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Abstract The proficiency of phyllosphere microbiomes in efficiently utilizing plant-provided nutrients is pivotal for their successful colonization of plants. The methylotrophic capabilities of Methylobacterium/Methylorubrum play a crucial role in this process. However, the precise mechanisms facilitating efficient colonization remain elusive. In the present study, we investigate the significance of methanol assimilation in shaping the success of mutualistic relationships between methylotrophs and plants. A set of strains originating from Methylorubrum extorquens AM1 are subjected to evolutionary pressures to thrive under low methanol conditions. A mutation in the phosphoribosylpyrophosphate synthetase gene is identified, which converts it into a metabolic valve. This valve redirects limited C1-carbon resources towards the synthesis of biomass by up-regulating a non-essential phosphoketolase pathway. These newly acquired bacterial traits demonstrate superior colonization capabilities, even at low abundance, leading to increased growth of inoculated plants. This function is prevalent in Methylobacterium/Methylorubrum strains. In summary, our findings offer insights that could guide the selection of Methylobacterium/Methylorubrum strains for advantageous agricultural applications.

Hot cracking is the most prevalent defect in the rapid solidification process of alloys, which seriously restricts the mechanical properties of the build. Solidification shrinkage is one of the key factors leading to hot cracking sensitivity, and it, together with tensile stress, causes pressure drops inside the liquid channel. However, the mechanism of solidification shrinkage on hot cracking is not clear. In this work, we established a non-equilibrium phase field model considering the density change during liquid-solid phase transformation. The effects of solidification shrinkage on the morphology and solute segregation of liquid channel in directional solidification were simulated by examples with different solid density. The solidification shrinkage will promote the release and diffusion of solute, leading to an increase in the proportion of high solute concentration liquid in the channel. The columnar dendrites continue to solidify, leading to a decrease in constitutional supercooling in the channel, thereby reducing the temperature at which the solid skeletons connect with each other. This results in the channel becoming narrow and elongated, increasing the hot cracking sensitivity. Finally, the solidification curves obtained from the phase field model and analytical model are input into the RDG (Rappaz, Drezet and Gremaud) model to predict the pressure drop in the system. The numerical results indicate that the maximum pressure drop in the channel occurs at the root and increases with solidification shrinkage. These results demonstrate that the phase field model, which takes into account the change of liquid-solid densities during phase transition, can accurately analyze the impact of solidification shrinkage on hot cracking sensitivity and the maximum pressure drop in the liquid channel.

Abstract In recent years, clear aligner can enhance individual appearance with dental defects, so it used more and more widely. However, in manufacturing process, there are still some problems, such as low degree of automation and high equipment cost. The problem of coordinate system mismatch between gingival curve point cloud and dental CAD model is faced to. The PCA-ICP registration algorithm is proposed, which includes coarse match algorithm and improve-ICP registration algorithm. The principal component analysis (PCA) based method can roughly find the posture relationship between the two point clouds. Using z-level dynamic hierarchical, the ICP registration can accurately find the posture between these two clouds. The final registration maximum distance error is 0.03 mm, which is smaller than robot machining error. Secondly, the clear aligner machining process is conducted to verify the registration effectiveness. Before machining, the path is generated based on the well registered gingival curve. After full registration, the tool path is calculated by establishing a local coordinate system between the workpiece and the tool to avoid interference. This path is calculated and generated as an executable program for ABB industrial robots. Finally, the robot was used for flexible cutting of clear aligners and was able to extract products, ensuring the effectiveness of the proposed research. This method can effectively solve the limitations of traditional milling path planning under such complex conditions.

Abstract Systemic Immune Inflammatory Index (SII) is a novel indicator of inflammation. However, no studies have reported the effect of SII on the association between metals and total fat (TOFAT). We aim to investigate the mediated effect of SII on the relationship between urinary metals and TOFAT in a US adult population. This cross-sectional study was conducted among adults with complete information on SII, urine metal concentrations, and TOFAT from the 2011–2018 National Health and Nutrition Examination Survey (NHANES). Multifactorial logistic regression and restricted cubic splines were used to explore the association between urine metal levels and TOFAT. Furthermore, serial mediation analyses were used to investigate the mediating effect of SII on metals and TOFAT. A total of 3324 subjects were included in this study. After adjusting for confounders, arsenic (As), cadmium (Cd), cobalt (Co), cesium (Cs), inorganic mercury (Hg), molybdenum (Mo), manganese (Mn), lead (Pb), antimony (Sb), and thallium(Tl) had negative decreased trends of odds ratios for TOFAT (all P for trend

Abstract The bidirectional migration of halides and silver causes irreversible chemical corrosion to the electrodes and perovskite layer, affecting long-term operation stability of perovskite solar cells. Here we propose a silver coordination-induced n-doping of [6,6]-phenyl-C61-butyric acid methyl ester strategy to safeguard Ag electrode against corrosion and impede the migration of iodine within the PSCs. Meanwhile, the coordination between DCBP and silver induces n-doping in the PCBM layer, accelerating electron extraction from the perovskite layer. The resultant PSCs demonstrate an efficiency of 26.03% (certified 25.51%) with a minimal non-radiative voltage loss of 126 mV. The PCE of resulting devices retain 95% of their initial value after 2500 h of continuous maximum power point tracking under one-sun irradiation, and > 90% of their initial value even after 1500 h of accelerated aging at 85 °C and 85% relative humidity.

Abstract Background The restoration of cerebrovascular regulation and improvement of cerebral blood flow in ischaemic regions are crucial for improving the clinical prognosis after stroke. An-Gong-Niu-Huang-Wan (AGNHW) is a famous traditional compound Chinese medicine that has been used for over 220 years to treat acute ischaemic stroke; however, its role in the regulation of cerebral blood flow is still unclear. The aim of the present study was to investigate the regulatory effect of AGNHW on cerebral blood flow and microcirculation after ischaemic stroke and to elucidate the underlying mechanisms involved. Methods Male C57BL/6 mice were subjected to distal middle cerebral artery occlusion (dMCAO) and randomly assigned to the sham, MCAO, or AGNHW groups. AGNHW was administered intragastrically 1 h after dMCAO. The rotarod test was utilized to evaluate behavioural function; TTC was used to determine the infarct volume; and ischaemic injury was assessed by detecting brain levels of SOD, MDA and NO. Then, cortical perfusion and acetazolamide-induced cerebrovascular reactivity were assessed using laser speckle contrast imaging, and the velocity and flux of red blood cells in cortical capillaries were detected using two-photon laser scanning microscopy. In addition, we employed RNA-Seq to identify variations in gene expression profiles and assessed endothelium-dependent changes in microcirculatory dysfunction by measuring vasoactive mediator levels. Results AGNHW significantly increased cerebral blood flow, reduced the infarct volume, and promoted functional recovery after cerebral ischaemia. AGNHW increased the velocity and flux of red blood cells in capillaries and improved cerebrovascular reactivity in the ischaemic cortex. Furthermore, AGNHW regulated endothelium-dependent microcirculation, as evidenced by decreases in the expression of endothelins (Edn1, Edn3 and Ednrb) and the ratios of brain and serum TXB2/6-keto-PGF1α and ET-1/CGRP. Conclusions AGNHW improved cerebral hypoperfusion, regulated cerebrovascular reactivity and attenuated microcirculatory dysfunction within the ischaemic cortex after stroke. This outstanding effect was achieved by modulating the expression of genes related to vascular endothelial cell function and regulating endothelium-dependent vasoactive mediators.

