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Abstract Background Acute-phase reactions (APRs) are common among people treated for the first time with zoledronate (ZOL). The current view is that both the APRs caused by ZOL and its efficacy are related to the mevalonic acid pathway. However, the relationship between APRs and ZOL efficacy remains unclear. Methods This was a prospective observational cohort study involving postmenopausal women with osteoporosis in Shanghai, China, for 1 year. A total of 108 patients with an average age of 67.4 ± 5.8 years were treated with 5 mg intravenous ZOL for the first time. Data on demographic characteristics, APRs, blood counts, bone turnover markers, including C-telopeptide collagen crosslinks (CTX) and N-terminal propeptide of type 1 collagen (PINP), and bone mineral density (BMD) were collected. Results (1) The results did not reveal a relationship between APRs and changes in bone turnover markers and BMD but showed that changes in body temperature (T) within 3 days after administration were positively correlated with changes in the BMD of the LS at Month 12 (β = 0.279 P = 0.034). (2) This effect was mediated mainly by changes in serum CTX (b = 0.046, 95% CI [0.0010–0.0091]). (3) The ROC curve revealed that when T increased by 1.95 °C, the sensitivity and specificity of identifying clinically important changes in LS BMD after 1 year were optimized. Conclusions In this study, we tested the hypothesis that people with elevated body T after initial ZOL treatment had greater improvements in BMD and better outcomes. Trial registration NCT, NCT03158246. Registered 18/05/2017.

Abstract Metastasis is the major culprit of treatment failure in nasopharyngeal carcinoma (NPC). Aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2), a core circadian gene, plays a crucial role in the development of various tumors. Nevertheless, the biological role and mechanism of ARNTL2 are not fully elucidated in NPC. In this study, ARNTL2 expression was significantly upregulated in NPC tissues and cells. Overexpression of ARNTL2 facilitated NPC cell migration and invasion abilities, while inhibition of ARNTL2 in similarly treated cells blunted migration and invasion abilities in vitro. Consistently, in vivo xenograft tumor models revealed that ARNTL2 silencing reduced nude mice inguinal lymph node and lung metastases, as well as tumor growth. Mechanistically, ARNTL2 negatively regulated the transcription expression of AMOTL2 by directly binding to the AMOTL2 promoter, thus reducing the recruitment and stabilization of AMOTL2 to LATS1/2 kinases, which strengthened YAP nuclear translocation by suppressing LATS-dependent YAP phosphorylation. Inhibition of AMOTL2 counteracted the effects of ARNTL2 knockdown on NPC cell migration and invasion abilities. These findings suggest that ARNTL2 may be a promising therapeutic target to combat NPC metastasis and further supports the crucial roles of circadian genes in cancer development.

The shear mechanical behavior is regarded as an essential factor affecting the stability of the surrounding rocks in underground engineering. The shear strength and failure mechanisms of layered rock are significantly affected by the foliation angles. Direct shear tests were conducted on cubic slate samples with foliation angles of 0°, 30°, 45°, 60°, and 90°. The effect of foliation angles on failure patterns, acoustic emission (AE) characteristics, and shear strength parameters was analyzed. Based on AE characteristics, the slate failure process could be divided into four stages: quiet period, step-like increasing period, dramatic increasing period, and remission period. A new empirical expression of cohesion for layered rock was proposed, which was compared with linear and sinusoidal cohesion expressions based on the results made by this paper and previous experiments. The comparative analysis demonstrated that the new expression has better prediction ability than other expressions. The proposed empirical equation was used for direct shear simulations with the combined finite-discrete element method (FDEM), and it was found to align well with the experimental results. Considering both computational efficiency and accuracy, it was recommended to use a shear rate of 0.01 m/s for FDEM to carry out direct shear simulations. To balance the relationship between the number of elements and the simulation results in the direct shear simulations, the recommended element size is 1 mm.

