Search

Stainless steel welding has been widely used in industrial manufacturing, and friction stir welding has been recognized to reduce production costs significantly. To fully utilize the different properties of 2507 super duplex stainless steel (SDSS) and 317L austenitic stainless steel (ASS), the mechanical and surface properties of 2507 SDSS and 317L ASS dissimilar stainless steel joints were improved using the friction stir welding (FSW) method. The influence of rotation speed on the microstructural characteristics, mechanical properties, and corrosion behavior of the weld joints was investigated by welding at a constant speed of 20 mm/min within the range of 300–600 rpm. Specifically, at 400 rpm, a welded joint with optimal performance was obtained. When the rotation speed is 400 rpm, the yield strength (YS) and ultimate tensile strength (UTS) of the welding joint are 493 and 692 MPa, respectively, and the elongation (EL) is 32 %. The tensile strength is higher than 317L ASS but lower than 2507 SDSS, the EL is lower than those of 317L ASS and 2507 SDSS, and the friction coefficient of the welded joint is 0.93, which is between 317L ASS and 2507 SDSS. Notably, the refinement of grains in the stirred zone significantly improved the corrosion resistance of the welded joint, considerably exceeding that of the 317L ASS but still lower than the 2507 SDSS. This work can provide a process reference for studying the mechanical and corrosion properties of dissimilar stainless steel FSW.

Objective: This study utilized network meta-analysis (NMA) to compare the efficacy of five commonly used traditional Chinese medicine monomers in reducing intimal hyperproliferation in arterial balloon injury models. Methods: Relevant literature up to January 2024 was systematically retrieved from seven major databases. The intima-to-media (I/M) ratio was chosen as the primary outcome measure. The risk of bias in animal studies was assessed using the SYstematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. Statistical analysis was conducted using Stata 17 software. Results: A total of 43 studies were included in this meta-analysis. NMA results showed that in the rat model, compared to the control group, GS (SMD: 0.99, 95%CI: 1.25 to −0.73), ASIV (SMD: 1.16, 95%CI: 1.65 to −0.67), TMP (SMD: 0.68, 95%CI: 1.31 to −0.05), and TPNS (SMD: 1.36, 95%CI: 1.91 to −0.80) exhibited inhibitory effects on postoperative intimal hyperproliferation, reducing the I/M ratio. In the rabbit model, compared to the control group, TPNS (SMD: 1.23, 95%CI: 1.97 to −0.49) inhibited postoperative intimal hyperproliferation and reduced the I/M ratio. Superiority ranking analysis suggested that total Panax notoginseng saponin (TPNS) might be the most effective traditional Chinese medicine monomer in reducing intimal hyperproliferation in arterial balloon injury models, lowering the I/M ratio. Conclusion: NMA indicates that traditional Chinese medicine monomers can effectively reduce postoperative intimal hyperproliferation in arterial balloon injury models, lowering the I/M ratio, with TPNS showing optimal efficacy. However, the research on TIIA is insufficient, and the limited sample size may affect the robustness of the results. Furthermore, the majority of research on traditional Chinese medicine monomers is currently limited to the experimental stage, lacking further clinical validation. Conducting standardized animal experiments and reporting their findings can enhance the quality of evidence from animal studies, laying the foundation for future clinical trials.

Overload failure under coupling conditions of elevated temperature and combined tension-bending (CTB) is one of the typical failure modes of aero-engine low-pressure compressor blade materials, which is commonly occurring in fighter engines performing low-altitude high-speed penetration missions. In this study, the elasto-plastic deformation behavior and fracture mechanism of Ti–6Al–4V titanium alloy under coupling conditions of elevated temperature and CTB were investigated by experiments and finite element analysis (FEA). CTB tests were conducted on Ti–6Al–4V alloy in the pre-tension ratio range of 0.60–0.90 and in the temperature range of 298 K–573 K. The results show that the maximum bending load, effective bending modulus, and total energy dissipated for the Ti–6Al–4V alloy at room temperature increase with the increase of the pre-tension ratio. The maximum bending load and the energy dissipated are significantly higher at elevated temperatures compared to that of room temperature, due to the elevated temperature induced deformation mode change from bending-dominated to tensile-dominated. The FEA results are in good agreement with the experimental results. SEM fractography indicated that the Ti–6Al–4V alloy fracture at elevated temperature showed only equiaxed dimples, which exhibited a tensile fracture mode. This study is valuable for the in-depth understanding of the deformation behavior and fracture mechanism of blade materials under elevated temperature and complex loads.

Summary: The dysfunction and clonal constriction of tumor-infiltrating CD8+ T cells are accompanied by alterations in cellular metabolism; however, how the cell-intrinsic metabolic pathway specifies intratumoral CD8+ T cell features remains elusive. Here, we show that cell-autonomous generation of nicotinamide adenine dinucleotide (NAD+) via the kynurenine pathway (KP) contributes to the maintenance of intratumoral CD8+ T cell metabolic and functional fitness. De novo NAD+ synthesis is involved in CD8+ T cell metabolism and antitumor function. KP-derived NAD+ promotes PTEN deacetylation, thereby facilitating PTEN degradation and preventing PTEN-dependent metabolic defects. Importantly, impaired cell-autonomous NAD+ synthesis limits CD8+ T cell responses in human colorectal cancer samples. Our results reveal that KP-derived NAD+ regulates the CD8+ T cell metabolic and functional state by restricting PTEN activity and suggest that modulation of de novo NAD+ synthesis could restore CD8+ T cell metabolic fitness and antitumor function.

Background/purpose: Glide path management (GPM) is a consequential clinical step that serves to influence predictably successful root canal therapy. However, the effect of GPM on the shaping ability of single-file system remains controversial. This study compared the performance of rotary single-file One Curve (OC) and reciprocating single-file Reciproc Blue (RCB) in combination with/without different glide path techniques: no glide path preparation (NG), PathFile (PF), ProGlider (PG) and WaveOne Gold Glider (WOGG), respectively. Materials and methods: 80 simulated curved canals (n = 10 canals/per group) were instrumented to an apical size of 0.25 mm using OC and RCB in combination with/without different glide path techniques, respectively. The amount of resin removal, canal transportation, and the degree of canal straightening were measured in Photoshop CS6 software. Statistical analysis of the data was performed by using Kruskal–Wallis test, followed by Dunn's post hoc test with Bonferroni correction (α = 0.05). Results: Post–glide path analysis found that WOGG and PG produced less canal transportation and curvature straightening than PF (P

3D point cloud semantic segmentation is crucial for 3D environment perception and scene understanding, where learning of local context in point clouds is a crucial challenge. Existing approaches typically explore local context based on the predefined neighbors of point clouds. However, the widely used K-nearest neighbor algorithm (KNN) is far from optimal in defining local neighbors. In this study, we propose NeiEA-Net, a conceptually simple and effective network for point cloud semantic segmentation. The key to our approach is to optimize the local neighbors in 3D Euclidean space by taking full advantage of high-dimensional feature space as much as possible. In addition, we introduce a neighbor feature aggregation module to adaptively aggregate features with different scales in the local neighbors to further reduce the redundant information, thereby effectively learning the local details of point clouds. Experiments conducted on three large-scale benchmarks, S3DIS, Toronto3D and SensatUrban, demonstrate the superiority of our network.

