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Abstract To reveal the velocity distribution law of a gas lift reverse circulation well washing flow field in drilling shaft sinking, a velocity mathematical model of well washing flow field is established. The theoretical analytical solutions and velocity distribution laws in the drill pipe and bottom hole were provided and validated through numerical simulations and similar model tests. Furthermore, this study explores the impacts of mud circulation, wind pressure, rock debris, and mud properties on the flow field distribution, presenting the sensitivity order of the factors. This study indicated the following findings. (1) The velocity theoretical model of well washing flow field was validated through numerical simulation and similar model tests, and the relative error ranged from 4.2 to 18.5%, demonstrating the high consistency. (2) The rock debris and mud experienced slight and consistent deceleration within the drill pipe. Upon reaching the gas input end, the axial upward return of the multiphase flow resulted in a “jumping” sharp increase. (3) The mud circulation, wind pressure, and void fraction positively correlated with the multiphase fluid velocity in the drill pipe, but negatively correlated with the mud density and slag content. The axial upward velocity of the rock debris decreased with increasing particle size and density. (4) The sensitivity of each factor to the discharge speed of rock debris was summarized as follows: air content > mud circulation > wind pressure > mud density > rock debris density > rock debris particle size > slag content. These findings could offer a theoretical basis for selecting well washing parameters and enhancing drilling and washing efficiency.

Abstract Background Vitamin K (VK), an essential fat-soluble nutrient, exists in two primary forms, vitamin K1 (VK1), and vitamin K2 (VK2). VK1 plays an essential role in blood coagulation, while VK2 plays a crucial role in managing bone calcification, supporting bone strength and health. However, comprehensive epidemiological data on VK remains sparse, particularly in children. This study aims to evaluate the levels and characteristics of VK in children of Wenzhou area, China. Methods A total of 3,342 children undergoing routine physical examinations in the outpatient department from December 2020 to August 2022 were recruited. The levels of VK (including VK1 and menaquinones (MK-4), a major form of VK2) and 25-hydroxy vitamin D (25(OH)D) in fasting serum samples from these children were measured using high-performance liquid chromatography-tandem mass spectrometry. The study analyzed the levels and distribution of VK and 25(OH)D across different sex, age, and weight groups, and explored their potential related factors. Results The median serum levels of MK-4 and VK1 were 0.12 (0.07, 0.21) ng/ml and 0.33 (0.18, 0.57) ng/ml, respectively. The reference ranges of MK-4 and VK1 were 0.01–0.58 ng/ml and 0.03–1.48 ng/ml, respectively. The median serum 25(OH)D level was 21.26 (17.30, 25.35) ng/ml. Moreover, there were no significant variations in the levels of MK-4 and VK1 across different age and sex groups. The level of MK-4 in the underweight group was significantly higher than that in the normal weight group. MK-4 level reached its peak in summer, while the VK1 concentration was at its lowest. Furthermore, a very weak positive correlation was revealed between MK-4 and VK1 levels. Conclusion In this study, we defined the median values and reference ranges of MK-4 and VK1 in a sample of Chinese children aged 0–18 years. MK-4 levels were higher in underweight children. Both MK-4 and VK1 levels exhibited seasonal variations. Further research is needed to explore the factors affecting MK-4 and VK1 levels.

Background: Senile osteoporosis (SOP) is a systemic bone disease characterized by increased susceptibility to fractures. However, there is currently no effective treatment for SOP. The Zhuangyao Jianshen Wan (ZYJSW) pill is traditionally believed to possess kidney-nourishing and bone-strengthening effects, demonstrating efficacy in treating fractures. Despite this, its effectiveness and mechanism in SOP remain unclear. This study aims to investigate the therapeutic potential of ZYJSW in treating SOP in senescence accelerated mouse prone 6 (SAMP6, P6) mice, and elucidate the underlying mechanisms. Methods: Four-month-old SAMP6 mice were categorized into six groups: the model group (SAMP6), low, medium, and high-dose ZYJSW treatment groups, calcitriol treatment (positive control 1) group, and metformin treatment (positive control 2) group. Gastric administration was carried out for 15 weeks, and a normal control group comprising four-month-old Senescence-Accelerated Mouse Resistant 1 (SAMR1) mice. Changes in body weight, liver and kidney function, bone protective effects, and muscle quality were evaluated using various assays, including H&E staining, Goldner staining, bone tissue morphology analysis, Micro-CT imaging, and biomechanical testing. Qualitative analysis and quality control of ZYJSW were performed via LC-MS/MS analysis. To explore mechanisms, network pharmacology and proteomics were employed, and the identified proteins were validated by Western blotting. Results: Oral administration of ZYJSW to P6 mice exerted preventive efficacy against osteopenia, impaired bone microstructure, and poor bone and muscle quality. ZYJSW attenuated the imbalance in bone metabolism by promoting bone formation, as evidenced by the upregulation of key factors such as Runt-related transcription factor 2 (RUNX2), Bone Morphogenetic Protein (BMP2), Osteoprotegerin (OPG) and Osteocalcin (OCN), while simultaneously inhibiting bone resorption through the downregulation of TNF receptor associated factor 6 (TRAF6), Tartrate resistant acid phosphatase (TRAP), Receptor activator for nuclear factor-κB ligand (RANKL) and Cathepsin K (CTSK). Additionally, ZYJSW enhanced muscle structure and function by counteracting the elevation of Ubiquitin (Ub), Muscle RING-finger protein-1 (Murf-1), F-Box Protein 32 (FBOX32), and Myogenin (Myog). Network pharmacology predictions, proteomics analysis corroborated by published literature demonstrated the role of ZYJSW involving in safeguarding mitochondrial biogenesis. This was achieved by suppressing GCN5L1 expression, contributing to the heightened expression of TFAM, PGC-1α, and nuclear respiratory factor-1 (NRF-1) proteins. ZYJSW also positively modulated Wnt signaling pathways responsible for bone formation, due to regulating expressions of key components like β-catenin, GSK-3β, and LRP5. In addition, ZYJSW causes the downregulation of the PI3K/Akt pathway by inhibiting the phosphorylation of both PI3K and Akt. Conclusions: The study highlights the significance of ZYJSW in preserving the health of both bone and muscle in P6 mice, potentially through the regulation of the GCN5L1-mediated PI3K/Akt/Wnt signaling pathway. The translational potential of this article: Our research provides evidence and a mechanistic rationale for ZYJSW as a candidate for SOP treatment, offering insights for further exploration and strategy development.

Abstract In this study, a feasibility of γ radiation detection using complementary metal-oxide semiconductor (CMOS) image sensors with a neural network algorithm to extract the γ rays interacted pixels has been investigated. The responses characteristics of the CMOS imaging sensor to γ-ray is studied by placed in a γ fields produced by standard60Co or137Cs isotope sources. The supported preview frame rate of the CMOS image sensor is 25 fps, establishing the functional relationship between the gray level histograms and the dose rate through the neural network, the high energy γ-ray from60Co and137Cs source radiation dose rate in µSv/h level can be detected using the CMOS imaging sensor. The results show that the proposed method can effectively identify the number of photon particles which detected by the radiation monitoring system based on CMOS image sensor, and infer that the CMOS imaging sensor with a radiation signal extraction algorithm can be used as a dose warner for radiation protection purpose.

The development of conductive coatings has significant implications for microelectronics and electrochemistry. However, conductive coatings may exhibit different electrochemical properties when prepared on different substrate materials. This research explores the comparative performance of graphene, graphene oxide (GO), and silver nanoparticle (Ag NP) composites as conductive coatings on diverse substrate materials, including polydimethylsiloxane (PDMS), polymethyl methacrylate (PMMA), and glass. The study employed various preparation methods, such as mixing conductive materials with substrate materials and preparing copolymer composite materials. The conductive coating approach was found to be the most straightforward and convenient, with broader development prospects and fewer restrictive conditions. The results indicate that the distinct surface characteristics of the substrate materials influence the conductive properties of coating materials. Consequently, results show that graphene exhibits the highest conductivity on all three substrates, while GO is more conductive than Ag NPs on PMMA and PDMS but less conductive than Ag NPs on glass. That offers valuable insights into the selection of substrate materials and coating materials for the preparation of conductive materials.

