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Abstract Multiple myeloma (MM) is a cancer of plasma cells caused by abnormal gene expression and interactions within the bone marrow (BM) niche. The BM environment significantly influences the progression of MM. Celastrol, a natural compound derived from traditional Chinese medicine, exhibits significant anticancer effects. This study aimed to identify specific targets of celastrol and develop more effective and less toxic treatment options for MM. Celastrol is used as a probe to determine its specific target, pyridoxine‐5′‐phosphate oxidase (PNPO). Increased levels of PNPO are associated with poor outcomes in MM patients, and PNPO promotes MM cell proliferation and induces osteoclast differentiation through exosomes. Mechanistically, PNPO oxidizes disheveled 3M282 (DVL3), leading to abnormal activation of the Wnt/β‐catenin pathway. Based on the critical sites of PNPOR95/K117, Eltrombopag is identified as a potential therapeutic candidate for MM. In addition, the experiments showed its efficacy in mouse models. Eltrombopag inhibited the growth of MM cells and reduced bone lesions by disrupting the interaction between PNPO and DVL3, as supported by preliminary clinical trials. The study highlights the importance of PNPO as a high‐risk gene in the development of MM and suggests that Eltrombopag may be a promising treatment option.

In this paper, we are devoted to establishing that the existence of positive solutions for a class of generalized quasilinear elliptic equations in $\mathbb{R}^{N}$ with Sobolev critical growth, which have appeared from plasma physics, as well as high-power ultrashort laser in matter. To begin, by changing the variable, quasilinear equations are transformed into semilinear equations. The positive solutions to semilinear equations are then presented using the Mountain Pass Theorem for locally Lipschitz functionals and the Concentration-Compactness Principle. Finally, an inverse translation reveals the presence of positive solutions to the original quasilinear equations.

ObjectiveTo understand the correlation between hepatitis C virus (HCV) antibodies and HCV RNA viral load in HIV co-infected individuals and to provide a basis for predicting HCV RNA based on HCV antibody detection. MethodsThe blood samples and relevant data were collected from 979 HIV-infected individuals with HCV antibody detection at the Yunnan Provincial Infectious Disease Hospital from November 2022 to March 2023. HCV antibodies were detected by enzyme-linked immunosorbent assay (ELISA), and HCV RNA was measured by real-time reverse transcription-PCR (qRT-PCR). T-test and chi-squared test were used for data analysis. ResultsAmong all participants, 17.9% (n = 176) were HCV antibody positive, and the positive rates were 17.1% (n = 110) and 19.6% (n = 66) for male and female participants, respectively. The rate of HCV antibody positivity was associated with age (χ2 = 107.662, P < 0.001), with the highest rate of 29.6% in participants aged 41 – 60 years and the lowest rate of 0% in participants younger than 20 years. Among participants who were HCV antibody positive, the HCV RNA positivity rate was 46.6%, with positive rates of 50.0% and 40.9% in male and female participants, respectively, and the positive rate was not related to age (P > 0.05). Spearman rank correlation analysis showed a positive correlation between HCV RNA positivity and HCV antibody levels (r = 0.237, P < 0.05). Receiver operating characteristic (ROC) curve analysis showed that an HCV antibody level ≥ 16.78 (signal to cutoff ratio, S/CO) indicated HCV RNA positivity. ConclusionThe rate of HCV antibody positivity was high in the HIV-infected population and positively correlated with HCV RNA levels, with an S/CO value of 16.78 being an optimal threshold for predicting HCV RNA positivity, which could be used in the diagnosis and management of patients co-infected with HIV and HCV.

Secondary lymphedema is a chronic disease associated with deformity of limbs and dysfunction; however, conventional therapies are not curative. Adipose-derived stem cells (ADSCs) based therapy is a promising way, but a single transplantation of ADSCs has limited efficacy. In this study, ADSCs were engineered in vitro and then transplanted into the site of lymphedema. Yes-associated protein (YAP), a crucial regulator of Hippo pathway, plays an important role in regulating stem cell functions. We examined the YAP expression in a mouse tail lymphedema model, and found that transplanted ADSCs exhibited high expression level of YAP and a large number of YAP positive cells existed in lymphedema environment. In vitro, the downregulation of YAP in ADSCs resulted in higher expression levels of genes related to lymphangiogenesis such as Lyve-1, VEGFR-3 and Prox-1. In vivo, YAP-engineered ADSCs generated abundant VEGFR-3-positive lymphatic vessels and significantly improved subcutaneous fibrosis. These results indicated that the transplantation of pre-engineered ADSCs by manipulating YAP is a promising strategy for lymphatic reconstruction.

Abstract Flexible pressure sensors can convert mechanical stimuli to electrical signals to interact with the surroundings, mimicking the functionality of the human skins. Piezocapacitive pressure sensors, a class of most widely used devices for artificial skins, however, often suffer from slow response-relaxation speed (tens of milliseconds) and thus fail to detect dynamic stimuli or high-frequency vibrations. Here, we show that the contact-separation behavior of the electrode-dielectric interface is an energy dissipation process that substantially determines the response-relaxation time of the sensors. We thus reduce the response and relaxation time to ~0.04 ms using a bonded microstructured interface that effectively diminishes interfacial friction and energy dissipation. The high response-relaxation speed allows the sensor to detect vibrations over 10 kHz, which enables not only dynamic force detection, but also acoustic applications. This sensor also shows negligible hysteresis to precisely track dynamic stimuli. Our work opens a path that can substantially promote the response-relaxation speed of piezocapacitive pressure sensors into submillisecond range and extend their applications in acoustic range.

Abstract Anomaly detection is a critical line of defense to ensure the network security of industrial cyber-physical systems. However, a significant issue in the anomaly detection is the insufficient labels of anomaly classes. With emergence of the new and unknown network attacks, accurately labeling these attacks can be a costly task. The issue of inadequate labeling may negatively impact the detection performance of many existing anomaly detection methods. To meet this gap, this paper proposes a semi-supervised collaborative learning paradigm called IDG-SemiAD, based on an immune detector generation algorithm. First, we design an immune detector generation algorithm based on a chaos map to generate abnormal samples from self-samples. Then, these abnormal samples are combined with self-samples and given specific labels to form a new training set. Finally, the LightGBM classifier is used for training and detection. Experiments on the widely used public dataset BATADAL show that the proposed IDG-SemiAD outperforms the classical v-detector method in terms of recall and f-score, with improvements of 8.2% and 8%, respectively, and outperforms deep learning-based anomaly detection methods, with a maximum improvements of up to 89.7% and 59.5% respectively.

