly divided into a normal control group (NC), model group (M), positive drug group (FLX), and eight iridoid administration groups. Firstly, PC12 cells were induced with CORT to simulate neuronal injury. Then, the MTT method and flow cytometry were applied to evaluate the protective effects of eight iridoid components on PC12 cell damage. Thirdly, a cell metabolomics study based on ultra-performance liquid chromatography–quadrupole–time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was performed to explore changes in relevant biomarkers and metabolic pathways following the intervention of administration. The MTT assay and flow cytometry analysis showed that the eight iridoid components can improve cell viability, inhibit cell apoptosis, reduce intracellular ROS levels, and elevate MMP levels. In the PCA score plots, the sample points of the treatment groups showed a trend towards approaching the NC group. Among them, AU, AJU, and RC had a weaker effect. There were 38 metabolites (19 metabolites each in positive and negative ion modes, respectively) identified as potential biomarkers during the experiment, among which 23 metabolites were common biomarkers of the eight iridoid groups. Pathway enrichment analysis revealed that the eight iridoid components regulated the metabolism mainly in relation to D-glutamine and D-glutamate metabolism, arginine biosynthesis, the TCA cycle, purine metabolism, and glutathione metabolism. In conclusion, the eight iridoid components could reverse an imbalanced metabolic state by regulating amino acid neurotransmitters, interfering with amino acid metabolism and energy metabolism, and harmonizing the level of oxidized substances to exhibit neuroprotective effects.

Background: Thesium chinense known as the “plant antibiotic” is a facultative root hemi-parasitic herb while Prunella vulgaris can serve as its host. However, the molecular mechanisms underlying the communication between T. chinense and its host remained largely unexplored. The aim of this study was to provide a comprehensive view of transferred metabolites and mobile mRNAs exchanged between T. chinense and P. vulgaris. Results: The wide-target metabolomic and transcriptomic analysis identified 5 transferred metabolites (ethylsalicylate, eriodictyol-7-O-glucoside, aromadendrin-7-O-glucoside, pruvuloside B, 2-ethylpyrazine) and 50 mobile genes between T. chinense and P. vulgaris, as well as haustoria formation related 56 metabolites and 44 genes. There were 4 metabolites (ethylsalicylate, eriodictyol-7-O-glucoside, aromadendrin-7-O-glucoside and pruvuloside B) that are transferred from P. vulgaris to T. chinense, whereas 2-ethylpyrazine was transferred in the opposite direction. Furthermore, we inferred a regulatory network potentially involved in haustoria formation, where three metabolites (N,N′-Dimethylarginine/SDMA, NG,NG-Dimethyl-L-arginine, 2-Acetoxymethyl-anthraquinone) showed significant positive correlations with the majority of haustoria formation-related genes. Conclusions: These results suggested that there was an extensive exchange of information with P. vulgaris including transferred metabolites and mobile mRNAs, which might facilitate the haustoria formation and parasition of T. chinense.

Background and Aims: Although type 2 innate lymphoid cells (ILC2s) were originally found to be liver-resident lymphocytes, the role and importance of ILC2 in liver injury remains poorly understood. In the current study, we sought to determine whether ILC2 is an important regulator of hepatic ischaemia/reperfusion injury (IRI). Methods: ILC2-deficient mice (ICOS-T or NSG) and genetically modified ILC2s were used to investigate the role of ILC2s in murine hepatic IRI. Interactions between ILC2s and eosinophils or macrophages were studied in coculture. The role of human ILC2s was assessed in an immunocompromised mouse model of hepatic IRI. Results: Administration of IL-33 prevented hepatic IRI in association with reduction of neutrophil infiltration and inflammatory mediators in the liver. IL-33-treated mice had elevated numbers of ILC2s, eosinophils, and regulatory T cells. Eosinophils, but not regulatory T cells, were required for IL-33-mediated hepatoprotection in IRI mice. Depletion of ILC2s substantially abolished the protective effect of IL-33 in hepatic IRI, indicating that ILC2s play critical roles in IL-33-mediated liver protection. Adoptive transfer of ex vivo-expanded ILC2s improved liver function and attenuated histologic damage in mice subjected to IRI. Mechanistic studies combining genetic and adoptive transfer approaches identified a protective role of ILC2s through promoting IL-13-dependent induction of anti-inflammatory macrophages and IL-5-dependent elevation of eosinophils in IRI. Furthermore, in vivo expansion of human ILC2s by IL-33 or transfer of ex vivo-expanded human ILC2s ameliorated hepatic IRI in an immunocompromised mouse model of hepatic IRI. Conclusions: This study provides insight into the mechanisms of ILC2-mediated liver protection that could serve as therapeutic targets to treat acute liver injury. Impact and Implications: We report that type 2 innate lymphoid cells (ILC2s) are important regulators in a mouse model of liver ischaemia/reperfusion injury (IRI). Through manipulation of macrophage and eosinophil phenotypes, ILC2s mitigate liver inflammation and injury during liver IRI. We propose that ILC2s have the potential to serve as a therapeutic tool for protecting against acute liver injury and lay the foundation for translation of ILC2 therapy to human liver disease.