Abstract Factor XII (FXII) is the zymogen of the plasma protease FXIIa that activates the intrinsic coagulation pathway and the kallikrein kinin-system. The role of FXII in inflammation has been obscure. Here, we report a single-domain antibody (nanobody, Nb) fused to the Fc region of a human immunoglobulin (Nb-Fc) that recognizes FXII in a conformation-dependent manner and interferes with FXIIa formation. Nb-Fc treatment inhibited arterial thrombosis in male mice without affecting hemostasis. In a mouse model of extracorporeal membrane oxygenation (ECMO), FXII inhibition or knockout reduced thrombus deposition on oxygenator membranes and systemic microvascular thrombi. ECMO increased circulating levels of D-dimer, alkaline phosphatase, creatinine and TNF-α and triggered microvascular neutrophil adherence, platelet aggregation and their interaction, which were substantially attenuated by FXII blockade. Both Nb-Fc treatment and FXII knockout markedly ameliorated immune complex-induced local vasculitis and anti-neutrophil cytoplasmic antibody-induced systemic vasculitis, consistent with selectively suppressed neutrophil migration. In human blood microfluidic analysis, Nb-Fc treatment prevented collagen-induced fibrin deposition and neutrophil adhesion/activation. Thus, FXII is an important mediator of inflammatory responses in vasculitis and ECMO, and Nb-Fc provides a promising approach to alleviate thrombo-inflammatory disorders.

The advent of 3D printing (3DP) has garnered significant interest from both academia and industry due to its potential to revolutionize engineering, manufacturing, and through its utilization of advanced materials. Even though the application of 3D printing in footwear design and manufacture is quite appreciated, academic discourse on the subject relative to footwear design and manufacture is rather scarce compared to other fields such as pharmaceuticals, electronics and food. The purpose of this review is to explore the techniques, the application trends and the impact of 3D printing technology concerning footwear design and manufacture. Using relevant data from many relevant sources, this study uncovered that 3D printing has significantly impacted shoe design and manufacture by enhancing production efficiency, environmental sustainability, material innovation and Inter-Industry Collaborative Projects among others. Most of the major players in the footwear industry such as Nike, Adidas, Reebok and New Balance already have many footwear releases based on 3D printing. Also discussed are some specific areas in which 3D printing is being applied in footwear design and manufacture. These areas include but are not limited to the design of smart shoes, shoe lasts, complex shoe geometries, avant-garde concept shoes and so on. This study is of particular importance to stakeholders in the footwear research and design industry as it provides important information about the current trends as well as the impact of 3D printing technology on the sector.

Abstract Background Monocytes and macrophages play an indispensable role in maintaining intestinal homeostasis and modulating mucosal immune responses in inflammatory bowel disease (IBD). Although numerous studies have described macrophage properties in IBD, the underlying mechanisms whereby the monocyte-macrophage lineage modulates intestinal homeostasis during gut inflammation remain elusive. Main body In this review, we decipher the cellular and molecular mechanisms governing the generation of intestinal mucosal macrophages and fill the knowledge gap in understanding the origin, maturation, classification, and functions of mucosal macrophages in intestinal niches, particularly the phagocytosis and bactericidal effects involved in the elimination of cell debris and pathogens. We delineate macrophage-mediated immunoregulation in the context of producing pro-inflammatory and anti-inflammatory cytokines, chemokines, toxic mediators, and macrophage extracellular traps (METs), and participating in the modulation of epithelial cell proliferation, angiogenesis, and fibrosis in the intestine and its accessory tissues. Moreover, we emphasize that the maturation of intestinal macrophages is arrested at immature stage during IBD, and the deficiency of MCPIP1 involves in the process via ATF3-AP1S2 signature. In addition, we confirmed the origin potential of IL-1B+ macrophages and defined C1QB+ macrophages as mature macrophages. The interaction crosstalk between the intestine and the mesentery has been described in this review, and the expression of mesentery-derived SAA2 is upregulated during IBD, which contributes to immunoregulation of macrophage. Moreover, we also highlight IBD-related susceptibility genes (e.g., RUNX3, IL21R, GTF2I, and LILRB3) associated with the maturation and functions of macrophage, which provide promising therapeutic opportunities for treating human IBD. Conclusion In summary, this review provides a comprehensive, comprehensive, in-depth and novel description of the characteristics and functions of macrophages in IBD, and highlights the important role of macrophages in the molecular and cellular process during IBD.

The test time of impulse tunnels is short, and the heat flux transducers can be easily interfered in the test time. Thus the aerothermal test data analysis of impulse tunnels is complex and usually carried out manually, which leads to low efficiency and nonuniform standards. In this paper, the signals of heat transducers used in the 1 m gun/shock dual-mode impulse tunnel at the China Academy of Aerospace Aerodynamics were investigated. A series of key parameters, e.g., the FFT voltage profile, the correlation profile of nozzle total pressure and transducer heat flux, as well as the time derivative of the heat flux profile, were determined. The characterization capabilities of these parameters with respect to significant features, e.g., the start/end time of the nozzle flow, the time boundary of different operation modes and the effectiveness of the transducer profiles, were certified. Moreover, a profile effectiveness estimation model, a test time interval selection algorithm and a transducer valid time selection algorithm were developed based on convolutional neural networks and density-based clustering algorithms. Thereby the aerothermal test data of impulse tunnels can be analyzed automatically with these data-driven methods. The results show that the accuracy of the profile effectiveness estimation model is as high as 98%. According to the comparison between algorithm and manual results in dealing with 3 568 profiles, about 91% of the results show a difference of less than 10%, which implies that the data-driven method has the value of application to wind tunnel tests.

Abstract Aims Portal venous pressure frequently increases after a major hepatectomy. We aimed to assess the outcomes of patients with hepatocellular carcinoma (HCC) with different post‐hepatectomy portal pressure statuses and the predictive factors correlated with prognosis and post‐hepatectomy portal hypertension (PHPH). Methods Data from consecutive patients who underwent curative‐intent hepatectomy for HCC at the Eastern Hepatobiliary Surgery Hospital and Mengchao Hepatobiliary Hospital of Fujian Medical University between January 2008 and December 2016 were retrospectively analyzed. Patients were followed up until March 1, 2022. PHPH was defined as new‐onset portal hypertension (PH) in patients without preoperative PH within 1 month of hepatectomy. Patients were classified into two groups according to the presence or absence of PHPH: non‐PH and PHPH. The clinicopathological characteristics were compared between the two groups. Univariate and multivariate analyses were used to identify independent risk factors for early and late recurrence of HCC, overall survival (OS), and PHPH. Results Disease‐free survival rates were significantly higher in the non‐PH group (n = 1068) than those in the PHPH group (n = 423) (62.0%, 39.0%, and 31.0% vs. 46.2%, 24.5%, and 19.3% at 1, 3, and 5 years, respectively; all p 40 U/L, and major hepatectomy were identified as independent risk factors for PHPH. Conclusions PHPH was associated with early recurrence of HCC and poor OS but not with late recurrence. Therefore, PHPH may be an attractive target for therapeutic interventions and follow‐up surveillance to improve prognosis.