Background/purpose: Calcium hydroxide [Ca(OH)2], a wildly used intracanal medicament, should be completely removed from the root canal before obturation to avoid negative effects on the treatment. This study evaluated the effectiveness of conventional needle irrigation (CNI), passive ultrasonic activation (PUI), photon-induced photoacoustic streaming (PIPS), XP-endo Finisher (XP) and EDDY for the removal of Ca(OH)2 from S-shaped root canal. Materials and methods: Eighty-four S-shaped root canals in resin blocks were prepared using Protaper Gold up to size #25/0.08 and filled with Ca(OH)2. Five groups were established according to the removal techniques (n = 16): CNI, PUI, PIPS, XP and EDDY group. The positive and negative control group (n = 2) were also established. Sodium hypochlorite 3% was used as the irrigant. Digital radiographs were used to measure the remaining Ca(OH)2. Statistical analysis of the data was performed by using the Kruskal–Wallis test, followed by Dunn's post hoc test with Bonferroni correction (α = 0.05). Results: All the tested techniques completely removed Ca(OH)2 from the straight portion and coronal curve of the S-shaped root canal in 100% of cases. Regarding the apical curve, PUI, EDDY, PIPS and XP removed significantly more Ca(OH)2 than CNI (P 0.05). The complete clearance of Ca(OH)2 from the apical curve was observed in 75%, 62.5%, 56.3%, 43.8% and 0% of cases of PUI, EDDY, PIPS, XP and CNI group, respectively. Conclusion: Irrigant activation enhanced Ca(OH)2 removal from the apical region of the S-shaped root canal. CNI was significantly less effective than all activation techniques.

Background/purpose: Gold metal technology improves flexibility and the resistance to cyclic fatigue of the endodontic mechanical files. This study compared the performance of ProTaper Gold (PTG) multiple file system and WaveOne Gold (WOG) single file system in simulated S-shaped root canals, which represents one of the most challenging root canal morphology. Materials and methods: Forty S-shaped canals (n = 20 canals/per group) in resin blocks were instrumented to an apical size of 0.25 mm using PTG and WOG Primary, respectively. The total amount of resin removal, canal transportation, centering ratio, and the degree of canal straightening were measured in Photoshop CS6 software. Statistical analysis was performed by using Mann–Whitney U-test (α = .05). Results: None of the files fractured during the instrumentation. The WOG group removed significantly less amount of resin at 0, 3, 6, 7 and 9 mm from the apex (P .05). Conclusion: The WOG Primary file has a less aggressive dentin cutting and more centered apical preparation. The PTG system is more advantageous in shaping the coronal curvature of S-shaped canal.

Hall thrusters function as power plants on spacecraft, and its development is crucial for the aerospace industry. The wall erosion of the on-orbit Hall thruster cannot be measured by the control center through ground measurement, but can obtain the discharge current low-frequency oscillation data. Therefore, this study proposes an inversion method to obtain the wall erosion information based on low-frequency oscillation signals and neural networks. Firstly, we use an improved one-dimensional quasi-neutral dynamic fluid mathematical model to build a low-frequency oscillation simulation platform which obtains the corresponding data by varying the cross-sectional area. Secondly, a nonlinear neural network model is established based on the obtained low-frequency oscillation data to invert the wall erosion information. The training function, transfer function, number of hidden layer nodes, and other parameters affecting the results are analyzed and the best model parameters are obtained. The Elman neural network is established and compared with the BP neural network and RBF neural network. The training results of the Elman neural network algorithm present small and stable errors, and the results of multiple predictions remain consistent. The root means square error, average absolute error, and average absolute percentage are 0.0084, 0.0637, and 0.045%, respectively.

Sulfonamide antibiotics (SAs) are widely used in medicine, animal husbandry and aquaculture, and excessive intake of SAs may pose potential toxicity to organisms. The toxicological mechanisms of two classical SAs, sulfamerazine (SMR) and sulfamethoxazole (SMT), were investigated by molecular docking, DFT and multi-spectroscopic techniques using HSA and BSA as model proteins. The quenching of HSA/BSA endogenous fluorescence by SMR was higher than that by SMT due to the stronger binding effect of the pyrimidine ring on HSA/BSA compared to the oxazole ring, and that result was consistent with that predicted by DFT calculations. Thermodynamic parameters show that the binding of SAs to HSA/BSA is an exothermic process that proceeds spontaneously (ΔG < 0). Marker competition experiments illustrate that the binding site of SMR/SMT on serum albumin is located in subdomain IIIA. The combination of SAs and HSA/BSA is mainly realized by hydrogen bond and hydrophobic interaction, and the concept is also supported by molecular modeling. The reduced α-helix content of HSA/BSA induced by SMR/SMT indicates a greater stretching of the protein α-helix structure of the SMR/SMT-HSA/BSA. The results could provide useful toxicological information on the hazards of SAs in response to growing concern that SAs may pose a toxic threat to organisms.

The gas-liquid counter-current flow limitation (CCFL) is closely related to efficient and safety operation of many equipment in industrial cycle. Air-water countercurrent flow experiments were performed in a tube with diameter of 25 mm to understand the triggering mechanism of CCFL. A parallel electrode probe was utilized to measure film thickness whereby the time domain and frequency domain characteristics of liquid film was obtained. The amplitude of the interface wave is small at low liquid flow rate while it becomes large at high liquid flow rate after being disturbed by the airflow. The spectral characteristic curve shows a peak-shaped distribution. The crest exists between 0 and 10 Hz and the amplitude decreases with the frequency increase. The analysis of visual observation and characteristic of film thickness indicate that two flooding mechanisms were identified at low and high liquid flow rate, respectively. At low liquid flow rate, the interfacial waves upward propagation is responsible for the formation of CCFL onset. While flooding at high liquid flow rate takes place as a direct consequence of the liquid bridging in tube due to the turbulent flow pattern. Moreover, it is believed that there is a transition region between the low and high liquid flow rate.

Given the prominence of 3D sensors in recent years, 3D point cloud scene data are worthy to be further investigated. Point cloud scene understanding is a challenging task because of its characteristics of large-scale and discrete. In this study, we propose a network called LEARD-Net, focuses on semantic segmentation for the large-scale point cloud scene data with color information. The proposed network contains three main components: (1) To fully utilize color information of point clouds rather than just as initial input features, we propose a robust local feature extraction module (LFE) to benefit the network focus on both spatial geometric structure, color information and semantic features. (2) We propose a local feature aggregation module (LFA) to benefit the network to focus on the local significant features while also focus on the entire local neighbor. (3) To allow the network to focus on both local and comprehensive features, we use residual and dense connections (ResiDense) to connect different-level LFE and LFA modules. Comparing with state-of-the-art networks on several large-scale benchmark datasets, including S3DIS, Toronto3D and Semantic3D, we demonstrate the effectiveness of our LEARD-Net.

Mast cells play a pivotal role in IgE-mediated allergic responses. Development of specific inhibitors against FcεRI-associated proximal signaling molecules in mast cells may represent a promising therapeutic strategy for allergic diseases. We examined whether a novel synthetic compound, 3-butyl-1-chloro-8-(2-methoxycarbonyl)phenyl-5H-imidazo[1,5-b]isoquinolin-10-one (U63A05), could suppress antigen-stimulated degranulation and cytokine secretion in mast cells and IgE-mediated passive cutaneous anaphylaxis (PCA) in mice. U63A05 reversibly and dose-dependently inhibited degranulation of rat basophilic leukemia (RBL)-2H3 mast cells and bone marrow–derived mast cells (BMMCs) stimulated by antigen (IC50 values for RBL-2H3 and BMMCs were 4.1 and 4.8 μM, respectively). The secretion of inflammatory cytokines was also suppressed in antigen-stimulated mast cells. However, degranulation by thapsigargin, a typical calcium inducer, was not inhibited by U63A05. U63A05 exerts its inhibitory effect, to the same extent as in degranulation, on the activating phosphorylation of Syk and downstream signaling molecules, including LAT and SLP-76. Further downstream, the activating phosphorylations of Akt, Erk1/2, p38, and JNK were also inhibited. Finally, antigen-stimulated PCA was dose-dependently suppressed in mice (ED50, 26.3 mg/kg). Taken together, the results suggest that U63A05 suppresses the activation of mast cells and the mast cell–mediated allergic response through the inhibition of Syk activation in mast cells. Keywords:: 3-butyl-1-chloro-8-(2-methoxycarbonyl)phenyl-5H-imidazo[1,5-b]isoquinolin-10-one (U63A05), mast cell, IgE, type I hypersensitive response, syk