Abstract Background Traditional pesticides are poorly water-soluble and suffer from low bioavailability. N-succinyl chitosan (NSCS) is a water-soluble chitosan derivative, has been recently used to encapsulate hydrophobic drugs to improve their bioavailability. However, it remains challenging to synthesize pesticides of a wide variety of water-soluble drugs and to scale up the production in a continuous manner. Results A synthetic method for preparing water-soluble nanopesticides with a polymer carrier was applied. The bioactive molecule BTL-11 was loaded into hollow NSCS to promote drug delivery, improve solubility and anti-fungal activity. The synthesized nanopesticides had well controlled sizes of 606 nm and the encapsulation rate was 80%. The release kinetics, drug toxicity and drug activity were further evaluated. The inhibitory activity of nanopesticides against Rhizoctonia solani (R. solani) was tested in vivo and in vitro. In vivo against R. solani trials revealed that BTL-11 has excellent control efficiency for cultivated rice leaf and sheath was 79.6 and 76.5%, respectively. By contrast, for BTL-11@NSCS NPs, the anti-fungal ability was strongly released and afforded significant control efficiencies of 85.9 and 81.1%. Those effects were significantly better than that of the agricultural fungicide azoxystrobin (51.5 and 66.5%). The proposed mechanism was validated by successfully predicting the synthesis outcomes. Conclusions This study demonstrates that NSCS is a promising biocompatible carrier, which can enhance the efficacy of pesticides, synergistically improve plant disease resistance, protect crop growth, and can be used for the delivery of more insoluble pesticides. Graphical Abstract

Here, we infer the historical biogeography and evolutionary diversification of the genus Lilium. For this purpose, we used the complete plastomes of 64 currently accepted species in the genus Lilium (14 plastomes were newly sequenced) to recover the phylogenetic backbone of the genus and a time-calibrated phylogenetic framework to estimate biogeographical history scenarios and evolutionary diversification rates of Lilium. Our results suggest that ancient climatic changes and geological tectonic activities jointly shaped the distribution range and drove evolutionary radiation of Lilium, including the Middle Miocene Climate Optimum (MMCO), the late Miocene global cooling, as well as the successive uplift of the Qinghai-Tibet Plateau (QTP) and the strengthening of the monsoon climate in East Asia during the late Miocene and the Pliocene. This case study suggests that the unique geological and climatic events in the Neogene of East Asia, in particular the uplift of QTP and the enhancement of monsoonal climate, may have played an essential role in formation of uneven distribution of plant diversity in the Northern Hemisphere.

Abstract Garnet-type Li6.5La3Zr1.5Ta0.5O12 (LLZO) is considered a promising solid electrolyte, but the surface degradation in air hinders its application for all-solid-state battery. Recent studies have mainly focused on the final products of the LLZO surface reactions due to lacking of powerful in situ characterization methods. Here, we use ambient pressure X-ray spectroscopies to in situ investigate the dynamical evolution of LLZO surface in different gas environments. The newly developed ambient pressure mapping of resonant Auger spectroscopy clearly distinguishes the lithium containing species, including LiOH, Li2O, Li2CO3 and lattice oxygen. The reaction of CO2 with LLZO to form Li2CO3 is found to be a thermodynamically favored self-limiting reaction. On the contrary, the reaction of H2O with LLZO lags behind that of CO2, but intensifies at high pressure. More interestingly, the results provide direct spectroscopic evidence for the existence of Li+/H+ exchange and reveal the importance of the initial layer formed on clean electrolyte surface in determining their air stability. This work demonstrates that the newly developed in situ technologies pave a new way to investigate the oxygen evolution and surface degradation mechanism in energy materials.

With the development of robotic welding automation, there is a strong interest in welding seam identification and localization methods with high accuracy, real-time performance, and robustness. This paper proposed a 3D workpiece weld identification and localization method based on DBSCAN (density-based spatial clustering of applications with noise) to realize stable feature extraction for multiple joint types. Firstly, this method employs combinatorial filtering to effectively eliminate non-target point clouds, including outliers and installation platform point clouds, which can minimize the computational load. Secondly, DBSCAN is used to classify workpiece point clouds into different clusters, which can be used for point cloud segmentation of flat workpieces and curved workpieces. Thirdly, the edge detection and feature extraction methods are used to obtain joint gap and weld feature points while combining the information of point clouds for different types of welds. Finally, based on the identification and localization of the welds, welding path planning and attitude planning are implemented. Experimentation results indicated that the proposed method exhibits robustness across various types of welded joints, including butt joints with straight seams, butt joints with curved seams, butt joints with curved workpieces, and lap joints. Meanwhile, the average error of joint gap detection was 0.11 mm and the processing time of a 90 mm straight-seam butt joint is 701.12 ms.

This comprehensive review inspects the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) across multiple organ systems. Examining their impact on the integumentary, respiratory, cardiovascular, urinary, and skeletal systems, the study highlights the versatility of MSC-EVs in addressing diverse medical conditions. Key pathways, such as Nrf2/HO-1, consistently emerge as central mediators of their antioxidative and anti-inflammatory effects. From expediting diabetic wound healing to mitigating oxidative stress-induced skin injuries, alleviating acute lung injuries, and even offering solutions for conditions like myocardial infarction and renal ischemia-reperfusion injury, MSC-EVs demonstrate promising therapeutic efficacy. Their adaptability to different administration routes and identifying specific factors opens avenues for innovative regenerative strategies. This review positions MSC-EVs as promising candidates for future clinical applications, providing a comprehensive overview of their potential impact on regenerative medicine.

PurposeOsteosarcoma (OS) is the most common type of primary malignant bone tumor. Transducing a functional TP53 gene can effectively inhibit OS cell activity. Poly lactic acid-glycolic acid (PLGA) nanobubbles (NBs) mediated by focused ultrasound (US) can introduce exogenous genes into target cells in animal models, but this technique relies on the passive free diffusion of agents across the body. The inclusion of superparamagnetic iron oxide (SPIO) in microbubbles allows for magnetic-based tissue localization. A low-intensity-focused ultrasound (LIFU) instrument was developed at our institute, and different intensities of LIFU can either disrupt the NBs (RLI-LIFU) or exert cytocidal effects on the target tissues (RHI-LIFU). Based on these data, we performed US-magnetic-mediated TP53-NB destruction and investigated its ability to inhibit OS growth when combined with LIFU both in vitro and in vivo.MethodsSeveral SPIO/TP53/PLGA (STP) NB variants were prepared and characterized. For the in vitro experiments, HOS and MG63 cells were randomly assigned into five treatment groups. Cell proliferation and the expression of TP53 were detected by CCK8, qRT-PCR and Western blotting, respectively. In vivo, tumor-bearing nude mice were randomly assigned into seven treatment groups. The iron distribution of Perls’ Prussian blue-stained tissue sections was determined by optical microscopy. TUNEL-DAPI was performed to examine apoptosis. TP53 expression was detected by qRT-PCR and immunohistochemistry.ResultsSPIO/TP53/PLGA NBs with a particle size of approximately 200 nm were prepared successfully. For in vitro experiments, ultrasound-targeted transfection of TP53 overexpression in OS cells and efficient inhibition of OS proliferation have been demonstrated. Furthermore, in a tumor-bearing nude mouse model, RLI-LIFU-magnetic-mediated SPIO/TP53/PLGA NBs increased the transfection efficiency of the TP53 plasmid, resulting in apoptosis. Adding RHI-LIFU to the treatment regimen significantly increased the apoptosis of OS cells in vivo.ConclusionCombining LIFU and US-magnetic-mediated SPIO/TP53/PLGA NB destruction is potentially a novel noninvasive and targeted therapy for OS.