Abstract Background Although sorafenib has been consistently used as a first-line treatment for advanced hepatocellular carcinoma (HCC), most patients will develop resistance, and the mechanism of resistance to sorafenib needs further study. Methods Using KAS-seq technology, we obtained the ssDNA profiles within the whole genome range of SMMC-7721 cells treated with sorafenib for differential analysis. We then intersected the differential genes obtained from the analysis of hepatocellular carcinoma patients in GSE109211 who were ineffective and effective with sorafenib treatment, constructed a PPI network, and obtained hub genes. We then analyzed the relationship between the expression of these genes and the prognosis of hepatocellular carcinoma patients. Results In this study, we identified 7 hub ERGs (ACTB, CFL1, ACTG1, ACTN1, WDR1, TAGLN2, HSPA8) related to drug resistance, and these genes are associated with the cytoskeleton. Conclusions The cytoskeleton is associated with sorafenib resistance in hepatocellular carcinoma. Using KAS-seq to analyze the early changes in tumor cells treated with drugs is feasible for studying the drug resistance of tumors, which provides reference significance for future research.

IntroductionImmunogenic cell death (ICD) is capable of activating the anti-tumor immune response of the organism; however, it is concurrently a complex process involving multiple factors. The specific factors that impact the occurrence of ICD remain undefined.MethodsThrough cluster analysis, patient specimens retrieved from the TARGET, TCGA, and GEO AML databases were categorized into two subtypes based on the expression levels of ICD-related genes: ICD-high and ICD-low. We compared the prognostic survival outcomes, pathway enrichment analysis, and immune cell infiltration between these two subtypes. Additionally, we identified factors related to AML development from multiple databases and verified the role of these factors both in vivo and in vitro in activating the immune response during the occurrence of ICD. Results and discussionIn the ICD-high subtype, there was a notable increase in the abundance of immune cell populations, along with the enrichment of pathways pertinent to the activation of various immune cells. Despite these immunological enhancements, this subgroup demonstrated a poorer prognosis. This phenomenon was consistently observed across various additional AML datasets, leading us to hypothesize that elevated expression of ICD genes does not invariably correlate with a favorable prognosis. Notably, STK10 exhibited elevated expression in AML, was associated with a poor prognosis, and showed synchronous expression patterns with ICD genes. Inhibition of STK10 led to the activation of ICD and the induction of an antitumor response. Moreover, when combined with other ICD inducers, it produced a synergistic anti-tumor effect. Our results reveal the impact of STK10 on ICD and underscore its key role in initiating ICD.

Incorporating authentic tactile interactions into virtual environments presents a notable challenge for the emerging development of soft robotic metamaterials. In this study, a vision‐based approach is introduced to learning proprioceptive interactions by simultaneously reconstructing the shape and touch of a soft robotic metamaterial (SRM) during physical engagements. The SRM design is optimized to the size of a finger with enhanced adaptability in 3D interactions while incorporating a see‐through viewing field inside, which can be visually captured by a miniature camera underneath to provide a rich set of image features for touch digitization. Employing constrained geometric optimization, the proprioceptive process with aggregated multi‐handles is modeled. This approach facilitates real‐time, precise, and realistic estimations of the finger's mesh deformation within a virtual environment. Herein, a data‐driven learning model is also proposed to estimate touch positions, achieving reliable results with impressive R2 scores of 0.9681, 0.9415, and 0.9541 along the x, y, and z axes. Furthermore, the robust performance of the proposed methods in touch‐based human–cybernetic interfaces and human–robot collaborative grasping is demonstrated. In this study, the door is opened to future applications in touch‐based digital twin interactions through vision‐based soft proprioception.

BackgroundChildhood maltreatment (CM) is increasingly recognized as a significant risk factor for major depressive disorder (MDD), yet the neural mechanisms underlying the connection between CM and depression are not fully understood. This study aims to deepen our understanding of this relationship through neuroimaging, exploring how CM correlates with depression.MethodsThe study included 56 MDD patients (33 with CM experiences and 23 without) and 23 healthy controls. Participants were assessed for depression severity, CM experiences, and underwent resting-state functional MRI scans. Independent Component Analysis was used to examine differences in functional connectivity (FC) within the Default Mode Network (DMN) among the groups.ResultsMDD patients with CM experiences exhibited significantly stronger functional connectivity in the left Superior Frontal Gyrus (SFG) and right Anterior Cingulate Cortex (ACC) within the DMN compared to both MDD patients without CM experiences and healthy controls. FC in these regions positively correlated with Childhood Trauma Questionnaire scores. Receiver Operating Characteristic (ROC) curve analysis underscored the diagnostic value of FC in the SFG and ACC for identifying MDD related to CM. Additionally, MDD patients with CM experiences showed markedly reduced FC in the left medial Prefrontal Cortex (mPFC) relative to MDD patients without CM experiences, correlating negatively with Childhood Trauma Questionnaire scores.ConclusionOur findings suggest that increased FC in the ACC and SFG within the DMN is associated with CM in MDD patients. This enhanced connectivity in these brain regions is key to understanding the predisposition to depression related to CM.

The tensile properties of 2219-T8 aluminum alloy TIG welding joint were significantly affected by the microstructure, local mechanical properties and weld geometry. This paper proposed a machine learning model to predict and optimize the tensile properties of 2219-T8 aluminum alloy TIG welding joint. The relationship between tensile strength of joint and weld geometry, weld zone and partially melted zone (PMZ) properties was developed by Kriging model combining whale optimization algorithm (WOA). This surrogate model demonstrated a high precision, with R2 = 0.952 and RMSE=3.77 MPa. The surrogate model, which also served as a welding process guide, was utilized to determine the ideal weld geometry corresponding to various weak zone properties. By applying the optimization process based on the surrogate model, the optimized joint strength coefficient reached 70 %, and elongation exceeded 4 %. The collaborative regulation mechanism of geometry and property was also discussed.

Triaxial compression tests were conducted on frozen sandy soils under a constant minimum principal stress (σ3 = 1.6 MPa) and various intermediate principal stresses (σ2 = 1.6, 3.4, 5.2, 7.0, 8.8, 9.8 MPa). The purpose of the research was to investigate the influence of intermediate principal stress on mechanical properties of frozen soil, and to establish a constitutive model to predict the stress-strain relationship of frozen soil under complex stress state. The test results obtained demonstrated that the crack damage stress and failure stress initially increase and then decrease with an increase in the intermediate principal stress. However, the crack initiation stress exhibits an initial increase up to a specific value, after which it stabilizes. From the perspective of crack propagation, the influence mechanism of intermediate principal stress on the strength was discussed. With the variation of stress state, the difference between intermediate principal strain and minimum principal strain gradually increases. The deformation difference was revealed using the stress superposition principle and Poisson's effect. Finally, the constitutive model based on the Weibull distribution and Drucker-Prager strength criterion can accurately represent the stress-strain relationships of frozen sandy soils under true triaxial stress states.

Rupture behaviors of a subduction megathrust define the slip type, the extent and the associated tsunami hazard. They are, however, difficult to be defined precisely due to limited fault-zone observations. Here, we integrate GNSS, tsunami-waveforms, seismic-profiles, and earthquake-cycle modeling to delineate the slip-extent of the 2020 Mw 7.8 Simeonof and the 2021 Mw 8.2 Chignik earthquakes in the Semidi segment; and to understand the possible structural and mechanical control on the distinct rupture behaviors of this segment and its neighboring Shumagin segment at the Aleutian-Alaska subduction zone. We show that both the Simeonof and Chignik earthquakes slipped a compact area at depth between ∼20 and 40 km that is well constrained by the combination of GNSS and tsunami-waveform data. We explain the distinct slip behaviors associated with the Semidi and Shumagin segments by highlighting the morphological changes in the fault along the strike direction. Beneath the Shumagin Island, we identify a structural-mechanical boundary that separates the megathrust into Semidi (east) and Shumagin (west) two segments. Semidi is gentle and curved; while Shumagin is steep and planar. The Semidi segment produces spatially-heterogenous stress field, and generates partial, full, complex ruptures as indicated in modeled cycles and in historical seismic observations. Meanwhile the Shumagin segment, coincides with the ocean-continent transition boundary – the Beringian margin, tend to generate slow-slip-events, tremors, otherwise, generates small or moderate seismicity as indicated in the modeled cycles and in seismic records since 1750. Our findings indicate that Semidi is likely to rupture in a chaotic fashion with major or large earthquakes, resulting a greater tsunami hazard like the 1938 Mw 8.2 event. The tsunami potential in the Unimak segment may also remain high.