We investigated whether oral administration of curcumin suppressed type II collagen–induced arthritis (CIA) in mice and its effect and mechanism on matrix metalloproteinase (MMP)-1 and MMP-3 production in CIA mice, RA fibroblast-like synoviocytes (FLS), and chondrocytes. CIA in mice was suppressed by oral administration of curcumin in a dose-dependent manner. Macroscopic observations were confirmed by histological examinations. Histological changes including infiltration of immune cells, synovial hyperplasia, cartilage destruction, and bone erosion in the hind paw sections were extensively suppressed by curcumin. The histological scores were consistent with clinical arthritis indexes. Production of MMP-1 and MMP-3 were inhibited by curcumin in CIA hind paw sections and tumor necrosis factor (TNF)-α–stimulated FLS and chondrocytes in a dose-dependent manner. As for the mechanism, curcumin inhibited activating phosphorylation of protein kinase Cδ (PKCδ) in CIA, FLS, and chondrocytes. Curcumin also suppressed the JNK and c-Jun activation in those cells. This study suggests that the suppression of MMP-1 and MMP-3 production by curcumin in CIA is mediated through the inhibition of PKCδ and the JNK/c-Jun signaling pathway. Keywords:: curcumin, matrix metalloproteinase (MMP)-1, MMP-3, protein kinase Cδ (PKCδ), collagen-induced arthritis

The prospect of employing chemoimmunotherapy targeted towards the endoplasmic reticulum (ER) presents an opportunity to amplify the synergistic effects of chemotherapy and immunotherapy. In this study, we initially validated celastrol (CEL) as an inducer of immunogenic cell death (ICD) by promoting ER stress and autophagy in colorectal cancer (CRC) cells. Subsequently, an ER-targeted strategy was posited, involving the codelivery of CEL with PD-L1 small interfering RNAs (siRNA) using KDEL peptide-modified exosomes derived from milk (KME), to enhance chemoimmunotherapy outcomes. Our findings demonstrate the efficient transportation of KME to the ER via the Golgi-to-ER pathway. Compared to their non-targeting counterparts, KME exhibited a significant augmentation of the CEL-induced ICD effect. Additionally, it facilitated the release of danger signaling molecules (DAMPs), thereby stimulating the antigen-presenting function of dendritic cells and promoting the infiltration of T cells into the tumor. Concurrently, the ER-targeted delivery of PD-L1 siRNA resulted in the downregulation of both intracellular and membrane PD-L1 protein expression, consequently fostering the proliferation and activity of CD8+ T cells. Ultimately, the ER-targeted formulation exhibited enhanced anti-tumor efficacy and provoked anti-tumor immune responses against orthotopic colorectal tumors in vivo. Collectively, a robust ER-targeted delivery strategy provides an encouraging approach for achieving potent cancer chemoimmunotherapy.

According to previous studies, D-dimer levels are associated with the prognosis of patients with pancreatic cancer (PC). However, the results of current studies are limited and controversial. Therefore, we performed this meta-analysis to assess the relationship between D-dimer levels and prognostic and pathological characteristics of PC patients. We first searched the databases of PubMed, Embase, The Cochrane Library, Web Of Science, CBM, VIP, CNKI and Wanfang to identify available studies. The relationship between pretreatment d-dimer levels and prognosis in PC patients was assessed using the combined hazard ratio (HR) and 95% confidence interval (CI). The combined odds ratio (OR) and 95% confidence interval (CI) were used in assessing the relationship between pathological characteristics and d-dimer levels in PC patients. Stata 12.0 software was used for all statistical analyses. In total, we included 13 studies involving 2777 patients. The results showed that elevated pre-treatment d -dimer levels were significantly associated with OS deterioration (HR = 1.46 95% CI: 1.34–1.59; p

The deintercalation of weakly bonded A element affects the microstructure and properties of MAX phases and their reinforced composites. In this work, the effect of M-site element on the interaction of Al-containing M2AlC (M = V, Cr) phase and Ag, and the induced properties of Ag/M2AlC electrical contact materials (ECMs) were investigated. Though Ag and Al are soluble to each other and can form intermetallics, the variation of M element significantly affected the vacancy formation of Al, and thereby the interfacial reaction of Ag/M2AlC. The difficult formation of Al vacancy in V2AlC contributed to no obvious interfacial reaction in Ag/V2AlC. But the easy deintercalation of Al atoms in Cr2AlC led to their massive replacement by Ag, which generated Ag nano-twins and Cr3C2 with the same crystallographic relationship in one original Cr2AlC, and Cr7C3 and Ag3Al as well. Due to the distinct interactions, the resistivities of Ag/V2AlC and Ag/Cr2AlC increased by roughly 1 and 5 times after sintering, respectively. The low resistivity and proper hardness of the sintered Ag/V2AlC, which were very close to those of the “all-purpose” commercial Ag/CdO, contributed to its superior arc erosion resistance.

In this study, the synergistic effect of the Nb content and cooling rate on the microstructural transformation, precipitation behavior, and mechanical properties of hot-rolled rebar was studied using a Gleeble-3800 thermal simulation machine, scanning electron microscopy, transmission electron microscopy, and a universal tensile testing machine. The results showed that the synergistic effect of Nb content and cooling rate could optimize the microstructure and precipitation behavior of rebar, promote ferrite and pearlite transformation, and reduce the ferrite grain size, pearlite lamellar spacing, and precipitated phase size, thereby improving the strength and plasticity of Nb-containing rebar. When the cooling rate was 3 °C/s and the Nb content was 0.035 wt%, the ferrite grain size decreased to 21.45 μm, the pearlite lamellar spacing refined to 0.222 μm, and the particle size of the (Nb, Ti, V) C precipitates reduced to 5 nm. Accordingly, the yield and tensile strength increased to 779 ± 6 MPa and 973 ± 8 MPa, respectively, the elongation at fracture increased to 16.35%, and the microhardness increased to 311.39 ± 8.0 HV.

Isothermal heat treatment experiments were used to studied the dissolution behavior and kinetics of the γ′ precipitates within the hot-extruded novel powder metallurgy Ni-based superalloy A1. The characteristics of the γ′ precipitates were accurately and rapidly extracted by deep learning methods. The JMAK models were established to predict the change of the area fraction of γ′ precipitates during heat treatment. The determination coefficient R2 of model is 0.99. The results indicate that the dissolution sequence, morphological evolution, and dissolution mechanisms of the three types of γ′ precipitates are different. The small-sized tertiary γ′ precipitates (γ′t) dissolve first, while the larger-sized primary γ′ precipitates (γ′p) dissolve last. After 15 min at 1120 °C, there were only a small amount of γ′ precipitates with 0.19 ± 0.03 % area fraction. And there was not significant changed over time. After 1 min at 1150 °C, the γ′ precipitates completely dissolved. During the process of low temperature subsolvus heat treatment (1060 °C, 1090 °C), the large-sized γ′s grown at the expense of consuming the small-sized γ′ precipitates, and the γ′s tend towards directional arrangement due to elastic interaction energy. During the subsolvus heat treatment process, the γ′p spilt due to elastic strain energy and the uneven diffusion of alloying elements, while neck-connected coalescence coarsening occurs due to the overlapping diffusion fields.

