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Objective: Metformin as a common antidiabetic drug, has recently found to exert its anti-cancer and immunomodulatory effect in numerous preclinical studies. This study aims to clarify the prognostic impact of metformin use in solid cancer patients receiving immune checkpoint inhibitors (ICIs).Methods: A retrospective cohort enrolling 516 solid cancer patients who received ICI-based therapy between 2018 and 2023 at three hospitals was analyzed. The primary endpoints included overall survival (OS) and progression-free survival (PFS). In addition, a bioinformatics analysis based on TCGA and GSE cohort was performed to investigate the prognostic significance of metformin target genes (MTGs) and their correlation with immune infiltration in non-small cell lung cancer (NSCLC) patients.Results: In the entire cohort, a total of 76 patients received metformin before and/or during ICI therapy. The global analysis demonstrated that metformin use was unrelated with the OS (p = 0.064) and PFS (p = 0.059) of ICI-treated cancer patients, which was confirmed in the subgroups of esophagus, hepatobiliary or pancreatic cancer (all p > 0.05). However, metformin use was significantly correlated with better OS (p = 0.012) and PFS (p = 0.005) in ICI-treated lung cancer patients. Metformin use was also identified as an independent favorable prognostic factor for these patients. The bioinformatics analysis identified five favorable prognostic MTGs (RPS6KA5, RORA, SH3BP5, NUPR1, and CD40LG) for NSCLC patients, all of which was downregulated in lung cancer tissues as compared with normal tissues. The expressions of five MTGs not only could effectively stratify the OS of NSCLC patients, but also was correlated with infiltration of immune cells such as CD4+ and CD8+ T cells.Conclusion: Metformin use was significantly correlated with better OS and PFS in ICI-treated lung cancer patients. MTGs has the potential to serve as novel clinical biomarkers or druggable targets for cancer immunotherapy. Considering study limitations, the actual impact of metformin use on ICI therapy needs to be clarified by more clinical trials.

Background: Pulmonary hypertension (PH) is a progressive and fatal cardiopulmonary disease characterized by vascular remodeling and is associated with endothelial-to-mesenchymal transition (EndoMT). The pigment epithelium-derived factor (PEDF), a secretory protein widely distributed in multiple organs, has been shown to demonstrate anti-EndoMT activity in cardiovascular diseases. In the present study, the role of PEDF in PH was investigated. Methods: For PEDF overexpression, Sprague Dawley rats were infected with an adeno-associated virus through injection via the internal jugular vein. To establish PH models, the animals were subjected to monocrotaline or Sugen/hypoxia. Four weeks later, pulmonary artery angiography was performed, and hemodynamic parameters, right ventricular function, and vascular remodeling were evaluated. EndoMT and cell proliferation in the pulmonary arteries were assessed via immunofluorescence staining. Moreover, pulmonary artery endothelial cells (PAECs) isolated from experimental PH rats were cultured to investigate the underlying molecular mechanisms involved. Results: PEDF expression was significantly downregulated in PAECs from PH patients and PH model rats. Overexpressed PEDF alleviated the development of PH by improving pulmonary artery morphology and perfusion, reducing pulmonary artery pressure, improving right ventricular function, and alleviating vascular remodeling. PEDF inhibits EndoMT and reduces excessive PAEC proliferation. Moreover, PEDF overexpression reduced EndoMT in cultured PAECs by competitively inhibiting the binding of wnt to LRP6 and downregulating phosphorylation at the 1490 site of LRP6. Conclusions: Our findings suggest that PEDF may be a potential therapeutic target for PH. We also found that PEDF can inhibit EndoMT in PAECs and may exert these effects by inhibiting the Wnt/LRP6/β-catenin pathway.

Addressing the issues of prolonged training times and low recognition rates in large model applications, this paper proposes a weight training method based on entropy gain for weight initialization and dynamic adjustment of the learning rate using the multilayer perceptron (MLP) model as an example. Initially, entropy gain was used to replace random initial values for weight initialization. Subsequently, an incremental learning rate strategy was employed for weight updates. The model was trained and validated using the MNIST handwritten digit dataset. The experimental results showed that, compared to random initialization, the proposed initialization method improves training effectiveness by 39.8% and increases the maximum recognition accuracy by 8.9%, demonstrating the feasibility of this method in large model applications.