Background: Moral evaluation is identified as the first stage in the theory of moral judgment, and academics believe that it may align with the social intuitionist model. This study aims to prove that the model’s emotional dominance hypothesis applies to moral evaluation by presenting a computational decision-making model that mathematically formalizes this emotional dominance decision-making process. We also compared different types of valence evaluation tasks to test the emotional priority hypothesis. Methods: We used a convenience sampling method to randomly recruit 30 enrolled college students. The drift-diffusion model was employed to analyze reaction times for words with various emotional and moral valences Additionally, we designed different valence evaluation tasks based on the response relevance hypothesis and evaluated the processing order through reaction time comparisons. Results: The analysis revealed that the emotional mechanism of immoral evaluation differs from moral evaluation. An increase in emotional valence accelerates the speed of evidence accumulation (v) for moral evaluation (M = 1.21, 0.2% < 0 < 99.8%) but lowers decision caution (a) in immoral evaluation (M = −0.64, 96.1% < 0 < 3.9%). In contrast, moral valence does not have a significant influence on evaluation processes (v, M = −0.28, 72.1% < 0 < 27.9%; a, M = −0.32, 79.3% < 0 < 20.7%). Furthermore, We found no significant difference in reaction times between moral and immoral words in the emotional evaluation task (F(1,29) = 0.55, p = 0.464, partial η2 = 0.02), but a significant difference existed in the moral evaluation task (F(1,29) = 17.99, p < 0.001, partial η2 = 0.38), indicating that the tendency of relatively fast immoral evaluation in emotional evaluation tasks may be caused by emotional priority. Conclusions: Our findings support the intuitive model’s emotional dominance hypothesis and introduce a new emotional mechanism into moral evaluation. This study clarifies the distinct emotional processes in moral and immoral evaluations, fills a gap in the research on moral evaluation, and offers insights into human decision-making in moral contexts.

Introduction: Electric bicycles (e-bikes) and bicycles in large Chinese cities have recently witnessed substantial growth in ridership. According to related accident trends, this study analyzed characteristics and spatial distribution in the period when e-bike-related accidents rapidly increased to propose priority measures to reduce accident casualties. Methods: For e-bike- and bicycle-related accident data from the Guangzhou Public Security Traffic Management Integrated System, linear regression was used to examine the trends in the number of accidents and age-adjusted road traffic casualties from 2011 to 2021. Then, for the period when e-bike-related accidents rapidly increased, descriptive statistics were computed regarding rider characteristics, illegal behaviors, road types, collision objects and their accident liability. One-way analysis of variance (ANOVA) followed by Bonferroni's multiple comparison test. P

Abstract Background Paris yunnanensis (Melanthiaceae) is a traditional Chinese medicinal plant of significant pharmaceutical importance. Due to previous taxonomic confusion, a congeneric species, Paris liiana, has been mistaken for P. yunnanensis and cultivated on a large scale, leading to the mixing of commercial products (i.e., seedlings and processed rhizomes) of P. yunnanensis with those of P. liiana. This may have adverse effects on quality control in the standardization of P. yunnanensis productions. As the lack of PCR amplifiable genomic DNA within processed rhizomes is an intractable obstacle to the authentication of P. yunnanensis products using PCR-based diagnostic tools, this study aimed to develop a PCR-free method to authenticate commercial P. yunnanensis products, by applying genome skimming to generate complete plastomes and nrDNA arrays for use as the molecular tags. Results Based on a dense intraspecies sampling of P. liiana and P. yunnanensis, the robustness of the proposed authentication systems was evaluated by phylogenetic inferences and experimental authentication of commercial seedling and processed rhizome samples. The results indicate that the genetic criteria of both complete plastomes and nrDNA arrays were consistent with the species boundaries to achieve accurate discrimination of P. yunnanensis and P. liinna. Owing to its desirable accuracy and sensitivity, genome skimming can serve as an effective and sensitive tool for monitoring and controlling the trade of P. yunnanensis products. Conclusion This study provides a new way to solve the long-standing problem of the molecular authentication of processed plant products due to the lack of PCR amplifiable genomic DNA. The proposed authentication system will support quality control in the standardization of P. yunnanensis products in cultivation and drug production. This study also provides molecular evidence to clarify the long-standing taxonomic confusion regarding the species delimitation of P. yunnanensis, which will contribute to the rational exploration and conservation of the species.

In this study, 24 chalcone derivatives containing benzoxazole were designed and synthesized, and the structures of all target compounds were confirmed by NMR and HRMS. The results of antibacterial activity showed that the median effective concentration (EC50) value of Z2 against Xanthomonas oryzae pv.oryzae (Xoo) was 8.10 μg/mL, which was better than thiodiazole copper (60.62 μg/mL), the antibacterial activity of Z2 was verified by scanning electron microscopy (SEM). Antibacterial mechanism of Z2 on Xoo was preliminarily explored, and the results showed concentrations were 100, 50 mg/L, which had a good cell membrane permeability to Xoo and can inhibit the EPS content and the production of extracellular enzymes, affecting the formation of biofilm, preliminary validation of the antibacterial effect of Z2 on Xoo. At 200 mg/L, Z2 had a better protective activity on harvested potatoes, which was comparable with thiodiazole copper. The activity against tobacco mosaic virus (TMV) was determined with half leaf dry spot method. The EC50 value of curative activity of Z15 was 101.97 μg/mL, which was superior to ningnanmycin (NNM) 294.27 μg/mL, and the EC50 value of protective activity of Z16 was 104.05 μg/mL, which was superior to NNM 185.73 μg/mL. Molecular docking results showed Z15, Z16 had a significantly higher affinity with tobacco mosaic virus coat protein (TMV-CP) than NNM. The above results indicated that chalcone derivatives containing benzoxazole have the potential to become antibacterial and antivirial agents.

Both salt rejection and pressure-bearing properties of the conventional thin film composite (TFC) polyamide reverse osmosis (RO) membrane are easily weakened at high temperature. In order to improve the high temperature resistance, in this work, a polyamide TFC RO membrane with covalent organic frameworks (COFs) intermediate layer was prepared. Firstly, the COFs layer was decorated on polyether sulfone (PES) support membrane by a unidirectional diffusion method and further modified for shrinking the micropore via the chemical crosslinking reaction with 1,3-diamino-2-propanol (DAPL) or ethylenediamine (EDA), and then continued the conventional interfacial polymerization of m-phenylene diamine (MPD) and trimesoyl chloride (TMC) on the resultant COFs layer for preparing the RO membrane. Furthermore, the correlationship between the microstructure of COFs layer and the separation performance of modified RO membrane was systematically investigated. Due to the introduction of the COFTpPa-DAPL intermediate layer with more regular microstructure and specific hydrophilicity, the resultant TFC-COFTpPa-DAPL RO membrane exhibited improvement in water flux by 30 ​% (reached to 50.5 ​L ​m−2 ​h−1) and higher salt rejection (>99.5 ​%) as compared with the conventional polyamide RO membrane and other reported temperature resistance RO membranes. Meanwhile, this TFC-COFTpPa-DAPL membrane showed good long-term separation stability during the RO process for 160 ​h. Especially, its water flux increased to 98.8 ​L ​m−2 ​h−1 without weakening salt rejection (about 99.4 ​%) at 70 ​°C. This study provides an effective way to fabricate the high temperature resistance TFC polyamide RO membrane with good comprehensive separation performance based on COFs intermediate layer.