FAK mediated tumour cell migration, invasion, survival, proliferation and regulation of tumour stem cells through its kinase-dependent enzymatic functions and kinase-independent scaffolding functions. At present, the development of FAK PROTACs has become one of the hotspots in current pharmaceutical research to solve above problems. Herein, we designed and synthesised a series of FAK-targeting PROTACs consisted of PF-562271 derivative 1 and Pomalidomide. All compounds showed significant in vitro FAK kinase inhibitory activity, the IC50 value of the optimised PROTAC A13 was 26.4 nM. Further, A13 exhibited optimal protein degradation (85% degradation at 10 nM). Meantime, compared with PF-562271, PROTAC A13 exhibited better antiproliferative activity and anti-invasion ability in A549 cells. More, A13 had excellent plasma stability with T1/2 >194.8 min. There are various signs that PROTAC A13 could be useful as expand tool for studying functions of FAK in biological system and as potential therapeutic agents.

Many oil and gas pipelines have to be laid on the seabed during the deep development of marine oil and gas resources, but the submarine pipeline suspension due to souring under marine hydrodynamic conditions is the important factor that leads to the vortex-induced vibration failure of pipelines. In terms of the poor adaptability of the existing sour protection measures to the submarine pipelines in strong tidal area, a scale physical model test was performed with a bidirectional water channel based on a submarine pipeline in the strong tidal area of Hangzhou Bay. Meanwhile, research was conducted on the sour protection effect of artificial grass for submarine pipelines under alternating tidal current conditions. The test results indicate that the local scour depth of submarine pipelines decreases with the increasing of the density and coverage width of artificial grass. When the coverage width increases to the critical value, the sour depth is reduced to be zero. By fitting the experimental data with the multiple regression fitting method, the relational expression of the density and critical width of artificial grass can be obtained. The research results could provide reference for the design and implementation of sour protection measures for submarine pipelines in strong tidal area.

Abstract Manipulating Gilbert damping is of critical importance in spintronic devices. Here, this work reports the damping anisotropy of Heusler‐alloy Co3−xFexAl single crystalline thin films using inductive ferromagnetic resonance. A colossal Gilbert damping anisotropy ratio of up to 1400%, nearly three times higher than the highest value reported among known metallic ferromagnets, is observed in the optimized sample Co1.4Fe1.6Al. The Gilbert damping anisotropy with strong fourfold symmetry is attributed to the variation of the spin–orbit coupling, which is further corroborated by the current‐orientation‐dependent anisotropic magnetoresistance ratio in Co1.4Fe1.6Al thin film. These results provide a practical approach to adjust Gilbert damping continuously and show great promise for future spintronic applications.

Objective To investigate the effect of cardiac valve calcification (CVC) on the prognosis of patients with chronic kidney disease (CKD). Methods A total of 343 CKD patients were retrospectively analyzed, and divided into two groups according to the presence or absence of cardiac valve calcification. All patients were followed until death, loss to follow-up, or the end point of the study (December 2021). Results The incidence of CVC among the 343 CKD patients was 29.7%, including 21 cases of mitral valve calcification, 63 cases of aortic valve calcification, and 18 cases of mitral valve combined with aortic valve calcification. The incidence of CVC in CKD stages 1–2 was 0.3%, 5.2% in CKD stages 3–4, and 24.2% in CKD stage 5 (P

Major histocompatibility complex I (MHC‐I) molecules present epitopes on the cellular surface of antigen‐presenting cells to prime cytotoxic clusters of differentiation 8 (CD8)+ T cells (CTLs), which then identify and eliminate other cells such as virus‐infected cells bearing the antigen. Human hepatitis virus cohort studies have previously identified MHC‐I molecules as promising predictors of viral clearance. However, the underlying functional significance of these predictions is not fully understood. Here, we show that expression of single MHC‐I isomers promotes virus‐induced liver immunopathology. Specifically, using the lymphocytic choriomeningitis virus (LCMV) model system, we found MHC‐I proteins to be highly up‐regulated during infection. Deletion of one of the two MHC‐I isomers histocompatibility antigen 2 (H2)–Db or H2‐Kb in C57Bl/6 mice resulted in CTL activation recognizing the remaining MHC‐I with LCMV epitopes in increased paucity. This increased CTL response resulted in hepatocyte death, increased caspase activation, and severe metabolic changes in liver tissue following infection with LCMV. Moreover, depletion of CTLs abolished LCMV‐induced pathology in these mice with resulting viral persistence. In turn, natural killer (NK) cell depletion further increased antiviral CTL immunity and clearance of LCMV even in the presence of a single MHC‐I isomer. Conclusion: Our results suggest that uniform MHC‐I molecule expression promotes enhanced CTL immunity during viral infection and contributes to increased CTL‐mediated liver cell damage that was alleviated by CD8 or NK cell depletion.