In this study, 304 antimicrobial stainless steel coatings were prepared by the electron beam melting of antimicrobial stainless steel powder, in an attempt to enhance the surface properties of Q345R steel. Besides, the effect of Cu-containing 304 powder coatings on the microstructure, mechanical properties, and electrochemical properties of the Q345R surface was investigated. The results indicated that the coating grain was refined, the dislocation density was increased, and both the plasticity and toughness were enhanced after the electron beam surface coating (EBSC) treatment. Additionally, the hardness of coatings was also enhanced under the three beam currents due to grain refinement and dislocation strengthening. At a beam current of 28 mA, the coating hardness reached a maximum of 384.078 HV, representing a two-fold increase compared with the base material (BM) hardness of 131.048 HV. Moreover, the abrasion resistance of the coating was superior to that of the BM. At a beam current of 28 mA, the wear volume and wear rate were minimized to only 10 % of the wear volume of substrates. In galvanic corrosion measurements, the coatings displayed better corrosion resistance than the substrates, and these samples at a beam current of 28 mA exhibited the best corrosion resistance. Overall, the E-beam surface melting 304 stainless steel coating can effectively improve the properties of Q345R carbon steel.

Magnesium (Mg) is abundant in humans. Studies have shown that Mg2+ significantly affects physiological processes such as osteogenesis, osteoblast adhesion and motility, immunomodulation, and angiogenesis. Mg-based alloy porous scaffolds have attracted increasing attention because of their degradability and mechanical properties. Hence, wire-cut EDM was used to fabricate porous scaffolds. In addition, fluoride treatment afforded an MgF2 coating, and racemic polylactic acid PDLLA was used as the carrier of rhBMP-2, which was evenly coated on the surface of the passivated porous alloy scaffold to slowly release growth factors and slow down the degradation rate. The rat femoral condyle defect model experiment was performed to study the in vivo bone regeneration capacity of porous scaffolds and compare the differences in the healing effect with or without rhBMP-2. The enhanced corrosion resistance of the porous scaffold was confirmed through in vitro immersion experiments. Micro-CT implied that porous scaffold with rhBMP-2 induced new bone formation and the new bone formation along the pores, as well as the histological examination in vivo. In summary, the porous scaffold promotes bone formation and has great potential for clinical translation.

The seed storage materials accumulate during seed development, and are essential for seed germination and seedling establishment. Here we employed two bi-parental populations of an F2:3 population developed from a cross of improved 220 (I220, small seeds with low starch) and PH4CV (large seeds with high starch), as well as recombinant-inbred lines (RILs) of X178 (high starch) and its improved introgression line I178 (low starch), to identify the genes that control seed storage materials. We identified a total of 12 QTLs for starch, protein and oil, which explained 3.44–10.79% of the phenotypic variances. Among them, qSTA2-1 identified in F2:3 and qSTA2-2 identified in the RILs partially overlapped at an interval of 7.314–9.554 Mb, and they explained 3.44–10.21% of the starch content variation, so they were selected for further study. Fine mapping of qSTA2-2 with the backcrossed populations of I220/PH4CV in each generation narrowed it down to a 199.7 kb interval that contains 14 open reading frames (ORFs). Transcriptomic analysis of developing seeds from the near-isogenic lines (NILs) of I220/PH4CV (BC5F2) showed that only 11 ORFs were expressed in 20 days after pollination (DAP) seeds. Five of them were upregulated and six of them were downregulated in NILI220, and the differentially expressed genes (DEGs) between NILI220 and NILPH4CV were enriched in starch metabolism, hormone signal transduction and glycosaminoglycan degradation. Of the eleven NILI220 differential expressed ORFs, ORF4 (Zm00001d002260) and ORF5 (Zm00001d002261) carry 75% protein sequence similarity, both encodes an glycolate oxidase, were the possible candidates of qSTA2-2. Further analysis and validation indicated that mutation of the qSTA2-2 locus resulted in the dysfunction of ABA accumulation, the embryo/endosperm ratio and the starch and hormone levels.

Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality. Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic, collectively known as ribosomopathy genes. Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer. Abnormal ribosome biogenesis and dysregulation of some ribosomopathy genes have also been found to be intimately associated with cancer development. The correlation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established. This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile, to excavate the potential role of these genes, which have not or rarely been reported in cancer, in the disease development across cancers. We plan to establish a theoretical framework between the ribosomopathy gene and cancer development, to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.

Cr–Fe–Ni–Co–Mo–Si–B amorphous coating was successfully prepared on 316 L steel using atmospheric plasma spraying (APS). The effects of different annealing temperatures on the crystallization process of amorphous coatings, thus on the corrosion resistance and mechanical properties of coatings were studied. The results indicated that heat treatment can increase the hardness of the amorphous coating by 12.5% and reduce the wear rate by 30%. In addition, compared to heat-treated coatings, the amorphous coating had the highest corrosion voltage (−0.506V) and lower corrosion current (5.609 × 10−6 A). The passivation film on the amorphous coating provided the best protection due to the relatively high content of Cr2O3. The molecular dynamics (MD) calculation results also indicated that the adsorption energy of hydrogen chloride molecules on Cr–Fe–Ni–Co–Mo–Si–B amorphous coating (−90.94 kcal/mol) was greater than that of 316 L (−293.03 kcal/mol).

The wide application of plastics has led to the ubiquitous presence of nanoplastics and microplastics in terrestrial environments. However, few studies have focused on the mechanism underlying the effects of plastic particles on soil microbiomes and resistomes, especially the differences between nanoplastics and microplastics. This study investigated the microbiome and resistome in soil exposed to polystyrene microplastics (mPS) or nanoplastics (nPS) through 16S rRNA and shotgun metagenomic sequencing. Distinct microbial communities were observed between mPS and nPS exposure groups, and nPS exposure significantly changed the bacterial composition even at the lowest amended rate (0.01%, w/w). The abundance of antibiotic resistance genes (ARGs) in nPS exposure (1%) was 0.26 copies per cell, significantly higher than that in control (0.21 copies per cell) and mPS exposure groups (0.21 copies per cell). It was observed that nanoplastics, bacterial community, and mobile genetic elements (MGEs) directly affected the ARG abundance in nPS exposure groups, while in mPS exposure groups, only MGEs directly induced the change of ARGs. Streptomyces was the predominant host for multidrug in the control and mPS exposure, whereas the primary host was changed to Bacillus in nPS exposure. Additionally, exposure to nPS induced several bacterial hosts to exhibit possible multi-antibiotic resistance characteristics. Our results indicated that the effects of plastic particles on the soil microbial community were size-dependent, and nano-sized plastic particles exhibited more substantial impacts. Both microplastics and nanoplastics promoted ARG transfer and diversified their bacterial hosts. These findings bear implications for the regulation of plastic waste and ARGs.