ABSTRACTObjective Gain or amplification 1q21 (1q21+) is one of the most common recurrent cytogenetic abnormalities in multiple myeloma (MM). Our aim was to explore the presentation and outcomes of patients with MM harboring 1q21 + .Methods We retrospectively analyzed the clinical features and survival outcomes in 474 consecutive patients with MM receiving immunomodulatory drugs or proteasome inhibitor-based regimens as first-line therapies.Results 1q21 + was detected in 249 (52.5%) patients. Patients with 1q21 + had a higher proportion of subtypes of IgA, IgD, and λ-light chain than non-1q21 + . 1q21 + was associated with more advanced ISS stage and was more frequently accompanied by del(13q), elevated lactate dehydrogenase and lower levels of hemoglobin and platelets. Patients with 1q21 + had shorter PFS (21 months vs. 31 months, P = 0.001) and OS (43 months vs. 72 months, P

The objective of this paper is to present an extended approach to address the stochastic multi-attribute decision-making problem. The novelty of this study is to consider the regret behavior of decision makers under a Pythagorean hesitant fuzzy environment. First, the group satisfaction degree of decision-making matrices is used to consider the different preferences of decision-makers. Second, the nonlinear programming model under different statues is provided to compute the weights of attributes. Then, based on the regret theory, a regret value matrix and a rejoice value matrix are constructed. Furthermore, the feasibility and superiority of the developed approach is proven by an illustrative example of selecting an air fighter. Eventually, a comparative analysis with other methods shows the advantages of the proposed methods.

To reduce resource loss and environmental pollution, green CLSC has become a hot issue that manufacturing enterprises pay attention to. In green CLSC, manufacturers would pay attention to the fairness of profit distribution when making sales efforts. Therefore, this paper studies a green closed-loop supply chain (CLSC) considering manufacturer sales efforts and fairness concerns. Then, the centralized model and decentralized model are built and analyzed. Afterward, a profit-sharing contract between members is designed to coordinate the supply chain. We made the following observations: (1) The manufacturers’ fairness concerns would reduce product green degree, sales effort and recycling rate of used products, which is not conducive to the sustainable development of the green closed-loop supply chain. (2) When the manufacturers’ fairness concerns are gradually strengthened, the optimal decisions would deviate even more from the optimal equilibrium results. (3) When the coefficient of fairness concerns and the ratio of profit-sharing satisfy a certain range, Pareto improvement can be effectively realized.

ObjectiveThe purpose of this study was to investigate the association between serum polyunsaturated fatty acids (PUFAs) and bone mineral density (BMD).MethodsWe performed a cross-sectional study based on data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. The weighted multiple linear regression model was utilized to determine the association between serum PUFAs and BMD. Further smoothed curve fitting and threshold effect analysis were conducted. Finally, we performed a subgroup analysis.ResultsIn total, 1979 participants aged 20-59 years were enrolled. After adjusting for all covariates, we found that serum docosapentaenoic acid (DPA) was positively associated with head BMD (β = 0.0015, 95% Cl: 0.0004, 0.0026, P = 0.008296) and lumbar spine BMD (β = 0.0005, 95% Cl: 0.0000, 0.0010, P = 0.036093), and serum eicosadienoic acid (EDA) was negatively associated with thoracic spine BMD (β = -0.0008, 95% Cl: -0.0016, -0.0000, P = 0.045355). Smoothed curve fitting revealed a nonlinear positive association between serum DPA and lumbar spine BMD. Threshold effect analysis indicated that the threshold of serum DPA was 81.4 µmol/L. Subgroup analysis revealed a positive correlation between serum DPA and head BMD in the subgroup aged 50-59 years (β = 0.0025, 95% Cl: 0.0002, 0.0049, P = 0.035249) and females (β = 0.0026, 95% Cl: 0.0008, 0.0044, P = 0.005005). There was a positive relationship between serum DPA and lumbar spine BMD in females (β = 0.0008, 95% Cl: 0.0001, 0.0015, P = 0.017900) and a negative association between serum EDA and thoracic spine BMD in the subgroup aged 30-39 years (β = -0.0016, 95% Cl: -0.0031, -0.0001, P = 0.041331), males (β = -0.0012, 95% Cl: -0.0023, -0.0001, P = 0.039364) and other races (β = -0.0021, 95% Cl: -0.0037, -0.0006, P = 0.008059).ConclusionThis study demonstrated a linear positive relationship between serum DPA and head BMD, a nonlinear positive association between serum DPA and lumbar spine BMD, and a linear negative correlation between serum EDA and thoracic spine BMD in US adults.

Summary: Comprehensive multiplatform analysis of Luminal B breast cancer (LBBC) specimens identifies two molecularly distinct, clinically relevant subtypes: Cluster A associated with cell cycle and metabolic signaling and Cluster B with predominant epithelial mesenchymal transition (EMT) and immune response pathways. Whole-exome sequencing identified significantly mutated genes including TP53, PIK3CA, ERBB2, and GATA3 with recurrent somatic mutations. Alterations in DNA methylation or transcriptomic regulation in genes (FN1, ESR1, CCND1, and YAP1) result in tumor microenvironment reprogramming. Integrated analysis revealed enriched biological pathways and unexplored druggable targets (cancer-testis antigens, metabolic enzymes, kinases, and transcription regulators). A systematic comparison between mRNA and protein displayed emerging expression patterns of key therapeutic targets (CD274, YAP1, AKT1, and CDH1). A potential ceRNA network was developed with a significantly different prognosis between the two subtypes. This integrated analysis reveals a complex molecular landscape of LBBC and provides the utility of targets and signaling pathways for precision medicine.

Optical orbital angular momentum (OAM) holography provides a critical method for holographic information storage systems and experimentally demonstrates the feasibility of holographic multiplexation. Herein, the elliptic perfect optical vortex orbital angular momentum (EPOV-OAM) multiplexed holography is proposed and experimentally implemented. The mode selectivity of the ellipticity and rotation angle are investigated, respectively, which demonstrates that those parameters can be used as additional encoded degrees of freedom for the holographic multiplexing. The combination of the topological charge (TC), scaling factor, rotation angle, ellipticity can provide a four-dimensional multiplexed holography for information encryption. Furthermore, the minimum interval of TC for holographic multiplexing could reach 0.01. The method proposed here can enhance the information capacity and the security level of the holographic optical encryption systems.

