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The current pathologic N (pN) classification exhibits limitations in the prognostic stratification of patients with pT3-4N0-2M0 gastric cancer (GC). Therefore, this study aimed to develop and validate a new lymph nodal staging method based on the number of examined lymph nodes (ELNs) and lymph node ratio (LNR).

Due to the decomposition temperature of Polyamide 66 (PA66) in the environment is close to its thermoforming temperature, it is difficult to construct porous scaffolds of PA66/nanohydroxyapatite (PA66/HAp) by fused deposition modeling (FDM) three-dimensional (3D) printing. In this study, we demonstrated for the first time a method for 3D printing PA66/HAp composites at room temperature, prepared PA66/HAp printing ink using a mixed solvent of formic acid/dichloromethane (FA/DCM), and constructed a series of composite scaffolds with varying HAp content. This printing system can print composite materials with a high HAp content of 60 wt %, which is close to the mineral content in natural bone. The physicochemical evaluation presented that the hydroxyapatite was uniformly distributed within the PA66 matrix, and the PA66/HAp composite scaffold with 30 wt % HAp content exhibited optimal mechanical properties and printability. The results of in vitro cell culture experiments indicated that the incorporation of HAp into the PA66 matrix significantly improved the cell adhesion, proliferation, and osteogenic differentiation of bone marrow stromal cells (BMSCs) cultured on the scaffold. In vivo animal experiments suggested that the PA66/HAp composite material with 30 wt % HAp content had the best structural maintenance and osteogenic performance. The three-dimensional PA66/HAp composite scaffold prepared by low temperature printing in the current study holds great potential for the repair of large-area bone defects.

Protein homeostasis is essential for cyanobacteria to maintain proper cellular function under adverse and fluctuating conditions. The AAA+ superfamily of proteolytic complexes in cyanobacteria plays a critical role in this process, including ClpXP, which comprises a hexameric ATPase ClpX and a tetradecameric peptidase ClpP. Despite the physiological effects of ClpX on growth and photosynthesis, its potential substrates and underlying mechanisms in cyanobacteria remain unknown. In this study, we employed a streptavidin–biotin affinity pull-down assay coupled with label-free proteome quantitation to analyze the interactome of ClpX in the model cyanobacterium Synechocystissp. PCC 6803 (hereafter Synechocystis). We identified 503 proteins as potential ClpX-binding targets, many of which had novel interactions. These ClpX-binding targets were found to be involved in various biological processes, with particular enrichment in metabolic processes and photosynthesis. Using protein–protein docking, GST pull-down, and biolayer interferometry assays, we confirmed the direct association of ClpX with the photosynthetic proteins, ferredoxin-NADP+oxidoreductase (FNR) and phycocyanin subunit (CpcA). Subsequent functional investigations revealed that ClpX participates in the maintenance of FNR homeostasis and functionality in Synechocystisgrown under different light conditions. Overall, our study provides a comprehensive understanding of the extensive functions regulated by ClpX in cyanobacteria to maintain protein homeostasis and adapt to environmental challenges.

Adjuvant chemotherapy (CT) constitutes the primary approach for treating resectable advanced gastric cancer (GC). However, the effectiveness of postoperative CT can differ across various patient groups. This retrospective study aimed to examine how variances in clinical and pathologic factors affect postoperative CT.

Hydrogen energy as a clean energy source has been widely studied in recent years. Catalytic hydrogen combustion (CHC) can be used to reduce nitrogen oxide emissions and improve safety by burning hydrogen at a lower temperature. This review analyzes the effect of the hetero/homogeneous reaction mechanism, typical catalyst types (noble metal catalysts, metal oxide catalysts, and perovskite oxides), and support materials (zirconium dioxide, titanium dioxide, anodic aluminum oxide, γ-alumina, and silicon carbide) of CHC. The fabrication methods for CHC catalysts, such as impregnation, chemical vapor deposition, physical vapor deposition, combustion, sol–gel, hydrothermal treatment, and additive manufacturing, are reviewed. A series of challenges in CHC include water poisoning, sulfur poisoning, and durability. Water poisoning was broadly studied, but durability and sulfur poisoning are limitedly explored. The applications of CHC involved power and heat generations. Power generation is depicted as gas turbines and portable power generation, and heat generation is presented as heater and cooking stoves. Moreover, CHC is further applied in safety devices for nuclear power plants and confined spaces. Eventually, research gaps and future direction of the CHC process are concerned and summarized.