Objective: Shenmai injection is a classic herbal prescription, and is often recommended for the treatment of anthracycline-induced cardiotoxicity. However, the efficacy and safety of Shenmai injection for the treatment of anthracycline-induced cardiotoxicity have not been reported. Materials and methods: We conducted a comprehensive search of eight literature databases and two clinical trial registries, retrieving all randomized controlled trials (RCTs) related to the treatment of anthracycline-induced cardiotoxicity with Shenmai injection from the establishment of the databases to July 1, 2023. Data analysis was performed using the Meta package in RStudio and RevMan 5.4. The GRADE pro3.6.1 software was utilized for assessing the quality of evidence. Results: A total of 16 RCTs including 2140 patients were included in this study. Meta-analysis showed that Shenmai injection had an advantage in improving ST-T segment changes (RR = 0.28; 95 % CI, 0.20 to 0.39; P

Oxidative dehydrogenation of propane (ODHP) is a reaction with significant practical significance. As for the industrial application of ODHP, it is challenging to achieve high activity and high propylene selectivity simultaneously. In this study, to overcome this obstacle, we designed a series of Cu/BN catalysts with unique morphologies for establishing a photothermal ODHP system with high efficiency and selectivity. Characterization and evaluation results revealed that Cu/BN-NS and Cu/BN-NF with enlarged specific surface areas exhibited higher catalytic activities. The localized surface plasmon resonance (LSPR) effect of Cu nanoparticles further enhanced the photothermal catalytic performances of Cu/BN catalysts under visible light irradiation. To the best of our knowledge, it is the first time to establish a BN-based photothermal ODHP catalytic system. This study is expected to pave pathways to realize high activity and propylene selectivity for the practical application of ODHP.

Abstract Background Identification of difficult laryngoscopy is a frequent demand in cervical spondylosis clinical surgery. This work aims to develop a hybrid architecture for identifying difficult laryngoscopy based on new indexes. Methods Initially, two new indexes for identifying difficult laryngoscopy are proposed, and their efficacy for predicting difficult laryngoscopy is compared to that of two conventional indexes. Second, a hybrid adaptive architecture with convolutional layers, spatial extraction, and a vision transformer is proposed for predicting difficult laryngoscopy. The proposed adaptive hybrid architecture is then optimized by determining the optimal location for extracting spatial information. Results The test accuracy of four indexes using simple model is 0.8320. The test accuracy of optimized hybrid architecture using four indexes is 0.8482. Conclusion The newly proposed two indexes, the angle between the lower margins of the second and sixth cervical spines and the vertical direction, are validated to be effective for recognizing difficult laryngoscopy. In addition, the optimized hybrid architecture employing four indexes demonstrates improved efficacy in detecting difficult laryngoscopy. Trial registration Ethics permission for this research was obtained from the Medical Scientific Research Ethics Committee of Peking University Third Hospital (IRB00006761-2015021) on 30 March 2015. A well-informed agreement has been received from all participants. Patients were enrolled in this research at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn , identifier: ChiCTR-ROC-16008598) on 6 June 2016.

Abstract Background Evidence exists of a strong association between inflammation and a decrease in skeletal muscle function and bone mineral density (BMD); however, the specific mechanisms of these associations remain unclear. Adipokines, as key regulators of the inflammatory response, may be implicated in these processes. The objective of this study was to explore the potential correlation between adipokines, skeletal muscle function and BMD in middle-aged and elderly individuals. Methods A comparative cross-sectional study was carried out at the Huadong Hospital Affiliated with Fudan University (Shanghai, China). A total of 460 middle-aged and elderly individuals were recruited, and 125 were enrolled in the analysis. Their biochemical indices, body composition, skeletal muscle function and BMD were measured. Bioinformatic analysis was also employed to identify potential adipokine targets linked to skeletal muscle function and BMD. To validate these targets, plasma and peripheral blood mononuclear cells (PBMCs) were harvested from these individuals and subjected to western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). Results Individuals in this cross-sectional study were categorized into 2 groups according to their median skeletal muscle mass (SMM) (28.8 kg for males and 20.6 kg for females). Individuals with lower SMM exhibited poorer grip strength (P = 0.017), longer 5-Times-Sit-to-Stand Test (FTSST) duration (P = 0.029), lower total hip BMD (P = 0.043), lower femoral neck BMD (P = 0.011) and higher levels of inflammatory markers in comparison with individuals with higher SMM. Bioinformatics analysis identified LEP, ADIPOQ, RBP4, and DPP4 as potential adipokine targets associated with skeletal muscle function and BMD. In vitro experiments demonstrated that individuals with decreased skeletal muscle function and BMD expressed higher levels of these adipokines. Conclusions Skeletal muscle function is positively correlated with BMD and negatively correlated with levels of inflammatory markers among middle-aged and elderly individuals. Those with lower skeletal muscle function and BMD tend to have a higher expression of LEP, ADIPOQ, RBP4 and DPP4.