Bacterial infection hampers wound repair by impeding the healing process. Concurrently, inflammation at the wound site triggers the production of reactive oxygen species (ROS), causing oxidative stress and damage to proteins and cells. This can lead to chronic wounds, posing severe risks. Therefore, eliminating bacterial infection and reducing ROS levels are crucial for effective wound healing. Nanozymes, possessing enzyme-like catalytic activity, can convert endogenous substances into highly toxic substances, such as ROS, to combat bacteria and biofilms without inducing drug resistance. However, the current nanozyme model with single enzyme activity falls short of meeting the complex requirements of antimicrobial therapy. Thus, developing nanozymes with multiple enzymatic activities is essential. Herein, we engineered a novel metalloenzyme called Ru-procyanidin nanoparticles (Ru-PC NPs) with diverse enzymatic activities to aid wound healing and combat bacterial infections. Under acidic conditions, due to their glutathione (GSH) depletion and peroxidase (POD)-like activity, Ru-PC NPs combined with H2O2 exhibit excellent antibacterial effects. However, in a neutral environment, the Ru-PC NPs, with catalase (CAT) activity, decompose H2O2 to O2, alleviating hypoxia and ensuring a sufficient oxygen supply. Furthermore, Ru-PC NPs possess exceptional antioxidant capacity through their superior superoxide dismutase (SOD) enzyme activity, effectively scavenging excess ROS and reactive nitrogen species (RNS) in a neutral environment. This maintains the balance of the antioxidant system and prevents inflammation. Ru-PC NPs also promote the polarization of macrophages from M1 to M2, facilitating wound healing. More importantly, Ru-PC NPs show good biosafety with negligible toxicity. In vivo wound infection models have confirmed the efficacy of Ru-PC NPs in inhibiting bacterial infection and promoting wound healing. The focus of this work highlights the quadruple enzymatic activity of Ru-PC NPs and its potential to reduce inflammation and promote bacteria-infected wound healing.

Abstract The emerging wearable skin-like electronics require the ultra-flexible organic transistor to operate at low voltage for electrical safety and energy efficiency and simultaneously enable high field-effect mobility to ensure the carrier migration ability and the switching speed of circuits. However, the currently reported low-voltage organic transistors generally present low mobility, originating from the trade-off between molecular polarity and surface polarity of the dielectrics. In this work, the orientation polarization of the dielectric is enhanced by introducing a flexible quaternary ammonium side chain, and the surface polarity is weakened by the shielding effect of the nonpolar methyl groups on the polar nitrogen atom. The resulting antisolvent QPSU dielectric enables the high-dielectric constant up to 18.8 and the low surface polarity with the polar component of surface energy only at 2.09 mJ/m2. Such a synergistic polarization engineering between orientation polarization and surface polarity makes the solution-processed ultraflexible transistors present the ultralow operational voltage down to −3 V, the ultrahigh charge-carrier mobility up to 8.28 cm2 V−1 s−1 at 1 Hz, excellent cyclic operational stability and long-term air stability. These results combined with the ultrathin thickness of transistor as low as 135 nm, the ultralight mass of 0.5 g/m2, the conformal adherence capability on human skin and 1-μm blade edge, and the strong mechanical robustness with stable electrical properties for 30,000 bending cycles, open up an available strategy to successfully realize low-voltage high-mobility solution-processed organic transistor, and presents the potential application of QPSU dielectric for the next-generation wearable imperceptible skin-like electronics.

In order to improve the production of coalbed methane vertical wells in the central and northern Zhengzhuang block, southern Qinshui Basin, Shanxi, China, this paper analyzes the reasons for the poor stimulation effect of medium-deep coalbed methane vertical wells, based on the ground stress test data and fracturing monitoring data of these evaluation wells in the study area, proposes targeted stimulation techniques, designs and carries out field comparative pilot studies and analyzes their results. The results show that there are three main reasons for the low production of these vertical wells in the study area. Firstly, the vertical fracture is dominant, resulting in the shorter length of hydraulic fractures. With the increase of burial depth, the length and width of fractures decreases at the same fracturing scale. Secondly, with the increase of burial depth, the embedment depth of proppants into coal rock increases and the closure of hydraulic fractures speeds up. As a result, the stable production time is short, and the main form of gas production curve is “single peak” type. Thirdly, after the initial fracturing, the coal body structure is much more broken, and new fractures are easy to enter the initial fractures, which increases the difficulty of creating new fractures, resulting in poor stimulation effect. In view of the above reasons, the paper proposes an innovative technology of pre-plug, large-scale and remote-support re-fracturing. Pre-plug means that relatively low displacement, sand ratio and scale are first used to fill initial fractures, and then large-scale re-fracturing is carried out to create new fractures. Large-scale fracturing refers to the fracturing with large displacement, large fluid volume and high sand ratio. In order to improve the stimulation effect of middle-deep reservoirs, the fracturing fluid volume is increased from 600−800 m3 to more than 1 300−2 000 m3, the displacement is increased from 6−8 m3/min to more than 10−14 m3/min, and a low viscosity fracturing fluid system combined with low density proppants is used to increase the sand ratio from 7%−8% to more than 10%−15%. Remote-support is a combination of self-suspended proppants and large displacement to increase proppants migration distance and increase the proportion of the propped fractures. The average daily production of a single well reached 1 380 m3, which was 1 190 m3 higher than that before, and nearly 1 000 m3 higher than the stable gas production of adjacent wells, realizing the production breakthrough of vertical wells in the low-production area of the middle-deep reservoir in the north of Zhengzhuang block. Results of the comparative pilot studies showed that the average net construction pressure increased by 3.3 MPa after pre-plug, compared with the initial fracturing, which means that new fractures were formed and resulted in the production increase by 1 000 m3 compared with that of the wells without the Pre-plug. The pilot results show that, in general, the larger the technical parameters of pre-plug, large-scale and remote-support re-fracturing, the better the production performance.

BackgroundPulmonary fibrosis currently lacks screening and diagnostic methods in the early stages and effective treatments in the later stages, so there is an urgent need to explore the mechanisms and develop targeted treatments.ObjectiveTo screen the expression of differentially expressed circular RNA (circRNA) hsa_circUCK2 under pathological conditions and to explore its effect on pulmonary fibrosis.MethodsIn the cell-based experiments, hsa_circUCK2 was knocked down in HPF-a cells using small interfering RNA (siRNA), and HPF-a cells were stimulated by TGF-β1. Four groups were set up: si-NC group, si-circUCK2 group, si-NC+TGF-β1-treated group, and si-circUCK2+TGF-β1-treated group. Western blot assay was used to detect the expression of fibronectin (FN1) in HPF-a cells of the four groups, scratch assay was used to detect the migration ability of HPF-a cells, and CCK-8 assay was used to detect the proliferation ability of HPF-a cells in the two groups with TGF-β1 stimulation, the si-NC+TGF-β1-treated group and the si-circUCK2+TGF-β1-treated group. In the animal experiments, forty-eighty healthy SPF-grade male C57BL/6 mice were randomly divided into four groups: saline+si-con group, saline+si-circ_0000115 group, SiO2+si-con group, and SiO2+si-circ_0000115 group. Mouse lung circRNA mmu_circ_0000115 (mouse homolog of hsa_circUCK2) was knocked down by tracheal drip injection of siRNA, and a mouse lung fibrosis model was constructed by tracheal drip injection of SiO2 suspension (0.2 g·kg−1, 50 mg·mL−1) after 48 h. Real-time fluorescence quantitative PCR was used to detect the knockout efficiency in each organ of the mouse, Western blot was applied to detect the expression of type I collagen α2 (COL1A2) in the lung tissues, and Sirius red was used to detect collagen synthesis in the lung tissues.ResultsIn the cell-based experiments, after the knockdown of hsa_circUCK2, the Western blot results showed that the expression level of the FN1 protein in TGF-β1-stimulated HPF-a cells was significantly down-regulated (P

Abstract Background Isatropolone A and C, produced by Streptomyces sp. CPCC 204095, belong to an unusual class of non-benzenoid aromatic compounds and contain a rare seven-membered ring structure. Isatropolone A exhibits potent activity against Leishmania donovani, comparable to the only oral drug miltefosine. However, its variably low productivity represents a limitation for this lead compound in the future development of new anti-leishmaniasis drugs to meet unmet clinical needs. Results Here we first elucidated the regulatory cascade of biosynthesis of isatropolones, which consists of two SARP family regulators, IsaF and IsaJ. Through a series of in vivo and in vitro experiments, IsaF was identified as a pathway-specific activator that orchestrates the transcription of the gene cluster essential for isatropolone biosynthesis. Interestingly, IsaJ was found to only upregulate the expression of the cytochrome P450 monooxygenase IsaS, which is crucial for the yield and proportion of isatropolone A and C. Through targeted gene deletions of isaJ or isaS, we effectively impeded the conversion of isatropolone A to C. Concurrently, the facilitation of isaF overexpression governed by selected promoters, prompted the comprehensive activation of the production of isatropolone A. Furthermore, meticulous optimization of the fermentation parameters was conducted. These strategies culminated in the attainment of an unprecedented maximum yield—980.8 mg/L of isatropolone A—achieved in small-scale solid-state fermentation utilizing the genetically modified strains, thereby establishing the highest reported titer to date. Conclusion In Streptomyces sp. CPCC 204095, the production of isatropolone A and C is modulated by the SARP regulators IsaF and IsaJ. IsaF serves as a master pathway-specific regulator for the production of isatropolones. IsaJ, on the other hand, only dictates the transcription of IsaS, the enzyme responsible for the conversion of isatropolone A and C. By engineering the expression of these pivotal genes, we have devised a strategy for genetic modification aimed at the selective and high-yield biosynthesis of isatropolone A. This study not only unveils the unique regulatory mechanisms governing isatropolone biosynthesis for the first time, but also establishes an essential engineering framework for the targeted high-level production of isatropolone A.