The mechanisms causing quality variations and key control factors of submarine-fan reservoirs in the gas field X of the Rovuma Basin, East Africa are analyzed based on core and well-log data in this paper. Depositional fabric, lithofacies difference and characteristics of genetic units are the fundamental reasons of reservoir quality variations. In the case of weak cementation, porosity and permeability of submarine-fan reservoirs are controlled by grain sorting and clay content, respectively. Reservoir quality variations for 5 main lithofacies are related to variable depositional fabrics and calcite cementation. Among them, massive medium-coarse sandstones with weak cementation have the highest porosity and permeability, and coarser or finer sandstones have poorer reservoir quality. The existence of bottom current can develop laminated sandstones, improving the pore structure and physical properties greatly. Lithofacies vary among different types, locations and stages of genetic units, and they control the distribution patterns of submarine-fan reservoir quality: the physical properties of channel shaft or lobe main body are better than those of the channel or lobe edge. The sandstone sorting and physical properties are gradually improved from near-source to far-source. When multi-stage sand bodies are superimposed, the sand-mud ratio in the later stage is higher than that in the earlier stage, making the physical properties get better in the later stage.

Abstract Uncovering the physical mechanisms that govern ultrafast charge and spin dynamics is becoming indispensable both at the fundamental level and to develop future spin‐based electronics. Recently it has been shown that femtosecond pulsed‐laser excitation of magnetic thin films produces intense and ultrafast spin‐polarized hot electrons, thus attracting a lot of attention. While spin‐polarized hot electrons are known to play a pivotal role in the ultrafast laser‐induced demagnetization, their effect on magnetization switching remains an open issue. This study uncovers the effect of spin‐polarized hot electrons generated by laser excitation on magnetization switching in a Co/Pt based perpendicular magnetic anisotropy‐based synthetic antiferromagnet (p‐SAF) using the time‐resolved magneto‐optical Kerr effect. It has been found that, at low pump fluence, the equivalent magnetic field generated by the hot‐electron spin current plays a dominant role in assisting the magnetization switching of the lower layer in the antiferromagnetic configuration, while the strong thermal stability of the Ruderman Kittel Kasuya Yosida exchange interaction inhibits the further weakening of the switching field at high pump fluence. This study provides a viable way to control the magnetization switching of the antiferromagnetically exchange‐coupled systems for spintronic applications with ultrafast control of the information operation.

A novel experimental technique conducted at a modified automatic split Hopkinson pressure bar (SHPB) for measuring the dynamic compressive behavior at ultra-high temperature up to 1700 °C was developed. A bidirectional electric synchronous assembly system, two high-precision delay controllers and an automatic control mechanism were employed to automate each section in the whole experiment process with high precision and high reliability. The cold contact time (CCT) between specimen and loading bars can be accurately and stably controlled to be shorter than 5 ms and the effect of CCT on temperature distribution can be eliminated. Based on this automatic high-temperature SHPB technique, an experimental investigation into the responses of a new in-service single-crystal Nickel-base superalloy DD10 subjected to impact loading at high temperature was undertaken. The influence of strain rate and temperature on the flow behavior of DD10 was tested and analyzed over a wide range of strain rate (0.001/s-4000/s) and temperature (25°C–1200 °C). The high temperature has an evident effect on the flow stress, strain hardening and strain rate sensibility. An anomalous peak of stress in true stress–temperature curve can be found, and the peak temperature increases with strain rate increasing. Through the microstructural observation, the influence of strain rate and temperature on the compressive deformation and fracture mechanism was discussed. At the high temperature above 1000 °C, the shear deformation mechanism of both γ matrix phase and γ′ precipitate phase is the dominant deformation mechanism at high strain rate, instead of the rafting mechanism of γ′ precipitate phase of under quasi-static loading condition.

Abstract Several retrofillings have been performed by different utilities in China. However, there is still insufficient understanding of the retrofilling procedures for minimising residual mineral oil and on the effect of the temperature rise of transformers. Following new detailed procedures, an out‐of‐service S11‐M‐315/10 (10 kV 315 kVA) and a new S13‐M‐400/10 (10 kV 400 kVA) distribution transformers were selected to retrofill their mineral oil with FR3, a soybean‐based natural ester. A method was proposed to predict the residual mineral oil content, which uses the kinematic viscosity at 60°C. This method fills a gap in the testing of residual mineral oil content. The mass ratios of residual mineral oil were 1.24% for the S11‐M‐315/10 transformer and 2.05% for the S13‐M‐400/10 transformer, based on the procedures in this study. The fire point of the mixed oil after retrofilling was 352°C, which meets the K‐class less‐flammable requirements, indicating a proper control of residual mineral oil. After retrofilling, the time of reaching the limits of the 1.5 times rated load was 30% longer than that of the mineral oil transformer. Two retrofilled transformers have been operating in good conditions since November 2019 for the S11‐M‐315/10 transformer and December 2020 for the S13‐M‐400/10 transformer.