Abstract Objective Guizhi Fuling Capsule (GZFL), a classic traditional Chinese medicine prescription, is often recommended for the treatment of uterine fibroids (UFs). However, the efficacy and safety of GZFL in combination with low-dose mifepristone (MFP) remains controversial. Materials and methods We searched eight literature databases and two clinical trial registries for randomized controlled trials (RCTs) of the efficacy and safety of GZFL combined with low-dose MFP in the treatment of UFs from database inception to April 24, 2022. Data analysis was performed using the Meta package in RStudio and RevMan 5.4. GRADE pro3.6.1 software was used for the assessment of evidence quality. Results Twenty-eight RCTs were included in this study, including a total of 2813 patients. The meta-analysis showed that compared with low-dose MFP alone, GZFL combined with low-dose MFP significantly reduced follicle stimulating hormone (p

Abstract Background Aerobic glycolysis has been recognized as one of the growth-promoting metabolic alterations of cancer cells. Emerging evidence indicates that nuclear factor κB (NF-κB) plays significant roles in metabolic adaptation in normal cells and cancer cells. However, whether and how NF-κB regulates metabolic reprogramming in hepatocellular carcinoma (HCC), specifically hepatitis B virus X protein (HBx)-initiated HCC, has not been determined. Methods A dataset of the HCC cohort from the TCGA database was used to analyse the expression of NF-κB family members. Expression of NF-κBp65 and phosphorylation of NF-κBp65 (p-p65) were detected in liver tissues from HBV-related HCC patients and normal controls. A newly established HBx +/+/NF-κBp65 f/f and HBx +/+ /NF-κBp65 Δhepa spontaneous HCC mouse model was used to investigate the effects of NF-κBp65 on HBx-initiated hepatocarcinogenesis. Whether and how NF-κBp65 is involved in aerobic glycolysis induced by HBx in hepatocellular carcinogenesis were analysed in vitro and in vivo. Results NF-κBp65 was upregulated in HBV-related HCC, and HBx induced NF-κBp65 upregulation and phosphorylation in vivo and in vitro. Hepatocyte-specific NF-κBp65 deficiency remarkably decreased HBx-initiated spontaneous HCC incidence in HBx-TG mice. Mechanistically, HBx induced aerobic glycolysis by activating NF-κBp65/hexokinase 2 (HK2) signalling in spontaneous hepatocarcinogenesis, and overproduced lactate significantly promoted HCC cell pernicious proliferation via the PI3K (phosphatidylinositide 3-kinase)/Akt pathway in hepatocarcinogenesis. Conclusion The data elucidate that NF-κBp65 plays a pivotal role in HBx-initiated spontaneous HCC, which depends on hyperactive NF-κBp65/HK2-mediated aerobic glycolysis to activate PI3K/Akt signalling. Thus, phosphorylation of NF-κBp65 will be a potential therapeutic target for HBV-related HCC.