Objectives Pharyngocutaneous fistula (PCF) formation following open surgical treatment of hypopharyngeal cancer (HPC) is a common and troublesome complication. To date, the postoperative protocol of restarting oral intake is not clear, and vast discrepancies exist in the literature and among institutions. This study aimed to explore the impact of a postoperative protocol of restarting oral intake on PCF formation after open surgical treatment of primary HPC, and its impact on overall survival (OS) and swallowing function based on the functional outcome swallowing scale (FOSS).Materials and Methods This was a prospective observational study of 42 patients who received open surgical treatment for primary HPC at Beijing Friendship Hospital between April 2019 and August 2021. This cohort included two groups: patients who restarted oral intake on the 10th postoperative day (Group 1), and those who started on the 20th (Group 2). The Chi-square test and Fisher’s exact chi-squared test were used for comparing qualitative data among the groups.Results Group 1 (n = 27) and Group 2 (n = 15) were comparable in clinical characteristics. PCF occurred in 7 (25.9%) patients in Group 1, while none occurred in Group 2 (P= 0.038). The 2-year OS of all 42 patients was 75.6%; 65.8% and 93.3% for Groups 1 and 2, respectively (P= 0.07). The swallowing function was satisfactory (FOSS Grades 0–III) for 19 (70.4%) patients in Group 1 and 15 (100%) patients in Group 2 (P= 0.035). Laryngeal preservation was achieved in 25 (59.5%) patients, while decannulation was successful in 22 (88.0%) patients.Conclusions Delayed oral feeding significantly reduces PCF after open surgical treatment of primary HPC, and improves the swallowing function outcome without jeopardizing the OS.

Background: Amplification of inosine monophosphate dehydrogenase II, EC 1,1,1,205 (IMPDH2) has been reported in various cancers, which results in transformation and tumorigenicity. In our current work, we have explored the oncogenic properties and the underlying pathophysiology of IMPDH2 in hepatoblastoma (HB).Methods: To investigate IMPDH2 expression in HB tissues and prognostic significance in HB patients, gene expression profiling interactive analysis (GEPIA) has been adopted. Immunohistochemistry has also helped to validate the protein expression of IMPDH2 in HB tissues. The effect of IMPDH2 overexpression or depletion on the proliferation of Hepatoblastoma cells in vitro has been evaluated by CCK8 assays and colony formation assays. Xenograft tumor growth of mice has been detected. Luciferase reporter assays have been conducted to determine the interaction of IMPDH2 and JunB, which was further asserted by pharmacological inhibition of JunB.Results: IMPDH2 was highly expressed in HB tissues. Experimentally, the proliferation and colony formation of HuH6 cells were increased by IMPDH2 overexpression. Conversely, genetic inactivation of IMPDH2 impaired the proliferative efficiency and colony-forming rate of HepG2 cells. Besides, the luciferase reporter assay validated IMPDH2 overexpression to be associated with enhanced JunB transcriptional activity, while its activity was diminished in the case of IMPDH2 depletion. JunB inhibitor neutralized the IMPDH2-mediated increased phosphorylation of JunB.Conclusion: Our findings, thus, suggest that IMPDH2 exhibits its oncogenic role in HB partially via JunB-dependent proliferation.