Underwater images often exhibit detail blurring and color distortion due to light scattering, impurities, and other influences, obscuring essential textures and details. This presents a challenge for existing super-resolution techniques in identifying and extracting effective features, making high-quality reconstruction difficult. This research aims to innovate underwater image super-resolution technology to tackle this challenge. Initially, an underwater image degradation model was created by integrating random subsampling, Gaussian blur, mixed noise, and suspended particle simulation to generate a highly realistic synthetic dataset, thereby training the network to adapt to various degradation factors. Subsequently, to enhance the network’s capability to extract key features, improvements were made based on the symmetrically structured blind super-resolution generative adversarial network (BSRGAN) model architecture. An attention mechanism based on energy functions was introduced within the generator to assess the importance of each pixel, and a weighted fusion strategy of adversarial loss, reconstruction loss, and perceptual loss was utilized to improve the quality of image reconstruction. Experimental results demonstrated that the proposed method achieved significant improvements in peak signal-to-noise ratio (PSNR) and underwater image quality measure (UIQM) by 0.85 dB and 0.19, respectively, significantly enhancing the visual perception quality and indicating its feasibility in super-resolution applications.

As a common benign anal condition, the high incidence and recurrence of hemorrhoids pose challenges for both patients and doctors. The classification of hemorrhoids plays a crucial role in assessing, diagnosing, and treating the condition. By using appropriate classification and corresponding treatment strategies, we can achieve higher cure rates and lower recurrence rates of hemorrhoids. Since the introduction of the Miles classification in 1919, various classifications have been developed, which include objective classifications based on anatomical or instrumental assessment and subjective classifications based on symptoms and patient sensations. These classifications aim to accurately evaluate the condition. In this study, we discuss the evaluation values of each classification in terms of their advantages, disadvantages, treatment relevance, reproducibility, practicality, and assessment value. We also analyze the significant and essential factors, principles of use, and components of assessment indicators of hemorrhoidal classification. This study proposes several strategies to address the limitations of current hemorrhoidal assessment methods. All these will provide a reference for the development regarding the assessment and classification of hemorrhoids and clinical diagnosis and management of hemorrhoids.

Abstract Background Proximal humeral fractures (PHFs) are the third most commonly occurring fractures in elderly patients. Most of these fractures can be treated with conservative methods, but the optimal surgical treatment strategy for unstable fractures in elderly patients remains controversial. This study aimed to compare the radiological and clinical outcomes between locking compression plate (LCP) fixation and LCP fixation with fibular allograft implantation for the treatment of comminuted PHFs. Methods We retrospectively reviewed 60 patients (mean age, 72.75 years) with closed 3- or 4-part fractures, and a minimum of 2 years of follow-up. Fracture reduction was quantitatively determined by humeral head height (HHH) and neck-shaft angle (NSA). The clinical outcome was evaluated by Constant-Murley score (CMS) and American Shoulder and Elbow Surgeons (ASES) score. Result The average radiological changes were higher in the LCP group than in the locking plate with fibular allograft group (HHH of 4.16 mm vs 1.18 mm [p

Large amounts of sensor data are frequently generated and streamed from sensors deployed on various buildings, in forests or in other application areas. In many of these areas, one difficulty is managing the velocity and volume of the big sensor data while still providing low time latency support for data analysis. Data aggregation can reduce the volume of big sensor data. However, data aggregation is a fundamental yet time-consuming operation in wireless sensor networks (WSNs), particularly in high-density WSNs. Therefore, researchers have started focusing on minimizing the latency of data aggregation, which has been proven to be an NP-hard problem. This paper proposes a cluster-based distributed data aggregation scheduling algorithm, distributed multi-power and multi-channel (DMPMC), that can minimize the data aggregation latency in multi-channel and multi-power WSNs. To save energy, low transmission power is used for packet transmissions inside a cluster, and high power is used for packet transmissions among clusters. Simulations are conducted to compare DMPMC with the best centralized algorithm in a single channel, named E-PAS, the best distributed algorithm in a single channel, named CLU-DDAS, and the best algorithm in multi-channels, named multi-channel. The results show that the DMPMC algorithm proposed in this paper achieves the lowest average latency.

The oxidation behavior and kinetics of (Zr, Ti)(C, N)–SiC ceramics subjected to a temperature of 850 °C-950 °C (typical operating temperatures range of Generation-IV nuclear reactors) for 1–4 h are investigated via X-ray diffraction, scanning electron microscopy, and weight gain testing. The results show that the microstructures of the ceramics after oxidation comprises primarily of m-(Zr, Ti)O2, c-(Zr, Ti)O2, and SiO2. After adding Si, the oxidation layer appears as a two-layer structure with both external and internal layers. The oxidation order of (Zr, Ti)(C, N)–SiC ceramics at 850 °C-950 °C is ZrSi > (Zr, Ti)(C, N) > SiC. Unoxidized SiC forms a “core-shell” structure with a dense external layer of SiO2. The dual effect of small SiO2 particles occupying cracks and the “core-shell” structure of SiC–SiO2 withstanding stresses can inhibit the propagation of cracks and reduce the porosity of the oxide layer. The oxidation of Z5T and Z5T5S exhibits linear oxidation kinetics, whereas the oxidation of Z5T10S and Z5T20S results in quasi-parabolic oxidation. By adding Si, the oxidation activation energy of Z5T20S (with the addition of 20 mol% Si) increases by 174 % compared to that of Z5T ceramic, thus improving the oxidation resistance of (Zr, Ti)(C, N)-based ceramics at 850 °C-950 °C.