Abstract In nature, structural and functional materials often form programmed three-dimensional (3D) assembly to perform daily functions, inspiring researchers to engineer multifunctional 3D structures. Despite much progress, a general method to fabricate and assemble a broad range of materials into functional 3D objects remains limited. Herein, to bridge the gap, we demonstrate a freeform multimaterial assembly process (FMAP) by integrating 3D printing (fused filament fabrication (FFF), direct ink writing (DIW)) with freeform laser induction (FLI). 3D printing performs the 3D structural material assembly, while FLI fabricates the functional materials in predesigned 3D space by synergistic, programmed control. This paper showcases the versatility of FMAP in spatially fabricating various types of functional materials (metals, semiconductors) within 3D structures for applications in crossbar circuits for LED display, a strain sensor for multifunctional springs and haptic manipulators, a UV sensor, a 3D electromagnet as a magnetic encoder, capacitive sensors for human machine interface, and an integrated microfluidic reactor with a built-in Joule heater for nanomaterial synthesis. This success underscores the potential of FMAP to redefine 3D printing and FLI for programmed multimaterial assembly.

Abstract Background Osteonecrosis of the femoral head caused by glucocorticoids (GIONFH) is a significant issue resulting from prolonged or excessive clinical glucocorticoid use. Astaxanthin, an orange-red carotenoid present in marine organisms, has been the focus of this study to explore its impact and mechanism on osteoblast apoptosis induced by dexamethasone (Dex) and GIONFH. Methods In this experiment, bioinformatic prediction, molecular docking and dynamics simulation, cytotoxicity assay, osteogenic differentiation, qRT-PCR analysis, terminal uridine nickend labeling (TUNEL) assay, determination of intracellular ROS, mitochondrial function assay, immunofluorescence, GIONFH rat model construction, micro-computed tomography (micro-CT) scans were performed. Results Our research demonstrated that a low dose of astaxanthin was non-toxic to healthy osteoblasts and restored the osteogenic function of Dex-treated osteoblasts by reducing oxidative stress, mitochondrial dysfunction, and apoptosis. Furthermore, astaxanthin rescued the dysfunction in poor bone quality, bone metabolism and angiogenesis of GIONFH rats. The mechanism behind this involves astaxanthin counteracting Dex-induced osteogenic damage by activating the Nrf2 pathway. Conclusion Astaxanthin shields osteoblasts from glucocorticoid-induced oxidative stress and mitochondrial dysfunction via Nrf2 pathway activation, making it a potential therapeutic agent for GIONFH treatment.

Abstract Background Intracerebral hemorrhage (ICH) is a devastating neurological disease causing severe sensorimotor dysfunction and cognitive decline, yet there is no effective treatment strategy to alleviate outcomes of these patients. The Mas axis-mediated neuroprotection is involved in the pathology of various neurological diseases, however, the role of the Mas receptor in the setting of ICH remains to be elucidated. Methods C57BL/6 mice were used to establish the ICH model by injection of collagenase into mice striatum. The Mas receptor agonist AVE0991 was administered intranasally (0.9 mg/kg) after ICH. Using a combination of behavioral tests, Western blots, immunofluorescence staining, hematoma volume, brain edema, quantitative-PCR, TUNEL staining, Fluoro-Jade C staining, Nissl staining, and pharmacological methods, we examined the impact of intranasal application of AVE0991 on hematoma absorption and neurological outcomes following ICH and investigated the underlying mechanism. Results Mas receptor was found to be significantly expressed in activated microglia/macrophages, and the peak expression of Mas receptor in microglia/macrophages was observed at approximately 3–5 days, followed by a subsequent decline. Activation of Mas by AVE0991 post-treatment promoted hematoma absorption, reduced brain edema, and improved both short- and long-term neurological functions in ICH mice. Moreover, AVE0991 treatment effectively attenuated neuronal apoptosis, inhibited neutrophil infiltration, and reduced the release of inflammatory cytokines in perihematomal areas after ICH. Mechanistically, AVE0991 post-treatment significantly promoted the transformation of microglia/macrophages towards an anti-inflammatory, phagocytic, and reparative phenotype, and this functional phenotypic transition of microglia/macrophages by Mas activation was abolished by both Mas inhibitor A779 and Nrf2 inhibitor ML385. Furthermore, hematoma clearance and neuroprotective effects of AVE0991 treatment were reversed after microglia depletion in ICH. Conclusions Mas activation can promote hematoma absorption, ameliorate neurological deficits, alleviate neuron apoptosis, reduced neuroinflammation, and regulate the function and phenotype of microglia/macrophages via Akt/Nrf2 signaling pathway after ICH. Thus, intranasal application of Mas agonist ACE0991 may provide promising strategy for clinical treatment of ICH patients.

As a feed additive, Benzoic Acid (BA) has been demonstrated to significantly enhance feed conversion efficiency, regulate gastrointestinal pH, and improve overall animal health. Young animals, highly susceptible to S. Typhimurium infection, suffer from high mortality rates and substantial economic losses due to this pathogen. Despite promising indications of BA's immunomodulatory potential in boosting intestinal immunity, its underlying mechanisms remain insufficiently understood. This study investigates how BA strengthens intestinal anti-infection defenses in young animals via immunomodulatory pathways, focusing on its impact on macrophage polarization and IgA-mediated immune responses. Employing in vitro cell experiments and animal models, we examined the macrophage phenotypic alterations following BA treatment. We assessed the expression of immune-related genes in the intestine through immunofluorescence staining, Western blotting, and quantitative real-time PCR. The results demonstrate that BA promotes M2 macrophage polarization by activating the mTOR/PPAR-γ/STAT3 signaling pathways. Furthermore, BA enhances the intestinal expression of the polymeric immunoglobulin receptor (PIgR), B-cell activating factor (BAFF) from the TNF family, and activation-induced cytidine deaminase (AID), thereby enhancing IgA production by B-cells. These results underscore the potential of BA to bolster innate immune functions in young chickens, mitigate intestinal damage caused by S. Typhimurium infection, and ultimately promote both animal health and food safety.

Vehicle Routing Problem with Uncertain Demands (VRPUD) is one of the research hotspots in the field of logistics scheduling. In this paper, a Discrete Jaya (DJaya) algorithm is presented for the VRPUD to minimize the total cost. A novel dividing-point-based coding scheme is designed to represent solutions with higher robustness. In addition, an efficient repair strategy is embedded into the decoding process to avoid the failure of producing feasible solutions. The best and worst solutions are employed to generate offspring solutions in DJaya. Several efficient local search methods are also presented to enhance the exploitation ability and increase the diversity of solutions. Based on the benchmark data sets of the VRPUD, numerical simulations are carried out for the proposed DJaya algorithm with uncertain demands. Computational results and comparisons with the state-of-the-art algorithms demonstrate the superiority of the proposed algorithm in solving VRPUD.

Bone-related disorders, such as osteoporosis, osteoarthritis, and osteosarcoma, have complex origins. Genetic, environmental factors, and significantly, oxidative stress due to Reactive Oxygen Species (ROS) play pivotal roles in these disorders. With their profound implications on global health, it becomes imperative to seek innovative therapeutic solutions. Nanozymes, known for their superior stability, cost-effectiveness, and tunable properties, present themselves as a prospective answer in mitigating ROS-driven bone ailments. This review explores the diverse applications and mechanisms of nanozymes in the context of bone health. They show potential in not only counteracting ROS-induced oxidative stress but also in modulating angiogenesis and showcasing antibacterial effects. We systematically analyze the effects of nanozymes on conditions such as osteonecrosis of the femoral head, skin flap transplantation, osteomyelitis, osteoarthritis, intervertebral disc disease, osteoporosis, and osteosarcoma, highlighting their potential roles in modulating disease processes. In addition, we discuss the challenges of applying nanozymes to orthopedic diseases. It offers insights into the transformative potential of nanozymes in bone therapeutics, underscoring the need to address challenges and capitalize on opportunities for their broader application in orthopedics.

