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This is an article in the field of metallurgical engineering. For the vanadium precipitation waste liquid of a waste catalyst in a zinc smelter in Shaanxi, the vanadium in the vanadium precipitation waste liquid was recovered by solvent extraction method. The effects of N235 volume fraction, extraction ratio, extraction time and extraction stage on the vanadium extraction rate were investigated. The results showed that the extraction system with 30%N235+5%TBP+65% sulfonated kerosene was used for four-stage countercurrent extraction, the extraction ratio of VO/VA= 2∶1, the extraction time was t=5 min, and the extraction rate of vanadium was 95.68%. The volume fraction of Na2CO3 was 5%, the extraction ratio of V'o/V'A =4∶1, the extraction time was t=4 min, and the extraction rate of vanadium was 98.25% after three-stage counter-current extraction.

Abstract The roadway space of coal mine is narrow, and the illumination is low and uneven. Dynamic mining is accompanied by dust and water mist. The accuracy and reliability of roadway data collected by vision and laser sensors are poor. Based on this, a digital modeling method of coal mine roadway based on millimeter-wave radar array is proposed. Firstly, aiming at the problem of complex environmental interference, combined with the characteristics of small amount of single frame data of millimeter-wave point cloud, a multi-layer filtering noise reduction processing and dynamic subgraph registration method of millimeter-wave point cloud is proposed to filter out interference points and realize single radar point cloud registration. Secondly, aiming at the problem that a single millimeter-wave radar cannot scan the complete roadway information at one time, combined with the characteristics of small elevation field of view of millimeter-wave radar, a millimeter-wave radar array acquisition system is built, and an improved iterative closest point (ICP) registration algorithm based on point cloud features is established to construct the roadway point cloud fusion model. Finally, aiming at the problem of uneven and sparse point cloud after array fusion, a Poisson surface reconstruction method based on point cloud density weighted interpolation is proposed to refine the roadway structure and realize the accurate reconstruction of digital roadway model. The experimental results show that the digital modeling method of millimeter-wave radar array can accurately obtain the information of roadway surrounding rock, the density of roadway point cloud is increased by 22.4%, and the average absolute error percentage of the width and height of the reconstructed roadway model is only 0.82% and 0.72%, which provides a new research method for the reconstruction of underground roadway and an important basis for the digital modeling method of coal mine roadway.

AbstractChinese herbs contain substances that regulate female hormones. Our study confirmed that Zingiberis rhizoma carbonisata contains Zingiberis rhizoma-based carbon dots (ZR-CDs), which exert regulatory effects on serum oestradiol and FSH in mice and show impacts on endometrial growth and follicular development that potentially affect the ability of female fertility. ZR-CDs were characterized to clarify the microstructure, optical features, and functional group characteristics. It shows that ZR-CDs are spherical carbon nanostructures ranging from 0.97 to 2.3 nm in diameter, with fluorescent properties and a surface rich in functional groups. We further investigated the impact of ZR-CDs on oestradiol and FSH in serum, growth, and the development of ovarian and uterine using normal female mice and exogenous oestradiol intervention model. It was observed that ZR-CDs accelerated oestrogen metabolism and attenuated oestradiol-induced endometrial hyperplasia. Simultaneously, ZR-CDs triggered an increase in FSH, even in the presence of high-serum oestradiol that inhibits FSH secretion. Our findings suggest that ZR-CDs could be a potential therapeutic treatment for anovulatory menstruation.

Motivated by the promising benefits of connected and autonomous vehicles (CAVs) in improving fuel efficiency, mitigating congestion, and enhancing safety, numerous theoretical models have been proposed to plan CAV multiple-step trajectories (time–specific speed/location trajectories) to accomplish various operations. However, limited efforts have been made to develop proper trajectory control techniques to regulate vehicle movements to follow multiple-step trajectories and test the performance of theoretical trajectory planning models with field experiments. Without an effective control method, the benefits of theoretical models for CAV trajectory planning can be difficult to harvest. This study proposes an online learning-based model predictive vehicle trajectory control structure to follow time–specific speed and location profiles. Unlike single-step controllers that are dominantly used in the literature, a multiple-step model predictive controller is adopted to control the vehicle’s longitudinal movements for higher accuracy. The model predictive controller output (speed) cannot be interpreted by vehicles. A reinforcement learning agent is used to convert the speed value to the vehicle’s direct control variable (i.e., throttle/brake). The reinforcement learning agent captures real-time changes in the operating environment. This is valuable in saving parameter calibration resources and improving trajectory control accuracy. A line tracking controller keeps vehicles on track. The proposed control structure is tested using reduced-scale robot cars. The adaptivity of the proposed control structure is demonstrated by changing the vehicle load. Then, experiments on two fundamental CAV platoon operations (i.e., platooning and split) show the effectiveness of the proposed trajectory control structure in regulating robot movements to follow time–specific reference trajectories.

Abstract Resin grout is widely used in geotechnical and underground engineering, and is often affected by different mine water solutions. This study considered the effects of different mine water solutions and soaking times on resin grout. Soaking tests and uniaxial compression tests were conducted to investigate the changes in the solution pH, relative specimen mass, and uniaxial compressive strength (UCS), and the deterioration of the resin grout’s mechanical properties caused by the mine water solution was analyzed. The corrosion mechanism of resin grout under the action of different mine water solutions was investigated through scanning electron microscopy tests. The results reveal that the pH value of the solution and the relative mass of the specimen gradually stabilized as the soaking time was extended, and the final solution was weakly alkaline. The increase in the acidity and alkalinity of the solution and the extension of the soaking time led to a gradual decrease in the UCS and elastic modulus of resin grout under the action of mine water. As the soaking was prolonged, the resin grout properties deteriorated to different degrees and Poisson’s ratio increased. Moreover, owing to the different types and degrees of mine water action on resin grout in different mine water environments, the changes in the resin grout microstructure were also different. The defined damage parameters can express the damage process of the resin grout’s UCS quantitatively under the action of mine water solution. Finally, beneficial engineering application countermeasures are proposed for different resin grout types used in roadway support applications in coal mines.

Abstract High sensitivity detection plays a vital role in science discoveries and technological applications. While intriguing methods utilizing collective many-body correlations and quantum entanglements have been developed in physics to enhance sensitivity, their practical implementation remains challenging due to rigorous technological requirements. Here, we propose an entirely data-driven approach that harnesses the capabilities of machine learning, to significantly augment weak-signal detection sensitivity. In an atomic force sensor, our method combines a digital replica of force-free data with anomaly detection technique, devoid of any prior knowledge about the physical system or assumptions regarding the sensing process. Our findings demonstrate a significant advancement in sensitivity, achieving an order of magnitude improvement over conventional protocols in detecting a weak force of approximately 10−25N. The resulting sensitivity reaches $$1.7(4)\times 1{0}^{-25}\,{{{{{{{\rm{N}}}}}}}}/\sqrt{{{{{{{{\rm{Hz}}}}}}}}}$$ 1.7 ( 4 ) × 1 0 − 25 N / Hz . Our machine learning-based signal processing approach does not rely on system-specific details or processed signals, rendering it highly applicable to sensing technologies across various domains.