The mode-division multiplexing technique combined with a few-mode erbium-doped fiber amplifier (FM-EDFA) demonstrates significant potential for solving the capacity limitation of standard single-mode fiber (SSMF) transmission systems. However, the differential mode gain (DMG) arising in the FM-EDFA fundamentally limits its transmission capacity and length. Herein, an innovative DMG equalization strategy using femtosecond laser micromachining to adjust the refractive index (RI) is presented. Variable mode-dependent attenuations can be achieved according to the DMG profile of the FM-EDFA, enabling DMG equalization. To validate the proposed strategy, DMG equalization of the commonly used FM-EDFA configuration was investigated. Simulation results revealed that by optimizing both the length and RI modulation depth of the femtosecond laser-tailoring area, the maximum DMG (DMGmax) among the 3 linear-polarized (LP) mode-group was mitigated from 10 dB to 1.52 dB, whereas the average DMG (DMGave) over the C-band was reduced from 8.95 dB to 0.78 dB. Finally, a 2-LP mode-group DMG equalizer was experimentally demonstrated, resulting in a reduction of the DMGmax from 2.09 dB to 0.46 dB, and a reduction of DMGave over the C band from 1.64 dB to 0.26 dB, with only a 1.8 dB insertion loss. Moreover, a maximum range of variable DMG equalization was achieved with 5.4 dB, satisfying the requirements of the most commonly used 2-LP mode-group amplification scenarios.

For the technical problem of low intelligence in the process of drilling and pressure relief in high stress mines, the research status of pressure relief technology and equipment at home and abroad is summarized and analyzed in this study. It is pointed out that the development of high-performance, highly reliable, and efficient fully autonomous drilling system of anti-impact drilling robot is an important development direction to solve the problem of rock burst prevention and control. To this end, the five key technologies that affect the performance of the drilling system, namely “the precise recognition of hole position, the precise perception of drilling tool posture, the wireless electromagnetic intelligent detection, the intelligent recognition of drilling tool operation status, and the precise control of the drilling system” have been summarized, and the solutions and methods have been provided. In response to the problem of accurate identification of pressure relief holes in complex and harsh environments, a SinGAN model for pressure relief hole image sample expansion is developed, which integrates image size adjustment and multi-stage training modes. The Faster RCNN optimized by multi-layer feature fusion is introduced, and a hole position recognition model based on an improved SqueezeNet lightweight network architecture is constructed to achieve an accurate and fast recognition of pressure relief hole positions. To address the issue of precise perception of drilling tool posture, the unscented Kalman filter optimized by improved gradient descent algorithm is designed for the initial alignment of Inertial Measurement Unit (IMU). Multiple IMU spatial array layouts are designed, and a BP neural network-based compensation method for drilling tool posture error is studied, aiming to improve the accuracy of drilling tool posture calculation and achieve a precise drilling pressure relief. Aiming at the precise detection of drilling conditions in complex geological environments, a wireless elec-tromagnetic transmission system architecture for underground measurement while drilling in coal mines has been established. The principles of adaptive modulation of weak electromagnetic wave signals and high-speed bidirec-tional electromagnetic transmission technology have been explored, and the measurement principles and imple-mentation processes of geological parameters, geological parameters, and engineering parameters at the bottom of the hole have been investigated. To address the issue of identifying the operational status of drilling systems, a multi-domain feature extraction architecture for drilling signals in the time domain, frequency domain, and time frequency domain, as well as a deep network advanced feature extraction architecture, have been constructed. In addition, the key component health status assessment and fault diagnosis techniques for drilling systems have been proposed, and a prediction model for sticking risk factors based on an improved bat optimized long-term and short-term memory network has been built to accurately predict the stuck status of pressure relief drilling tools. In terms of the issue of precise control of drilling systems, the working principle of the hydraulic system of the drilling system is analyzed, and a precise control scheme for the drilling system considering the characteristics of coal and rock is formulated. The principle of solving the optimal control parameters of the drilling system based on torque and position is explored, aiming to achieve intelligent collaborative control and parallel operation of the drilling return system and feed system.

Abstract Ovarian cancer is the leading cause of gynecological cancer-related death. Drug resistance is the bottleneck in ovarian cancer treatment. The increasing use of novel drugs in clinical practice poses challenges for the treatment of drug-resistant ovarian cancer. Continuing to classify drug resistance according to drug type without understanding the underlying mechanisms is unsuitable for current clinical practice. We reviewed the literature regarding various drug resistance mechanisms in ovarian cancer and found that the main resistance mechanisms are as follows: abnormalities in transmembrane transport, alterations in DNA damage repair, dysregulation of cancer-associated signaling pathways, and epigenetic modifications. DNA methylation, histone modifications and noncoding RNA activity, three key classes of epigenetic modifications, constitute pivotal mechanisms of drug resistance. One drug can have multiple resistance mechanisms. Moreover, common chemotherapies and targeted drugs may have cross (overlapping) resistance mechanisms. MicroRNAs (miRNAs) can interfere with and thus regulate the abovementioned pathways. A subclass of miRNAs, “epi-miRNAs”, can modulate epigenetic regulators to impact therapeutic responses. Thus, we also reviewed the regulatory influence of miRNAs on resistance mechanisms. Moreover, we summarized recent phase I/II clinical trials of novel drugs for ovarian cancer based on the abovementioned resistance mechanisms. A multitude of new therapies are under evaluation, and the preliminary results are encouraging. This review provides new insight into the classification of drug resistance mechanisms in ovarian cancer and may facilitate in the successful treatment of resistant ovarian cancer.

Abstract Background The causal association between gut microbiome and HIV infection remains to be elucidated. We conducted a two-sample mendelian randomization analysis to estimate the causality between gut microbiome and HIV infection. Methods Publicly released genome-wide association studies summary data were collected to perform the mendelian analysis. The GWAS summary data of gut microbiome was retrieved from the MiBioGen consortium, which contains 18 340 samples from 24 cohorts. GWAS summary data of HIV infection was collected from the R5 release of FinnGen consortium, including 357 HIV infected cases and 218 435 controls. The SNPs were selected as instrumental variables according to our selection rules. And SNPs with a F-statistics less than ten were regarded as weak instrumental variables and excluded. Mendelian randomization analysis was conducted by five methods, including inverse variance weighted (IVW), MR-Egger, weighted median, weighted mode, and simple mode. The Cochran’s Q test and MR-Egger intercept test were performed to identify heterogeneity and pleiotropy. Leave-one-out analysis were used to test the sensitivity of the results. Results Fifteen gut microbiota taxa showed causal effects on HIV infection according to the MR methods. Four taxa were observed to increase the risk of HIV infection, including Ruminococcaceae (OR: 2.468[1.043, 5.842], P: 0.039), Ruminococcaceae UCG005 (OR: 2.051[1.048, 4.011], P: 0.036), Subdoligranulum (OR: 3.957[1.762, 8.887], P < 0.001) and Victivallis (OR: 1.605[1.012, 2.547], P=0.044). Erysipelotrichaceae was protective factor of HIV infection (OR: 0.278[0.106, 0.731], P < 0.001) and Methanobrevibacter was also found to be associated with reduced risk of HIV infection (OR: 0.509[0.265, 0.980], P=0.043). Horizontal pleiotropy was found for Fusicatenibacter (P