Thrombolytic agents have thus far yielded limited therapeutic benefits in the treatment of thrombotic disease due to their short half-life, low targeting ability, and association with serious adverse reactions, such as bleeding complications. Inspired by the natural roles of platelets during thrombus formation, we fabricated a platelet-based delivery system (NO@uPA/PLTs) comprising urokinase (uPA) and arginine (Arg) for targeted thrombolysis and inhibition of re-embolism. The anchoring of uPA to the platelet surface by lipid insertion increased the thrombotic targeting and in vivo circulation duration of uPA without disturbing platelet functions. Nitric oxide (NO) generated by the loaded Arg inhibited platelet aggregation and activation at the damaged blood vessel, thereby inhibiting re-embolism. NO@uPA/PLTs effectively accumulated at the thrombi in pulmonary embolism and carotid artery thrombosis model mice and exerted superior thrombolytic efficacy. In addition, the platelet delivery system showed excellent thrombus recurrence prevention ability in a mouse model of secondary carotid artery injury. The coagulation indicators in vivo showed that the platelet-based uPA and NO co-delivery system possessed a low hemorrhagic risk, providing a promising tool for rapid thrombolysis and efficient inhibition of posttreatment re-embolism.

Alfalfa (Medicago sativa L.) is a widely planted perennial legume forage plant with excellent quality and high yield. In production, it is very important to determine alfalfa growth dynamics and forage yield in a timely and accurate manner. This study focused on inverse algorithms for predicting alfalfa forage yield in large-scale alfalfa production. We carried out forage yield and aboveground biomass (AGB) field surveys at different times in 2022. The correlations among the reflectance of different satellite remote sensing bands, vegetation indices, and alfalfa forage yield/AGB were analyzed, additionally the suitable bands and vegetation indices for alfalfa forage yield inversion algorithms were screened, and the performance of the statistical models and machine learning (ML) algorithms for alfalfa forage yield inversion were comparatively analyzed. The results showed that (1) regarding different harvest times, the alfalfa forage yield inversion model for first-harvest alfalfa had relatively large differences in growth, and the simulation accuracy of the alfalfa forage yield inversion model was higher than that for the other harvest times, with the growth of the second- and third-harvest alfalfa being more homogeneous and the simulation accuracy of the forage yield inversion model being relatively low. (2) In the alfalfa forage yield inversion model based on a single parameter, the moisture-related vegetation indices, such as the global vegetation moisture index (GVMI), normalized difference water index (NDWI) and normalized difference infrared index (NDII), had higher coefficients of correlation with alfalfa forage yield/AGB, and the coefficients of correlation R2 values for the first-harvest alfalfa were greater than 0.50, with the NDWI correlation being the best with an R2 value of 0.60. (3) For the alfalfa forage yield inversion model constructed with vegetation indices and band reflectance as multiparameter variables, the random forest (RF) and support vector machine (SVM) simulation accuracy was higher than that of the alfalfa forage yield inversion model based on a single parameter; the first-harvest alfalfa R2 values based on the multiparameter RF and SVM models were both 0.65, the root mean square errors (RMSEs) were 329.74 g/m2 and 332.32 g/m2, and the biases were −0.47 g/m2 and −2.24 g/m2, respectively. The vegetation indices related to plant water content can be considered using a single parameter inversion model for alfalfa forage yield, the vegetation indices and band reflectance can be considered using a multiparameter inversion model for alfalfa forage yield, and ML algorithms are also an optimal choice. The findings in this study can provide technical support for the effective and strategic production management of large-scale alfalfa.

Abstract To develop inhibitors targeting DNA damage repair pathways is important to improve the effectiveness of chemo- and radiotherapy for cancer patients. Rad51 mediates homologous recombination (HR) repair of DNA damages. It is widely overexpressed in human cancers and overwhelms chemo- and radiotherapy-generated DNA damages through enhancing HR repair signaling, preventing damage-caused cancer cell death. Therefore, to identify inhibitors of Rad51 is important to achieve effective treatment of cancers. Transcription factor Nanog is a core regulator of embryonic stem (ES) cells for its indispensable role in stemness maintenance. In this study, we identified Nanog as a novel inhibitor of Rad51. It interacts with Rad51 and inhibits Rad51-mediated HR repair of DNA damage through its C/CD2 domain. Moreover, Rad51 inhibition can be achieved by nanoscale material- or cell-penetrating peptide (CPP)-mediated direct delivery of Nanog-C/CD2 peptides into somatic cancer cells. Furthermore, we revealed that Nanog suppresses the binding of Rad51 to single-stranded DNAs to stall the HR repair signaling. This study provides explanation for the high γH2AX level in unperturbed ES cells and early embryos, and suggests Nanog-C/CD2 as a promising drug candidate applied to Rad51-related basic research and therapeutic application studies.