Since 2020, with in-depth research on the Shuangji structural belt in the Jimsar Depression, Junggar Basin and high-yield oil flow data obtained from the Triassic Jingjingzigou Formation in the Well Satan 1, it has been demonstrated that the Jimsar and Jinan depressions have promising potential for conventional oil and gas exploration. Objective To further study the geological characteristics and exploration potential of the Jimsar and Jinan depressions, Methods this paper comprehensively analyses data from core samples, logging, well logging, and seismic surveys; identifies regional unconformities; categorizes different tectonic stages; and establishes the correlation between tectonic and stratigraphic evolution. Based on this, the development process of each stratum is restored, and the coupling relationship between tectonics and the evolution of uplift and depression within the research area is established, and the prototype basin is restored. Results This study revealed five large unconformities in the Jimsar and Jinan depressions, which have undergone four episodes of tectonic activity. The stratigraphic evolution characteristics of the study area ranged from "north high and south low" in the Early Permian to "south high and north low" in the Palaeogene and Neogene. The original basin also changed from a "multiconvex and multiconcave" pattern in the Early Permian to a "few convex and large concave" structural pattern in the Palaeogene and Neogene. Conclusion The establishment of the coupling relationship between tectonics and the evolution of uplift and depression at different times and the restoration of the prototype basin during each period lays an important foundation for clarifying the basin characteristics of the Jimsar and Jinan depressions during different periods and helps to enhances oil and gas exploration in these areas.

Abstract The (re)hemorrhage in patients with sporadic cerebral cavernous malformations (CCM) was the primary aim for CCM management. However, accurately identifying the potential (re)hemorrhage among sporadic CCM patients in advance remains a challenge. This study aims to develop machine learning models to detect potential (re)hemorrhage in sporadic CCM patients. This study was based on a dataset of 731 sporadic CCM patients in open data platform Dryad. Sporadic CCM patients were followed up 5 years from January 2003 to December 2018. Support vector machine (SVM), stacked generalization, and extreme gradient boosting (XGBoost) were used to construct models. The performance of models was evaluated by area under receiver operating characteristic curves (AUROC), area under the precision-recall curve (PR-AUC) and other metrics. A total of 517 patients with sporadic CCM were included (330 female [63.8%], mean [SD] age at diagnosis, 42.1 [15.5] years). 76 (re)hemorrhage (14.7%) occurred during follow-up. Among 3 machine learning models, XGBoost model yielded the highest mean (SD) AUROC (0.87 [0.06]) in cross-validation. The top 4 features of XGBoost model were ranked with SHAP (SHapley Additive exPlanations). All-Elements XGBoost model achieved an AUROCs of 0.84 and PR-AUC of 0.49 in testing set, with a sensitivity of 0.86 and a specificity of 0.76. Importantly, 4-Elements XGBoost model developed using top 4 features got a AUROCs of 0.83 and PR-AUC of 0.40, a sensitivity of 0.79, and a specificity of 0.72 in testing set. Two machine learning-based models achieved accurate performance in identifying potential (re)hemorrhages within 5 years in sporadic CCM patients. These models may provide insights for clinical decision-making.

Abstract We demonstrate enhanced acoustic sensing arising from the synergy between resonator-based acoustic sensor and deep learning. We numerically verify that both vibration amplitude and phase are enhanced and preserved at and off the resonance in our compact acoustic sensor housing three cavities. In addition, we experimentally measure the response of our sensor to single-frequency and siren signals, based on which we train convolutional neural networks (CNNs). We observe that the CNN trained by using both amplitude and phase features achieve the best accuracy on predicting the incident direction of both types of signals. This is even though the signals are broadband and affected by noise thought to be difficult for resonators. We attribute the improvement to a complementary effect between the two features enabled by the combination of resonant effect and deep learning. This observation is further supported by comparing to the CNNs trained by the features extracted from signals measured on reference sensor without resonators, whose performances fall far behind. Our results suggest the advantage of this synergetic approach to enhance the sensing performance of compact acoustic sensors on both narrow- and broad-band signals, which paves the way for the development of advanced sensing technology that has potential applications in autonomous driving systems to detect emergency vehicles.

This study investigated the synergistic potential of an oncolytic herpes simplex virus armed with interleukin 12 (VT1092M) in combination with immune checkpoint inhibitors for enhancing antitumor responses. The potential of this combination treatment to induce systemic antitumor immunity was assessed using bilateral subcutaneous tumor and tumor re-challenge mouse models. The antitumor efficacy of various OV and ICI treatment combinations and the underlying mechanisms were explored through diverse analytical techniques, including flow cytometry and RNA sequencing. Using VT1092M, either alone or in combination with an anti-PD-L1 antibody, significantly reduced the sizes of both the injected and untreated abscopal tumors in a bilateral tumor mouse model. The combination therapy demonstrated superior antitumor efficacy to the other treatment conditions tested, which was accompanied by an increase in T cell numbers and CD8+ T cell activation. Results from the survival and tumor re-challenge experiments showed that the combination therapy elicited long-term, tumor-specific immune responses, which were associated with tumor clearance and prolonged survival. Immune cell depletion assays identified CD8+ T cells as the crucial mediators of systemic antitumor immunity during combination therapy. In conclusion, the combination of VT1092M and PD-L1 blockade emerged as a potent inducer of antitumor immune responses, surpassing the efficacy of each monotherapy. This synergistic approach holds promise for achieving robust and sustained antitumor immunity, with potential implications for preventing tumor metastasis in patients with cancer.

Dysregulation of apoptosis occurs in different types of malignant tumors and is likely to influence the tumor evolution, as well as clinical prognosis. However, the limited number of studies investigating the predictive power of apoptosis-related genes (ARGs) in gastric cancer indicates a gap in the current research. 174 ARGs who differentially expressed were screened using public databases, including the Gene Expression Omnibus and the Molecular Signatures Database. Univariate and LASSO regression analyses were rigorous approaches to recognize the 12 optimal genes (CTHRC1, PDGFRL, VCAN, GJA1, LOX, UPP1, ANGPT2, CRIM1, HIF1A, APOD, RNase1, and ID1) that make up the prognostic risk model. Molecular mutations, related signaling pathways, and immune system characteristics in different subgroups defined by the risk model were analyzed using different R packages. Moreover, based on the database of Genomics of Drug Sensitivity in Cancer, chemotherapy sensitivity was predicted among the risk subgroups. As a result, there were differences in mutation profiles, signaling pathways, and infiltrated immune cells between patients in various risk groups. Moreover, the low-risk group displayed greater sensitivity to chemotherapy than the high-risk group. Risk model provided a better prognostic value than the T, N, and M stages, according to the receiver operating characteristic curve. Finally, in a nomogram, the risk model and clinical factors were combined to visualize the survival rates of patients with GC. In response to the differential expression of apoptosis-related genes, a novel model for predicting the prognosis of GC patients was developed. This model may be highly valuable for guiding doctors to deliver treatment plans tailored to the need of patients with GC.

Abstract Root tips can sense moisture gradients and grow into environments with higher water potential. This process is called root hydrotropism. Here, we report three closely related receptor-like kinases (RLKs) that play critical roles in root hydrotropism: ALTERED ROOT HYDROTROPIC RESPONSE 1 (ARH1), FEI1, and FEI2. Overexpression of these RLKs strongly reduce root hydrotropism, but corresponding loss-of-function mutants exhibit an increased hydrotropic response in their roots. All these RLKs show polar localization at the plasma membrane regions in root tips. The biosynthesis of the cell wall, cutin, and wax (CCW) is significantly impaired in root tips of arh1-2 fei1-C fei2-C. A series of known CCW mutants also exhibit increased root hydrotropism and reduced osmotic tolerance, similar to the characteristics of the triple mutant. Our results demonstrat that the integrity of the cell wall, cutin, and root cap wax mediate a trade-off between root hydrotropism and osmotic tolerance.

Cancer immunotherapy, exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy, is revolutionizing cancer therapy. They induce long-term tumor regression and overall survival benefit in many types of cancer. With the advances in our knowledge about the tumor immune microenvironment, remarkable progress has been made in the development of small-molecule drugs for immunotherapy. Small molecules targeting PRR-associated pathways, immune checkpoints, oncogenic signaling, metabolic pathways, cytokine/chemokine signaling, and immune-related kinases have been extensively investigated. Monotherapy of small-molecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor resistance. Here, we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.