Abstract Aims/Introduction To evaluate the relative contributions of the area under the C‐peptide curve (AUCC) in diabetic retinopathy (DR) during an oral glucose tolerance test and C‐peptide release test in patients with type 2 diabetes. Materials and Methods We retrospectively analyzed the data of 969 patients. Their general characteristics were retrieved. A series of parameters for assessing pancreatic β‐cells function, such as the AUCC for six time periods: 0–60 min (AUCC0–60), 0–120 min (AUCC0–120), 0–180 min (AUCC0–180), 60–120 min (AUCC60–120), 60–180 min (AUCC60–180) and 120–180 min (AUCC120–180); the area under the glucose‐time curve for six time periods: 0–60 min (AUCG0–60), 0–120 min (AUCG0–120), 0–180 min (AUCG0–180), 60–120 min (AUCG60–120), 60–180 min (AUCG60–180) and 120–180 min (AUCG120–180) and their related indexes, were calculated through 0–180 min oral glucose tolerance test and C‐peptide release test. We used univariate analysis to examine the potential factors affecting DR. Spearman's correlation was used to analyze the correlation between AUCC‐related indexes and DR. The logistic regression model was used to investigate AUCC and its related indexes’ contribution to incidence DR. A smooth curve fitting model was used to determine the correlation, non‐linear relationship, and threshold effect between AUCC and DR. Results Of the 969 patients with type 2 diabetes, 469 (48.40%) and 500 (51.60%) were classified as the DR group and non‐DR group. Compared with the non‐DR group, the DR patients had lower AUCC and AUCC/AUCG. Spearman's correlation analysis showed that AUCC‐related indexes were all negatively correlated with DR. The logistic regression analysis determined that there were associations between AUCC and DR in the adjusted models. The odds ratio values of AUCC0–60, AUCC0–120, AUCC0–180, AUCC0–60/AUCG0–60, AUCC0–120/AUCG0–120, AUCC0–180/AUCG0–180, AUCC60–120, AUCC60–180, AUCC120–180, AUCC60–120/AUCG60–120, AUCC60–180/AUCG60–180 and AUCC120–180/AUCG120–180 were 0.817 (0.750, 0.890), 0.925 (0.895, 0.955), 0.951 (0.932, 0.970), 0.143 (0.060, 0.340), 0.194 (0.093, 0.406), 0.223 (0.116, 0.427), 0.886 (0.842, 0.933), 0.939 (0.915, 0.963), 0.887 (0.846, 0.930), 0.253 (0.133, 0.479), 0.282 (0.160, 0.497) and 0.355 (0.220, 0.573), respectively. AUCC showed a non‐linear relationship with DR, with an inflection point. The inflection points of AUCC180/AUCG180, AUCC60–120, AUCC60–180, AUCC120–180, AUCC60–120/AUCG60–120, AUCC60–180/AUCG60–180, AUCC120–180/AUCG120–180 and DR were 17.51, 0.542, 6.6, 15.7, 8.23, 0.534, 0.593 and 0.808 (P

In order to further improve the development effect of coalbed methane wells, a variety of seismic attributes of the target coal seam are extracted, and production distribution samples of developed wells are established. On this basis, through the fitting analysis of all seismic attributes and yield samples, the index weight method is used to calculate that the cumulative contribution rate of coherence and root mean square amplitude to yield is more than 85%, so the two seismic attributes of coherence and root mean square amplitude are selected. Finally, through the fitting correlation coefficient between the two attributes and the yield, the comprehensive attribute prediction formula was established, and the favorable development units were divided. The correlation between forecast results and developed well production is enhanced. The results show that development units can be accurately divided through well data and seismic attribute optimization technology.

The southern Qinshui Basin is rich in coalbed methane resources, but the geological and engineering conditions are complex, the adaptability of Fanzhuang mature technology popularization in neighboring areas is poor, and the development of coalbed methane scale benefits faces severe challenges. In order to solve the problems of coalbed methane in the southern Qinshui Basin, such as “difficult well location deployment, long drilling cycle, easy collapse of naked eye wells, and low single well production”, a number of key technologies such as integrated geological engineering technology have been carried out, and a number of key technologies have been formed, such as “three properties” coal reservoir evaluation, controllable horizontal well drilling and completion, segmented fracturing, and dredging-type drainage, and field tests and promotion have been carried out. The research results show that through the organic combination of geology and engineering, the geological model provides technical support for engineering technology optimization, and engineering practice continuously corrects the geological model to improve the accuracy; the coal seam drilling rate of horizontal well is 95%, the drilling complexity of single well is reduced by 40% on average, the production capacity reaches 90%, and the average daily production of single well is more than 8 000 m3.

Abstract Photothermal therapy (PTT) is a cancer-targeted treatment approach.The occurrence of tumors may be related to microbial infections (Viruses, bacteria, fungi, etc.), which probably provokes anti-tumor immunity. However, T cells in the context of cancer become exhausted and dysfunctional. Galectin-9 (Gal-9) is highly expressed in normal tissues and associates with body immune tolerance, and was firstly evidenced with much higher expression on the primary solid tumors than CD80/86 (B7) and CD274 (PD-L1) here, which suggests that Gal-9 may be a key factor in inhibiting the anti-tumor immunity, and its receptor T cell immunoglobulin and mucin domain 3 (TIM-3) was discovered on the cytotoxic T lymphocytes (CTL) with high expression as well based on the single cell analysis. The immune checkpoint communications showed that the Gal-9/TIM-3 axis played the most vital role on negatively regulating the anti-tumor immunity of CTL for melanoma. Then, we used a novel transdermal photothermal nanosensitizer (FSGG) loading Gal-9 siRNA (FSGG/siGal-9) for knocking the tumor cells down Gal-9 to block the Gal-9/TIM-3 axis and prohibit CTL exhaustion synergizing PTT against melanoma, which evidenced good effects on inhibiting tumor growth and enhancing anti-tumor immunity, named “photothermal immunotherapy”. This paper provides a new perspective for tumor prevention and treatment.

Intratumoral microbiota can regulate the tumor immune microenvironment (TIME) and mediate tumor prognosis by promoting inflammatory response or inhibiting anti-tumor effects. Recent studies have elucidated the potential role of local tumor microbiota in the development and progression of lung adenocarcinoma (LUAD). However, whether intratumoral microbes are involved in the TIME that mediates the prognosis of LUAD remains unknown. Here, we obtained the matched tumor microbiome and host transcriptome and survival data of 478 patients with LUAD in The Cancer Genome Atlas (TCGA). Machine learning models based on immune cell marker genes can predict 1- to 5-year survival with relative accuracy. Patients were stratified into high- and low-survival-risk groups based on immune cell marker genes, with significant differences in intratumoral microbial communities. Specifically, patients in the high-risk group had significantly higher alpha diversity (p < 0.05) and were characterized by an enrichment of lung cancer-related genera such as Streptococcus. However, network analysis highlighted a more active pattern of dominant bacteria and immune cell crosstalk in TIME in the low-risk group compared to the high-risk group. Our study demonstrated that intratumoral microbiota-immune crosstalk was strongly associated with prognosis in LUAD patients, which would provide new targets for the development of precise therapeutic strategies.

Recent discoveries in mRNA modification have highlighted N1-methyladenosine (m1A), but its role in preeclampsia (PE) pathogenesis remains unclear. In this study, we utilized methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) to identify m1A peaks and the expression profile of mRNA in the decidua of humans with early-onset PE (EPE), late-onset PE (LPE), and normal pregnancy (NP). We assessed the m1A modification patterns in preeclamptic decidua using 10 m1A modulators. Our bioinformatic analysis focused on differentially methylated mRNAs (DMGs) and differentially expressed mRNAs (DEGs) in pairwise comparisons of EPE vs. NP, LPE vs. NP, and EPE vs. LPE, as well as m1A-related DEGs. The comparisons of EPE vs. NP, LPE vs. NP, and EPE vs. LPE identified 3110, 2801, and 2818 DMGs, respectively. We discerned three different m1A modification patterns from this data. Further analysis revealed that key PE-related DMGs and m1A-related DEGs predominantly influence signaling pathways critical for decidualization, including cAMP, MAPK, PI3K-Akt, Notch, and TGF-β pathways. Additionally, these modifications impact pathways related to vascular smooth muscle contraction, estrogen signaling, and relaxin signaling, contributing to vascular dysfunction. Our findings demonstrate that preeclamptic decidua exhibits unique mRNA m1A modification patterns and gene expression profiles that significantly alter signaling pathways essential for both decidualization and vascular dysfunction. These differences in m1A modification patterns provide valuable insights into the molecular mechanisms influencing the decidualization process and vascular function in the pathogenesis of PE. These m1A modification regulators could potentially serve as potent biomarkers or therapeutic targets for PE, warranting further investigation.