Objective: To investigate the associations between dynapenic obesity and the risk of dementia, and the modifying effects of age, sex, and the APOE gene, using a large population-based cohort. Methods: 279,884 participants aged 55 and above from the UK Biobank were included. The participants were classified into four categories based on body mass index and hand grip strength: healthy, obesity, dynapenia, and dynapenic obesity. The incident dementia was identified based on linked hospital records and death register data. Cox proportional hazards regression models were used to estimate the associations, followed by age-, sex-, and apolipoprotein E (APOE) gene-stratified analyses. Results: During the median follow-up of 12.4 years, 5,170 (1.8%) participants developed dementia. Compared with the healthy group, participants with dynapenic obesity had 67% higher dementia risk (hazard ratio [HR]: 1.67, 95% confidence interval [CI]: 1.44–1.94). Compared with the healthy group, higher risks of dementia in participants with dynapenic obesity were respectively observed in male (HR: 2.03, 95% CI: 1.65–2.50), younger (

The diversification of future aquaculture feed formulas is expected to rise due to the increasing fish feed production. Changes in formulas and the corresponding adjustments to processing parameters can create variations in the pellet physical quality (PPQ). Despite these potential changes in PPQ, the impact of varying PPQ on the physiological response of fish is often undervalued or overlooked. In this study, we investigated the effect of protein sources and extrusion processing conditions through PPQ on the gastrointestinal chyme emptying, feed intake and digestibility of spotted seabass. Four diets were formulated following a 2×2 factorial design, with two protein sources (fish meal [FM] and cottonseed protein concentrate [CPC]) and two processing conditions (PC-M, preconditioning water content 30 % and die temperature 120 °C vs. PC-H, preconditioning water content 22 % and die temperature 140 °C). Fish (46 g) were fed twice daily to apparent satiation. Feed intake, nutrient digestibility and fish performance were evaluated over a 20-day experimental period. At the end of the experiment, chyme was collected after fish were fed restrictively one meal (0.95 % BW/d) to determine gastrointestinal emptying and water fluxes. Chyme was quantitatively collected from stomach and intestine at 2, 4, 6, 8, 12 and 24 h postprandial. Altering protein source affected PPQ as well as nutrient digestibility. Compared to FM-pellets, CPC-pellet lowered nutrients and energy digestibility. In addition, CPC-pellets led to a decrease in postprandial plasma glucose level and hepatosomatic index than FM-pellets. Processing conditions steered PPQ and influenced the physiological response of fish. PC-M resulted in a 23 % increase in stomach water flux at 4 h postprandial and a 2 % rise in stomach chyme water content than PC-H. Moreover, PC-H led to higher protein and fat digestibility than PC-M. Both protein source and processing condition treatments did not differ in feed intake, gastric emptying of fish.

Objective: The senescence process is pivotal in both the onset and advancement of lung adenocarcinoma (LUAD), influencing cell growth, immune evasion, the potential for metastasis, and resistance to treatments. Senescent cells' dual nature, both harmful and advantageous, adds complexity to understanding their expression patterns and clinical relevance in LUAD. In this study, we sought to evaluate the predictive value of the senescence-related signature in survival outcomes and immunotherapy efficacy in patients with LUAD. Materials and methods: We integrated data from 1449 LUAD cases sourced from different publicly accessible datasets and a clinical cohort of Chinese LUAD patients. The Cox regression analysis employing the least absolute shrinkage and selection operator (LASSO) was performed on 156 senescence-associated genes to develop the senescence-related signature. Kaplan-Meier analysis and time-dependent receiver operating characteristic curves were utilizaed to assess the prognostic significance of the senescence-related signature. Functional annotation, immune infiltration analysis, and gene set variation analysis were applied to investigate the association of the senescence-related signature with anti-tumor immunity in LUAD. Immunotherapy cohorts of non-small cell lung cancer, urothelial carcinoma, skin cutaneous melanoma, and glioblastoma patients were included to assess the senescence-related signature in predicting immunotherapy efficacy. Results: The senescence-related signature, which encompasses seven senescence-related genes, namely, FOXM1, VDAC1, PPP3CA, MAPK13, PIK3CD, RRAS, and CCND3, was identified to have predictive significance across multiple LUAD cohorts and demonstrated a negative association with antitumor immunity and tumor-infiltrating neutrophils. Patients exhibiting low expression levels of the senescence-related signature responded more favorably to immune checkpoint inhibitors in various solid tumors, including LUAD. Inhibiting FOXM1 pharmacologically with thiostrepton produced tumor-suppressive effects and improved immunotherapy responses in a Lewis lung carcinoma mouse model. Conclusions: The senescence-related signature demonstrates potential in predicting patient prognosis and immunotherapy efficacy in LUAD.

Aims: To investigate the therapeutic effect of acupuncture on acute inflammatory nerve root injury by regulating lymphatic function. Main methods: A mouse model of L5 nerve root compression was used to simulate acute nerve root injury. After modeling, acupuncture treatment was given each day for one week. Pain thresholds were assessed before and after modeling and treatment. Immunofluorescence staining was performed to observe the distribution astrocytes and neurons in the lumbar spinal cord, the innervation rate of neuromuscular junctions (NMJs), lymphatic endothelial cells (LECs) of lumbar aortic lymph nodes, and the percentage of M1 macrophages. The number of each type of immune cells in the lumbar aortic lymph nodes (LALNs) was measured by flow cytometry. Key findings: The model group showed a significant decrease in pain threshold in the affected lower limb, while acupuncture treatment was able to significantly increase it. Acupuncture significantly repaired astrocytes and neurons in the lumbar spinal cord of the compressed segment, increased the innervation rate of nerve endings at NMJs, reduced LECs in the LALNs, reduced the proportion of M1 macrophages in the LALNs, and significantly reduced mononuclear neutrophils and monocytic neutrophils. Significance: Acupuncture can reduce pain, promote nerve repair in mice with acute nerve root injury, and suppress immune responses in lumbar aortic lymph nodes.

The escalating adoption of laparoscopic surgical techniques has demonstrated their capacity to yield improved clinical outcomes. However, concomitant with the advantages of this minimally invasive approach, certain adverse complications have been reported. In this report, we present a noteworthy case involving a 72-year-old male patient who underwent laparoscopic inguinal hernia repair. The surgical procedure proceeded without noteworthy complications, and the patient maintained hemodynamic stability throughout. However, the post-anesthetic recovery was compromised by the onset of subcutaneous emphysema and bilateral tension pneumothorax. Immediate intervention was imperative, prompting the performance of an emergent needle thoracostomy, subsequently followed by the implementation of a closed drainage system within the thoracic cavity. These interventions proved efficacious in mitigating the patient's distressing symptoms. Although pneumothorax complications in the context of laparoscopic surgery are infrequent, it is imperative for anesthetists to remain vigilant regarding the potential occurrence of subcutaneous emphysema and pneumothorax in the perioperative period. This case underscores the significance of meticulous perioperative monitoring and rapid intervention, particularly in laparoscopic procedures, where the insufflation of carbon dioxide into the abdominal cavity can predispose patients to these rare yet potentially life-threatening complications. Heightened awareness among healthcare providers regarding the possibility of such events is pivotal in ensuring the safety and well-being of surgical patients.

Micro–nano-plastic (MNP) particles (p) in the environment can enter the human body and pose a potential threat to human health. However, it is unknown whether these substances are present in polypropylene (PP) plastic-bottled injections, which are used as high-frequency intravenous infusions to treat diseases. Therefore, the objective of this study was to identify and quantify insoluble MNP particles in 16 batches of injectable formulations within the validity period. Primarily, ethylene–propylene copolymer or P(E–P) micro-plastic (MP) particles (2–10 μm, 216 p/mL) were identified by micro-Raman spectroscopy, and nano-particles (

Biomineralization plays an important role in various physiological activities in both nature and living organisms. Organisms regulate the crystal nucleation, crystal phase, and crystal growth kinetics of inorganic phases through organic regulation, forming minerals with multi-level order, thereby playing a role in biological support, protection, and metabolic regulation. Unlike general inorganic minerals, biominerals are subtly regulated by organic organisms (such as small organic molecules, peptides, proteins, nucleic acids) and complex environments, possessing biological characteristics and becoming a part of living organisms. It can be seen that the process of biomineralization is not only the process of manufacturing biomaterials, but also the process of using materials to regulate organisms themselves. The biomimetic strategy based on biomineralization can achieve a huge transformation from the biomimetic preparation of functional materials to the biomimetic composite of organisms and materials. In this review, we briefly introduce biomimetic structures inspired by nature itself, and emphasize the important role of the relationship between organisms and materials in the process of biomineralization. We also briefly explore biominerals and their mechanisms. At the same time, a series of functional materials (such as self-cleaning hydrophobic materials, artificial spider silk fibers, mother of pearl like composite materials, humidity responsive materials, and bioprinting materials) synthesized through biomimetic strategies inspired by biomanufacturing materials were systematically elucidated. And a brief discussion was given on the synthesis of new functional organisms using biomimetic strategies to regulate organisms, such as using functional materials to regulate biomimetic repair of hard tissues, using biomineralization strategies to coat vaccines to improve their thermal stability during transportation and drug delivery efficiency in vivo, and constructing functional biomimetic artificial organelles on demand. Finally, this article summarizes the current opportunities and challenges based on biomineralization, providing further feasible guidance for future material regulation of life.