Gas tungsten arc welding (GTAW) based wire arc additive manufacturing (WAAM) process is first used to fabricate a thin wall of LA103Z magnesium-lithium alloy. Results indicate that the grain size of the LA103Z thin-walled bottom region significantly differs from that of the middle and top regions. The main phases present in the LA103Z thin wall include α-Mg and β-Li phases, along with some particulate second phases (LiAl, Li2MgAl). Moreover, the thermal action of the subsequent sedimentary layer promotes the transformation of β-Li→α-Mg+β-Li and Li2MgAl →LiAl phase. The mechanical properties of the LA103Z thin wall are affected by a combination of factors such as grain size, the proportion of the α-Mg phase, and morphology. The tensile strength of the LA103Z thin-walled samples in the bottom, middle, and top regions is measured at 195.1 MPa, 181.8 MPa, and 201.4 MPa, respectively, with corresponding elongation percentages of 3.4%, 7.3%, and 12.4%. In the building direction, the tensile strength is recorded as 177.7 MPa, with an elongation percentage of 7%. The study reveals that WAAM-GTAW has the potential to make magnesium-lithium alloys more widely available.

In this paper, the 316L stainless steel matrix composite strengthened by TiB2 was successfully fabricated using laser cladding additive manufacturing technology. The microstructures of 316L/TiB2 with the addition of TiB2 (mass fractions of 0, 3 and 6, respectively) were characterised. Hardness tests and tensile tests were conducted to evaluate the physical and mechanical properties of the samples. The results indicated that all prepared samples exhibit a complex cellular microstructure composed of sub-grains. The matrix phase was verified as γ austenite with a honeycomb-like reinforcement phases forming along the boundaries. Further analysis revealed the net-like reinforcements were (Fe,Cr)2B and M3B2 (M is Cr, Fe, Mo, Ni, Ti) phases. The Microhardness of the samples with 0 wt%,3 wt% and 6 wt% of TiB2 were 148 HV, 170 HV and 186 HV, respectively. The addition of 3 wt% and 6 wt% TiB2 composites increased the yield strength by 22 % and 29 %, respectively, compared to 316L composite. Also, the tensile strength and modulus of elasticity of the reinforcement composites were improved by 8 % and 13 %, respectively. However, the elongation of the reinforcement composites was reduced by 36 % and 47 %, respectively. The reinforcement with high strength and modulus is formed in 316L/TiB2 composite, which leads to a reduction in grain size while enhancing the density of large-angle grain boundaries. Multiple strengthening effects dominated by Orowan strengthening were simultaneously experienced during the preparation process, which improved the mechanical properties of the composites.

To achieve the safe and stable structural condition of the roof along the goaf under the roof cutting by dense drilling method, the stress distribution and fracture process of the roof strata between normal and dense drilling conditions were studied. Based on rock fracture theory and elastic theory, the stress distribution of the surrounding rock between dense drilling and the fracture process were analyzed before and after mining, clarifying the cutting mechanism of dense drilling and the interaction mechanism of concentrated stress between adjacent drilling. The calculation formula for the tensile-shear stress of the surrounding rock between dense drilling in the arc-shaped triangular panel structure at the end of the working face was derived. Based on this, the influence of different parameters on the tensile-shear stress of the surrounding rock between drilling was analyzed, and a determination method for the key parameters of roof cutting by dense drilling holes along the goaf was proposed. Research has shown that the dense drilling mainly increases the concentration of the surrounding rock's tensile and shear stress by changing the stress conditions around the densely drilled holes before and after mining, causing the expansion and connection of fractures between drilling and forming key rock layers for cutting. Before mining, the drill holes are mainly affected by horizontal compression stress, and after mining, the stress gradually changes to the tensile and shear stress caused by the rotation and subsidence of the goaf roof, and the state of the surrounding rock between the holes transitions from the weakening stage to the formation of crack stage, and then to the fracture stage. The magnitude of the tensile and shear stress of the surrounding rock between the densely drilled holes mainly depends on the thickness of the key rock layer and the ratio of the hole diameter to the hole spacing, and is negatively correlated with the hole height and spacing, and positively correlated with the angle and diameter of the drill holes. Based on this, a method for determining the key parameters of intensive drilling and cutting is proposed, and a plan for intensive drilling and cutting in the goaf with hard roof conditions on the 3124 N working face of Longtan Mine is designed, with a hole length of 8.3 m, an angle of 15°, a hole diameter of 48 mm, and a spacing of 500 mm. The deformation of the goaf roof after cutting is controllable and the overall stability is good, which proves that the arrangement parameters of intensive drilling and cutting are reasonable, and the determination method for the key parameters of roof cutting by dense drilling holes is effective and feasible.

Abstract The rapid and accurate identification of single‐phase earth fault is of prime concern for many scholars from industry and academia, because its fault characteristics are extremely weak while the related potential hazard is extremely severe. In this context, this paper borrows from Deep Learning and in turn innovatively puts forward a multilayer perceptron (MLP)‐based single‐phase earth fault detection model augmented with kernel principal component analysis (KPCA). First, KPCA is applied to building fault feature extraction engineering via the transformation of fault features from low‐dimensional linear indivisible space to high‐dimensional one. Second, a MLP‐based model is used for basic model reference where many optimization strategies together with dropout technique are introduced and custom‐designed in tuning this model to achieve the best detection accuracy and convergence characteristic. Numerical studies demonstrate the superiority of the proposed KPCA‐MLP‐based single‐phase earth fault detection model.

Abstract Bathymetry data over lake areas are not included in the current and previous NGS (National Geodetic Survey) geoid models. Lake surfaces are simply treated as land surfaces during the modeling regardless of the apparent density difference between water and rock, resulting in artificial masses that distort the model from the actual gravity field and the corresponding geoid surface. In this study, compiled high-resolution bathymetry data provided by National Centers for Environmental Information are used to identify the real volume of water bodies. Under the mass conservation principle, two strategies are deployed to properly account the water body bounded by the mean lake surface and the bathymetry indicated lake floor into the current NGS geoid modeling scheme, where the residual terrain modeling method is used to account for topographic effects. The first strategy condenses water bodies into equivalent rock masses, with the cost of changing the geometrical shape of the water body. The second one keeps the shape of the water body unchanged but replaces the water and rock densities inside each topographical column bounded by the geoid surface and the mean lake surface by an averaged density. Both strategies show up to 1-cm geoid changes when compared with the previous geoid model that does not consider bathymetric information. All three geoid models are evaluated by local GNSS/Leveling benchmarks and multi-year-multi-mission altimetry indicated mean lake surface heights. The results show that both strategies can improve the geoid model precision. And the second strategy yields more realistic results. Graphical Abstract

Increasing the number of teats in sheep helps to improve the survival rate of sheep lambs after birth. In order to analyze the candidate genes related to the formation of multiple teats in Hu sheep, the present study was conducted to investigate the genetic pattern of multiple teats in Hu sheep. In this study, based on genome-wide data from 157 Hu sheep, Fst, xp-EHH, Pi and iHS signaling were performed, and the top 5% signal regions of each analyzed result were annotated based on the Oar_v4.0 for sheep. The results show that a total of 142 SNP loci were selected. We found that PTPRG, TMEM117 and LRP1B genes were closely associated with polypodium formation in Hu sheep, in addition, among the candidate genes related to polypodium we found genes such as TMEM117, SLC25A21 and NCKAP5 related to milk traits. The present study screened out candidate genes for the formation of multiple teats at the genomic level in Hu sheep.