In order to elucidate the mechanism of the effect of Ta content on the high temperature behaviour of the alloys, the high temperature oxidation and thermal corrosion experiments were carried out on the three alloys with different Ta contents (2.72, 3.10 and 4.00 wt.%). The results of high temperature oxidation and hot corrosion show that because Ta has a higher valence state than Al, it can reduce the indiffusion of O, and the rate at which Ta diffuses within the alloy matrix is relatively slow since it has a larger atomic radius. As a result, the diffusion of the Al element is inhibited as the Ta content increases. Therefore, adding Ta inhibits the formation of Al2O3in the surface oxide and promotes the formation of Cr2O3. Thus, Ta promotes oxidised film growth on the sample surface, which inhibits the diffusion of S, O and other elements into the matrix. Additionally, Cr2O3is not easy to dissolve in molten salt, which ultimately makes the alloy have high oxidation resistance and thermal corrosion resistance.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome with cardiac dysfunction, fluid retention and reduced exercise tolerance as the main manifestations. Current treatment of HFpEF is using combined medications of related comorbidities, there is an urgent need for a modest drug to treat HFpEF. Geniposide (GE), an iridoid glycoside extracted from Gardenia Jasminoides, has shown significant efficacy in the treatment of cardiovascular, digestive and central nervous system disorders. In this study we investigated the therapeutic effects of GE on HFpEF experimental models in vivo and in vitro. HFpEF was induced in mice by feeding with HFD and L-NAME (0.5 g/L) in drinking water for 8 weeks, meanwhile the mice were treated with GE (25, 50 mg/kg) every other day. Cardiac echocardiography and exhaustive exercise were performed, blood pressure was measured at the end of treatment, and heart tissue specimens were collected after the mice were euthanized. We showed that GE administration significantly ameliorated cardiac oxidative stress, inflammation, apoptosis, fibrosis and metabolic disturbances in the hearts of HFpEF mice. We demonstrated that GE promoted the transcriptional activation of Nrf2 by targeting MMP2 to affect upstream SIRT1 and downstream GSK3β, which in turn alleviated the oxidative stress in the hearts of HFpEF mice. In H9c2 cells and HL-1 cells, we showed that treatment with GE (1 μM) significantly alleviated H2O2-induced oxidative stress through the MMP2/SIRT1/GSK3β pathway. In summary, GE regulates cardiac oxidative stress via MMP2/SIRT1/GSK3β pathway and reduces cardiac inflammation, apoptosis, fibrosis and metabolic disorders as well as cardiac dysfunction in HFpEF.

Introduction: Further clinical validation is required to determine whether transcutaneous electrical acupoint stimulation (TEAS) can replace opioids and be used in combination with remimazolam for sedation during gastrointestinal endoscopy. Methods: A total of 108 outpatients who underwent diagnostic gastrointestinal endoscopy were randomly divided into three groups: fentanyl plus remimazolam group (group C), TEAS plus remimazolam group (group E), and placebo-TEAS plus remimazolam group (group P). The assessments of patient satisfaction, physician satisfaction, and pain scale score during the examination constituted the primary endpoints of the study. The secondary endpoints were the time of recovery, recovery of normal behavioral function and discharge, incidence of adverse reactions, and dose of remimazolam. Results: Compared with group C, group E had a greater median score for patient satisfaction at follow-up and a slightly lower median score for physician satisfaction. The pain score of group E was slightly greater than that of group C, but the difference was not significant. However, in group C, the incidence of hypoxemia, the rate of nausea and the severity of vertigo were greater, and the number of patients discharged and resuming normal behavioral function was greater than those in the other two groups. The dose of remimazolam in group C and group E was less than that in group P. Conclusions: TEAS combined with moderate sedation of remimazolam can provide an ideal sedative effect, which preferably suppresses discomfort caused by gastrointestinal endoscopy and has fewer sedation-related complications. Trial Registration: ID: NCT05485064; First registration (29/07/2022); Last registration (02/11/2022) (Clinical Trials.gov).

Gasdermin (GSDM) family proteins, known as the executors of pyroptosis, undergo protease-mediated cleavage before inducing pyroptosis. We here discovered a form of pyroptosis mediated by full-length (FL) GSDME without proteolytic cleavage. Intense ultraviolet-C irradiation-triggered DNA damage activates nuclear PARP1, leading to extensive formation of poly(ADP-ribose) (PAR) polymers. These PAR polymers are released to the cytoplasm, where they activate PARP5 to facilitate GSDME PARylation, resulting in a conformational change in GSDME that relieves autoinhibition. Moreover, ultraviolet-C irradiation promotes cytochrome c-catalysed cardiolipin peroxidation to elevate lipid reactive oxygen species, which is then sensed by PARylated GSDME, leading to oxidative oligomerization and plasma membrane targeting of FL-GSDME for perforation, eventually inducing pyroptosis. Reagents that concurrently stimulate PARylation and oxidation of FL-GSDME, synergistically promoting pyroptotic cell death. Overall, the present findings elucidate an unreported mechanism underlying the cleavage-independent function of GSDME in executing cell death, further enriching the paradigms and understanding of FL-GSDME-mediated pyroptosis.