COVID-19 pandemic remains serious around the world and causes huge deaths and economic losses. To investigate the effect of vaccination and isolation delays on the transmission of COVID-19, we propose a mathematical model of COVID-19 transmission with vaccination and isolation delays. The basic reproduction number is computed, and the global dynamics of the model are proved. When R01. Based on the public information, parameter values are estimated, and sensitivity analysis is carried out by the partial rank correlation coefficients (PRCCs) and the extended version of the Fourier amplitude sensitivity test (eFAST). Our results suggest that the isolation rates of asymptomatic and symptomatic infectious individuals have a significant impact on the transmission of COVID-19. When the COVID-19 is epidemic, the optimal control strategies of our model with vaccination and isolation delays are analyzed. Under the limited resource with constant and time-varying isolation rates, we find that the optimal isolation rates may minimize the cumulative number of infected individuals and the cost of disease control, and effectively contain the transmission of COVID-19. Our study may help public health to prevent and control the COVID-19 spread.

Background: Phosphaturic mesenchymal tumor (PMT) is a very rare tumor of bone and soft tissue that has no specific clinical manifestations. Here we present 2 cases of PMT in the right thigh, including comparatively adequate immunohistochemistry. Case Presentation: We described 2 cases of PMT in the right thigh with manifestations of hypophosphatemia. PET-CT examination showed that both patients had lesions with increased expression of somatostatin receptors in the right thigh. Bland cells and dirty calcified stroma were exhibited under the microscope. And immunohistochemical detection of FGF-23 was positive. Conclusions: PMT is a very uncommon tumor for which diagnosis and treatment are often delayed. Considering the importance of surgery for the treatment of this disease, a full understanding of its clinicopathological features will facilitate the diagnosis of this disease.

Bioaugmentation of native grass ensiling with Lactobacillus plantarum or Lactobacillus buchneri or Pediococcus pentosaceus on the ensiling performance and bacterial community was investigated after 30 days of the fermentation process. The native grass was inoculated with distilled water, Lactobacillus plantarum, Lactobacillus plantarum, and Lactobacillus buchneri, and Lactobacillus plantarum, Lactobacillus buchneri, and Pediococcus pentosaceus as the CON treatment, T1 treatment, T2 treatment, and T3 treatment, respectively. The addition of lactic acid bacteria was added at a total of 1 × 106 colony-forming unit/g of fresh weight. As expected, the markedly (p < 0.05) lower water-soluble carbohydrate content was tested in the T2 and T3 treatments compared to the CON and T1 treatments. Compared to the CON and T1 treatment, significantly (p < 0.05) higher crude protein content, and lower acid detergent fiber and neutral detergent fiber contents were found in the T2 and T3 treatments. Compared to the CON treatment, the pH significantly (p < 0.05) decreased in the lactic acid bacteria (LAB) inoculated silage, and the lowest pH was measured in the T3 treatment. Similarly, significantly higher lactic acid and acetic acid contents were also found in the T3 treatment compared to those in other treatments. After 30 days of ensiling, the Shannon and Chao1 indexes in silages decreased compared to that in the fresh materials (FMs). The principal coordinate analysis indicated that both FM and silage were distinctly separated in each treatment with no interactions on the confidence ellipse (R = 0.8933, p = 0.001). At the phylum level, the dominant phylum was shifted from Proteobacteria to Firmicutes after the fermentation process. Interestingly, Weissella dominated the fermentation in the CON treatment and Lactobacillus dominated the fermentation in all inoculated LAB silages at the genus level. Results of functional prediction analyses showed that the metabolism of amino acid, cofactors, and vitamins, and membrane transport was reduced, while the metabolism of nucleotide and majority carbohydrates was increased after ensiling. The complex LAB (Lactobacillus plantarum, Lactobacillus buchneri, and Pediococcus pentosaceus) exhibited the potential possibility to decrease pH and enhance the relative abundance of LAB in response to obtaining high-quality silage by the synergistic effects. These results suggested that the complex LAB could improve the ensiling performance of native grass silage, and lay a theoretical basis for inoculant application in native grass.

The existence of the bottom oil–water transition zone (BTZ) greatly impairs the performance of the conventional steam-assisted gravity drainage (SAGD) process and its mitigation measures are very limited. In order to accelerate oil production and decrease the Steam-to-Oil Ratio (SOR), a promising technology involving a steam drive and gravity drainage (SDGD) process by placing dual-horizontal wells with high permeability in the BTZ was systematically studied. This paper conducted two-dimensional (2D) and three-dimensional (3D) physical simulations as well as 2D numerical simulation of the SDGD process to explore the mechanism, potential, and application conditions. The research findings indicate that the SDGD process in the BTZ with enhanced permeability through dilation stimulation can achieve higher oil production and lower SOR than the SAGD process. This process fully leverages the advantage of the BTZ to quickly establish inter-well thermal and hydraulic connectivity. The steam chamber first forms around the injector and then spreads towards the producer. By exerting the horizontal displacement of drained oil, oil production rapidly ramps up and keeps at a high rate under the synergistic effect of steam drive and gravity drainage. These insights enhance our understanding of the mechanism, potential, and application conditions of the SDGD process in the confined BTZ to develop super heavy oil or oil sands.