Proton exchange membrane water electrolysis (PEMWE) with high‐purity H2 and O2 products and swift response to electricity fluctuation is of great interest for renewable energy, chemical and pharmaceutical industries. Ruthenium oxide shows promise as an alternative to iridium oxide catalysts in PEMWE but suffers from severe anodic corrosion. Herein, a pluralistic electronic structure modulation approach is presented to address the instability issue of Ru, by in situ growing MnxRu1−xO2 solid solution on MnO2, coated carbon fibers (MnxRu1−xO2/MnO2/CFs). Due to higher ion electronegativity, Mn dopants in the MnxRu1−xO2 solid solution accept electrons, activating the Ru site. Simultaneously, the MnO2 support donates electrons to prevent Ru site overoxidation and dissolution due to its lower work function than the MnxRu1−xO2 solid solution. As a result, the MnxRu1−xO2/MnO2/CFs catalyst exhibits a low overpotential of 161 mV at 10 mA cm−2 and a remarkable stability exceeding 600 h. Profiting by its improved oxygen evolution reaction (OER) kinetic activity, the MnxRu1−xO2/MnO2/CF‐based PEMWE shows a low cell voltage of 1.9 V at 2 A cm−2, and stably operate at current density of 500 mA cm−2 for 24 h. This work shows the potential of the pluralistic electronic structure modulation to boost activity and stability of Ru‐based acidic OER electrocatalysts.

Summary: During space travel, microgravity leads to disturbances in cognitive function, while the underlying mechanism is still unclear. Simulated microgravity mice showed neuronal age-like changes in the hippocampus of our study. In the context of microgravity, we discovered m6A modification reshapes in the hippocampal region. When paired with RNA-seq and MeRIP-seq, Shox2 was found to be a powerful regulator in hippocampal neuron that respondes to microgravity. Decreased expression of senescence-associated secretory phenotype factors and improved genes related to synapses led to the restoration of memory function in the hippocampus upon increased expression of Shox2. Moreover, we discovered that IGF2BP2 was required for the m6A modification of the Shox2, and overexpressed IGF2BP2 in the hippocampus protected against both neuronal senescence and learning and memory decline caused by loss of gravity. Accordingly, our research identified the hippocampal IGF2BP2-Shox2 axis as a possible therapeutic approach to maintaining cognitive function during space travel.

Coal rock dynamic disasters such as rockburst and gas outbursts pose severe threats to the safe and efficient mining of coal mines in China; however, the mechanical mechanisms of those disasters are still unknown. Therefore, the evolution law and constitutive model of damage and fracture of coal rock was emphatically studied, starting from the rockburst-gas disaster that occurred at the coal mine roadway. Firstly, the X-ray high-precision micro-CT scanning experiment was performed, and the high-resolution 3D digital core of burst-prone coal was built utilizing 3D reconstruction technology. Furthermore, the box-counting dimension method and the 3D visual image processing software AVIZO were used to calculate the characteristic parameters of mineral bands and crack structures inside the coal sample. Secondly, a damage-fracture constitutive model considering three-parameter Weibull distribution, gas influence, and effective stress was proposed, based on CT scanning reconstruction and statistical strength theory. Thirdly, the triaxial compression experiments of gas-bearing coal were conducted, the model parameters were calculated using experimental results, the model was verified, and the damage evolution law of the progressive failure process of coal rock was revealed. Specifically, the experimental results of micro-CT scanning reconstruction and fractal calculation show that the surface area ratio and fractal dimension of the mineral bands are 0.0035−0.0137 and 1.1214−1.2342 respectively, while that of the fracture structures are 0.0006−0.0040 and 1.0651−1.1454 respectively. The surface area ratio and fractal dimension of mineral bands are generally larger than those of fracture structures, indicating that the number of discontinuous structures of burst-prone coal is significant, and its distribution is complex. Furthermore, the experimental results show that stress-strain curves are characterized by the class I curve; shear fracture usually occurs under triaxial compressive loads. The peak strength and peak strain increase with the rise in confining pressure. Moreover, the determination method of seven parameters within the damage fracture model is given, and those parameters and damage variable are solved based on experimental results. The calculation results show that this model can accurately reflect the progressive failure characteristics of coal rock, such as compressive deformation, quasi-linear elastic deformation, plastic deformation, peak strength, and post-peak softening. Additionally, in the first two stages, the damage variable of coal rock is less than 0.2. When it enters the plastic stage, especially in the post-peak step, the damage variable increases sharply until the failure occurs. Hence, the concept of damage threshold is proposed; here, the damage threshold of 0.2 is recommended as the early warning value of damage fracture of coal rock. The findings will further promote the development of damage mechanics and provide a theoretical basis for the prevention and control of coal and rock dynamic disasters.

Abstract Molecular folding regulation with environmental stimuli is critical in living and artificial molecular machine systems. Herein, we described a macrocycle, cyclo[4] (1,3-(4,6-dimethyl)benzene)[4](1,3-(4,6-dimethyl)benzene)(4-pyridine). Under 298 K, it has three stable stiff atropisomers with names as 1 (C s symmetry), 2 (C s symmetry), and 3 (C 4v symmetry). At 393 K, 1 can reversibly transform into 2, but at 473 K, it can irrevocably transform into 3. At 338 K, 3 and (PhCN)2PdCl2 complex to produce the metal-organic cage 4. Only at 338 K does the combination of 1 or 2 and (PhCN)2PdCl2 create a gel-like structure. Heating both gels to 473 K transforms them into 4. In addition to offering a thermally accelerated method for modifying self-assembled systems using macrocyclic building blocks, this study also has the potential to develop the nanoscale transformation material with a thermal response.

Aiming at the problems of low intelligence of current tunneling equipment, difficulty in describing over-excavation, under-excavation and abnormal collision in tunneling process, and difficulty in adapting traditional automatic cutting and memory cutting technology to complex geological conditions, a digital twin-driven virtual teaching memory cutting control method for cantilever roadheader is proposed. By analyzing the research situation of digital twin technology in the field of intelligent coal mining, the overall scheme of memory cutting control system of cantilever roadheader driven by digital twin is designed, and the key technology of memory cutting of cantilever roadheader under complex working conditions is studied. Firstly, the characteristics of digital twin and virtual reality technology are fully utilized to study the virtual teaching strategy under complex working conditions. Based on the Unity3D platform, the virtual twin model of the working face and equipment with the same size of the corresponding entity, the kinematics model of the cutting unit and the virtual collision detection model are established. The virtual model movement is controlled through the intelligent interactive interface at the virtual end, and the teaching trajectory is designed and optimized according to the worker’s experience, so that it can be used as the target expected trajectory of trajectory tracking to make up for the excessive dependence on the worker’s experience caused by the traditional underground manual teaching due to the harsh working conditions. Secondly, in order to improve the quality of section forming, the control method of teaching trajectory tracking and reproduction in memory automatic cutting stage is studied. The dynamic model of cutting part is established by Lagrange method, and the tracking control accuracy of end effector to teaching trajectory is improved by combining iterative learning with sliding mode control. Finally, the simulation control platform of the memory cutting of the cantilever roadheader is built. Through the real-time data transmission and interaction between the virtual space and the physical space and between the modules, the three-dimensional visual simulation of the memory cutting virtual teaching and trajectory tracking control process is completed in the virtual space, and then the memory automatic cutting trajectory tracking control command is generated and sent to the end effector of the physical entity of the cantilever roadheader to drive it to carry out the section forming cutting according to the teaching trajectory. At the same time, the physical sensor collects the pose data of the cantilever roadheader fuselage and the cutting arm, and reversely drives the virtual model to move synchronously. The closed-loop control of robot virtual model and physical entity is realized. On this basis, the virtual and real synchronization of the system, the motion consistency between the virtual prototype and the physical prototype, and the trajectory tracking and reproduction control accuracy are verified. The experimental results show that the system data transmission delay is low, which can ensure the virtual and real consistency and synchronization, and the trajectory tracking control accuracy meets the actual use requirements. This method provides a new idea for memory cutting and intelligent control of tunneling equipment.