Background: Bevacizumab (BV) is widely used in routine cancer treatment and clinical therapy in combination with many other agents. This study aims to describe and analyse post-market cases of pulmonary haemorrhage and haemoptysis reported with different BV treatment regimens by mining data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.Methods: Data were collected from the FAERS database between 2004 Q1 and 2023 Q1. Disproportionality analysis including the reporting odds ratio (ROR) was employed to quantify the signals of disproportionate reporting of pulmonary haemorrhage and haemoptysis adverse events (AEs) associated with BV-related treatment regimens. The demographic characteristics, time to onset and outcomes were further clarified.Results: A total of 55,184 BV-associated reports were extracted from the FAERS database, of which 497 reports related to pulmonary haemorrhage and haemoptysis. Overall, the median onset time of pulmonary haemorrhage and haemoptysis AEs was 43 days (interquartile range (IQR) 15-117 days). In the subgroup analysis, BV plus targeted therapy had the longest median onset time of 90.5 days (IQR 34-178.5 days), while BV plus chemotherapy had the shortest of 40.5 days (IQR 14–90.25). BV plus chemotherapy disproportionately reported the highest percentage of death (148 deaths out of 292 cases, 50.68%). Moreover, the BV-related treatments including four subgroups in our study demonstrated the positive signals with the association of disproportionate reporting of pulmonary haemorrhage and haemoptysis. Notably, BV plus chemotherapy showed a significant higher reporting risk in pulmonary haemorrhage and haemoptysis signals of disproportionate reporting in comparison to BV monotherapy (ROR 5.35 [95% CI, 4.78–6.02] vs. ROR 4.19 [95% CI, 3.56–4.91], p = 0.0147).Conclusion: This study characterized the reporting of pulmonary haemorrhage and haemoptysis, along with the time to onset and demographic characteristics among different BV-related treatment options. It could provide valuable evidence for further studies and clinical practice of BV.

Chinese mitten crab, Eriocheir sinensis, is a migratory crustacean that grows in freshwater and reproduces in seawater. As a traditional aquatic product treasure in China, the industry of E. sinensis has become one of the unique freshwater fishery pillar industries. With years of development, a relatively complete industrial chain model has been initially formed, and its culture area, output and trade are constantly growing. However, the lag of aquatic product processing industry limits the large-scale development of the E. sinensis industry chain. In order to further explore the industry advantages and scale, it is urgent to vigorously develop the E. sinensis processing industry and promote the industrial optimization and upgrading. Moreover, strengthen scientific and technological support and reduce market risks by means of technological innovation to promote the healthy development of the industrial chain. This review expounds the current situation and existing problems of crab product processing in China, and the prospects of future product processing and sustainable utilization, in order to provide new insights for the large-scale development of E. sinensis industry chain.

Background: Immune checkpoint inhibitors (ICIs), including anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibodies, have become a standard treatment for multiple cancer types. However, ICIs can induce immune-related adverse events, with hepatitis-related adverse events (HRAEs) being of particular concern. Our objective is to identify and characterize HRAEs that exhibit a significant association with ICIs using real-world data.Methods: In this observational and retrospective pharmacovigilance study, we extracted real-world adverse events reports from the FDA Adverse Event Reporting System database spanning from the first quarter of 2004 to the first quarter of 2023. We conducted both Frequentist and Bayesian methodologies in the framework of disproportionality analysis, which included the reporting odds ratios (ROR) and information components (IC) to explore the intricate relationship between ICIs and HRAEs.Results: Through disproportionality analysis, we identified three categories of HRAEs as being significantly related with ICIs, including autoimmune hepatitis (634 cases, ROR 19.34 [95% CI 17.80–21.02]; IC025 2.43), immune-mediated hepatitis (546 cases, ROR 217.24 [189.95–248.45]; IC025 4.75), and hepatitis fulminant (80 cases, ROR 4.56 [3.65–5.70]; IC025 0.49). The median age of patients who report ICI-related HRAEs was 63 years (interquartile range [IQR] 53.8–72), with a fatal outcome observed in 24.9% (313/1,260) of these reports. Cases pertaining to skin cancer, lung cancer, and kidney cancer constituted the majority of these occurrences. Patients treated with anti-PD-1 or anti-PD-L1 antibodies exhibited a higher frequency of immune-mediated hepatitis in comparison to those undergoing anti-CTLA-4 monotherapy, with a ROR of 3.59 (95% CI 1.78–6.18). Moreover, the dual ICI therapy demonstrated higher reporting rates of ICI-related HRAEs compared to ICI monotherapy.Conclusion: Our findings confirm that ICI treatment carries a significant risk of severe HRAEs, in particular autoimmune hepatitis, immune-mediated hepatitis, and hepatitis fulminant. Healthcare providers should exercise heightened vigilance regarding these risks when managing patients receiving ICIs.

BackgroundST-segment elevation myocardial infarction (STEMI) persists to be prevalent in the elderly with a dismal prognosis. The capacity of endothelial progenitor cells (EPCs) is reduced with aging. Nevertheless, the influence of aging on the functionality of EPCs in STEMI is not fully understood.MethodThis study enrolled 20 younger STEMI patients and 21 older STEMI patients. We assessed the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events Risk (GRACE) scores in two groups. Then, we detected EPC migration, proliferation, adhesion, and plasma interleukin (IL)-18 and IL-23 concentrations in two groups. In addition, we analyzed the interconnection between age, EPC function, plasma IL-18 and IL-23 concentrations, and GRACE or TIMI scores in STEMI patients.ResultGRACE and TIMI scores in older STEMI patients were higher than in younger STEMI patients, whereas EPC function declined. GRACE and TIMI scores were found to have an inverse relationship with the EPC function. In older STEMI patients, plasma concentrations of IL-18 and IL-23 increased. Plasma IL-18 and IL-23 concentrations were adversely connected to EPC capacity and positively related to GRACE and TIMI scores. Moreover, age was positively correlated with plasma IL-18 or IL-23 concentrations, as well as GRACE or TIMI scores. However, age was adversely correlated with EPC function.ConclusionIn patients with STEMI, aging results in declined EPC function, which may be associated with inflammatory cytokines. The current investigation may offer new perception about mechanism and therapeutic targets of aging STEMI.

Memory is closely associated with neuronal activity and dendritic spine formation. Low-intensity transcranial ultrasound stimulation (TUS) improves the memory of individuals with vascular dementia (VD). However, it is unclear whether neuronal activity and dendritic spine formation under ultrasound stimulation are involved in memory improvement in VD. In this study, we found that seven days of TUS improved memory in VD model while simultaneously increasing pyramidal neuron activity, promoting dendritic spine formation, and reducing dendritic spine elimination. These effects lasted for 7 days but disappeared on 14 d after TUS. Neuronal activity and dendritic spine formation strongly corresponded to improvements in memory behavior over time. In addition, we also found that the memory, neuronal activity and dendritic spine of VD mice cannot be restored again by TUS of 7 days after 28 d. Collectively, these findings suggest that TUS increases neuronal activity and promotes dendritic spine formation and is thus important for improving memory in patients with VD.