During deep geothermal resource development, the estimation of drilling efficiency and tool wear in extremely hard rocks relies primarily on CAI testing. However, the degradation of rocks caused by high-temperature water cooling conditions leads to unpredictable changes in CAI. To address this issue, this study conducted P-wave velocity, hardness, thermal conductivity testing, BTS experiments, CAI testing, and NMR testing on granite samples subjected to water cooling at different temperatures (25–600 °C). The study analyzed the degradation mechanisms of granites under high temperature-water cooling conditions, the relationship between various parameters and the CAI index, and established a dual-parameter fitting model. The results indicate that the degradation of rocks under hightemperature-water cooling conditions is primarily attributed to mineral thermal reactions, thermal expansion effects at high temperatures, and rapid cooling-induced thermal contraction effects. Once the degradation effects exceed the skeleton constraint limit, macroscopic cracks gradually form within the granite. The formation of macroscopic cracks has a mitigating effect on abrasivity. The research findings on the correlation between CAI and various parameters can provide important theoretical support for the application of high-temperature rock breaking engineering.

Antibiotics and sedatives are used in freshwater fish culture and transportation, and residue in freshwater fish pose potential risks to human health. Therefore, a throughput method was developed to detect antibiotic and sedative residues in fish, simultaneously quantifying 68 antibiotics and 9 sedatives in freshwater fish using a modified QuEChERS extraction method and UPLC-MS/MS. Matrix-matched calibrations demonstrated good correlation coefficients (R2 > 0.995), with a recovery range of 66.2–118.5%. The intra-day and inter-day relative standard deviation (RSD) were below 9.7% and 12.8%, respectively. The limits of detection (LOD) and quantification (LOQ) were 0.08–1.46 μg/kg and 0.25–4.86 μg/kg, respectively. 68.8% of analytes had weak matrix effects, and 13.0% had moderate matrix effects. In addition, diazepam and many types of antibiotics were detected in30 freshwater fish. The validation parameters were in agreement with the acceptable criteria of the Codex guidelines. The method was effective in analyzing antibiotic and sedative residues in freshwater fish.

Acute spontaneous subdural hematoma (SDH) of arterial origin is rare in the field of neurosurgery. We report a 57-year-old male patient developed sudden onset headache and right hemiparesis. He had no history of head trauma.A computed tomography demonstrated an acute left-sided SDH. A computed tomography angiogram (CTA) demonstrated active contrast extravasation from a small cortical middle cerebral artery (MCA) branch into the left-sided SDH. Endoscopic surgery was performed to evacuate the hematoma,we verified the arterial origin of the bleeding and coagulated the bleeding point. Postoperatively the patient’s symptoms clearly improved. He was discharged 7 days after surgery. In a case of acute spontaneous SDH, the possibility of a cortical artery origin should be considered, The initial radiologic investigation in a patient with a spontaneous acute SDH should be a CT and CTA. Endoscopic hematoma evacuation of acute spontaneous SDH may be a safe and effective method in some cases.

Single-pixel imaging is an advanced computational imaging technique based on compressive sensing that offers higher signal-to-noise ratio and broader application scope compared to traditional imaging techniques. However, conventional reconstruction algorithms suffer from issues such as long processing time and low reconstruction accuracy during the sampling and reconstruction processes. Deep learning-based compressed reconstruction networks can circumvent the complex iterative computations of traditional algorithms and achieve fast, high-quality reconstruction. In this paper, we propose a Variational Multi-Scale Error Compensation Network (VMSE) based on variational autoencoders. VMSE designs an error compensation network to enhance the feature representation capability of the sampling reconstruction network. We employ multiple latent variables to generate error features at different scales in the intermediate layers of the error compensation network, compensating the reconstructed image. Additionally, we design a module that simultaneously learns in the spatial and frequency domains, which is used for upsampling and complementing the missing high-frequency information in the frequency domain. On the MNIST dataset, when the sampling rate is 0.025, VMSE achieved higher Peak Signal-to-Noise Ratio(PSNR) and Structural Similarity Index(SSIM) scores, especially with an SSIM score of 0.963, significantly surpassing Reconnet and DR2Net's scores of 0.930 and 0.920, respectively. This was further corroborated by practical experiments, where at low sampling rates, VMSE could reconstruct outlines more clearly compared to TVAL3.

Abstract The liver is essential for metabolic homeostasis. The onset of liver cancer is often accompanied by dysregulated liver function, leading to metabolic rearrangements. Overwhelming evidence has illustrated that dysregulated cellular metabolism can, in turn, promote anabolic growth and tumor propagation in a hostile microenvironment. In addition to supporting continuous tumor growth and survival, disrupted metabolic process also creates obstacles for the anticancer immune response and restrains durable clinical remission following immunotherapy. In this review, we elucidate the metabolic communication between liver cancer cells and their surrounding immune cells and discuss how metabolic reprogramming of liver cancer impacts the immune microenvironment and the efficacy of anticancer immunotherapy. We also describe the crucial role of the gut–liver axis in remodeling the metabolic crosstalk of immune surveillance and escape, highlighting novel therapeutic opportunities.

Aimed at the new application scenario of laser, a test platform was established to study the coating material da-mage features induced by the interaction of the Ma=6 tangential air flow and the continuous laser irradiation. The laser-damaged characteristics of the coating materials in still air and Ma=6 ground-simulated airflows, as well as the corresponding interference flow structures, were presented. Compared with the laser-irradiation ablation phenomenon of the coating materials in still air, the laser-induced damage characteristics of coating materials are significantly different in hypersonic tangential airflows. Under the interaction of hypersonic airflows, the coating materials show a larger damage area when the laser power is low, while the coating materials form deeper ablation pits when the laser power is high. Due to the disturbance from the material ablation, flow patterns similar to those produced by a thermal jet or small protrusion are formed around the ablative structure of coating materials. This phenomenon, in turn, affects the ablation of coating materials, producing a strong coupling phenomenon between hypersonic flow and laser ablation. The results can provide important guidance for engineering applications.

Aiming at the effects of motor parameter ingress and load mutation on the speed control of permanent magnet synchronous linear motor (PMSLM) motors, this paper designs a PMSLM improved model-free sliding-mode speed control strategy based on the variable-gain model-assisted linear expansion observer (TMLESO). First, time-varying gain-based model-assisted linear expansion observer (MLESO) is designed to improve the accuracy of LESO generalized perturbation estimation. Next, the TMLESO is constructed by combining the MLESO and the time-varying function to solve the problem of large initial peaks. Finally, a model-free sliding-mode velocity controller with adaptable boundary layer thickness is constructed to reduce the effect of sliding-mode jitter on velocity tracking and improve the dynamic performance of the system. The effectiveness of the proposed control strategy is analyzed through simulations and experiments.