Bladder cancer stands as a prevalent global malignancy, exhibiting notable sex-based variations in both incidence and prognosis. Despite substantial strides in therapeutic approaches, the formidable challenge of drug resistance persists. The genomic landscape of bladder cancer, characterized by intricate clonal heterogeneity, emerges as a pivotal determinant in fostering this resistance. Clonal evolution, encapsulating the dynamic transformations within subpopulations of tumor cells over time, is implicated in the emergence of drug-resistant traits. Within this review, we illuminate contemporary insights into the role of clonal evolution in bladder cancer, elucidating its influence as a driver in tumor initiation, disease progression, and the formidable obstacle of therapy resistance.

Pharmacogenetic testing technology can effectively determine the individual differences among patients and scientifically assist doctors to select the most suitable drugs for each patient. In this study, an electrochemical biosensor based on magnetic α-Fe2O3/Fe3O4 heterogeneous nanosheets was constructed to detect Vitamin K epoxide reductase complex 1 type AA (VKORC1*2). Firstly, we fabricated magnetic α-Fe2O3/Fe3O4 heterogeneous nanosheets as the substrate material for electrochemical biosensors. Subsequently, the material surface was modified with Au nanoparticles to facilitate the connection of sensing probes and enhance current signal amplification. The electrochemical biosensor showed a negative linear relationship with the concentrations of target DNA (tDNA, VKORC1*2 gene) within 1 pM − 1 μM, a limit of detection was (LOD) = 0.36 pM, and a limit of quantification was (LOQ) = 1.19 pM. The biosensor demonstrated exceptional specificity, reproducibility, and stability. In real sample analysis, it exhibited a recovery range of 96.63 % − 110.57 % (RSD ≤ 3.07 %) for various tDNA concentrations, thereby indicating its promising potential in clinical diagnostics.

Utilizing computer-based scales for cognitive and psychological evaluations allows for the collection of objective data, such as response time. This cross-sectional study investigates the significance of response time data in cognitive and psychological measures, with a specific focus on its role in evaluating sleep quality through the Insomnia Severity Index (ISI) scale. A mobile application was designed to administer scale tests and collect response time data from 2729 participants. We explored the relationship between symptom severity and response time. A machine learning model was developed to predict the presence of insomnia symptoms in participants using response time data. The result revealed a statistically significant difference (p

Inflammation is a complex physiological phenomenon, which is the body's defensive response, but abnormal inflammation can have adverse effects, and many diseases are related to the inflammatory response. AMPK, as a key sensor of cellular energy status, plays a crucial role in regulating cellular energy homeostasis and glycolipid metabolism. In recent years, the anti-inflammation effect of AMPK and related signalling cascade has begun to enter everyone's field of vision – not least the impact on metabolic diseases. A great number of studies have shown that anti-inflammatory drugs work through AMPK and related pathways.Herein, this article summarises recent advances in compounds that show anti-inflammatory effects by activating AMPK and attempts to comment on them.

Background: Recently, numerous studies have reported the interaction between senescence and oxidative stress in cancer. However, there is a lack of a comprehensive understanding of the precise mechanisms involved. Aim: Therefore, our review aims to summarize the current findings and elucidate by presenting specific mechanisms that encompass functional pathways, target genes, and related aspects. Methods: Pubmed and Web of Science databases were retrieved to search studies about the interaction between senescence and oxidative stress in cancer. Relevant publications in the reference list of enrolled studies were also checked. Results: In carcinogenesis, oxidative stress-induced cellular senescence acts as a barrier against the transformation of stimulated cells into cancer cells. However, the senescence-associated secretory phenotype (SASP) is positively linked to tumorigenesis. In the cancer progression stage, targeting specific genes or pathways that promote oxidative stress-induced cellular senescence can suppress cancer progression. In terms of treatment, many current clinical therapies combine with novel drugs to overcome resistance and reduce side effects by attenuating oxidative stress-induced senescence. Notably, emerging drugs control cancer development by enhancing oxidative stress-induced senescence. These studies highlight the complacted effects of the interplay between oxidative stress and senescence at different cancer stages and among distinct cell populations. Future research should focus on characterizing the roles of distinct senescent cell types in various tumor stages and identifying the specific components of SASP. Concludsion: We've summarized the mechanisms of senescence and oxidative stress in cancer and provided illustrative figures to guide future research in this area.

Due to its adjustable pore structure, the metal–organic frameworks (MOFs) have attracted much attention in the treatment of organic dye molecules in wastewater. However, the general tuning of the pore channels of MOFs is mainly by changing the chain length of the organic ligands and metal nodes. This approach not only limits the types of MOFs, but also limits the treatment of a large number of dye methylene blue (MB) and methyl orange (MO) dye molecules in the wastewater. Hence, we synthesized photoresponsive Zn-AzDC/TPA MOF as adsorbents to adsorb and release organic dye molecules in a photo-controlled manner. The photoresponsive Zn-AzDC/TPA was prepared using a mixed ligand strategy, in which the azobenzene carboxylic acid derivative (AzDC) served as a photoresponsive ligand and terephthalic acid (TPA) served as a non-active ligand in coordination with zinc ion. The optical and structural properties of the synthesized Zn-AzDC/TPA was characterized by UV–vis, FT-IR, PXRD, SEM, TEM, TGA, and pore analysis. Interestingly, it was found that the photoresponsive AzDC unit of Zn-AzDC/TPA demonstrated reversible trans–cis isomerization under the alternating UV and visible light, resulting in reversible changes in the pore size of the Zn-AzDC/TPA. Its photoresponse properties can trapp and release dye molecules under light-driven conditions. This result provides a new direction for the application of photoresponsive MOF and also lays a foundation for the study of diversified optically responsive materials.

Cavitation erosion is a general phenomenon in the fields of aviation, navigation, hydraulic machinery, and so on, causing great damage to fluid machinery. With the vast requirements in deep ocean applications, it is urgent to study the mechanism of cavitation erosion and the cavitation erosion resistance of different materials under high hydrostatic pressure to predict and avoid the effect of cavitation erosion. In this work, the spatially confined cavitation bubble cloud associated with Gaussian-like intensity distribution sonoluminescence (SL) was produced by a spherically focused ultrasound transducer with two opening ends near metallic plates under different hydrostatic pressures (0.1, 3, 6, and 10 MPa). The cavitation erosion effects on copper, 17-4PH stainless steel and tungsten plates were studied. Through coupling analysis towards the SL intensity distribution, the macro/micro morphology of cavitation erosion, and the physical parameters of different metallic materials (hardness, yield strength, and melting point), it is found that with increasing hydrostatic pressure, the erosion effect is intensified, the depth of cavitation pits increases, the phenomenon of melting can be observed on materials with relatively low melting points, and the cavitation erosion experienced an evolution process from high-temperature creep to fracture. This work has also established a method for the evaluation of materials’ cavitation erosion resistance with measurable SL intensity distribution, which is promising to promote the designing and selection of anti-cavitation materials in deep-sea applications.