In the conventional FDEM (Combined Finite and Discrete Element Method), each contact pair might have multiple contact points where friction forces are applied, leading to non-unique friction force assignments and potentially introducing computational errors. This study introduces a new contact friction algorithm for FDEM based on the resultant normal contact force. This method necessitates determining the friction force at a unique equivalent contact point, thereby significantly simplifying the computational flow and reducing memory usage. A series of numerical tests are performed to validate the effectiveness of the proposed contact model. Using collision and block sliding tests, the proposed contact friction model is verified to be able to accurately capture the frictional effect between discrete bodies and circumvent the problematic kinetic energy dissipation issue associated with the original contact friction algorithm. For the Brazilian splitting and uniaxial compression tests, the simulated results closely align with those generated using the original contact friction algorithm and match the experimental measurements well, demonstrating the applicability of the proposed algorithm in fracturing analysis. Furthermore, by using the proposed contact friction algorithm, a computational efficiency enhancement of 8% in contact force evaluation can be achieved.

Acute myeloid leukemia is the most prevalent type of leukemia in adults and is prone to relapse and chemoresistance, with a low long-term survival rate. Therefore, the identification of quality biomarkers constitutes an urgent unmet need. High expression of beta-1,4-galactosyltransferase 1 (B4GALT1) has been observed in several cancer types; however, its function in acute myeloid leukemia has rarely been studied. Therefore, our study obtained gene expression data from The Cancer Genome Atlas (TCGA) database to analyze the relationship between B4GALT1 and LAML. We compared the expression of B4GALT1 in LAML and healthy samples using the Wilcoxon rank-sum test. Furthermore, the association between B4GALT1 and survival rates was investigated using Kaplan-Meier analysis and Cox regression. The nomogram obtained by Cox analysis predicts the effect of B4GALT1 on the prognosis. To assess B4GALT1-related genes’ enrichment pathway and function and the correlation between B4GALT1 and immune features, GO/KEGG, protein-protein interaction network, and single sample gene set enrichment analysis were used. In addition, B4GALT1-specific siRNAs were used to verify the effect of B4GALT1 on apoptosis. The results showed that B4GALT1 is overexpressed in LAML and has some reference value in the diagnostic and prognostic assessment of LAML. Moreover, functional enrichment showed that B4GALT1 and its 63 associated genes were closely associated with the negative regulation of the apoptotic signaling pathway. Silencing B4GALT1 significantly promoted apoptosis. In addition, B4GALT1 expression was positively correlated with the infiltration levels of macrophages, regulatory T-cell (Tregs), and Th17 cells; in contrast, B4GALT1 expression was negatively correlated with the infiltration levels of T helper cells, Mast cells, and NK cells. In conclusion, our study shows that B4GALT1 may play a vital role in the occurrence of LAML.

Difficult laryngoscopy is associated with airway injury, and asphyxia. There are no guidelines or gold standards for detecting difficult laryngoscopy. There are many opinions on which predictors to use to detect difficult laryngoscopy exposure, and no comprehensively unified comparative analysis has been conducted. The efficacy and accuracy of deep learning (DL)-based models and machine learning (ML)-based models for predicting difficult laryngoscopy need to be evaluated and compared, under the circumstance that the flourishing of deep neural networks (DNN) has increasingly left ML less concentrated and uncreative. For the first time, the performance of difficult laryngoscopy prediction for a dataset of 671 patients, under single index and integrated multiple indicators was consistently verified under seven ML-based models and four DL-based approaches. The top dog was a simple traditional machine learning model, Naïve Bayes, outperforming DL-based models, the best test accuracy is 86.6%, the F1 score is 0.908, and the average precision score is 0.837. Three radiological variables of difficult laryngoscopy were all valuable separately and combinedly and the ranking was presented. There is no significant difference in performance among the three radiological indicators individually (83.06% vs. 83.20% vs. 83.33%) and comprehensively (83.74%), suggesting that anesthesiologists can flexibly choose appropriate measurement indicators according to the actual situation to predict difficult laryngoscopy. Adaptive spatial interaction was imposed to the model to boost the performance of difficult laryngoscopy prediction with preoperative cervical spine X-ray.