Abstract There is a growing body of evidence indicating a close association between inflammatory bowel disease (IBD) and disrupted intestinal homeostasis. Excessive production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with an increase in M1 proinflammatory macrophage infiltration during the activation of intestinal inflammation, plays a pivotal role in disrupting intestinal homeostasis in IBD. The overabundance of ROS/RNS can cause intestinal tissue damage and the disruption of crucial gut proteins, which ultimately compromises the integrity of the intestinal barrier. The proliferation of M1 macrophages contributes to an exaggerated immune response, further compromising the intestinal immune barrier. Currently, intestinal nanomaterials have gained widespread attention in the context of IBD due to their notable characteristics, including the ability to specifically target regions of interest, clear excess ROS/RNS, and mimic biological enzymes. In this review, we initially elucidated the gut microenvironment in IBD. Subsequently, we delineate therapeutic strategies involving two distinct types of nanomedicine, namely inorganic nanoparticles and natural product nanomaterials. Finally, we present a comprehensive overview of the promising prospects associated with the application of nanomedicine in future clinical settings for the treatment of IBD (graphic abstract). Graphical Abstract Different classes of nanomedicine are used to treat IBD. This review primarily elucidates the current etiology of inflammatory bowel disease and explores two prominent nanomaterial-based therapeutic approaches. First, it aims to eliminate excessive reactive oxygen species and reactive nitrogen species. Second, they focus on modulating the polarization of inflammatory macrophages and reducing the proportion of pro-inflammatory macrophages. Additionally, this article delves into the treatment of inflammatory bowel disease using inorganic metal nanomaterials and natural product nanomaterials

The color and texture of camouflaged objects closely resemble their backgrounds, making it difficult to distinguish between the target and the background. Additionally, camouflaged environments are complex, with some camouflaged objects overlapping significantly with the background, further complicating the identification of camouflaged target areas. To address these challenges, we present a novel double-branch camouflaged object detection algorithm, termed TDNet, inspired by biological vision and based on the classical convolutional neural network ResNet50. TDNet employs a two-stage target detection structure that utilizes location segmentation to accurately identify detection targets. Specifically, we introduce an internal feature interaction mechanism (IFE) that enhances camouflaged target feature representations through multi-dimensional spatial feature enhancement and multi-channel feature interaction, enabling the rough segmentation of camouflaged regions. To mitigate the issue of blurred boundaries of camouflaged targets, we devise a cross-layer feature fusion mechanism (CFU) to refine the borders of camouflaged regions. Moreover, we employ a multi-supervised approach to constrain the model’s degradation process, ensuring the accuracy of camouflaged object detection. Experimental results demonstrate that our proposed method outperforms nine classical camouflaged object detection algorithms, achieving state-of-the-art performance. We will release the code and the test maps at https://github.com/zc199823/TDNet.

In the marine field, infrared detection technology is of great significance for timely localization and detection of ships in security missions. However, since infrared ship targets are often in the environmental conditions of small pixel occupancy, low contrast and complex background, it poses a great challenge for multiship detection, classification, and localization tasks. Therefore, to address these problems we propose an edge information-guided infrared ship target detection (EGISD-YOLO) network, in which a dense-csp structure is designed to improve the csp module of YOLO to increase the reusability of the backbone feature information, and in addition, to address the noise and interference generated by the image in the complex background, a deconvolutional channel attention module (DCA) is designed to link the contextual language to the image, which relates the contextual semantics to obtain the local information of the target. Crucially, we propose an edge-guided structure that takes the edge information of low-level features as a cue to fuse with deep-level features to enrich the target contour and thus improve the target localization ability, so that the network still possesses robustness under low-contrast conditions, and finally, we add a small-size prediction head at the end of the network to further increase the detection ability of weak targets. The proposed EGISD-YOLO is experimentally demonstrated to have better detection performance for infrared ship targets.

In recent years, jute, as an important natural fiber crop, has become more and more significant in the production process of insect pests, causing serious harm to agricultural production. Especially in the field of crop pest identification with complex backgrounds, fuzzy features, and multiple small targets, the lack of datasets specifically for jute pests has led to the large limitations of traditional pest identification models in terms of generalization. At the same time, the research on models specifically for jute pest detection is still in its infancy. To solve this problem, we constructed a large-scale image dataset containing nine types of jute pests, which was highly targeted and could effectively support model training and evaluation. In this study, we developed a deep convolutional neural network model based on YOLOv7, namely JutePest-YOLO. The model has optimized the Backbone, Head, and loss functions of the baseline model, and introduced the new ELAN-P module and P6 detection layer, which effectively improved the model’s ability to identify jute pests in complex backgrounds. The experimental results showed that compared with the baseline model, the Precision, Recall, and F1 scores of the JutePest-YOLO model were improved by 3.45%, 1.76%, and 2.58%, respectively; the mAP@0.5 and mAP@0.5:0.95 was improved by 2.24% and 3.25%, and the overall model’s computation (GFLOPS) was reduced by 16.05%. Compared to other advanced methods such as YOLOv8s, JutePest-YOLO has achieved superior performance in terms of detection accuracy, with a precision of 98.7% and mAP@0.5 reaching 95.68%. As a result, JutePest-YOLO not only achieved significant improvement in recognition accuracy but also optimized computational efficiency. It’s a high-performance, lightweight solution for jute pest detection.

Realizing a spatial phase modulation (SPM) from 0 to 2π is vital for achieving precise light field manipulation, when the phase-only spatial light modulator (SLM) is driven by the voltage. However, insufficient bias voltage degrades the quality of the generated structured light. Here, we propose a superpixel method that consists of 2 × 2 adjacent pixels to equalize the imperfect SPM response, when the bias voltage is insufficient. Meanwhile, a look-up table (LUT) is established between the target light field and the superpixel equalized light field, for reducing the computational complexity of phase hologram generation. When the phase modulation depth is reduced from 2π to 1.67π, we can generate the vortex beams with better quality by the superpixel technique. Characterizing the spatial phase distribution of vortex beams through interferometry verifies the correct function of the superpixel enabled SPM equalization method. In addition, the peak signal-to-noise ratio (PSNR) is used as the metric to quantitatively evaluate the quality of the generated vortex beam. Compared with the phase modulation distortion caused by the insufficient bias voltage, the PSNR after the superpixel enabled SPM equalization is improved by 4.5 dB. Our results would facilitate various applications mediated by power-efficient phase modulation utilizing the SLM.

Generalized two-dimensional (2D) Airy beam is a kind of self-accelerating beam with variable initial angle between its two wings, manifested itself as an initial angle determined parabolic trajectory during the free-space propagation. However, the independent and flexible manipulation of both the transverse optical field and longitudinal trajectory of the generalized 2D Airy beam has not been achieved yet which limits its application in the various fields. Herein, we report on tailoring of the propagation properties of the generalized 2D Airy beam based on the catastrophe theory, where analytical expression of its propagation trajectory is derived. In order to clarify the relationship between the transverse optical field distribution and the longitudinal trajectory, we analytically put forward a generation vector, facilitating the tailoring of both longitudinal trajectory and transverse distribution of optical field simultaneously. Consequently, we can effectively generate the generalized 2D Airy beam and precisely manipulate the evolution of its peak intensity. Once the initial and terminal points of trajectory are determined in advance, we can flexibly tailor the trajectory of 2D Airy beam, with the help of corresponding generation vector. Meanwhile, when the longitudinal trajectory is fixed, we can flexibly rotate the transverse optical field distribution of the generalized 2D Airy beam and manipulate its initial angle. Experimental verifications of the manipulation capabilities for the longitudinal trajectory, initial angle, and the rotation of transverse optical field are provided to validate our theoretical results.

Abstract Karst formations in Southwest China are significantly developed. With the increase in tunnel construction year by year, constructing tunnels in areas of karst geology is inevitable. There are great safety risks associated with exposed karst caves, and the water inside the caves can seriously impact the tunnel structure and its filling materials. Traditional cave disposal technology mainly focuses on safe crossing treatment at the construction stage; however, problems such as backfill collapse and floor floating caused by karst water erosion during the service period are not considered. Therefore, proposals for a new construction scheme to ensure the stability and safety of the tunnel during the service period are urgently needed. Using Huangchongyan Tunnel as an example, we propose a safe crossing scheme of ‘plate–pile–bedrock’ for karst caves, based on a comparison of karst cave treatment schemes at home and abroad. In addition, considering the impact of karst water on the tunnel, we developed a ‘bottom to top’ reverse drainage structure, which solved the problem of floating during tunnel service. In our study, we developed a full life cycle disposal scheme to enable safe passage through tunnels in karst caves, providing a reference for the design and construction of similar projects.