Pulmonary hypertension (PH) was once a devastating and fatal disease entity, the outlook of which has been significantly improved by the continued progress of medical treatment algorithms. However, some patients still ultimately fail to achieve an adequate clinical response despite receiving maximal medical treatment. Historically, lung transplantation (LTx) has been the only effective therapeutic option that could lead to satisfactory outcomes and save these advanced patients’ lives. However, patients with PH tend to have the highest mortality rates on the transplant waiting list; especially after comprehensive medical treatment, they continue to deteriorate very rapidly, eventually missing optimal transplantation windows. Balancing optimized medical treatment with the appropriate timing of referral and listing has been highly controversial in LTx for patients with PH. The 2021 consensus document for the selection of lung transplant candidates from the International Society for Heart and Lung Transplantation (ISHLT) updated the specific recommendations for the LTx referral and listing time for patients with PH based on objective risk stratification. Herein, we review the evolving PH-related concepts and highlight the optimization of LTx referral and listing for patients with PH, as well as their management on the waiting list.

Abstract Background En bloc resection of malignant tumors involving upper thoracic spine is technically difficult. We surgically treated a patient with grade 2 chondrosarcoma involving T1–5, left upper thoracic cavity, and chest wall. Case presentation A 37 years old, male patient was referred to our hospital for a huge lump involved left shoulder and chest wall. In order to achieve satisfied surgical margins, anterior approach, posterior approach, and lateral approach were carried out sequentially. After en bloc tumor resection, the upper thoracic spine was reconstructed with a 3D-printed modular vertebral prosthesis, and the huge chest wall defect was repaired by a methyl methacrylate layer between 2 pieces of polypropylene mesh. Postoperatively, the patient suffered from pneumonia and neurological deterioration which fully recovered eventfully. At 24 months after operation, the vertebral prosthesis and internal fixation were intact; there was no tumor local recurrence, and the patient was alive with stable pulmonary metastases. Conclusion This case report describes resection of a huge chondrosarcoma involving not only multilevel upper thoracic spine, but also entire left upper thoracic cavity and chest wall. Although with complications, en bloc tumor resection with combined surgical approach and effective reconstructions could improve oncologic and functional prognosis in carefully selected spinal tumor patients.

Using different strains of the lymphocytic choriomeningitis virus (LCMV), Xu, Wang et al. show that a slow viral propagation limits type I interferon (IFN-I) production and viral persistence in mice. This study suggests a reduced viral propagation as a mechanism for immune evasion and viral persistence.

Polypropylene-fiber-reinforced foamed concrete (PPFRFC) is often used to reduce building structure weight and develop engineering material arresting systems (EMASs). This paper investigates the dynamic mechanical properties of PPFRFC with densities of 0.27 g/cm3, 0.38 g/cm3, and 0.46 g/cm3 at high temperatures and proposes a prediction model to characterize its behavior. To conduct the tests on the specimens over a wide range of strain rates (500~1300 s−1) and temperatures (25~600 °C), the conventional split-Hopkinson pressure bar (SHPB) apparatus was modified. The test results show that the temperature has a substantial effect on the strain rate sensitivity and density dependency of the PPFRFC. Additionally, the analysis of failure models demonstrates that with the melting of polypropylene fibers, the level of damage in PPFRFC under dynamic loading increases, resulting in the generation of a greater number of fragments.

In the process of development and utilization of a large-scale borehole heat exchanger (BHE) array system, the phenomenon of load shifting within BHE array can be observed. In this paper, OpenGeoSys software coupled with TESPy toolkit is used to establish a comprehensive numerical model of BHE system (without depicting the heat pump part), and the behaviors of load shifting between BHEs with different design parameters are studied. The results show that the outlet temperature of single BHE and BHE array is generally rising, and the soil temperature around the BHE has accumulated unbalanced heat. The soil temperature near the BHEs array fluctuates more obviously than the single BHE system, and the distribution is uneven. At the end of the 15th year, the soil temperature near the center BHE increased by 2 °C compared with the initial soil temperature, which was more favorable in winter, but was not conducive to the performance improvement in summer. Further analysis by changing the inter-borehole spacing shows that with the increase of the inter-borehole spacing, the load shifting behaviors are gradually weakened, and the maximum shifted load of the central BHE is linear with the change of the inter-borehole spacing. After changing the layout methods, we observe that the more intensive the layout is, the more load shifting behavior is, and the unbalanced rate of soil temperature distribution around the linear layout is lower than other layouts. With the increase in the number of BHEs, the load shifting behaviors are further enhanced. By analyzing the proportion of shifted load amount relative to the average value, it is found that the system will take a longer time to reach heat balance with the increase of BHEs’ number. A shutdown of part of BHEs for a certain period of time will help to improve the long-term operational efficiency of the large-scale shallow ground source heat pump (GSHP) system.