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To satisfy the requirement of real-time and accurate control of the system, a time-delay prediction control system based on the PSO-RBF neural network model is established to solve the effect of time delay on the control system’s performance. Firstly, a network control model with a time delay is established to predict the control system’s output to solve the uncertainty of the output time delay. Secondly, an improved offline prediction model of RBF networks is proposed to solve the problem of the low accuracy of time-delay prediction in PSO-RBF networks. To solve the problem that the PSO algorithm is prone to fall into local optimality, a nonlinear adjustment formula for the parameters of the PSO algorithm based on the number of iterations is proposed, and the TS algorithm is used to make the optimal global solution. Finally, in order to compensate for the problem of time delay, an online RBF network prediction controller is designed, the parameters of the online RBF network are adjusted by the gradient descent method, and a target function with the differential component is proposed to evaluate the optimization effect of the rolling optimization stage. The results from the true-time simulation platform show that the delay prediction control system based on the PSO-RBF network model proposed in this paper improves the IAE by 59.9% and 31.7%, respectively, compared to the traditional PID controller and fuzzy PID control under the influence of uncertainty disturbances. Therefore, the time-delay prediction control system proposed in this paper has good control capability for the time-delay compensation problem and system output.

In this paper, we consider the groups of isometries of metric spaces arising from finitely generated additive abelian groups. Let A be a finitely generated additive abelian group. Let R={1,ϱ} where ϱ is a reflection at the origin and T={ta:A→A,ta(x)=x+a,a∈A}. We show that (1) for any finitely generated additive abelian group A and finite generating set S with 0∉S and −S=S, the maximum subgroup of IsomX(A,S) is RT; (2) D⊴RT if and only if D≤T or D=RT′ where T′={h2:h∈T}; (3) for the vector groups over integers with finite generating set S={u∈Zn:|u|=1}, IsomX(Zn,S)=On(Z)Zn. The paper also includes a few intermediate technical results.

The activation of carbon dioxide (CO2) molecules and separation/transfer of photoinduced charge carriers are two crucial factors influencing the efficiency of CO2 photoreduction. Herein, we report a p-type Bi2Te3/commercial TiO2 (pBT/P25) nanocomposite for enhanced CO2 photoreduction. Upon light irradiation, a temperature gradient formed in pBT induces the Seebeck effect to build a thermoelectric field, which promotes the charge carriers’ separation/transfer. Additionally, pBT with a strong light absorption capacity generates the photothermal effect favoring the activation of CO2 molecules. In addition, the excellent electric conductivity and large work function render pBT an efficient cocatalyst for further improving the charge carriers’ separation/transfer. Owing to the synergistic enhancement effect of pBT on the activation of CO2 molecules and promotion of charge separation/transfer, we achieved the highest CO evolution rate over pBT(2)/P25 of 19.2 μmol·gcat−1·h−1, which was approximately 5.5 times that of bare P25. This work suggests that a thermoelectric material/semiconductor nanocomposite could be developed as an efficient photo-thermo-electro-chemical conversion system for enhanced CO2 reduction via promoting the charge carriers’ separation/transfer.

Let (X,d) be a directionally (γ,m)-limited space with every γ∈(0,∞). In this setting, we aim to study an analogue of the classical theory of Ap(μ) weights. As an application, we establish some weighted estimates for the Hardy–Littlewood maximal operator. Then, we introduce the relationship between directionally (γ,m)-limited spaceand geometric doubling. Finally, we obtain the weighted norm inequalities of the Calderón–Zygmund operator and commutator in non-homogeneous space.

A monetary model is established to introduce that bitcoin does have the characteristics of a price rise when the economic situation is terrible under high risk aversion. At this time, Bitcoin has the property of a safe-haven asset, and when economic conditions are good and risk aversion is low, Bitcoin has a pro-cyclical nature. At this time, Bitcoin has a stronger property as a medium of exchange. To show the movement law of the bitcoin price, we make a logarithmic linearization of the model and simulation, and the result is consistent with the theoretical analysis. To better understand the role of bitcoin in the real economy, several standard portfolio models are used to measure the similarities and differences between gold and bitcoin in an investment portfolio. After the outbreak of COVID-19, bitcoin has shown stronger safe-haven asset properties.