Abstract Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive cartilage degradation and inflammation. In recent years, mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) have attracted widespread attention for their potential role in modulating OA pathology. However, the unpredictable therapeutic effects of exosomes have been a significant barrier to their extensive clinical application. In this study, we investigated whether fucoidan-pretreated MSC-derived exosomes (F-MSCs-Exo) could better protect chondrocytes in osteoarthritic joints and elucidate its underlying mechanisms. In order to evaluate the role of F-MSCs-Exo in osteoarthritis, both in vitro and in vivo studies were conducted. MiRNA sequencing was employed to analyze MSCs-Exo and F-MSCs-Exo, enabling the identification of differentially expressed genes and the exploration of the underlying mechanisms behind the protective effects of F-MSCs-Exo in osteoarthritis. Compared to MSCs-Exo, F-MSCs-Exo demonstrated superior effectiveness in inhibiting inflammatory responses and extracellular matrix degradation in rat chondrocytes. Moreover, F-MSCs-Exo exhibited enhanced activation of autophagy in chondrocytes. MiRNA sequencing of both MSCs-Exo and F-MSCs-Exo revealed that miR-146b-5p emerged as a promising candidate mediator for the chondroprotective function of F-MSCs-Exo, with TRAF6 identified as its downstream target. In conclusion, our research results demonstrate that miR-146b-5p encapsulated in F-MSCs-Exo effectively inhibits TRAF6 activation, thereby suppressing inflammatory responses and extracellular matrix degradation, while promoting chondrocyte autophagy for the protection of osteoarthritic cartilage cells. Consequently, the development of a therapeutic approach combining fucoidan with MSC-derived exosomes provides a promising strategy for the clinical treatment of osteoarthritis.

ADSCs are a large number of mesenchymal stem cells in Adipose tissue, which can be applied to tissue engineering. ADSCs have the potential of multi-directional differentiation, and can differentiate into bone tissue, cardiac tissue, urothelial cells, skin tissue, etc. Compared with other mesenchymal stem cells, ADSCs have a multitude of promising advantages, such as abundant number, accessibility in cell culture, stable function, and less immune rejection. There are two main methods to use ADSCs for tissue repair and regeneration. One is to implant the “ADSCs-scaffold composite” into the injured site to promote tissue regeneration. The other is cell-free therapy: using ADSC-exos or ADSC-CM alone to release a large number of miRNAs, cytokines and other bioactive substances to promote tissue regeneration. The tissue regeneration potential of ADSCs is regulated by a variety of cytokines, signaling molecules, and external environment. The differentiation of ADSCs into different tissues is also induced by growth factors, ions, hormones, scaffold materials, physical stimulation, and other factors. The specific mechanisms are complex, and most of the signaling pathways need to be further explored. This article reviews and summarizes the mechanism and clinical application of ADSCs in tissue injury repair so far, and puts forward further problems that need to be solved in this field, hoping to provide directions for further research in this field.

Infrared multi-band small and dim target detection is an important research direction in the fields of modern remote sensing and military surveillance. However, achieving high-precision detection remains challenging due to the small scale, low contrast of small and dim targets, and their susceptibility to complex background interference. This paper innovatively proposes a dual-band infrared small and dim target detection method (MM-IRSTD). In this framework, we integrate a convolutional self-attention mechanism module and a self-distillation mechanism to achieve end-to-end dual-band infrared small and dim target detection. The Conv-Based Self-Attention module consists of a convolutional self-attention mechanism and a multilayer perceptron, effectively extracting and integrating input features, thereby enhancing the performance and expressive capability of the model. Additionally, this module incorporates a dynamic weight mechanism to achieve adaptive feature fusion, significantly reducing computational complexity and enhancing the model’s global perception capability. During model training, we use a spatial and channel similarity self-distillation mechanism to drive model updates, addressing the similarity discrepancy between long-wave and mid-wave image features extracted through deep learning, thus improving the model’s performance and generalization capability. Furthermore, to better learn and detect edge features in images, this paper designs an edge extraction method based on Sobel. Finally, comparative experiments and ablation studies validate the advancement and effectiveness of our proposed method.

This paper addresses performance degradation in nonlinear flux linkage algorithms, arising from estimation errors in rotor flux linkage due to fluctuations in current and temperature. We introduce a parameter-adaptive flux linkage model using MRAS, which dynamically adjusts the rotor flux linkage, significantly minimizing estimation errors and improving control performance. When the rotor flux linkage of the motor undergoes sudden changes, the nonlinear flux linkage model shows a speed fluctuation of 5%, whereas the parameter-adaptive flux linkage model reduces the error to 0.6%. The algorithm demonstrates strong robustness when the stator resistance undergoes a sudden change. The control effectiveness under conditions such as load start and load mutation is excellent. Simulations and experiments demonstrate that the parameter-adaptive flux linkage model improves the estimation accuracy of the rotor position when motor parameters change.

Background: Anti-tumor necrosis factor (TNF) monoclonal antibodies, especially infliximab (IFX) and adalimumab (ADA), are considered the first-line treatment for active Crohn’s disease (CD). However, the predictive role of therapeutic drug monitoring (TDM) of serum anti-TNF in monitoring the treatment of inflammatory bowel disease (IBD) remains controversial. Objectives: To explore the correlation between serum anti-TNF levels and early endoscopic response in active CD using a TDM-based nomogram. Design: Cross-sectional study. Methods: The simplified endoscopic activity score for CD (SES-CD), Crohn’s disease activity index (CDAI), laboratory parameters, and the serum trough levels of IFX and ADA were assessed. Results: The trough levels of IFX or ADA were significantly higher in patients with endoscopic response compared to non-responders in the development cohort ( p

Understanding the variation of rock permeability with temperature and confining pressure is the foundation for projects such as high-level radioactive waste disposal, deep geothermal exploitation, and carbon dioxide storage. This paper presents an experimental study of the permeability evolution of thermally damaged Beishan granite under effective stress. The results show that temperature has a significant impact on the permeability of granite, and there is an obvious threshold temperature (400–500 °C), initial permeability and permeability change rate increased gradually with temperature. The permeability of Beishan granite shows non-linear decreasing trend with the increase of effective stress, ultimately tending towards stability. The microstructure of granite after thermal damage can be observed by scanning electron microscopy and used to assist in explaining the microscopic mechanism of permeability changes. A new granite permeability prediction model is proposed, which integrates permeability with temperature and effective stress, providing an important reference for the safety of high-level radioactive waste disposal.

Abstract Phycobiliproteins (PBPs), one of the functional proteins from algae, are natural pigment–protein complex containing various amino acids and phycobilins. It has various activities, such as anti-inflammatory and antioxidant properties. And are potential for applications in food, cosmetics, and biomedicine. Improving their metabolic yield is of great interest. Microalgaes are one of the important sources of PBPs, with high growth rate and have the potential for large-scale production. The key to large-scale PBPs production depends on accumulation and recovery of massive productive alga in the upstream stage and the efficiency of microalgae cells breakup and extract PBPs in the downstream stage. Therefore, we reviewed the status quo in the research and development of PBPs production, summarized the advances in each stage and the feasibility of scaled-up production, and demonstrated challenges and future directions in this field.

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is a type of hematologic tumor with malignant proliferation of hematopoietic progenitor cells. However, traditional clinical treatment of T-ALL included chemotherapy and stem cell transplantation always lead to recurrence and poor prognosis, thus new therapeutic targets and drugs are urgently needed for T-ALL treatment. In this study, we showed that TET1 (ten-eleven translocation 1), a key participant of DNA epigenetic control, which catalyzes the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) to modulate gene expression, was highly upregulated in human T-ALL and negatively correlated with the prognosis of patients. Knockdown of TET1 suppressed T-ALL growth and progression, suggesting that TET1 inhibition maybe an effective way to fight T-ALL via DNA epigenetic modulation. Combining structure-guided virtual screening and cell-based high-throughput screening of FDA-approved drug library, we discovered that auranofin, a gold-containing compound, is a potent TET1 inhibitor. Auranofin inhibited the catalytic activity of TET1 through competitive binding to its substrates binding pocket and thus downregulated the genomic level of 5hmC marks and particularly epigenetically reprogramed the expression of oncogene c-Myc in T-ALL in TET1-dependent manner and resulted in suppression of T-ALL in vitro and in vivo. These results revealed that TET1 is a potential therapeutic target in human T-ALL and elucidated the mechanism that TET1 inhibitor auranofin suppressed T-ALL through the TET1/5hmC/c-Myc signaling pathway. Our work thus not only provided mechanism insights for T-ALL treatment, but also discovered potential small molecule therapeutics for T-ALL.