Abstract Background Adoptive cell therapy has achieved great success in treating hematological malignancies. However, the production of chimeric antigen receptor T (CAR-T) cell therapy still faces various difficulties. Natural killer (NK)-92 is a continuously expandable cell line and provides a promising alternative for patient’s own immune cells. Methods We established CAR-NK cells by co-expressing natural killer group 2 member D (NKG2D) and IL-21, and evaluated the efficacy of NKG2D-IL-21 CAR-NK cells in treating lung cancer in vitro and in vivo. Results Our data suggested that the expression of IL-21 effectively increased the cytotoxicity of NKG2D CAR-NK cells against lung cancer cells in a dose-dependent manner and suppressed tumor growth in vitro and in vivo. In addition, the proliferation of NKG2D-IL-21 CAR-NK cells were enhanced while the apoptosis and exhaustion of these cells were suppressed. Mechanistically, IL-21-mediated NKG2D CAR-NK cells function by activating AKT signaling pathway. Conclusion Our findings provide a novel option for treating lung cancer using NKG2D-IL-21 CAR-NK cell therapy.

This is an essay in the field of ceramics and composites. In order to study the effect of activated gold tailings content on the mechanical properties, microstructural properties and hydration properties of concrete, the mechanical properties, XRD, TG-DTG and hydration characteristics tests of different content of gold tailings concrete were carried out. The results showed that when the grinding time was 30 min, the specific surface area of the gold tailings reached the maximum and the crystallinity reached the minimum. When the content of gold tailings was 30%, the basic mechanical and physical properties of concrete reached the best state. In addition, the microstructure performance, hydration heat release rate and heat release of concrete mixed with active gold tailings are better than those of concrete mixed with inactive gold tailings. With the continuous increase of the grinding time of gold tailings, Changing law of the cumulative curve of gold tailings particle size showed a trend of first increasing and then becoming stable. And with the continuous increase of grinding time, the accumulation of gold tailings particle size was getting larger and larger.

This is an essay in the field of ceramics and composites. For decades, space exploration has been a hot topic. With the launch of Chang'e 5, China officially opened the first extraterrestrial celestial body sampling return journey. The lunar base construction program in China is officially on the agenda. Lunar exploration is the first step for human to conduct deep space exploration, and the utilization of lunar in-situ resources is of great significance for lunar exploration. Additive manufacturing is an effective means to carry out in-situ lunar resource utilization to build a lunar base. This paper describes the basic properties of lunar soil and the characteristics and composition of simulated lunar soil, and focuses on summarizing the current research progress of simulated lunar soil additive manufacturing in China and abroad. Important challenges are presented for the key technology of additive manufacturing for the lunar weathering layer (i.e., lunar soil). The development prospect of additive manufacturing technology and possible ways of implementation are discussed around China's lunar base construction project.

Abstract The broad employment of clean hydrogen through water electrolysis is restricted by large voltage requirement and energy consumption because of the sluggish anodic oxygen evolution reaction. Here we demonstrate a novel alternative oxidation reaction of green electrosynthesis of valuable 3,3’-diamino-4,4’-azofurazan energetic materials and coupled with hydrogen production. Such a strategy could greatly decrease the hazard from the traditional synthetic condition of 3,3’-diamino-4,4’-azofurazan and achieve low-cell-voltage hydrogen production on WS2/Pt single-atom/nanoparticle catalyst. The assembled two-electrode electrolyzer could reach 10 and 100 mA cm–2 with ultralow cell voltages of 1.26 and 1.55 V and electricity consumption of only 3.01 and 3.70 kWh per m3 of H2 in contrast of the conventional water electrolysis (~5 kWh per m3). Density functional theory calculations combine with experimental design decipher the synergistic effect in WS2/Pt for promoting Volmer–Tafel kinetic rate during alkaline hydrogen evolution reaction, while the oxidative-coupling of starting materials driven by free radical could be the underlying mechanism during the synthesis of 3,3’-diamino-4,4’-azofurazan. This work provides a promising avenue for the concurrent electrosynthesis of energetic materials and low-energy-consumption hydrogen production.

Abstract Background Particulate matter (PM) air pollution poses a significant risk to respiratory health and is especially linked with various infectious respiratory diseases such as influenza. Our previous studies have shown that H5N1 virus infection could induce alveolar epithelial A549 cell death by enhancing lysosomal dysfunction. This study aims to investigate the mechanisms underlying the effects of PM on influenza virus infections, with a particular focus on lysosomal dysfunction. Results Here, we showed that PM nanoparticles such as silica and alumina could induce A549 cell death and lysosomal dysfunction, and degradation of lysosomal-associated membrane proteins (LAMPs), which are the most abundant lysosomal membrane proteins. The knockdown of LAMPs with siRNA facilitated cellular entry of both H1N1 and H5N1 influenza viruses. Furthermore, we demonstrated that silica and alumina synergistically increased alveolar epithelial cell death induced by H1N1 and H5N1 influenza viruses by enhancing lysosomal dysfunction via LAMP degradation and promoting viral entry. In vivo, lung injury in the H5N1 virus infection-induced model was exacerbated by pre-exposure to silica, resulting in an increase in the wet/dry ratio and histopathological score. Conclusions Our findings reveal the mechanism underlying the synergistic effect of nanoparticles in the early stage of the influenza virus life cycle and may explain the increased number of respiratory patients during periods of air pollution.

Abstract Aiming at the mismatch between the cutter combination of the furrowing device and the operating parameters, and resulting in low quality of furrowing and other problems, the theoretical analysis of the furrowing cutting operation is carried out and the influence law of the furrowing parameters on the trajectory, performance and quality of the furrowing movement is obtained. The influence of trenching parameters on trenching trajectory, performance and quality was obtained. The response surface method was applied to design and carry out field experiments. With the increase of cutter head speed and forward speed, the width and depth of trenching and the thickness of floating soil at the bottom of trenching decreased first and then increased, while the operation power consumption presented the increasing trend gradually. The optimization model of trenching performance quality was constructed to obtain the optimal parameter combination of influencing factors. Field experiments were carried out to verify the optimization results. The optimisation results were verified through field tests, which showed that the average depth of furrowing was 472 mm, the width was 332 mm, the thickness of soil return was 134 mm, and the operating power consumption was 19.95 kW. The results showed that the average depth of furrowing was 472 mm, the width was 332 mm, and the thickness of soil return was 134 mm. The optimization model could meet the operation quality indexes, and provide a theoretical basis for the design of the disc subsection cutting trenching device to select the operation parameter combination required by low power consumption and deep trenching.

Objectives The intramedullary nail is considered the gold standard for treating AO/OTA type A3.3 intertrochanteric fractures. However, it still faces a significant rate of failure, mainly due to the critical factor of comminuted lateral wall defects leading to inadequate proximal sliding compression. The primary objective of this study is to investigate the requirement of sliding compression in the treatment of unstable AO/OTA type A3.3 intertrochanteric fractures. To achieve this, we conduct a comparative analysis between two approaches: InterTAN alone and proximal femoral anti‐rotation blade nailing (PFNA) combined with lateral wall reconstruction for treating AO/OTA type A3.3 intertrochanteric fractures with lateral wall damage. Methods A retrospective analysis was conducted on the clinical data of patients who underwent intramedullary nailing fixation for AO/OTA type A3.3 intertrochanteric fractures at our hospital from January 2012 to January 2022. Patient characteristics as well as treatment details, including operative time, intraoperative blood loss, weight‐bearing time, fracture healing time, tip apex distance (TAD) loss, Harris hip scores (HHS), Parker–Palmer mobility score (PPMS), and postoperative complications, were collected and analyzed. Continuous variables were analyzed using independent sample t‐tests, while categorical variables were examined using the chi‐square test. For group comparisons, variance analysis was applied, and pairwise comparisons were conducted using the LSD‐t test. Results These patients were divided into PFNA combined with lateral wall reconstruction group (sliding compression group) and InterTAN fixation group (static fixation group) based on surgical methods. The operation time, intraoperative bleeding loss, HHS at 12 months and PPMS at 12 months in the sliding compression group were significantly higher than those in the static fixation group, and time to weight‐bearing and fracture healing time were significantly lower than those in the static fixation group (p 0.05). At 6 months postoperatively, femoral neck length was shortened compared to 2 days postoperatively in both groups, and the sliding compression group had a significantly greater degree of femoral neck shortening than the static fixation group (p

Brake pads play a vital role in controlling the operation of high-speed trains with over 300 km/h. Currently the copper-based composites produced by powder metallurgy techniques have been proved as one of the ideal materials. However，the braking performance is strongly influenced by the chemical composition, production, microstructure as well as the working conditions. The intrinsic mechanism of the thermal fade and wear loss under thermal and mechanical coupled influence has not yet been fully revealed. As of late, machine learning algorithms have attracted widespread attention and extraordinary results has been accomplished in materials science and engineering. In this study the algorithms for predicting the braking performance of copper-based brake pads are developed. A new PM copper-based alloy, was designed via the models of the coefficient of friction (COF) and wear loss. The braking test results of this alloy show that the average COF was 0.37 at stable stage I and thermal recession decrease only 0.012 at stage II when under 350 km/h/0.48 MPa continuous braking for 10 times. And the total wear loss is only 1.30 g when under braking from 200 km/h to 350 km/h with pressure from 0.31 MPa to 0.48 MPa. Compared with the commercial brake pads, our designed alloy exhibits excellent braking performance with COF for thermal fade reduced to 21% and the total wear loss reduced to 20%.