To explore the solution of the two-step method applied in the rapid construction of super large cross-section tunnels passing through IV-and V-grade surrounding rock sections in karst cave areas, based on an engineering example of the Lianhuashan Tunnel, we use the numerical calculation method to analyze the stability of surrounding rock and the design parameters of the control measures for super large cross-section tunnels during the construction of the step method. The calculated results show that the working face of IV-grade surrounding rock can be stabilized by an advanced small pipe, and the stability of the supporting structure should be controlled mainly by IV-grade surrounding rock. In order to control the stability of the tunnel face, it is necessary to use an advanced large pipe shed in the surrounding V-grade rock. The reinforcement range of the advanced large pipe shed is 120° and the length is 20 m. This is the most economical design parameter of the advanced large pipe shed, ensuring the deformation control effect. For control of the stability of the supporting structure, under the condition that the working space is suitable for large machinery, the settlement of the arch of the supporting structure can be obviously reduced by shortening the step cycle footage and reducing the step length, and the peripheral convergence of the supporting structure can be obviously reduced by reducing the step height. After comprehensive analysis and considering the development of karst caves, the advanced support measures, design parameters, bench excavation design parameters, initial support measures, karst cave treatment measures, and bench construction process of IV- and V-grade surrounding rock is determined. The application verification shows that the research results have a good control effect on the stability of the surrounding rock and cave and are suitable for large-scale mechanical operations, which can significantly improve the excavation speed of the super large cross-section tunnel passing through the IV- and V-grade surrounding rock sections in the karst cave area.

To evaluate the earthquake disaster resistance capability of highway tunnels, it is necessary to study an index system for the earthquake disaster resistance capability of highway tunnels. This paper uses a literature research method. The damage of highway tunnels in 12 earthquake disasters recorded in detail in China and abroad was investigated. According to the types of hazard-beating bodies and damage forms, 17 seismic damage scenes of highway tunnels are classified. According to different damage scenes, the fault tree analysis model is used to identify the damage-causing factors. Combined with the industry standards, norms and research results related to the earthquake resistance of highway tunnels, the evaluation indices are analyzed from three perspectives: engineering geological factors, tunnel structural factors and operation management factors. According to the principle of index system construction, a four-level index system is constructed, which takes the earthquake disaster resistance capability of highway tunnels as the target layer; engineering geological factors, tunnel structural factors and operation management factors as the criterion layer indices; 12 indicators as the index layer and 35 specific indicators. The established index system for the earthquake disaster resistance capability of highway tunnels has strong scientific, rational and application value and can provide a reference for the evaluation of the earthquake disaster resistance capability of highway tunnels and can also provide important support for the safe operation and sustainable development of highway tunnels.

Abstract Objective To explore the psychological experience of Juvenile patient’s parents in Fangcang shelter hospital during the Omicron wave of COVID-19 pandemic. Methods A qualitative study was conducted by using a phenomenological research method. Sixteen parents of juvenile patients with COVID-19 were recruited from National Exhibition and Convention Center (Shanghai, China) Fangcang shelter hospital (FSH) using purposive sampling. Data were collected by face-to-face in-depth interviews over 27 days, from April 9 to May 6, 2022. The interview data were analyzed using Colaizzi seven-step analysis method. Results The psychological experiences of the parents of juvenile patients in the Fangcang shelter hospital were summarized into three themes: "perception regarding the FSH", "worried about the unmet needs of juvenile patients ", and "the psychological burden after discharge". These themes were classified into 9 sub-themes, including the acceptance of FSH, adaptability to FSH, concerns about cross-infection in the FSH, special needs of infants and young children, psychological needs of preschool children, the learning demands of school-age children, concern about re-positive, fear of sequelae, worry about social acceptance. Conclusion Juvenile patients and their parents in the Fangcang shelter hospitals have both positive and negative experiences. It is suggested that facilities for minors should be planned in advance. Humanistic care for adolescent patients and health education for the public are also critical.

Abstract This paper proposed a collaborative neurodynamic optimization (CNO) method to solve traveling salesman problem (TSP). First, we construct a Hopfield neural network (HNN) with $$n \times n$$ n × n neurons for the n cities. Second, to ensure the convergence of continuous HNN (CHNN), we reformulate TSP to satisfy the convergence condition of CHNN and solve TSP by CHNN. Finally, a population of CHNNs is used to search for local optimal solutions of TSP and the globally optimal solution is obtained using particle swarm optimization. Experimental results show the effectiveness of the CNO approach for solving TSP.

A model for calculating the topological deviation of the actual tooth surface based on the coordinates of the detected cylindrical gear tooth surface points is established. The 3D tooth surface topological deviation map is constructed,and tooth profile deviation curve and helix deviation curve at different positions are obtained by slicing along the direction of tooth length and tooth height. The extraction method of tooth profile deviation and helix deviation is established. The experimental test and analysis results are compared with the report of Gleason 650GMS Gear Measurement Center to verify the accuracy of the method and provide a theoretical basis for the comprehensive evaluation and digital control of tooth surface accuracy.

BackgroundTranexamic acid (TXA) has previously been shown to be effective in reducing intraoperative blood loss (IBL) and transfusion requirements in spine surgery. A conventional TXA regimen is a simple preoperative or intraoperative administration. However, the hyperfibrinolysis caused by surgical trauma lasts at least 24 h, and a single dose of TXA cannot cover the whole process of hyperfibrinolysis. Moreover, its ability to control postoperative blood loss (PBL) may be insufficient. Therefore, this study aimed to explore the effects and safety of sequential perioperative intravenous TXA for reducing bleeding after posterior lumbar interbody fusion (PLIF).MethodsPatients requiring PLIF were randomly divided into two groups. All patients were intravenously injected with 1 g of TXA 15 min before skin resection. Every day after the surgery, 200 ml saline was intravenously injected for 1–3 days in Group A, while Group B received 1 g of TXA instead of saline. The total blood loss (TBL), IBL, PBL, HCT, Hb, blood transfusion volume, inflammation-related indicators, and complications were recorded.ResultsTBL, PBL, and hidden blood loss (HBL) in Group B were significantly lower than those in Group A (P < 0.05). The maximum decreases in HCT and Hb in Group B were also significantly lower than those in Group A (P < 0.05), and the drainage removal time (DRT) was sooner in Group B than in Group A (P = 0.003). On the 3rd and 5th days after surgery, the level of CRP in Group B was significantly lower than that in Group A (P < 0.05). Similarly, IL-6 levels were significantly lower in Group B for the first 5 days postoperatively (P < 0.001). Sex, operation time, level of decompression, length of incision, and change in HCT were significant predictors of both TBL and HBL. TBL was also significantly associated with BMI and preoperative fibrinogen, while postoperative TXA was a significant predictor of HBL only.ConclusionIntravenous injection of 1 g of TXA 15 min before skin resection combined with continuous intravenous injection of 1 g of TXA 1 to 3 days after PLIF can reduce postoperative bleeding and shorten the time to drainage tube removal. In addition, it can also inhibit the postoperative inflammatory response.Clinical trial registrationChiCTR2200056210.