Abstract Type 2 innate lymphoid cells (ILC2s) are a subset of ILCs with critical roles in immunoregulation. However, the possible role of ILC2s as immunotherapy against allograft rejection remains unclear. Here, we show that IL‐33 significantly prolonged islet allograft survival. IL‐33‐treated mice had elevated numbers of ILC2s and regulatory T cells (Tregs). Depletion of Tregs partially abolished the protective effect of IL‐33 on allograft survival, and additional ILC2 depletion in Treg‐depleted DEREG mice completely abolished the protective effects of IL‐33, indicating that ILC2s play critical roles in IL‐33‐mediated islet graft protection. Two subsets of ILC2s were identified in islet allografts of IL‐33‐treated mice: IL‐10 producing ILC2s (ILC210) and non‐IL‐10 producing ILC2s (non‐ILC10). Intravenous transfer of ILC210 cells, but not non‐ILC10, prolonged islet allograft survival in an IL‐10‐dependent manner. Locally transferred ILC210 cells led to long‐term islet graft survival, suggesting that ILC210 cells are required within the allograft for maximal suppressive effect and graft protection. This study has uncovered a major protective role of ILC210 in islet transplantation which could be potentiated as a therapeutic strategy.

Abstract Background Our objective was to investigate the efficacy of the beta-3 adrenergic receptor (β3-AR) agonist BRL37344 for the prevention of liver steatosis and inflammation associated with nonalcoholic fatty liver disease (NAFLD). Methods Four groups were established: a control group (given a standard diet), a high-fat diet (HFD) group, an HFD + β3-AR agonist (β3-AGO) group, and an HFD + β3-AR antagonist (β3-ANT) group. All rats were fed for 12 weeks. The β3-AR agonist BRL37344 and the antagonist L748337 were administered for the last 4 weeks with Alzet micro-osmotic pumps. The rat body weights (g) were measured at the end of the 4th, 8th, and 12th weeks. At the end of the 12th week, the liver weights were measured. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed with a Hitachi automatic analyzer. The lipid levels of the triglycerides (TGs), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) and the concentrations of free fatty acids (FFAs) were also measured. An oil red O kit was used to detect lipid droplet accumulation in hepatocytes. Steatosis, ballooning degeneration and inflammation were histopathologically determined. The protein and mRNA expression levels of β3-AR, peroxisome proliferator-activated receptor-alpha (PPAR-α), peroxisome proliferator-activated receptor-gamma (PPAR-γ), mitochondrial carnitine palmitoyltransferase-1 (mCPT-1), and fatty acid translocase (FAT)/CD36 were measured by western blot analysis and RT-qPCR, respectively. Results After treatment with the β3-AR agonist BRL37344 for 4 weeks, the levels of ALT, AST, TGs, TC, LDL-C and FFAs were decreased in the NAFLD model group compared with the HFD group. Body and liver weights, liver index values and lipid droplet accumulation were lower in the HFD + β3-AGO group than in the HFD group. Decreased NAFLD activity scores (NASs) also showed that liver steatosis and inflammation were ameliorated after treatment with BRL37344. Moreover, the β3-AR antagonist L748337 reversed these effects. Additionally, the protein and gene expression levels of β3-AR, PPAR-α, and mCPT-1 were increased in the HFD + β3-AGO group, whereas those of PPAR-γ and FAT/CD36 were decreased. Conclusion The β3-AR agonist BRL37344 is beneficial for reducing liver fat accumulation and for ameliorating liver steatosis and inflammation in NAFLD. These effects may be associated with PPARs/mCPT-1 and FAT/CD36.

This study reviews the development history of PetroChina's overseas oil and gas field development technologies, summarizes the characteristic technologies developed, and puts forward the development goals and technological development directions of overseas business to overcome the challenges met in overseas oil and gas production. In the course of PetroChina's overseas oil and gas field production practice of more than 20 years, a series of characteristic technologies suitable for overseas oil and gas fields have been created by combining the domestic mature oil and gas field production technologies with the features of overseas oil and gas reservoirs, represented by the technology for high-speed development and stabilizing oil production and controlling water rise for overseas sandstone oilfields, high efficiency development technology for large carbonate oil and gas reservoirs and foamy oil depletion development technology in use of horizontal wells for extra-heavy oil reservoirs. Based on in-depth analysis of the challenges faced by overseas oil and gas development and technological requirements, combined with the development trends of oil and gas development technologies in China and abroad, overseas oil and gas development technologies in the future are put forward, including artificial intelligence reservoir prediction and 3D geological modeling, secondary development and enhanced oil recovery(EOR) of overseas sandstone oilfields after high speed development, water and gas injection to improve oil recovery in overseas carbonate oil and gas reservoirs, economic and effective development of overseas unconventional oil and gas reservoirs, efficient development of marine deep-water oil and gas reservoirs. The following goals are expected to be achieved: keep the enhanced oil recovery (EOR) technology for high water-cut sandstone oilfield at international advanced level, and make the development technology for carbonate oil and gas reservoirs reach the international advanced level, and the development technologies for unconventional and marine deep-water oil and gas reservoirs catch up the level of international leading oil companies quickly. Key words: overseas oil and gas field production, sandstone oilfield, large carbonate oilfield, unconventional oil and gas field, marine deep-water oil and gas, technological progress, development direction