T-2 toxin is one of trichothecene mycotoxins, which can impair appetite and decrease food intake. However, the specific mechanisms for T-2 toxin-induced anorexia are not fully clarified. Multiple research results had shown that gut microbiota have a significant effect on appetite regulation. Hence, this study purposed to explore the potential interactions of the gut microbiota and appetite regulate factors in anorexia induced by T-2 toxin. The study divided the mice into control group (CG, 0 mg/kg BW T-2 toxin) and T-2 toxin-treated group (TG, 1 mg/kg BW T-2 toxin), which oral gavage for 4 weeks, to construct a subacute T-2 toxin poisoning mouse model. This data proved that T-2 toxin was able to induce an anorexia in mice by increased the contents of gastrointestinal hormones (CCK, GIP, GLP-1 and PYY), neurotransmitters (5-HT and SP), as well as pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) in serum of mice. T-2 toxin disturbed the composition of gut microbiota, especially, Faecalibaculum and Allobaculum, which was positively correlated with CCK, GLP-1, 5-HT, IL-1β, IL-6 and TNF-α, which played a certain role in regulating host appetite. In conclusion, gut microbiota changes (especially an increase in the abundance of Faecalibaculum and Allobaculum) promote the upregulation of gastrointestinal hormones, neurotransmitters, and pro-inflammatory cytokines, which may be a potential mechanism of T-2 toxin-induced anorexia.

Plant diversity and productivity, two crucial properties that sustain ecosystem structures, functions, and services, are intrinsically linked to numerous ecological fields, making productivity–richness relationships (PRR) a central ecological concern. Despite extensive research from the Darwinian era to the 21st century, the various shapes of PRR and their underlying theories have sparked ongoing debates. While several processes, theories, and integrative models have been proposed to explain PRR, a comprehensive understanding of the types of PRR, the effects of these processes on plant productivity and richness, and the relationships between PRR shapes remains elusive. This paper proposes a new integrative framework that focuses on these aspects, aiming to elucidate the diverse shapes of PRR and their interconnections. We review recent integrative methods that explain the roles of processes and the varying shapes in PRR to support this new framework. The paper traces the distinct phases in PRR research, including the discovery of PRR shapes, tests of influencing processes, and integrative research. We discuss the application of the Structural Equation Model (SEM), Statistical Dynamical Model (SDM), and Differential Dynamical Model (DDM) in integrative research. This integrative framework can guide theoretical and applied ecologists in identifying, deriving, explaining, and predicting the interconnected but distinct shapes of PRR. The humped, asymptotic, positive, negative, and irregular shapes of PRR are interconnected, with one shape potentially transforming into another. The balance between the positive and negative effects of different processes determines the different shapes of PRR, ultimately leading to a globally positive effect of plant diversity on plant productivity and other ecosystem functions.

Older adults are highly susceptible to developing cognitive impairment(CI). Various factors contribute to the prevalence of CI, but the potential relationships among these factors remain unclear. This study aims to explore the relevant factors associated with CI in Chinese older adults and analyze the potential relationships between CI and these factors.We analyzed the data on 6886 older adults aged≥60 from the China Health and Retirement Longitudinal Study (CHARLS) 2018. Lasso regression was initially used to screening variables. Bayesian Networks(BNs) were used to identify the correlates of CI and potential associations between factors. After screening with Lasso regression, 11 variables were finally included in the BNs. The BNs, by establishing a complex network relationship, revealed that age, education, and indoor air pollution were the direct correlates affecting the occurrence of CI in older adults. It also indicated that marital status indirectly influenced CI through age, and residence indirectly linked to CI through two pathways: indoor air pollution and education.Our findings underscore the effectiveness of BNs in unveiling the intricate network linkages among CI and its associated factors, holding promising applications. It can serve as a reference for public health departments to address the prevention of CI in the elderly.

Summary: The nature and function of perisaccadic receptive field (RF) remapping have been controversial. We use a delayed saccade task to reduce previous confounds and examine the remapping time course in the lateral intraparietal area and frontal eye fields. In the delay period, the RF shift direction turns from the initial fixation to the saccade target. In the perisaccadic period, RFs first shift toward the target (convergent remapping), but around the time of saccade onset/offset, the shifts become predominantly toward the post-saccadic RF locations (forward remapping). Thus, unlike forward remapping that depends on the corollary discharge (CD) of the saccade command, convergent remapping appears to follow attention from the initial fixation to the target. We model the data with attention-modulated and CD-gated connections and show that both sets of connections emerge automatically in neural networks trained to update stimulus retinal locations across saccades. Our work thus unifies previous findings into a mechanism for transsaccadic visual stability.

Almonertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is highly selective for EGFR-activating mutations as well as the EGFR T790M mutation in patients with advanced non-small cell lung cancer (NSCLC). However, the development of resistance inevitably occurs and poses a major obstacle to the clinical efficacy of almonertinib. Therefore, a clear understanding of the mechanism is of great significance to overcome drug resistance to almonertinib in the future. In this study, NCI-H1975 cell lines resistant to almonertinib (NCI-H1975 AR) were developed by concentration-increasing induction and were employed for clarification of underlying mechanisms of acquired resistance. Through RNA-seq analysis, the HIF-1 and TGF-β signaling pathways were significantly enriched by gene set enrichment analysis. Lipocalin-2 (LCN2), as the core node in these two signaling pathways, were found to be positively correlated to almonertinib-resistance in NSCLC cells. The function of LCN2 in the drug resistance of almonertinib was investigated through knockdown and overexpression assays in vitro and in vivo. Moreover, matrix metalloproteinases-9 (MMP-9) was further identified as a critical downstream effector of LCN2 signaling, which is regulated via the LCN2-MMP-9 axis. Pharmacological inhibition of MMP-9 could overcome resistance to almonertinib, as evidenced in both in vitro and in vivo models. Our findings suggest that LCN2 was a crucial regulator for conferring almonertinib-resistance in NSCLC and demonstrate the potential utility of targeting the LCN2-MMP-9 axis for clinical treatment of almonertinib-resistant lung adenocarcinoma.

Objective: To investigate the efficacy of stereotactic radiotherapy (CyberKnife) in treating primary trigeminal neuralgia and to summarize the treatment experience. Methods: A retrospective analysis was conducted on the efficacy and efficacy of CyberKnife treatment in 33 patients with primary trigeminal neuralgia from August 2012 to April 2023. Targets are selected in the trigeminal nerve root and half-moon segment. The length of treatment is about 6–8 mm, the prescribed dose is 54–65 Gy. Classified according to the (BNI) scale, trigeminal neuralgia and sensory impairment. Follow-up assessed the time and extent of pain relief and the time and extent of numbness. Wilcoxon Signed Ranks Test was used to analyze pain scores before and after radiotherapy. The KM curve analysis using the R survival package was used to analyze the survival. Results: Among them, 12 were males (36.4%) and 21 females (63.6%), with an average age of 67.76 ± 10.62 years. Facial numbness scores after treatment averaged 2.61 ± 0.86. Pain relief started on average 28.26 ± 47.27 days. The pain scores of 33 patients before and after radiotherapy were statistically significant (P