Ewing sarcoma (ES) is the second most common malignant bone tumor in children and has a poor prognosis due to early metastasis and easy recurrence. Necroptosis is a newly discovered cell death method, and its critical role in tumor immunity and therapy has attracted widespread attention. Thus, the emergence of necroptosis may provide bright prospects for the treatment of ES and deserves our further study. Here, based on the random forest algorithm, we identified 6 key necroptosis-related genes (NRGs) and used them to construct an NRG signature with excellent predictive performance. Subsequent analysis showed that NRGs were closely associated with ES tumor immunity, and the signature was also good at predicting immunotherapy and chemotherapy response. Next, a comprehensive analysis of key genes showed that RIPK1, JAK1, and CHMP7 were potential therapeutic targets. The Cancer Dependency Map (DepMap) results showed that CHMP7 is associated with ES cell growth, and the Gene Set Cancer Analysis (GSCALite) results revealed that the JAK1 mutation frequency was the highest. The expression of 3 genes was all negatively correlated with methylation and positively with copy number variation (CNV). Finally, an accurate nomogram was constructed with this signature and clinical traits. In short, this study constructed an accurate prognostic signature and identified 3 novel therapeutic targets against ES.

BackgroundPolygonatum kingianum has been widely used as a traditional Chinese medicine as well as a healthy food. Because of its highly variable morphology, this medicinal plant is often difficult to distinguish from other related verticillate leaf types of the Polygonatum species. The contaminants in P. kingianum products not only decrease the products’ quality but also threaten consumer safety, seriously inhibiting the industrial application of P. kingianum.MethodsNine complete chloroplast (cp) genomes of six verticillate leaf types of the Polygonatum species were de novo assembled and systematically analyzed.ResultsThe total lengths of newly sequenced cp genomes ranged from 155,437 to 155,977 bp, including 86/87 protein-coding, 38 tRNA, and 8 rRNA genes, which all exhibited well-conserved genomic structures and gene orders. The differences in the IR/SC (inverted repeats/single-copy) boundary regions and simple sequence repeats were detected among the verticillate leaf types of the Polygonatum cp genomes. Comparative cp genomes analyses revealed that a higher similarity was conserved in the IR regions than in the SC regions. In addition, 11 divergent hotspot regions were selected, providing potential molecular markers for the identification of the Polygonatum species with verticillate leaf types. Phylogenetic analysis indicated that, as a super barcode, plastids realized a fast and efficient identification that clearly characterized the relationships within the verticillate leaf types of the Polygonatum species. In brief, our results not only enrich the data on the cp genomes of the genus Polygonatum but also provide references for the P. kingianum germplasm resource protection, herbal cultivation, and drug production.ConclusionThis study not only accurately identifies P. kingianum species, but also provides valuable information for the development of molecular markers and phylogenetic analyses of the Polygonatum species with verticillate leaf types.

In this study, 24 chalcone derivatives containing indole were designed and synthesized. Some of the target compounds exhibited significant antiviral and antibacterial effects. The results of EC50 test against tobacco mosaic virus showed that the EC50 value of curative activity of D11 was 107.4 μg/mL, which was better than the commercial drug ningnanmycin 311.5 μg/mL, and the EC50 value of protective activity of D16 was 106.6 μg/mL, which was superior to ningnanmycin 205.4 μg/mL, the inactivated activity of D11 was comparable to that of ningnanmycin. Microscale thermophoresis experiments demonstrated D11 (Kd = 0.0030 ± 0.0014 μmol/L) had a stronger binding ability with tobacco mosaic virus capsid protein (TMV-CP), which was much higher than that of ningnanmycin (Kd = 2.6062 ± 1.1767 μmol/L). Molecular docking results showed D11 had a significantly higher affinity with TMV protein than ningnanmycin. In addition, the malondialdehyde (MDA), peroxidase (POD), succinate dehydrogenase content (SDH) assay showed D11 could improve the disease resistance of tobacco. The results of bacterial inhibition activity showed that the EC50 value of D23 against Xoo was 50.3 μg/mL, which was better than the commercial drugs thiodiazole copper (79.8 μg/mL) and bismerthiazol (106.2 μg/mL), the bacterial inhibition activity of D23 was verified by scanning electron microscopy.

The purpose of this paper was to develop a novel triangular fuzzy method for multi-attribute decision-making to eliminate the influence of indicator weights on scheme selection and account for the regret psychology of decision-makers. Therefore, considering the consequences of regret aversion and subjective weighting, we propose a multi-attribute decision-making method with triangular fuzzy number based on regret theory and catastrophe progression. First, to eliminate the influence of various dimensions on the decision-making results, the decision matrix is described by a triangular fuzzy number, and the regret value matrix and rejoicing value matrix are independently constructed by applying regret theory. Second, the importance ranking of attributes is improved to eliminate the influence of subjective weighting by employing the maximizing deviation method; and the comprehensive catastrophe progression attribute is calculated to rank the alternatives. Finally, an instance of investment project selection is provided to prove the availability and superiority. In conclusion, the proposed method not only considers decision-makers' bounded rationality for decision-making, but it also expands the application of catastrophe progression methods under the condition of a triangular fuzzy environment.

Summary Aminoglycosides are one of the oldest classes of antimicrobials that are being used in current clinical practice, especially on multi‐drug resistant Gram‐negative pathogenic bacteria. However, the serious side effects at high dosage such as ototoxicity, neuropathy and nephrotoxicity limit their applications in clinical practice. Approaches that potentiate aminoglycoside killing could lower down their effective concentrations to a non‐toxic dosage for clinical treatment. In this research, we screened a compound library and identified sanguinarine that acts synergistically with various aminoglycosides. By checkerboard and dynamical killing assay, we found that sanguinarine effectively potentiated aminoglycoside killing on diverse bacterial pathogens, including Escherichia coli, Acinetobacter baumannii, Klebsiella pneumonia and Pseudomonas aeruginosa. The mechanistic studies showed an elevated intracellular ROS and DNA oxidative level in the bacterial cells treated by a combination of sanguinarine with aminoglycosides. Furthermore, an enhanced level of sanguinarine was observed in bacteria in the presence of aminoglycosides, suggesting that aminoglycosides promote the uptake of sanguinarine. Importantly, sanguinarine was shown to promote the elimination of persister cells and established biofilm cells both in vivo and in vitro. Our study provides a novel insight for approaches to lower down the clinical dosages of aminoglycosides.

For deep foundation pit with rich water and deep sand layer, construction safety problems such as water and sand gushing may occur during excavation. Base sealing with well point dewatering is a common measure to ensure the safety of foundation pit excavation. This paper is based on an open-cut construction project of a metro station in Taiyuan. The fluid-structure coupling analysis and comparison of foundation pit excavation process were carried out by using finite element software. Combined with the field inspection data, the influence of different bottom sealing forms and dewatering on the deformation of foundation pit was studied. The results show that the bottom sealing reinforcement can effectively reduce the maximum lateral displacement of diaphragm wall, the maximum surface settlement, and the maximum uplift of basement. The amount of deformation is reduced by about 50% compared with that without reinforcement. With the same reinforcement thickness, the reinforcement effect is better starting from the basement. The new support system composed of bottom sealing reinforcement zone and diaphragm wall can control the seepage of groundwater and the deformation of foundation pit well with the well point dewatering.