To address the issue of multipoint leakage detection in energy transportation systems, a multiscale convolutional neural network based on kurtosis and Kullback-Leibler divergence (KKL-MSCNN) was proposed for multipoint leakage detection in energy transportation systems. Initially, the collected infrasound data undergo complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN). Furthermore, a hierarchical processing technique for intrinsic mode functions (IMFs) is proposed to reconstruct IMFs at two different feature levels. Following this, a lightweight MSCNN is constructed, comprising two channels. The reconstructed IMF features are then extracted through serial and parallel convolution at varying scales, facilitating the completion of pipeline leakage level classification. In comparison to conventional methods, the proposed approach achieves a significant 20.26% increase in accuracy for multipoint leakage detection.

Video object segmentation has been applied to various computer vision tasks, such as video editing, autonomous driving, and human-robot interaction. However, the methods based on deep neural networks are vulnerable to adversarial examples, which are the inputs attacked by almost human-imperceptible perturbations, and the adversary (i.e., attacker) will fool the segmentation model to make incorrect pixel-level predictions. This will rise the security issues in highly-demanding tasks because small perturbations to the input video will result in potential attack risks. Though adversarial examples have been extensively used for classification, it is rarely studied in video object segmentation. Existing related methods in computer vision either require prior knowledge of categories or cannot be directly applied due to the special design for certain tasks, failing to consider the pixel-wise region attack. Hence, this work develops an object-agnostic adversary that has adversarial impacts on VOS by first-frame attacking via hard region discovery. Particularly, the gradients from the segmentation model are exploited to discover the easily confused region, in which it is difficult to identify the pixel-wise objects from the background in a frame. This provides a hardness map that helps to generate perturbations with a stronger adversarial power for attacking the first frame. Empirical studies on three benchmarks indicate that our attacker significantly degrades the performance of several state-of-the-art video object segmentation models.

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Telomere dysfunction is intricately linked to the aging process and stands out as a prominent cancer hallmark. Here we demonstrate that telomerase activity is differentially regulated in cancer and normal cells depending on the expression status of fructose-1,6-bisphosphatase 1 (FBP1). In FBP1-expressing cells, FBP1 directly interacts with and dephosphorylates telomerase reverse transcriptase (TERT) at Ser227. Dephosphorylated TERT fails to translocate into the nucleus, leading to the inhibition of telomerase activity, reduction in telomere lengths, enhanced senescence and suppressed tumor cell proliferation and growth in mice. Lipid nanoparticle-mediated delivery of FBP1mRNA inhibits liver tumor growth. Additionally, FBP1 expression levels inversely correlate with TERT pSer227 levels in renal and hepatocellular carcinoma specimens and with poor prognosis of the patients. These findings demonstrate that FBP1 governs cell immortality through its protein phosphatase activity and uncover a unique telomerase regulation in tumor cells attributed to the downregulation or deficiency of FBP1 expression.

Chirality is an important natural characteristic of organic molecules, and chiral organic molecules have shown extensive application in areas such as pharmaceutical development and material science. Benefiting from the ability to achieve circularly polarized luminescence (CPL), chiral luminescent materials have shown potential applications in anti-glare display, optical communication and, 3D display, etc. Due to the ability to harvest both singlet and triplet excitons by a fast reverse intersystem crossing process without involving noble metals, chiral thermally activated delayed fluorescence (TADF) materials with point chirality, axial chirality, planar chirality and helical chirality are regarded as the state-of-the-art materials for circularly polarized organic light-emitting diodes (CP-OLEDs). In recent years, the chiral TADF materials and CP-OLEDs have rapidly developed, but unfortunately, the dissymmetry factors (g) are far from the requirement of practical applications. The ideal emitters and devices should have both high efficiency and a gfactor, or at least a balance between these two elements. This review gives an overview of recent progress in chiral TADF materials, with a particular focus on the chiral skeleton, CPL property and device performance. Furthermore, the molecular design concept, device structure and methods to improve the gfactors of chiral materials and CP-OLEDs are also discussed.