Background: With regard to head and neck squamous cell carcinoma (HNSCC), its occurrence and advancement are controlled by genetic and epigenetic anomalies. PIWI-interacting RNAs (piRNAs) are recognized with significance in tumor, but the precise molecular mechanisms of piRNAs in HNSCC largely remain undisclosed. Methods: Differentially expressed piRNAs were identified by RNA sequencing. The expression of piR-hsa-23533 was evaluated using quantitative real-time PCR and RNA in situ hybridization. The impacts of piR-hsa-23533 on the proliferation and apoptosis of HNSCC cells were investigated by a series of in vitro and in vivo assays. Results: piR-hsa-23533 exhibits upregulation within HNSCC cells and tissues. Besides, piR-hsa-23533 overexpression promotes proliferation while inhibiting apoptosis in vitro and in vivo, while piR-hsa-23533 silencing has an opposite function. From the mechanistic perspective, piR-hsa-23533 can bind to Ubiquitin-specific protease 7 (USP7), as shown through RNA pull-down and RNA immunoprecipitation assays, promoting USP7 mRNA and protein expression. Conclusions: These findings highlight the functional importance of piR-hsa-23533 in HNSCC and may assist in the development of anti-HNSCC therapeutic target.

Recycled concrete aggregate (RCA) presents several challenges such as irregular shape, high water absorption, high crushing value, and low apparent density, which restrict its application in concrete. Although carbonation technology offers a more effective solution, its effect on inferior RCA remains unclear. Compared to its common counterpart, inferior RCA is characterized by longer aging time, lower crushing value, and reduced carbonizable substances. This study focuses on low-quality RCA, employing a method of impregnation and carbonation with cement slurry to strengthen the properties of RCA. The investigation studied the carbonation system (hydration time + carbonation time), water–cement ratio of the cement paste, and carbonation effects and mechanisms via mercury injection, nanoindentation tests, X-ray diffraction, and scanning electron microscopy. The findings indicate that the optimal carbonation system involves hydration for 1 d and carbonation for 14 d (H1d + C14d). In this system, the water–cement ratio exhibits minimal influence on carbonation depth. After the impregnation–carbonation treatment, RCA displayed the best performance improvement at a water–cement ratio of 0.8 (0.8-RCA). This condition resulted in a 15.41% reduction in crushing value and an 18.00% decrease in porosity alongside a 21.42% increase in apparent density. Moreover, the interfacial transition zone (ITZ) between aggregate and mortar and the elastic modulus of adhesive mortar are improved after strengthening. Compared with the primitive RCA, the distribution of Ca2+ in the adhesive mortar of the strengthened RCA was more uniform and denser. The moderately fluid cement slurry penetrated the RCA pores easily, enabling CaCO3 produced by carbonation to efficiently fill defects.

This study investigates the complexity of spatial soil modelling, particularly focusing on the challenge of variable vertical support in traditional soil data collection. Traditional soil sampling, described in terms of horizons, often fails to accurately pinpoint the specific depths for specific soil properties. This gap is significant, as depth-specific data is crucial for a thorough understanding of soil formation processes and for assessing potential environmental impacts. In digital soil mapping (DSM), the prevalent reliance on standardised depth intervals and mass-preserving spline functions for data resampling results in a modelling approach that tends to disregard depth-related details, thereby introducing potential uncertainties.To address these limitations, this work explores how effectively Gaussian process regression (GPR) can model soil in 3D. This technique comprises two key components: a mean function and a semivariogram-like kernel. Unlike conventional methods that make a single prediction, GPR provides detailed probability distributions. This capability allows for the quantification of prediction uncertainty at various points, offering insights for decision-making and risk assessment purposes. Moreover, GPR has the capability to make volume or block estimates and assess associated uncertainties. Enabling volume-based predictions enriches the range of strategies available for land management.In this research, we employ GPR as a novel 3D soil modelling technique and compare its performance with traditional spline-based methods. The comparison is conducted through a case study on a farm in northern New South Wales, Australia, focusing on the 3D mapping of soil pH and electrical conductivity (EC). Our results demonstrate the ability of GPR to estimate soil properties across various volumes, utilising data from multiple vertical supports, thereby offering a more versatile approach for soil modelling in diverse spatial contexts.

LZTR1 is a substrate specific adaptor for E3 ligase involved in the ubiquitination and degradation of RAS GTPases, which inhibits the RAS/RAF/MEK/ERK signaling to suppress the pathogenesis of Noonan syndrome and glioblastoma. However, it's still unknown whether LZTR1 destabilizes RAS GTPases to suppress HCC progression by inhibiting these signaling pathway. Lenvatinib is the first-line drug for the treatment of advanced HCC, however, it has high drug resistance. To explore the roles of LZTR1 in HCC progression and the underlying mechanisms of lenvatinib resistance, techniques such as bioinformatics analysis, immunohistochemical staining, RT-qPCR, Western blot, cell functional experiments, small interfering RNA transfection and cycloheximide chase assay were applied in our study. Among these, bioinformatics analysis and immunohistochemical staining results indicated that LZTR1 protein was aberrantly expressed at low levels in HCC tissues, and low protein expression of LZTR1 was associated with poor prognosis of HCC patients. In vitro functional experiments confirmed that low expression of LZTR1 promoted HCC cell proliferation and migration via the aberrant activation of the RAS/RAF/MEK/ERK signaling due to the dysregulation of LZTR1-induced KRAS ubiquitination and degradation. Transwell assays revealed that blocking of LZTR1-mediated KRAS degradation could induce lenvatinib resistance in HCC cells. In conclusion, our study revealed that LZTR1 knockdown promoted HCC cell proliferation and migration, and induced lenvatinib resistance via activating the RAS/RAF/MEK/ERK signaling, which may provide new ideas for HCC treatment.

Study region: The Fenhe River Basin, China Study focus: The hydrological parameters remained constant in a changing environment may no longer be applicable. The split-sample calibration method based on sliding window division (SWD-SSC) was proposed as a time-varying method, which confronts a challenge in the past due to the small number of samples and discontinuity. The annual LULC input and 11-year-block sliding scheme in distributed SWAT model were used to calibrate parameters. Sensitive parameters related to runoff, vegetation canopy and soil moisture demonstrated how characteristics change over time. Non-linear relationships for parameter variations were constructed by multiple algorithms combined with vegetation indexes, land use, human activity such as social economy factors. New hydrological insights for the region: SWD-SSC method performed well during the whole periods. When the same parameters sets were applied to all periods, the accuracy will be inferior to SWD-SSC with a decrease by 12–200% in NSE. Random Forests and Back-Propagation neural network show best performance in describing the relationship between hydrological parameters and environmental factors. The impact of climate change and human activities on runoff account for 33.2% and 66.8%. The impact of land use changes on runoff are 10.9% (-2.53 mm) and 8.7% (-1.35 mm) by time-varying parameters fixed parameters, respectively. These findings aid in the comprehension of hydrological processes and enhance simulation accuracy under changing environment, ensuring future regional water safety.