Pressure resistance welding is usually used to seal the connection between the cladding tube and the end plug made of zirconium alloy. The seal welded joint has a direct effect on the service performance of the fuel rod cladding structure. In this paper, the pressure resistance welded joints of zirconium alloy tube-plug structure were obtained by thermal-mechanical simulation experiments. The microstructure and microhardness of the joints were both analyzed. The effect of processing parameters on the microstructure was studied in detail. The results showed that there was no β-Zr phase observed in the joint, and no obvious element segregation. There were different types of Widmanstätten structure in the thermo-mechanically affected zone (TMAZ) and heat affected zone (HAZ) of the cladding tube and the end plug joint because of the low cooling rate. Some part of the grains in the joint grew up due to overheating. Its size was about 2.8 times that of the base metal grains. Due to the high dislocation density and texture evolution, the microhardnesses of TMAZ and HAZ were both significantly higher than that of the base metal, and the microhardness of the TMAZ was the highest. With the increasing of welding temperature, the proportion of recrystallization in TMAZ decreased, which was caused by the increasing of strain rate and dislocation annihilation.

Purpose: This study assesses the efficacy and safety of self-expandable (SE) versus balloon-expandable (BE) stent grafts for managing visceral artery aneurysms (VAAs), focusing on procedural success and complication rates. Materials and Methods: We conducted a retrospective analysis of VAA patients treated at our institution from April 2006 to September 2021. The study reviewed patient demographics, aneurysm characteristics, treatment details, and outcomes, including endoleaks. Results: Among the 23 patients analyzed, splenic artery aneurysms represented 44% of cases. Fifteen patients were treated with balloon-expandable stent grafts (BE SGs), and eight patients were treated with self-expandable stent grafts (SE SGs). For saccular aneurysms, the average neck size was 10.10 ± 8.70 mm in the BE group versus 18.50 ± 3.40 mm in the SE group (p = 0.23), with an average sac size of 20.10 ± 18.9 mm in the BE group versus 15.60 ± 12.7 mm in the SE group (p = 0.16). The average sac-to-neck ratio was 1.69 ± 2.23 in the BE group versus 1.38 ± 0.33 in the SE group (p = 0.63). The BE group exhibited a significantly higher endoleak rate (60%) compared to the SE group (12.5%; p = 0.03). Conclusions: While further investigation is needed to fully assess the outcomes of stent graft treatment for VAAs, initial data show a significantly higher endoleak rate with BE SGs compared to SE SGs. The SE SGs may offer better outcomes due to their superior ability to conform to tortuous and mobile visceral arteries.

This is an essay in the field of mining engineering. Panzhihua is the largest vanadium-titanium magnetite resource base in China. With the development and utilization of vanadium titanium resources, a large number of tailings have been produced, which not only occupies a lot of lands but also useful ingredients are not fully utilized, resulting in resource waste. At the same time, there are certain safety and environmental risks. This paper selects 22 representative tailings ponds in the Panzhihua area to conduct systematic research on tailings resource potential, valuable element occurrence characteristics, availability, and economic value. Analysis shows that Panzhihua tailings contain a large number of valuable components and have a huge potential resource. The amount of iron metallicity is 52 million tons, with an average grade of 10.87%, titanium metallicity is 29.07 million tons, with an average grade of 6.08%, rare earth metallicity is 130300 tons, with an average grade of 272 g/t, cobalt metallicity is 42300 tons, with an average grade of 88 g/t, scandium metallicity is 122100 tons, with an average grade of 26 g/t, and the Phosphorus pentoxide is 2.49 million tons, with an average grade of 0.52%. There are two main directions for the multipurpose utilization of mineral tailings resources. One is secondary development and utilization, with advanced recovery and utilization of valuable elements such as iron, titanium, sulfur, cobalt, and phosphorus. The second is overall utilization, which is based on secondary recycling and appropriate allocation for the production of insulation building materials, cement, ceramics, glass, refractory materials, soil amendments, concrete, and construction sand. To achieve the overall utilization of tailings and ultimately solve the problems of tailings resource utilization, reduction, and harmless treatment.

This is an essay in the field of mineral processing engineering. Extraction of the vanadium titano-magnetite ore deposits in the Panxi Region, the biggest vanadium titano-magnetite mineral resource base, results in the production of a significant volume of tailings. The tailings have a high recovery potential of the strategic mineral resources (eg.,Vi, Ti, Fe, Co, Cu, Ni, P, and Sc). Based on the process mineralogy study, we determine the comprehensive utilization technology flowsheet and conduct a systematic recovery test of tailing samples from the Hongge mine in the Panxi Region. By the process of (1) flotation of sulfur, (2) low-intensity magnetic separation of iron, (3) high-intensity magnetic separation and flotation of titanium, (4) flotation of Phosphorous, we obtain the sulfur-cobalt concentrate (Co 0.175%), the iron concentrate (TFe 56.57%), the titanium concentrate (TiO2 45.97%) and phosphorous concentrate (P2O5 31.73%). These results show that the systematic recovery test of tailings can reduce the production of a volume of tailings with significant economic and social benefits.

Objective Distal clavicle fracture classification directly affects the treatment decisions. It is unclear whether the classification systems implemented differ depending on surgeons' backgrounds. This study aimed to compare the interobserver agreement of four classification systems used for lateral clavicle fractures by shoulder specialists and general trauma surgeons. Methods Radiographs of 20 lateral clavicle fractures representing a full spectrum of adult fracture patterns were analyzed by eight experienced shoulder specialists and eight general trauma surgeons from 10 different hospitals. All cases were graded according to the Orthopedic Trauma Association (OTA), Neer, Jäger/Breitner, and Gongji classification systems. To measure observer agreement, Fleiss' kappa coefficient (κ) was applied and assessed. Results When only X‐ray films were presented, both groups achieved fair agreement. However, when the 3D‐CT scan images were provided, improved interobserver agreement was found in the specialist group when the OTA, Jäger/Breitner, and Gongji classification systems were used. In the generalist groups, improved agreement was found when using the Gongji classification system. In terms of interobserver reliability, the OTA, Neer, and Jäger/Breitner classification systems showed better agreement among shoulder specialists, while a slightly lower level of agreement was found using the Gongji classification system. For the OTA classification system, interobserver agreement had a mean kappa value of 0.418, ranging from 0.446 (specialist group) to 0.402 (generalist group). For the Neer classification system, interobserver agreement had a mean kappa value of 0.368, ranging from 0.402 (specialist group) to 0.390 (generalist group). For the Jäger/Breitner classification system, the inter‐observer agreement had a mean kappa value of 0.380, ranging from 0.413 (specialist group) to 0.404 (generalist group). For the Gongji classification system, interobserver agreement had a mean kappa value of 0.455, ranging from 0.480 (specialist group) to 0.485 (generalist group). Conclusion Generally speaking, 3D‐CT scans provide a richer experience that can lead to better results in most classification systems of lateral clavicle fractures, highlighting the value of digitization and specialization in diagnosis and treatment. Competitive interobserver agreement was exhibited in the generalist group using the Gongji classification system, suggesting that the Gongji classification is suitable for general trauma surgeons who are not highly experienced in the shoulder field.