Traditional value chains link factors of production and production to final consumption, adding economic value. To reduce the negative effects of the value chain on the environment and societies, the sustainable business model must be integrated into all parts of the global value chain. This necessitates responsible production and procurement, but all participants must recognise the importance of reusing resources, increasing the product life cycle, and minimising waste. However, this does not imply that all value chain participants in the value chain have equal responsibilities, as they have varying degrees of dominance, interests, and environmental and societal impact in their value chain-related activities. We claim that regional trade agreements are the key to balancing each other’s interests in an international value chain, assisting participants in reaching a consensus. On the other hand, existing regional trade agreements have flaws in how they distribute value. Furthermore, their standard-setting does not contribute to developing a sustainable global value chain because it ignores the impact of the sustainable business models of value chain participants on the global value chain. So, the article will focus on reconstructing global value chains by introducing a sustainable business model and using regulatory incentive systems to guide value chain participants in fulfilling corporate social and environmental responsibilities. As a result, this article discusses how a sustainable business model can aid in developing the global value chain in a sustainable direction, as well as how regulation can help.

Most of the current bioinspired sensory neuron (BSN) focus on the single-mode sensory data, due to the problems of power supply and integration complexity when involving multimodal sensing signals. This work presents a bimodal BSN consisting of a piezoelectric nanogenerator and a photosynaptic transistor to implement the tactile-visual fusion. The PNG serving as a tactile sensor can effectively drive and modulate the photosynaptic transistor. Since there is no additional energy supply and moving parts, this bimodal BSN has low consumption but high integration level. The strengthened and modulated synaptic plasticity of the sensory neuron based on the synergistic effect of pressure and light stimuli are demonstrated. The pattern recognition results simulated by artificial neural networks confirm that multiple sense fusion with higher recognition accuracy outperforms the single sense.

Unsupervised domain adaption has been widely adopted in tasks with scarce annotated data. Unfortunately, mapping the target-domain distribution to the source-domain unconditionally may distort the essential structural information of the target-domain data, leading to inferior performance. To address this issue, we first propose to introduce active sample selection to assist domain adaptation regarding the semantic segmentation task. By innovatively adopting multiple anchors instead of a single centroid, both source and target domains can be better characterized as multimodal distributions, in which way more complementary and informative samples are selected from the target domain. With only a little workload to manually annotate these active samples, the distortion of the target-domain distribution can be effectively alleviated, achieving a large performance gain. In addition, a powerful semi-supervised domain adaptation strategy is proposed to alleviate the long-tail distribution problem and further improve the segmentation performance. Extensive experiments are conducted on public datasets, and the results demonstrate that the proposed approach outperforms state-of-the-art methods by large margins and achieves similar performance to the fully-supervised upperbound, i.e., 71.4% mIoU on GTA5 and 71.8% mIoU on SYNTHIA. The effectiveness of each component is also verified by thorough ablation studies.

Cartilage is a nonedible byproduct with little saleable value. However, previous studies have proposed the possibility of producing peptides from cartilage with immune function modulation potential. The current study aimed to investigate the potential anti-inflammatory activity of peptides derived from sturgeon (Acipenser schrenckii) cartilage in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Five peptide sequences, including four novel peptides, were identified from ethanol-soluble cartilage hydrolysates. Among these five peptides, LTGP, LLLE, LLEL and VGPAGPAGP reduced the production of nitric oxide (NO) and interleukin-6 (IL-6) while increasing interleukin-10 (IL-10) excretion. Transcriptome analysis suggested the inhibition of activated mitogen-activated protein kinase (MAPK) and interleukin-17 (IL-17) signaling pathways after LLEL intervention. MAPK, which is involved in the IL-17 signaling pathway, was further proved to be blocked by downregulating the phosphorylation of p38, extracellular-signal regulated protein kinase (ERK), and c-jun N-terminal kinase (JNK). This novel peptide offers an attractive approach to develop functional foods.