Abstracts Quantitatively defining the relationship between laser powder bed fusion (LPBF) process parameters and the resultant microstructures for LPBF fabricated alloys is one of main research challenges. To date, achieving the desired microstructures and mechanical properties for LPBF alloys is generally done by time-consuming and costly trial-and-error experiments that are guided by human experience. Here, we develop an approach whereby an image-driven conditional generative adversarial network (cGAN) machine learning model is used to reconstruct and quantitatively predict the key microstructural features (e.g., the morphology of martensite and the size of primary and secondary martensite) for LPBF fabricated Ti-6Al-4V. The results demonstrate that the developed image-driven machine learning model can effectively and efficiently reconstruct micrographs of the microstructures within the training dataset and predict the microstructural features beyond the training dataset fabricated by different LPBF parameters (i.e., laser power and laser scan speed). This study opens an opportunity to establish and quantify the relationship between processing parameters and microstructure in LPBF Ti-6Al-4V using a GAN machine learning-based model, which can be readily extended to other metal alloy systems, thus offering great potential in applications related to process optimisation, material design, and microstructure control in the additive manufacturing field.

In precise space operation tasks, the impact of disturbing torques on the space flexible robotic arm (SFRA) cannot be ignored. Besides, the slender structure of the SFRA is very likely to generate vibration of the robotic arm. These are all potential hidden dangers in space safety. To quantify the potential risk, an accurate dynamics model of the SFRA considering the disturbing torque is built by Lagrange principle and the assumed modal method (AMM). Moreover, the effects of the disturbing torque, modal order and nonlinear terms on the deformation accuracy of the SFRA are compared. It is observed that the simplified dynamics model with neglecting the nonlinear terms (NNTs) has a high model accuracy and be easily solved. Therefore, the NNTs simplified model is chosen for deriving the transfer function of the SFRA. The parameters of the PI controller are adjusted in real time based on fuzzy rules to reduce the tracking error in the SFRA. In addition, the disturbance observer is designed to observe and compensate of the disturbance torque in the SFRA. The control method of adjusting controller parameters with fuzzy rules based on the disturbance observer greatly improves the rotational control accuracy of the SFRA. Finally, the validity of aforementioned control strategy is confirmed by simulation analysis and experimental results.

Three-section landslides are renowned for their immense size, concealed development process, and devastating impact. This study conducted physical model tests to simulate one special geological structure called a three-section-within landslide. The failure process and precursory characteristics of the tested samples were meticulously analyzed using video imagery, micro-seismic (MS) signals, and acoustic emission (AE) signals, with a focus on event activity, intensity, and frequency. A novel classification method based on AE waveform characteristics was proposed, categorizing AE signals into burst signals and continuous signals. The findings reveal distinct differences in the evolution of these signals. Burst signals appeared exclusively during the crack propagation and failure stages. During these stages, the cumulative AE hits of burst signals increased gradually, with amplitude rising and then declining. High-amplitude burst signals were predominantly distributed in the middle- and high-frequency bands. In contrast, cumulative AE hits of continuous signals escalated rapidly, with amplitude monotonously increasing, and high-amplitude continuous signals were primarily distributed in the low-frequency band. The emergence of burst signals and high-frequency AE signals indicated the generation of microcracks, serving as early-warning indicators. Notably, the early-warning points of AE signals were detected earlier than those of video imagery and MS signals. Furthermore, the early-warning point of burst signals occurred earlier than those of continuous signals, and the early-warning point of the classification method preceded that of overall AE signals.

This study involved the preparation of natural rubber-based composites incorporating varying proportions of heavy metals and rare earth oxides (Sm2O3, Ta2O5, and Bi2O3). The investigation analyzed several parameters of the samples, including mass attenuation coefficients (general, photoelectric absorption, and scattering), linear attenuation coefficients (μ), half-value layers (HVLs), tenth-value layers (TVLs), mean free paths (MFPs), and radiation protection efficiencies (RPEs), utilizing the Monte Carlo simulation software Geant4 and the WinXCom database across a gamma-ray energy spectrum of 40–150 keV. The study also compared the computational discrepancies among these measurements. Compared to rubber composites doped with single-component fillers, multi-component mixed shielding materials significantly mitigate the shielding deficiencies observed with single-component materials, thereby broadening the γ-ray energy spectrum for which the composites provide effective shielding. Subsequently, the simulation outcomes were juxtaposed with experimental data derived from a 133Ba (80 keV) γ-source. The findings reveal that the simulated results align closely with the experimental observations. When compared to the WinXCom database, the Geant4 software demonstrates superior accuracy in deriving radiation shielding parameters and notably enhances experimental efficiency.

Metro stray currents flowing into transformer-neutral points cause the high neutral DC and a transformer to operate in the DC bias state.Because neutral DC caused by stray current varies with time, the neutral DC value cannot be used as the only characteristic indicator to evaluate the DC bias risk level. Thus, unified characteristic extraction and assessment methods are proposed to evaluate the DC bias risk of a transformer caused by stray current, considering the signals of transformer-neutral DC and vibration. In the characteristic extraction method, the primary characteristics are obtained by comparing the magnitude and frequency distributions of transformer-neutral DC and vibration with and without metro stray current invasion. By analyzing the correlation coefficients, the final characteristics are obtained by clustering the primary characteristics with high correlation. Then, the magnitude and frequency characteristics are extracted and used as indicators to evaluate the DC bias risk. Moreover, to avoid the influence of manual experience on indicator weights, the entropy weight method (EWM) is used to establish the assessment model. Finally, the proposed methods are applied based on the neutral DC and vibration test data of a certain transformer. The results show that the characteristic indicators can be extracted, and the transformer DC bias risk can be evaluated by using the proposed methods.

Abstract In clinics, hepcidin levels are elevated in various anemia‐related conditions, particularly in iron‐refractory anemia and in high inflammatory states that suppress iron absorption, which remains an urgent unmet medical need. To identify effective treatment options for various types of iron‐refractory anemia, the potential effect of hypoxia and pharmacologically‐mimetic drug FG‐4592 (Roxadustat) are evaluated, a hypoxia‐inducible factor (HIF)‐prolyl hydroxylase (PHD) inhibitor, on mouse models of iron‐refractory iron‐deficiency anemia (IRIDA), anemia of inflammation and 5‐fluorouracil‐induced chemotherapy‐related anemia. The potent protective effects of both hypoxia and FG‐4592 on IRIDA as well as other 2 tested mouse cohorts are found. Mechanistically, it is demonstrated that hypoxia or FG‐4592 could stabilize duodenal Hif2α, leading to the activation of Fpn transcription regardless of hepcidin levels, which in turn results in increased intestinal iron absorption and the amelioration of hepcidin‐activated anemias. Moreover, duodenal Hif2α overexpression fully rescues phenotypes of Tmprss6 knockout mice, and Hif2α knockout in the gut significantly delays the recovery from 5‐fluorouracil‐induced anemia, which can not be rescued by FG‐4592 treatment. Taken together, the findings of this study provide compelling evidence that targeting intestinal hypoxia‐related pathways can serve as a potential therapeutic strategy for treating a broad spectrum of anemia, especially iron refractory anemia.