Developing catalysts for biomass electrooxidation are critical in electric refinery. The reaction mechanism, however, is still ambiguous. Here, the authors reveal how proton and oxygen anion deintercalation in hydroxide determine the elementary reaction steps in a model reaction of glycerol oxidation.

To prevent large-scale water inrush accidents during the excavation process of a water-rich tunnel, a method, based on a random forest (RF) algorithm, for predicting the hazard level of water inrush is proposed. By analyzing hydrogeological conditions, six factors were selected as evaluating indicators, including stratigraphic lithology, inadequate geology, rock dip angle, negative terrain area ratio, surrounding rock grade, and hydrodynamic zonation. Through the statistical analysis of 232 accident sections, a dataset of water inrush accidents in water-rich tunnels was established. We preprocessed the dataset by detecting and replacing outliers, supplementing missing values, and standardizing the data. Using the RF model in machine learning, an intelligent prediction model for the hazard of water inrush in water-rich tunnels was established through the application of datasets and parameter optimization processing. At the same time, a support vector machine (SVM) model was selected for comparison and verification, and the prediction accuracy of the RF model reached 98%, which is higher than the 87% of the SVM. Finally, the model was validated by taking the water inrush accident in the Yuanliangshan tunnel as an example, and the predicted results have a high degree of consistency with the actual hazard level. This indicates that the RF model has good performance when predicting water inrush in water-rich tunnels and that it can provide a new means by which to predict the hazard of water inrush in water-rich tunnels.

Abstract Interferon regulatory factors (IRFs) play a key role in many aspects of immune response, and IRF1, IRF3, and IRF7 are positive regulators of IFN induction in mammals. However, IRF3, as the most critical regulatory factor in mammals, is naturally absent in birds, which attracts us to study the functions of other members of the avian IRF family. In the present study, we cloned goose IRF1 (GoIRF1) and conducted a series of bioinformatics analyses to compare the protein homology of GoIRF1 with that of IRF1 in other species. The overexpression of GoIRF1 in DF-1 cells induced the activation of IFN-β, and this activation is independent of the dosage of the transfected GoIRF1 plasmids. The overexpression of GoIRF1 in goose embryonic fibroblasts (GEFs) induced the expression of IFNs, proinflammatory cytokines, and IFN-stimulated genes (ISGs); it also inhibited the replication of green fluorescent protein (GFP)-tagged Newcastle disease virus (NDV) (NDV-GFP) and GFP-tagged vesicular stomatitis virus (VSV) (VSV-GFP). Our results suggest that GoIRF1 is an important regulator of IFNs, proinflammatory cytokines, and ISGs and plays a role in antiviral innate immunity in geese.

While (oxy)hydroxides are effective oxygen evolution electrocatalysts, the impacts of pre-catalyst properties on catalyst activities are challenging to assess. Here, authors find Mo dopants in Ni-Fe (oxyhydroxides) to promote lattice oxygen participation and to boost oxygen evolution activities.

Tailoring the oxygen redox reactivity in Li-rich cathode is crucial for developing high-energy batteries. Here, the authors report a strategy to obtain a flexible crystal structure and enhance the oxygen redox reversibility.

Background/objectiveWe retrospectively analyzed the effective and safety of continuous low-dose cyclophosphamide combined with prednisone (CP) in relapsed and refractory multiple myeloma (RRMM) patients with severe complications.MethodsA total of 130 RRMM patients with severe complications were enrolled in this study, among which 41 patients were further given bortezomib, lenalidomide, thalidomide or ixazomib on the basis of CP regimen (CP+X group). The response to therapy, adverse events (AEs), overall survival (OS) and progression-free survival (PFS) were recorded.ResultsAmong the 130 patients, 128 patients received therapeutic response assessment, with a complete remission rate (CRR) and objective response rate (ORR) of 4.7% and 58.6%, respectively. The median OS and PFS time were (38.0 ± 3.6) and (22.9±5.2) months, respectively. The most common AEs were hyperglycemia (7.7%), pneumonia (6.2%) and Cushing’s syndrome (5.4%). In addition, we found the pro-BNP/BNP level was obviously decreased while the LVEF (left ventricular ejection fraction) was increased in RRMM patients following CP treatment as compared with those before treatment. Furthermore, CP+X regimen further improved the CRR compared with that before receiving the CP+X regimen (24.4% vs. 2.4%, P=0.007). Also, both the OS and PFS rates were significantly elevated in patients received CP+X regimen following CP regimen as compared with the patients received CP regimen only.ConclusionThis study demonstrates the metronomic chemotherapy regimen of CP is effective to RRMM patients with severe complications.

A series of myricetin derivatives containing amide and hydrazide were designed and synthesized. All the compounds were characterized by NMR and HRMS. Bioactivity test showed that some of the target compounds had excellent anti-tobacco mosaic virus (TMV) activity. In particular, the median effective concentration (EC50) values of the anti-TMV curative and protective activities of N-(2-(2-(2-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)acetyl)hydrazineyl)-2-oxoethyl)-4-(trifluoromethyl)benzamide (G9) were 202.3 and 164.0 μg/mL respectively, superior to ningnanmycin (329.1, 230.3 μg/mL). Microscale thermophoresis (MST) and molecular docking showed that G9 had an excellent binding affinity with tobacco mosaic virus coat protein (TMV-CP) (Kd = 0.158 ± 0.024 μM), which was better than that of ningnanmycin (Kd = 2.074 ± 0.818 μM). Moreover, there were many interaction forces between G9 and the key amino acid residues of TMV-CP. The chlorophyll content and peroxidase (POD) activity of tobacco leaves treated with G9 increased significantly, indicating that G9 could improve the photosynthesis of tobacco leaves and stimulate the resistance of tobacco leaves to TMV. The insecticidal activity of G9 against Mythimna separata (M. separate) was found to be 95.2% at 200 μg/mL, which was close to bufenozide (100%). The insecticidal activity of myricetin was significantly improved after the introduction of active groups of amide and hydrazide, which could be further explored.

Abstract The anomalous Hall effect (AHE) is a quantum coherent transport phenomenon that conventionally vanishes at elevated temperatures because of thermal dephasing. Therefore, it is puzzling that the AHE can survive in heavy metal (HM)/antiferromagnetic (AFM) insulator (AFMI) heterostructures at high temperatures yet disappears at low temperatures. In this paper, an unconventional high‐temperature AHE in HM/AFMI is observed only around the Néel temperature of AFM, with large anomalous Hall resistivity up to 40 nΩ cm is reported. This mechanism is attributed to the emergence of a noncollinear AFM spin texture with a non‐zero net topological charge. Atomistic spin dynamics simulation shows that such a unique spin texture can be stabilized by the subtle interplay among the collinear AFM exchange coupling, interfacial Dyzaloshinski–Moriya interaction, thermal fluctuation, and bias magnetic field.