In this paper, for solving the nonlinear control problem of the missile intercepting the maneuvering target, a novel nonlinear zero-sum differential game guidance law is proposed via the neuro-dynamic programming approach. First, the continuous-time nonlinear differential game problem is transformed into solving the nonlinear Hamilton–Jacobi–Isaacs (HJI) equation. Then, a critic neural network is designed to solve the corresponding nonlinear HJI equation. An adaptive weight tuning law for the critic weights is proposed, where an additional term is added to ensure the stability of the closed-loop nonlinear system. Furthermore, the uniform ultimate boundedness of the closed-loop system and the critic NN weights estimation error are proved with the Lyapunov approach. Finally, some simulation results are presented to demonstrate the effectiveness of the proposed differential game guidance law for nonlinear interception.

The second near-infrared (NIR-II) window laser-activated agents have attracted broad interest in an orthotopic cancer theranostic. However, developing NIR-II photothermal agents (PTAs) with advanced photothermal conversion efficiency (PTCE) and tumor-specific response elevation remains a crucial challenge. Herein, a hollow gold nanorod (AuHNR) with a strong localized surface plasmon resonance (LSPR) peak in the NIR-II window was coated with MnO2and chitosan to obtain AuHNR@MnO2@CS (termed AuMC) by a one-step method. Upon exposure to the tumor microenvironment (TME), the overexpressed GSH triggered degradation of the MnO2layer to release Mn2+and resulted in the PTCE elevation owing to exposure of the AuHNR. Consequently, photoacoustic and magnetic resonance imaging for accurate diagnosis, Mn2+-mediated chemodynamic therapy, and AuHNR elevating PT therapy for precise treatment could be achieved. Both in vitroand in vivoexperiments confirmed the good performance of the AuMC on an orthotopic bladder cancer precise theranostic. This study provided NIR-II activated, TME-response PT conversion efficiency enhanced PTAs and offered a tumor-selective theranostic agent for orthotopic bladder cancer in clinical application.

Diabetes-related vascular complications include diabetic cardiovascular diseases (CVD), diabetic nephropathy (DN) and diabetic retinopathy, etc. DN can promote the process of end-stage renal disease. On the other hand, atherosclerosis accelerates kidney damage. It is really an urge to explore the mechanisms of diabetes-exacerbated atherosclerosis as well as new agents for treatment of diabetes-exacerbated atherosclerosis and the complications. In this study we investigated the therapeutic effects of fisetin, a natural flavonoid from fruits and vegetables, on kidney injury caused by streptozotocin (STZ)-induced diabetic atherosclerosis in low density lipoprotein receptor deficient (LDLR−/−) mice. Diabetes was induced in LDLR−/−mice by injecting STZ, and the mice were fed high-fat diet (HFD) containing fisetin for 12 weeks. We found that fisetin treatment effectively attenuated diabetes-exacerbated atherosclerosis. Furthermore, we showed that fisetin treatment significantly ameliorated atherosclerosis-enhanced diabetic kidney injury, evidenced by regulating uric acid, urea and creatinine levels in urine and serum, and ameliorating morphological damages and fibrosis in the kidney. In addition, we found that the improvement of glomerular function by fisetin was mediated by reducing the production of reactive oxygen species (ROS), advanced glycosylation end products (AGEs) and inflammatory cytokines. Furthermore, fisetin treatment reduced accumulation of extracellular matrix (ECM) in the kidney by inhibiting the expression of vascular endothelial growth factor A (VEGFA), fibronectin and collagens, while enhancing matrix metalloproteinases 2 (MMP2) and MMP9, which was mainly mediated by inactivating transforming growth factor β (TGFβ)/SMAD family member 2/3 (Smad2/3) pathways. In both in vivo and in vitro experiments, we demonstrated that the therapeutic effects of fisetin on kidney fibrosis resulted from inhibiting CD36 expression. In conclusion, our results suggest that fisetin is a promising natural agent for the treatment of renal injury caused by diabetes and atherosclerosis. We reveal that fisetin is an inhibitor of CD36 for reducing the progression of kidney fibrosis, and fisetin-regulated CD36 may be a therapeutic target for the treatment of renal fibrosis.