Abstract Impaired angiogenesis is one of the predominant reasons for non-healing diabetic wounds. Cobalt is well known for its capacity to induce angiogenesis by stabilizing hypoxia-inducible factor-1α (HIF-1α) and subsequently inducing the production of vascular endothelial growth factor (VEGF). In this study, Co-containing borate bioactive glasses and their derived fibers were fabricated by partially replacing CaO in 1393B3 borate glass with CoO. Fourier transform infrared (FTIR) spectroscopy and nuclear magnetic resonance (NMR) analyses were performed to characterize the effect of Co incorporation on the glass structure, and the results showed that the substitution promoted the transformation of [BO3] into [BO4] units, which endow the glass with higher chemical durability and lower reaction rate with the simulated body fluid (SBF), thereby achieving sustained and controlled Co2+ ion release. In vitro biological assays were performed to assess the angiogenic potential of the Co-containing borate glass fibers. It was found that the released Co2+ ion significantly enhanced the proliferation, migration and tube formation of the Human Umbilical Vein Endothelial Cells (HUVECs) by upregulating the expression of angiogenesis-related proteins such as HIF-1α and VEGF. Finally. In vivo results demonstrated that the Co-containing fibers accelerated full-thickness skin wound healing in streptozotocin (STZ)-induced diabetic rat model by promoting angiogenesis and re-epithelialization. Graphical Abstract

The Zhangheng-1 electromagnetic satellite is the space-based observation platform of China's stereoscopic earthquake observation system. Its scientific objective is to obtain the global geomagnetic field, electromagnetic field (waves), ionospheric plasma parameters, and high-energy particles for monitoring the dynamic variation of the ionosphere and the seismo-ionospheric disturbances over China and its surrounding areas to compensate for the deficiency of the ground-based observation system. The project explores new ways of earthquake monitoring and prediction by using space science. The first test probe of the Zhangheng-1 electromagnetic satellite series was successfully launched in February 2018, and has been stably operating in orbit for more than four years. The second is an operational probe that will be launched in early 2023. The in-flight commissioning test and cross-calibration work show that the Zhangheng-1 electromagnetic satellite can provide good data quality to support geophysics and space physics studies, and has obtained valuable scientific results in recent years. The global geomagnetic reference model built by Zhenghang-1 data is the first global geomagnetic field model built using only Chinese satellite data, allowing Chinese scientists to take an important role in the computation of the global geomagnetic reference model (IGRF) for the first time in over a century. The ionospheric electron density 3D model based on Zhangheng-1 satellite data can present the ionospheric structure characteristics. In natural hazards monitoring, Zhangheng-1 has shown good response ability to disturbances related to earthquakes, volcano eruptions, and geomagnetic storms. In terms of the lithosphere-atmosphere-ionosphere coupling mechanism study, the full-wave calculation method can provide the electromagnetic field changes between the lithosphere-ionosphere waveguide and the ionospheric wave propagation feature. The results from the full-wave model prove the capability of the Zhangheng-1 satellite's electromagnetic payloads to detect low-frequency electromagnetic emissions induced from the earthquake epicenter. The simulation and observation studies suggest that the Zhangheng-1 satellite can reflect seismic activities, very low frequency (VLF) transmitter, magnetic anomalies in the lithosphere, and lightning activities in the atmosphere. These recent scientific results show that the Zhangheng-1 electromagnetic satellite is consistent with other similar types of electromagnetic satellites worldwide, indicating its great potential in scientific application.

Objective The use of minimally invasive endoluminal treatment for urethral strictures has been a subject for debate for several decades. The aim of this study was to review and discuss the safety, efficacy and factors influencing the clinical application of balloon dilation for the treatment of male urethral strictures.Design Systematic review and meta-analysis.Data sources Embase, Medline, Web of Science, Cochrane Library and Scopus were searched for publications published before 17 July 2022.Study selection Two independent researchers screened and assessed the results, and all clinical studies on balloon dilation for the treatment of urethral strictures in men were included.Data extraction and synthesis The success rate, rate of adverse events, International Prostate Symptom Scores, maximum uroflow (Qmax) and postvoid residual urine volume were the main outcomes. Stata V.14.0 was used for statistical analysis.Results Fifteen studies with 715 patients were ultimately included in this systematic review. The pooled results of eight studies showed that the reported success rate of simple balloon dilation for male urethral strictures was 67.07% (95% confidence interval [CI]: 55.92% to 77.36%). The maximum urinary flow rate at 3 months (risk ratio [RR]= 2.6510, 95% CI: 1.0681 to 4.2338, p

Abstract Crystalline organic–inorganic hybrids, which exhibit colorimetric responses to ionizing radiation, have recently been recognized as promising alternatives to conventional X‐ray dosimeters. However, X‐ray‐responsive organic–inorganic hybrids are scarce and the strategy to fine‐tune their detection sensitivity remains elusive. Herein, an unprecedented mixed‐ligand strategy is reported to modulate the X‐ray detection efficacy of organic–inorganic hybrids. Deliberately blending the stimuli‐responsive terpyridine carboxylate ligand (tpc−) and the auxiliary pba− group with different ratios gives rise to two OD thorium‐bearing clusters (Th‐102 and Th‐103) and a 1D coordination polymer (Th‐104). Notably, distinct X‐ray sensitivity is evident as a function of molar ratio of the tpc− ligand, following the trend of Th‐102 > Th‐103 > Th‐104. Moreover, Th‐102, which is exclusively built from the tpc− ligands with the highest degree of π–π interactions, exhibits the most sensitive radiochromic and fluorochromic responses toward X‐ray with the lowest detection limit of 1.5 mGy. The study anticipates that this mixed‐ligand strategy will be a versatile approach to tune the X‐ray sensing efficacy of organic–inorganic hybrids.

Abstract PF‐06835919, a ketohexokinase inhibitor, presented as an inducer of cytochrome P450 3A4 (CYP3A4) in vitro (human primary hepatocytes), and static mechanistic modeling exercises predicted significant induction in vivo (oral midazolam area under the plasma concentration‐time curve [AUC] ratio [AUCR] = 0.23–0.79). Therefore, a drug–drug interaction study was conducted to evaluate the effect of multiple doses of PF‐06835919 (300 mg once daily × 10 days; N = 10 healthy participants) on the pharmacokinetics of a single oral midazolam 7.5 mg dose. The adjusted geometric means for midazolam AUC and its maximal plasma concentration were similar following co‐administration with PF‐06835919 (vs. midazolam administration alone), with ratios of the adjusted geometric means (90% confidence interval [CI]) of 97.6% (90% CI: 79.9%–119%) and 98.9% (90% CI: 76.4%–128%), respectively, suggesting there was minimal effect of PF‐06835919 on midazolam pharmacokinetics. Lack of CYP3A4 induction was confirmed after the preparation of subject plasma‐derived small extracellular vesicles (sEVs) and conducting proteomic and activity (midazolam 1′‐hydroxylase) analysis. Consistent with the midazolam AUCR observed, the CYP3A4 protein expression fold‐induction (geometric mean, 90% CI) was low in liver (0.9, 90% CI: 0.7–1.2) and non‐liver (0.9, 90% CI: 0.7‐1.2) sEVs (predicted AUCR = 1.0, 90% CI: 0.9–1.2). Likewise, minimal induction of CYP3A4 activity (geometric mean, 90% CI) in both liver (1.1, 90% CI: 0.9–1.3) and non‐liver (0.9, 90% CI: 0.5‐1.5) sEVs was evident (predicted AUCR = 0.9, 90% CI: 0.6‐1.4). The results showcase the integrated use of an oral CYP3A probe (midazolam) and plasma‐derived sEVs to assess a drug candidate as inducer.

Robots play a critical role as the physical agent of human operators in exploring the ocean. However, it remains challenging to grasp objects reliably while fully submerging under a highly pressurized aquatic environment with little visible light, mainly due to the fluidic interference on the tactile mechanics between the finger and object surfaces. This study investigates the transferability of grasping knowledge from on‐land to underwater via a vision‐based soft robotic finger that learns 6D forces and torques (FT) using a supervised variational autoencoder (SVAE). A high‐framerate camera captures the whole‐body deformations while a soft robotic finger interacts with physical objects on‐land and underwater. Results show that the trained SVAE model learns a series of latent representations of the soft mechanics transferable from land to water, presenting a superior adaptation to the changing environments against commercial FT sensors. Soft, delicate, and reactive grasping enabled by tactile intelligence enhances the gripper's underwater interaction with improved reliability and robustness at a much‐reduced cost, paving the path for learning‐based intelligent grasping to support fundamental scientific discoveries in environmental and ocean research.