Takeover is a critical factor in the safety of autonomous driving. Takeover refers to the action of a human driver assuming control of an autonomous vehicle from its automated driving system. This can occur when the vehicle encounters a situation it cannot handle, when the system requests the driver to take control, or when the driver chooses to intervene for safety or other reasons. This study explored how traditional steering-wheel driving habits affect takeover performance in joystick-controlled autonomous vehicles. We conducted an experiment using a joystick-controlled Dongfeng Sharing-VAN autonomous vehicle in a low-speed campus environment. The participants were divided into three groups based on their driving experience: the individuals who have no licence and no experience (NN Group), the drivers who have licence but not experienced (HN Group), and the drivers who have licence and have been experienced (HH Group), representing varying levels of driving habits. The experiment focused on two takeover tasks: passive takeover and active takeover. We evaluated takeover performance using takeover time and takeover quality as key metrics. The results from the passive takeover task indicated that traditional driving habits had a significant negative impact on takeover performance. The HH Group took 2.65 s longer to complete the task compared to the NN Group, while the HN Group took 3.78 s longer. When we analyzed takeover time in stages, the initial stage showed the most significant difference in takeover time among the three groups. In the active takeover task, driving habits did not significantly affect takeover braking in front of obstacles in a low-speed driving environment. These findings suggest that conventional driving habits can hinder passive takeover in joystick-controlled autonomous vehicles. This insight can be valuable for developing training programs and guidelines for drivers transitioning from conventional to autonomous driving.

Summary: Background: Previous trials of renal denervation (RDN) have been designed to investigate reduction of blood pressure (BP) as the primary efficacy endpoint using non-selective RDN without intraoperatively verified RDN success. It is an unmet clinical need to map renal nerves, selectively denervate renal sympathetic nerves, provide readouts for the interventionalists and avoid futile RDN. We aimed to examine the safety and efficacy of renal nerve mapping/selective renal denervation (msRDN) in patients with uncontrolled hypertension (HTN) and determine whether antihypertensive drug burden is reduced while office systolic BP (OSBP) is controlled to target level (＜140 mmHg). Methods: We conducted a randomized, prospective, multicenter, single-blinded, sham-controlled trial. The study combined two efficacy endpoints at 6 months as primary outcomes: The control rate of patients with OSBP ＜140 mmHg (non-inferior outcome) and change in the composite index of antihypertensive drugs (Drug Index) in the treatment versus Sham group (superior outcome). This design avoids confounding from excess drug-taking in the Sham group. Antihypertensive drug burden was assessed by a composite index constructed as: Class N (number of classes of antihypertensive drugs) × (sum of doses). 15 hospitals in China participated in the study and 220 patients were enrolled in a 1:1 ratio (msRDN vs Sham). The key inclusion criteria included: age (18–65 years old), history of essential HTN (at least 6 months), heart rate (≥70 bpm), OSBP (≥150 mmHg and ≤180 mmHg), ambulatory BP monitoring (ABPM, 24-h SBP ≥130 mmHg or daytime SBP ≥135 mmHg or nighttime SBP ≥120 mmHg), renal artery stenosis (＜50%) and renal function (eGFR ＞45 mL/min/1.73 m2). The catheter with both stimulation and ablation functions was inserted in the distal renal main artery. The RDN site (hot spot) was selected if SBP increased (≥5 mmHg) by intra-renal artery (RA) electrical stimulation; an adequate RDN was confirmed by repeated electronic stimulation if no increase in BP otherwise, a 2nd ablation was performed at the same site. At sites where there was decreased SBP (≥5 mmHg, cold spot) or no BP response (neutral spot) to stimulation, no ablation was performed. The mapping, ablation and confirmation procedure was repeated until the entire renal main artery had been tested then either treated or avoided. After msRDN, patients had to follow a predefined, vigorous drug titration regimen in order to achieve target OSBP (＜140 mmHg). Drug adherence was monitored by liquid chromatography-tandem mass spectrometry analysis using urine. This study is registered with ClinicalTrials.gov (NCT02761811) and 5-year follow-up is ongoing. Findings: Between July 8, 2016 and February 23, 2022, 611 patients were consented, 220 patients were enrolled in the study who received standardized antihypertensive drug treatments (at least two drugs) for at least 28 days, presented OSBP ≥150 mmHg and ≤180 mmHg and met all inclusion and exclusion criteria. In left RA and right RA, mapped sites were 8.2 (3.0) and 8.0 (2.7), hot/ablated sites were 3.7 (1.4) and 4.0 (1.6), cold spots were 2.4 (2.6) and 2.0 (2.2), neutral spots were 2.0 (2.1) and 2.0 (2.1), respectively. Hot, cold and neutral spots was 48.0%, 27.5% and 24.4% of total mapped sites, respectively. At 6 M, the Control Rate of OSBP was comparable between msRDN and Sham group (95.4% vs 92.8%, p = 0.429), achieved non-inferiority margin −10% (2.69%; 95% CI −4.11%, 9.83%, p ＜ 0.001 for non-inferiority); the change in Drug Index was significantly lower in msRDN group compared to Sham group (4.37 (6.65) vs 7.61 (10.31), p = 0.010) and superior to Sham group (−3.25; 95% CI −5.56, −0.94, p = 0.003), indicating msRDN patients need significantly fewer drugs to control OSBP ＜140 mmHg. 24-hour ambulatory SBP decreased from 146.8 (13.9) mmHg by 10.8 (14.1) mmHg, and from 149.8 (12.8) mmHg by 10.0 (14.0) mmHg in msRDN and Sham groups, respectively (p 0.05 between groups). Safety profiles were comparable between msRDN and Sham groups, demonstrating the safety and efficacy of renal mapping/selective RDN to treat uncontrolled HTN. Interpretation: The msRDN therapy achieved the goals of reducing the drug burden of HTN patients and controlling OSBP

Lymph nodes (LNs) occupy a critical position in initiating and augmenting immune responses, both spatially and functionally. In cancer immunotherapy, tumor-specific vaccines are blooming as a powerful tool to suppress the growth of existing tumors, as well as provide preventative efficacy against tumorigenesis. Delivering these vaccines more efficiently to LNs, where antigen-presenting cells (APCs) and T cells abundantly reside, is under extensive exploration. Formulating vaccines into nanomedicines, optimizing their physiochemical properties, and surface modification to specifically bind molecules expressed on LNs or APCs, are common routes and have brought encouraging outcomes. Alternatively, porous scaffolds can be engineered to attract APCs and provide an environment for them to mature, proliferate and migrate to LNs. A relatively new research direction is inducing the formation of LN-like organoids, which have shown positive relevance to tumor prognosis. Cutting-edge advances in these directions and discussions from a future perspective are given here, from which the up-to-date pattern of cancer vaccination will be drawn to hopefully provide basic guidance to future studies.

Study region: The Kunlun Mountains on Tibetan Plateau Study focus: The Tibetan Plateau, well known as Asian Water Tower, holds immense potential for the formation of glacial mineral water. The present research focuses on the hydrochemical and isotopic signatures and formation pattern of natural glacial mineral water in the alpine region on Tibetan Plateau. New hydrological insights for the region: The investigated mineral groundwater has outstanding water quality and slightly alkaline nature. It is with fresh hydrochemical facies of HCO3-Na·Ca type with total dissolved solids (TDS) in the range of 384–964 mg/L, and featured by notably rich strontium with the concentrations of 0.67–0.81 mg/L, far exceeding the recommended mineral water minimum threshold of 0.20 mg/L. The mineral groundwater is originated from the glacier meltwater of mountainous area with elevation over 4500 m. It subsequently infiltrates into the bedrock and move within the groundwater system with a residence time of approximately 52 years. Its hydrochemical constituents are naturally governed by water-rock interactions of silicates dissolution, cation exchange, and celestite and strontianite dissolution. A conceptual model is proposed to outline the formation pattern of glacial mineral water in alpine region on Tibetan Plateau. Findings of this study can fill the study gap regarding glacial mineral water on Tibetan Plateau, and further contribute to the future study and development of natural glacial mineral water in alpine regions worldwide.