The visual cryptography scheme (VCS) is usually considered unconditionally secure, meaning that participants in the forbidden subset cannot access any secret information. However, this assumes that the random number sequence (RNS) used in the secret sharing process is completely inaccessible to attackers. In reality, the random number generator could have vulnerabilities or backdoors, allowing attackers to obtain RNS. Thus, we study an extreme scenario where attackers successfully acquire RNS. Our work explores the relationship between VCS security and RNS, revealing intriguing findings when there is complete or partial leakage of secret information. To enhance VCS security, we propose three innovative algorithms designed to prevent attackers from accessing all original secret image information, even when they possess RNS and shares within the forbidden subset. Theoretical and experimental results demonstrate the effectiveness of these proposed schemes in enhancing the security of existing VCSs.

Summary: Duodenogastric reflux (DGR) is closely associated with gastric inflammation and tumorigenesis; however, the precise mechanism is unclear. Hence, we aim to clarify this molecular mechanism and design an effective therapeutic strategy based on it. The present study found that DGR induced TXNIP/NLRP3 inflammasome activation and triggered pyroptosis in gastric mucosa in vitro and in vivo, in which endoplasmic reticulum (ER) stress via PERK/eIF2α/CHOP signaling was involved. Mechanistically, farnesoid X receptor (FXR) antagonized the DGR-induced PERK/eIF2α/CHOP pathway and reduced TXNIP and NLRP3 expression. Moreover, FXR suppressed NLRP3 inflammasome activation by physically interacting with NLRP3 and caspase-1. Administration of the FXR agonist OCA protected the gastric mucosa from DGR-induced barrier disruption and mucosal inflammation. In conclusion, our study demonstrates the involvement of TXNIP/NLRP3 inflammasome-mediated pyroptosis in DGR-induced gastric inflammation. FXR antagonizes gastric barrier disruption and mucosal inflammation induced by DGR. Restoration of FXR activity may be a therapeutic strategy for DGR-associated gastric tumorigenesis.

Duodenogastric reflux (DGR) has been linked to the onset of gastric cancer (GC), although the precise mechanism is yet obscure. Herein, we aimed to investigate how refluxed bile acids (BAs) and macrophages are involved in gastric carcinogenesis. In both active human bile reflux gastritis and the murine DGR model, ubiquitin specific protease 50 (USP50) was dramatically raised, and macrophages were the principal leukocyte subset that upregulated USP50 expression. Enhancing USP50 expression amplified bile acid-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and subsequent high-mobility group box protein 1 (HMGB1) release, while USP50 deficiency resulted in the reversed alteration. Mechanistically, USP50 interacted with and deubiquitinated apoptosis-associated speck-like protein containing CARD (ASC) to activate NLRP3 inflammasome. The release of HMGB1 contributes to gastric tumorigenesis by PI3K/AKT and MAPK/ERK pathways. These results may provide new insights into bile reflux-related gastric carcinogenesis and options for the prevention of DGR-associated GC.

Due to the demands for both environmental protection and modernization of the goose industry in China, the traditional goose waterside rearing systems have been gradually transitioning to the modern intensive dryland rearing ones, such as the net-floor mixed rearing system (MRS) and cage rearing system (CRS). However, the goose immune responses to different dryland rearing systems remain poorly understood. This study aimed to investigate and compare the age-dependent effects of MRS and CRS on the splenic histomorphological characteristics and immune-related genes expression profiles among three economically important goose breeds, including Sichuan White goose (SW), Gang goose (GE), and Landes goose (LD). Morphological analysis revealed that the splenic weight and organ index of SW were higher under CRS than under MRS (p

As the largest peripheral lymphoid organ in poultry, the spleen plays an essential role in regulating the body’s immune capacity. However, compared with chickens and ducks, information about the age- and breed-related changes in the goose spleen remains scarce. In this study, we systematically analyzed and compared the age-dependent changes in the morphological, histological, and transcriptomic characteristics between Landes goose (LG; Anser anser) and Sichuan White goose (SWG; Anser cygnoides). The results showed a gradual increase in the splenic weights for both LG and SWG until week 10, while their splenic organ indexes reached the peak at week 6. Meanwhile, the splenic histological indexes of both goose breeds continuously increased with age, reaching the highest levels at week 30. The red pulp (RP) area was significantly higher in SWG than in LG at week 0, while the splenic corpuscle (AL) diameter was significantly larger in LG than in SWG at week 30. At the transcriptomic level, a total of 1710 and 1266 differentially expressed genes (DEGs) between week 0 and week 30 were identified in spleens of LG and SWG, respectively. Meanwhile, a total of 911 and 808 DEGs in spleens between LG and SWG were identified at weeks 0 and 30, respectively. Both GO and KEGG enrichment analysis showed that the age-related DEGs of LG or SWG were dominantly enriched in the Cell cycle, TGF−beta signaling, and Wnt signaling pathways, while most of the breed-related DEGs were enriched in the Neuroactive ligand−receptor interaction, Cytokine−cytokine receptor interaction, ECM−receptor interaction, and metabolic pathways. Furthermore, through construction of protein-protein interaction networks using significant DEGs, it was inferred that three hub genes including BUB1, BUB1B, and TTK could play crucial roles in regulating age-dependent goose spleen development while GRIA2, GRIA4, and RYR2 could be crucial for the breed-specific goose spleen development. These data provide novel insights into the splenic developmental differences between Chinese and European domestic geese, and the identified crucial pathways and genes are helpful for a better understanding of the mechanisms regulating goose immune functions.

The identification of aging- and longevity-associated genes is important for promoting healthy aging. By analyzing a large cohort of Chinese centenarians, we previously found that single-nucleotide polymorphisms (SNPs) in the SLC39A11 gene (also known as ZIP11) are associated with longevity in males. However, the function of the SLC39A11 protein remains unclear. Here, we found that SLC39A11 expression is significantly reduced in patients with Hutchinson–Gilford progeria syndrome (HGPS). In addition, we found that zebrafish with a mutation in slc39a11 that significantly reduces its expression have an accelerated aging phenotype, including a shortened average lifespan, muscle atrophy and reduced swimming, impaired muscle regeneration, gut damage, and abnormal morphology in the reproductive system. Interestingly, these signs of premature aging were more pronounced in male zebrafish than in females. RNA-sequencing analysis revealed that cellular senescence may serve as a potential mechanism for driving this slc39a11 deficiency-induced phenotype in mutant zebrafish. Moreover, immunofluorescence showed significantly increased DNA damage and reactive oxygen species signaling in slc39a11 mutant zebrafish. Using inductively coupled plasma mass spectrometry (ICP-MS), we found that manganese significantly accumulates in slc39a11 mutant zebrafish, as well as in the serum of both global Slc39a11 knockout and hepatocyte-specific Slc39a11 knockout mice, suggesting that this metal transporter regulates systemic manganese levels. Finally, using cultured human fibroblasts, we found that both knocking down SLC39A11 and exposure to high extracellular manganese increased cellular senescence. These findings provide compelling evidence that SLC39A11 serves to protect against the aging process, at least in part by regulating cellular manganese homeostasis.

In the rapidly advancing field of modern medicine, despite the availability of sophisticated techniques, suturing remains a fundamental procedure in both surgical and internal medicine operations. However, this traditional method inevitably gives rise to issues such as inflammation, fibrosis, or secondary damage. Laser tissue welding and soldering technologies offer a non-contact approach to surgical suturing with advantages including simplicity of operation, reduced fibrosis tendency, and ensured wound closure strength. Nevertheless, its applications have been attempts at clinical trials but no actual implementation. The development and implementation of this technique have the potential to revolutionize both internal and external surgery by enabling automated suture placement. This holds significant importance for ensuring suture quality and postoperative performance. This article provides a detailed summary and discussion on the current applications of this biotechnologies in various organ systems within the human body, as well as an exploration into the interaction mechanisms between tissues and lasers. Additionally, it presents a comprehensive analysis and discussion on laser types suitable for bio tissue laser soldering. Prospects for addressing tissue fibrosis resulting from laser contactless suturing are also explored. These insights will serve as valuable references and guidance for future advancements in utilizing lasers as viable alternatives in human surgical suturing.