Abstract Background New therapies are urgently needed in melanoma particularly in late-stage patients not responsive to immunotherapies and kinase inhibitors. Methods Drug screening, IC50 determinations as well as synergy assays were detected by the MTT assay. Apoptosis using Annexin V and 7AAD staining was assessed using flow cytometry. TUNEL staining was performed using immunocytochemistry. Changes in phosphorylation of key molecules in PI3K/Akt/mTOR and other relevant pathways were detected by western blot as well as immunocytochemistry. To assess in vivo anti-tumor activity of Tegaserod, syngeneic intravenous and subcutaneous melanoma xenografts were used. Immunocytochemical staining was performed to detect expression of active Caspase-3, cleaved Caspase 8 and p-S6 in tumors. Evaluation of immune infiltrates was carried out by flow cytometry. Results Using a screen of 770 pharmacologically active and/or FDA approved drugs, we identified Tegaserod (Zelnorm, Zelmac) as a compound with novel anti-cancer activity which induced apoptosis in murine and human malignant melanoma cell lines. Tegaserod (TM) is a serotonin receptor 4 agonist (HTR4) used in the treatment of irritable bowel syndrome (IBS). TM’s anti-melanoma apoptosis-inducing effects were uncoupled from serotonin signaling and attributed to PI3K/Akt/mTOR signaling inhibition. Specifically, TM blunted S6 phosphorylation in both BRAFV600E and BRAF wildtype (WT) melanoma cell lines. TM decreased tumor growth and metastases as well as increased survival in an in vivo syngeneic immune-competent model. In vivo, TM also caused tumor cell apoptosis, blunted PI3K/Akt/mTOR signaling and decreased S6 phosphorylation. Furthermore TM decreased the infiltration of immune suppressive regulatory CD4+CD25+ T cells and FOXP3 and ROR-γt positive CD4+ T cells. Importantly, TM synergized with Vemurafenib, the standard of care drug used in patients with late stage disease harboring the BRAFV600E mutation and could be additively or synergistically combined with Cobimetinib in both BRAFV600E and BRAF WT melanoma cell lines in inducing anti-cancer effects. Conclusion Taken together, we have identified a drug with anti-melanoma activity in vitro and in vivo that has the potential to be combined with the standard of care agent Vemurafenib and Cobimetinib in both BRAFV600E and BRAF WT melanoma.

Spin polarization and the Gilbert damping, as the two key parameters of the magnetic materials for spintronic applications, were suggested to be inversely proportional to each other in a series of Heusler alloys. Recently, large anisotropic Gilbert damping was found in Co2FeAl thin films, implying that spin polarization may be also anisotropic. Here, we report an isotropic spin polarization with a constant value of 60% in a 20-nm Co2FeAl thin film with a B2 structure, using spin- and angle-resolved photoemission spectroscopy and time-resolved magneto-optical Kerr effect. Furthermore, this result was also supported by the ab initio calculations that the difference of the spin polarization between all the orientations is less than 1% for the Co2FeAl thin film. This finding provides profound insight into the spin polarization in Co2FeAl alloys.

Poor chip solder joints can severely affect the quality of the finished printed circuit boards (PCBs). Due to the diversity of solder joint defects and the scarcity of anomaly data, it is a challenging task to automatically and accurately detect all types of solder joint defects in the production process in real time. To address this issue, we propose a flexible framework based on contrastive self-supervised learning (CSSL). In this framework, we first design several special data augmentation approaches to generate abundant synthetic, not good (sNG) data from the normal solder joint data. Then, we develop a data filter network to distill the highest quality data from sNG data. Based on the proposed CSSL framework, a high-accuracy classifier can be obtained even when the available training data are very limited. Ablation experiments verify that the proposed method can effectively improve the ability of the classifier to learn normal solder joint (OK) features. Through comparative experiments, the classifier trained with the help of the proposed method can achieve an accuracy of 99.14% on the test set, which is better than other competitive methods. In addition, its reasoning time is less than 6 ms per chip image, which is in favor of the real-time defect detection of chip solder joints.

A high-sensitivity N2O photoacoustic sensor using a 4.53 μm quantum cascade laser was developed. Sharply enhancement of photoacoustic signal of N2O with the increasing of humidity was investigated experimentally. Finally, 2.3 % water vapor was added to the analyzed sample to improve the vibrational-translational (VT) relaxation rate of N2O molecule transition, and therefore enhance the N2O photoacoustic signal. High performance with a minimum detection limit of 28 ppbv in 1 s and a measurement precision of 34 ppbv have been achieved, respectively. Kalman adaptive filtering was used to remove the shot-to-shot variability related to the real-time noise in the measurement data and further improve the measurement precision. Without sacrificing the time resolution of the system, the Kalman adaptive filtering improves the measurement precision of the system by 2.3 times. The ability of the N2O photoacoustic sensor was demonstrated by continuous measurement of atmospheric N2O concentration for a period of 7 h.