Abstract Despite the low cost and high capacity of Ni‐rich layered oxides (NRLOs), their widespread implementation in electric vehicles is hindered by capacity decay and O release. These issues originate from chemo‐mechanical heterogeneity, which is mainly related to oxygen anion redox (OAR). However, what to tune regarding OAR in NRLOs and how to tune it remains unknown. In this study, a close correlation between the OAR chemistry and Li/Ni antisite defects is revealed. Experiments and calculations show the opposite effects of aggregative and dispersive Li/Ni antisite defects on the NiO6 configuration and Ni spin state in NRLOs. The resulting broad or narrow spans for the energy bands caused by spin states lead to different OAR chemistries. By tuning the Li/Ni antisite defects to be dispersive rather than aggregative, the threshold voltage for triggering OAR is obviously elevated, and the generation of bulk‐O2‐like species and O2 release at phase transition nodes is fundamentally restrained. The OAR is regulated from irreversible to reversible, fundamentally addressing structural degradation and heterogeneity. This study reveals the interaction of the Li/Ni antisite defect/OAR chemistry/chemo‐mechanical heterogeneity and presents some insights into the design of high‐performance NRLO cathodes.

BackgroundGanoderma lucidum is reportedly the best source of traditional natural bioactive constituents. Ganoderma triterpenoids (GTs) have been verified as an alternative adjuvant for treating leukemia, cancer, hepatitis and diabetes. One of the major triterpenoids, Resinacein S, has been found to regulate lipid metabolism and mitochondrial biogenesis. Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that has become a major public health problem. Given the regulatory effects on lipid metabolism of Resinacein S, we sought to explore potential protective effects against NAFLD.MethodsResinacein S was extracted and isolated from G. lucidum. And mice were fed with high fat diet with or without Resinacein S to detect hepatic steatosis. According to Network Pharmacology and RNA-seq, we analyzed the hub genes of Resinacein S against NAFLD disease.ResultsOur results can be summarized as follows: (1) The structure of Resinacein S was elucidated using NMR and MS methods. (2) Resinacein S treatment could significantly attenuate high-fat diet (HFD)-induced hepatic steatosis and hepatic lipid accumulation in mouse. (3) GO terms, KEGG pathways and the PPI network of Resinacein S induced Differentially Expressed Genes (DEGs) demonstrated the key target genes of Resinacein S against NAFLD. (4) The hub proteins in PPI network analysis could be used for NAFLD diagnosis and treatment as drug targets.ConclusionResinacein S can significantly change the lipid metabolism in liver cells and yield a protective effect against steatosis and liver injury. Intersected proteins between NAFLD related genes and Resinacein S-induced DEGs, especially the hub protein in PPI network analysis, can be used to characterize targets of Resinacein S against NAFLD.

Sustainable business model innovation (SBMI) and green technology innovation (GTI) are keys to creating shared social and business value, and both are essential elements of responsible innovation. However, SBMI or GTI is unable to develop a sustainable business. The main purpose of this study is to analyze sustainable dual innovation as a conceptual framework based on the panel data of 1468 Chinese manufacturing A-share listed companies from 2010 to 2020, and it has obtained three essential findings. First, there is a significant matching effect between SBMI and GTI on sustainable corporate performance (SCP). Companies report higher levels of SCP when there is a higher congruence in SBMI with GTI. Secondly, organizations with high SBMI-low GTI realize superior SCP compared to organizations with low SBMI-high GTI. The high SBMI-low GTI becomes an ideal choice for most companies and avoids the “destructive factors” brought by low SBMI-high GTI. Finally, a highly aggressive corporate strategy has a “magnifying effect” on the impact of the combination of SBMI and GTI on SCP. The research provides a comprehensive understanding and collective impact of SBMI and GTI on SCP. Overall, findings provide a theoretical basis for enterprises to decide on the consistency/inconsistency trade-off between SBMI and GTI. Moreover, it encourages to enterprises must develop an aggressive strategy to balance.

AimThe treatment of Alzheimer’s disease (AD) is still a worldwide problem due to the unclear pathogenesis and lack of effective therapeutic targets. In recent years, metabolomic and gut microbiome changes in patients with AD have received increasing attention, and the microbiome–gut–brain (MGB) axis has been proposed as a new hypothesis for its etiology. Considering that electroacupuncture (EA) efficiently moderates cognitive deficits in AD and its mechanisms remain poorly understood, especially regarding its effects on the gut microbiota, we performed urinary metabolomic and microbial community profiling on EA-treated AD model mice, presenilin 1/2 conditional double knockout (PS cDKO) mice, to observe the effect of EA treatment on the gut microbiota in AD and find the connection between affected gut microbiota and metabolites.Materials and methodsAfter 30 days of EA treatment, the recognition memory ability of PS cDKO mice was evaluated by the Y maze and the novel object recognition task. Urinary metabolomic profiling was conducted with the untargeted GC-MS method, and 16S rRNA sequence analysis was applied to analyze the microbial community. In addition, the association between differential urinary metabolites and gut microbiota was clarified by Spearman’s correlation coefficient analysis.Key findingsIn addition to reversed cognitive deficits, the urinary metabolome and gut microbiota of PS cDKO mice were altered as a result of EA treatment. Notably, the increased level of isovalerylglycine and the decreased levels of glycine and threonic acid in the urine of PS cDKO mice were reversed by EA treatment, which is involved in glyoxylate and dicarboxylate metabolism, as well as glycine, serine, and threonine metabolism. In addition to significantly enhancing the diversity and richness of the microbial community, EA treatment significantly increased the abundance of the genus Mucispirillum, while displaying no remarkable effect on the other major altered gut microbiota in PS cDKO mice, norank_f_Muribaculaceae, Lactobacillus, and Lachnospiraceae_NK4A136 group. There was a significant correlation between differential urinary metabolites and differential gut microbiota.SignificanceElectroacupuncture alleviates cognitive deficits in AD by modulating gut microbiota and metabolites. Mucispirillum might play an important role in the underlying mechanism of EA treatment. Our study provides a reference for future treatment of AD from the MGB axis.

Considering the consumer’s anticipated regret caused by price discount, the impact of anticipated regret and manufacturers’ fairness concerns on pricing and profits is explored, and a revenue-sharing contract to optimize the profits of supply chain is explored. In centralized decision-making model with manufacturer’s fairness neutrality and retailer-led decentralized decision-making model with the manufacturer’s fairness concerns, numerical simulation and model comparison is used to analyse regret sensitivity coefficient, consumer heterogeneity, the fairness concern coefficient on pricing decisions and profit coordination. Our results reveal that consumer’s anticipated regret has a negative impact on product prices, retailer’s profit and manufacturer’s profit. Manufacturer’s fairness concerns also increase product price and reduce profits of all parties. Retailer-led supply chain can share the revenue to achieve Pareto optimization. When formulating promotional strategies, retailers should consider the characteristics of anticipated regrets of consumers.