Introduction: Depression is a common illness worldwide. However, the current treatments available for depression only achieve relative success, often come with several side effects, and are associated with high costs. Aurantii Fructus Immaturus (AFI) has a rich historical legacy in Traditional Chinese Medicine (TCM) for its traditional use as a treatment for depression. In this research, our primary objective is to examine the potential antidepressant properties and the mechanisms at play behind a particular bioactive compound found in AFI, which is referred to as carbon dots derived from AFI Carbonisata (AFIC-CDs).Methods: Extracted and isolated the AFIC-CDs from the decoction of AFIC, then characterized the morphological structure and functional groups comprehensively. We then utilized two distinct models to investigate the anti-depressive properties of AFIC-CDs: the chronic unpredictable mild stress (CUMS) model and the reserpine-induced pain-depression dyad model. In the CUMS model, we assessed immobile time and measured neurotransmitter levels in the mouse brain cortex. In the pain-depression dyad model, we evaluated immobile time, neurotransmitter levels, interleukin-1 (IL-1β) and tumor necrosis factor-α (TNF-α) levels, and the expression of mRNA of brain-derived neurotrophic factor (BDNF) and tryptophan hydroxylase 2 (Tph2).Results: AFIC-CDs were found to have abundant chemical groups, and their diameter ranged from 2 to 10 nm. In the CUMS model, AFIC-CDs demonstrated significant effects. They reduced the immobile time of the mice and increased the levels of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) in the mouse brain cortex. In the pain-depression dyad model, the AFIC-CDs groups decreased the immobile time, showed effect in increasing both the neurotransmitters’ levels and the expression of mRNA of BDNF and Tph2, and decreased the IL-1β and TNF-α levels in mouse brain cortex. Taken together, these results strongly indicate that AFIC-CDs possess significant antidepressant activity.Conclusion: AFIC-CDs demonstrate promising therapeutic potential in the treatment of depression, suggesting that they may become a valuable candidate for depression management. This not only extends the understanding of the biological activity of carbon dots (CDs) but also opens up new possibilities for the development of effective depression treatment strategies.

With the continuous development of flexible transparent electrodes, silver nanowires have been widely used due to their excellent optoelectronic properties and flexibility. However, their progress has been hindered by high contact resistance. In this study, femtosecond laser post-processing was applied to the silver nanowire transparent electrodes, and the effect of laser power density on the welding of silver nanowires was investigated. The results showed that femtosecond laser could achieve welding between silver nanowires, but excessively high laser energy density could cause the melting of the nanowires. When the femtosecond laser energy density reached the critical energy density of approximately 2546 J·m−2, at which nanowires underwent spheroidization, the average sheet resistance of the silver nanowire electrodes was minimized to 18.89 Ω·sq−1, and the figure of merit (FoM) of the electrodes reached its maximum at 126.99, which was close to twice the initial value. Moreover, the non-uniformity factor (NUF) was also small, at 1.6%, indicating good conductivity and uniformity. Additionally, the influence of femtosecond laser irradiation on the transmittance of the silver nanowire transparent electrodes was insignificant, and the number of effective pulses had no obvious effect on the welding efficiency of the silver nanowires.

Abstract Brain expressed X-linked gene 2 (BEX2) encoded protein was originally identified to promote transcription by interacting with several transcription factors in the DNA–binding complexes. Recently, BEX2 was found to be localized in cytosol and/or mitochondria and regulate apoptosis in cancer cells and tumor growth. However, the molecular mechanism underlying its roles in cancer cells remains unclear. Here, we report that crotonylated BEX2 plays an important role in inhibiting chemotherapeutic agent-induced apoptosis via enhancing mitophagy in human lung cancer cells. BEX2 promotes mitophagy by facilitating interaction between NDP52 and LC3B. Moreover, BEX2 crotonylation at K59 is critical in the BEX2-mediated mitophagy in lung cancer cells. The K59R mutation of BEX2 inhibits mitophagy by affecting the interaction of NDP52 and LC3B. BEX2 expression is elevated after anticancer drug treatment, and its overexpression inhibits chemotherapy-induced apoptosis. In addition, inhibition of BEX2-regulated mitophagy sensitizes tumor cells to apoptosis. Furthermore, BEX2 promotes tumor growth and inhibits apoptosis by regulating mitophagy in vivo. We also confirm that BEX2 is overexpressed in lung adenocarcinoma and is associated with poor prognosis in lymph node metastasis-free cancer. Therefore, combination treatment with pharmaceutical approaches targeting BEX2-induced mitophagy and anticancer drugs may represent a potential strategy for NSCLC therapy.

Gene editing with a CRISPR/Cas system is a novel potential strategy for treating human diseases. Pharmacological inhibition of phosphoinositide 3-kinase (PI3K) δ suppresses retinal angiogenesis in a mouse model of oxygen-induced retinopathy. Here we show that an innovative system of adeno-associated virus (AAV)-mediated CRISPR/nuclease-deficient (d)CasX fused with the Krueppel-associated box (KRAB) domain is leveraged to block (81.2% ± 6.5%) in vitro expression of p110δ, the catalytic subunit of PI3Kδ, encoded by Pik3cd. This CRISPR/dCasX-KRAB (4, 269 bp) system is small enough to be fit into a single AAV vector. We then document that recombinant AAV serotype (rAAV)1 efficiently transduces vascular endothelial cells from pathologic retinal vessels, which show high expression of p110δ; furthermore, we demonstrate that blockade of retinal p110δ expression by intravitreally injected rAAV1-CRISPR/dCasX-KRAB targeting the Pik3cd promoter prevents (32.1% ± 5.3%) retinal p110δ expression as well as pathological retinal angiogenesis in a mouse model of oxygen-induced retinopathy. These data establish a strong foundation for treating pathological angiogenesis by AAV-mediated CRISPR interference with p110δ expression.

This study examines the effects of iron ore tailing (IOT) replacement ratios and the hybridization of steel fiber (SF) and polyethylene (PE) fiber (PF) on the mechanical, sulfate freeze–thaw (F–T) resistance, and microscopic characteristics of IOT concrete. The mechanical properties of specimens including compressive strength (fcu) and splitting tensile strength (fsts) were evaluated. Sulfate F–T cycle indices of specimens including surface damage, fcu loss, relative dynamic elastic modulus (RDEM), and mass loss are examined. Meanwhile, microscopic characteristics are analyzed using industrial computer technology (CT) and scanning electron microscopy (SEM). Results indicated that IOT replacement ratios below 40% positively influenced mechanical properties and sulfate F–T resistance, whereas ratios exceeding 40% exhibited adverse effects. Incorporating hybrid SF and PF further enhanced the mechanical properties and sulfate F–T resistance of IOT concrete. The IOT concrete containing 1.5% SF and 0.6% PF (designated T40S1.5P0.6) demonstrates significantly improved mechanical properties and sulfate F–T resistance. A set of parameters was proposed to predict the fsts. The Weibull damage model, capable of quantitatively reflecting the F–T damage of IOT concrete, was established. The pore structure of IOT concrete gradually deteriorates with increasing sulfate F–T cycles. The pore characteristics of T40S1.5P0.6 were superior. This was further validated through SEM observations.

Long-term spaceflight is known to induce disruptions in circadian rhythms, which are driven by a central pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus, but the underlying molecular mechanisms remain unclear. Here, we developed a rat model that simulated microgravity and isolation environments through tail suspension and isolation (TSI). We found that the TSI environment imposed circadian disruptions to the core body temperature, heart rate, and locomotor-activity rhythms of rats, especially in the amplitude of these rhythms. In TSI model rats’ SCNs, the core circadian gene NR1D1 showed higher protein but not mRNA levels along with decreased BMAL1 levels, which indicated that NR1D1 could be regulated through post-translational regulation. The autophagosome marker LC3 could directly bind to NR1D1 via the LC3-interacting region (LIR) motifs and induce the degradation of NR1D1 in a mitophagy-dependent manner. Defects in mitophagy led to the reversal of NR1D1 degradation, thereby suppressing the expression of BMAL1. Mitophagy deficiency and subsequent mitochondrial dysfunction were observed in the SCN of TSI models. Urolithin A (UA), a mitophagy activator, demonstrated an ability to enhance the amplitude of core body temperature, heart rate, and locomotor-activity rhythms by prompting mitophagy induction to degrade NR1D1. Cumulatively, our results demonstrate that mitophagy exerts circadian control by regulating NR1D1 degradation, revealing mitophagy as a potential target for long-term spaceflight as well as diseases with SCN circadian disruption.

Abstract Biosorbents have been extensively studied for heavy metal adsorption due to their advantages of low cost and high efficiency. In the study, the living and non-living biomass of Cupriavidus necator GX_5 previously isolated were evaluated for their adsorption capacity and/or removal efficiency for Cd (II) through batch experiments, SEM and FT-IR investigations. The maximum removal efficiency rates for the live and dead biomass were 60.51% and 78.53%, respectively, at an optimum pH of 6, a dosage of 1 g/L and an initial Cd (II) concentration of 5 mg/L. The pseudo-second-order kinetic model was more suitable for fitting the experimental data, indicating that the rate-limiting step might be chemisorption. The Freundlich isotherm model fit better than the Langmuir isotherm model, implying that the adsorption process of both biosorbents was heterogeneous. FT-IR observation reflected that various functional groups were involved in Cd (II) adsorption: –OH, –NH, C=O, C–O and C–C groups for the living biomass and –OH, –NH, C–H, C = O, C–N and N–H groups for the dead biomass. Our results imply that non-living biosorbents have a higher capacity and stronger strength for absorbing Cd (II) than living biomass. Therefore, we suggest that dead GX_5 is a promising adsorbent and can be used in Cd (II)-contaminated environments.

As a reinforcing phase, TiB2 exhibits exceptional wettability and stability when mixed with steel matrices, making it an ideal reinforcement for steel matrix composites. In this paper, we add TiB2 for additive manufacturing of 18Ni300 steel for weight reduction and reinforcement. TiB2 reinforced 18Ni300 matrix composites were prepared by laser cladding. SEM, EDS, and XRD were used to observe the joints' interface and fracture characteristics and analyse the substance composition. Tissue analysis was then performed using EBSD and TEM. According to the TEM and XRD results, there is a martensite structure within the cell, and the cell boundary is an austenite structure. After adding TiB2, a reinforcing phase ((Mo, Fe)3B2) is distributed at the boundary of the cell structure. The high hardness of boride increases the microhardness of the composite material. The yield strength, modulus, and elongation of the samples prepared with 18Ni300 powder are lower than that of forged 18Ni300, but the tensile strength reaches 1134 MPa. The addition of TiB2 increases the composite material's yield strength and elastic modulus significantly. This strengthening technique, which employs the addition of ceramic particles to martensitic steel, is currently not widely used. This experiment provides a theoretical basis and process reference for preparing high-stiffness and lightweight ceramic particle reinforced metal matrix composites.

Multiorbital optical lattices have been attracting rapidly growing research interest in the last several years, providing fascinating opportunities for orbital-based quantum simulations. Here, we consider bosonic atoms loaded in the degenerate p-orbital bands of a two-dimensional triangular optical lattice. This system is described by a multiorbital Bose-Hubbard model. We find the confined atoms in this system develop spontaneous orbital polarization, which forms a chiral Skyrmion lattice pattern in a large regime of the phase diagram. This is an orbital version of the skyrmion, reminiscent of those in spin systems. The emergence of the Skyrmion lattice is confirmed in both bosonic dynamical mean-field theory (BDMFT) and exact diagonalization (ED) calculations. By analyzing the quantum-tunneling-induced orbital-exchange interaction in the strong interaction limit, we find the Skyrmion lattice state arises due to the interplay of p-orbital symmetry and the geometric frustration of the triangular lattice. We provide experimental consequences of the orbital Skyrmion state that can be readily tested in cold atom experiments. Our study implies orbital-based quantum simulations could bring exotic scenarios unexpected from their spin analog.

The Energy Internet adopts the mechanism of “regional coordination and hierarchical control” to realize the clean power compatibility and reliability in power operation. In the network topology, the traditional tree network is transformed to the hierarchical partition network. First, this paper analyzes the topological features of “hierarchical control, intra-layer partition, interregional interconnection, and regional autonomy” of the Energy Internet. On this basis, the hierarchical ring network autonomy (HRNA) topological generation and evolution mechanism of the Energy Internet is proposed, and the different levels of a Beijing power grid framework are taken as an example to expand and evolve to the Energy Internet. Based on the comparison and analysis of the network characteristics constructed in this paper with relevant literature studies, this mechanism generates a network that is close to the Internet in terms of average degree, network diameter, and aggregation coefficient. However, there is no centrality node with a higher degree of nodes in the Internet topology, which better reflects the equivalence concept of the Energy Internet.

Graded permittivity materials have gained significant attention due to their exceptional ability to regulate electric fields. Multi-material stereolithography (SLA) 3D printing has opened up new possibilities for creating such materials. However, conventional SLA printers typically generate graded material using fixed printing parameters and multiple feedstocks with limited differences, resulting in a constrained capacity for modulating the electric field distribution. To address this limitation, we have developed a multi-material, parameter-controllable SLA strategy, enabling us to assign varying printing parameters for each building layer and switch between feedstocks with significant differences. Solid insulators with graded permittivity are optimised through electric field distribution simulations and subsequently manufactured using our innovative multi-material SLA approach. A 4-layered graded insulator effectively decreases the maximum electric field strength from 82.5–30.8 kV/mm. Both flashover tests and partial discharge signals confirm that graded insulators outperform homogeneous ones in electrical insulation.

Local sheep in the northeastern Tarim Basin can adapt to dry and low-rainfall regional environments. In this study, three local sheep breeds in the northeastern Tarim Basin, LOP (LOP) sheep, Bayinbuluke (BYK) sheep, and Kunlun (KUN, also known as the Qiemo sheep) sheep, and three introduced sheep breeds, Suffolk (SUF) sheep, Dorset (APD) sheep, and Texel (TEX) sheep, were analyzed for genetic diversity, population structure, and selective signature using the Illumina OvineSNP50K BeadChip. We found that LOP, BYK, and KUN had lower observed heterozygosity and expected heterozygosity than TEX, SUF, and ADP, which were differentiated based on geographic distribution. We performed fixation index (FST) analysis on three local sheep breeds in the northeastern Tarim Basin (LOP, BYK, and KUN) and introduced sheep breeds (TEX, SUF, and ADP) to measure genetic differentiation. Nucleotide diversity (PI) analysis was performed on single-nucleotide polymorphism (SNP) data of LOP, BYK, and KUN. A total of 493 candidate genes were obtained by taking the intersection at a threshold of 5%. Among them, SMAD2, ESR2, and HAS2 were related to reproductive traits. PCDH15, TLE4, and TFAP2B were related to growth traits. SOD1, TSHR, and DNAJB5 were related to desert environmental adaptation. Analyzing the genetic patterns of local sheep in the northeastern Tarim Basin can protect the germplasm resources of local sheep and promote the development and utilization of sheep genetic resources.