Residual stress refers to self-equilibrating stress present within materials, with the potential to significantly affect manufacturing processes and performance. Therefore, accurately and quantitatively measuring residual stress is always of great importance. This study provides a comprehensive review of various characterization techniques for residual stress, including their principles, development history, applications, and limitations. Initially, several destructive techniques such as the hole-drilling method, ring-core method, deep hole drilling method, slitting method, and contour method are summarized. Subsequently, three nondestructive techniques based on X-ray/electron diffraction, magnetic signals, and ultrasonic signals are evaluated. In the final part of this overview, special attention is given to a newly-developed technique for measuring residual stress, which combines incremental focused ion beam (FIB) milling and digital image correlation (DIC). Our review aims to guide further investigations on residual stress and identify the future development of techniques for measuring residual stress.

Novel TiC-based ceramics were prepared by reactive hot-pressing at 1400–1600 °C using TiC, Si and ZrC powders as raw reactants for the first time. The effects of ZrC addition and temperature on the microstructure and mechanical properties of ceramics were investigated. The Ti3SiC2 phase existed when the content of ZrC was 10 mol%. The Zr-rich solid solution appeared and the Ti3SiC2 disappeared with 30 mol% ZrC addition. The flexural strength of ceramics was improved due to grain refinement by the pinned SiC, the formation of solid solutions and the Ti3SiC2 phase. The main toughening mechanism can be crack bridging by the layered Ti3SiC2 and crack deflection by the ZrSi particle. TiC-36 mol% Si-10 mol% ZrC (raw composition) exhibits good comprehensive mechanical properties (Vickers hardness of 21.8 GPa, flexural strength of 580 MPa, and indentation fracture toughness of 6.7 MPa m1/2), which reach or exceed most TiC-based ceramics in previous reports.

Strength and ductility synergy in ultrafine-grained AZQ310 alloy sheet was successfully improved at the expense of grain boundary segregation via multi-pass rolling. Before rolling, the as-extruded alloy has high yield strength (TYS, 382 MPa) but poor elongation (4.1%) mainly due to the ultra-fine grains (414 nm) and the co-segregation of Al/Zn atoms at grain boundaries. More importantly, this non-equilibrium segregation dies away during the rolling process, and the sheet exhibits a tensile yield strength of 370 MPa, an ultimate strength of 422 MPa, and an elongation of 9.8% along the rolling direction after 5th pass rolling. The results show that the high strength-ductility synergy is mainly attributed to the ultra-fine grains and residual dislocations. Furthermore, it is surprising that the yield point phenomenon (YPP) prominently in as-extruded sample is weakened and finally eliminated in as-rolled sheets. Microstructure evolution in the room temperature tensile test manifests that the underlying reason for the YPP is the stress-induced grain growth and grain boundary segregation, which in turn expounds the difficulty in the refining of ultrafine-grained Mg alloys by traditional processing methods.

Background: Traffic-related air pollution (TRAP) is a risk factor for cognitive function, whereas healthy lifestyles are associated with better cognition. We aimed to examine their joint effects on cognition among the Chinese elderly. Methods: The data from the Chinese Longitudinal Healthy Longevity Survey was used. Participants’ cognitive performance was assessed by the Chinese version of the mini-mental state examination. Residential proximity to major roadways was obtained through self-report and categorized into five categories: > 300 m, 201–300 m, 101–200 m, 50–100 m, and 300 m from major roadways and adopting a healthy lifestyle had a significantly decreased risk of cognitive impairment. Stratified analysis indicated that the associations between TRAP and cognitive impairment were more pronounced among participants adopting an unhealthy lifestyle compared to the participants adopting a healthy lifestyle. Conclusions: TRAP may impair cognitive function, and its detrimental impacts may be lessened by healthy lifestyles.

As an integral part of the digital economy era, the digital transformation of businesses can have a certain impact on their green total factor productivity, but causal identification of this impact remains limited. To address these shortcomings, this study selects 20 categories of heavily polluting enterprises based on the industry classification standards of the China Securities Regulatory Commission in 2012. Using listed company data from 2015 to 2019 and combining the global Malmquist-Luenberger productivity index, the study employs the Slacks Based Measure-Directional Distance Function model to assess the relationship between digitalization and green total factor productivity of enterprises. The research findings are as follows: 1) The promotion of digital transformation by businesses can significantly facilitate the improvement of green total factor productivity. 2) The results of the mediation effect test indicate that advanced digital technologies can enhance green total factor productivity by optimizing the internal financial conditions of enterprises. 3) Model construction demonstrates that market competition and investor sentiment play a moderating role in green total factor productivity. 4) Threshold regression analysis confirms that higher managerial capabilities enable the better digital transformation of enterprises, leading to higher green total factor productivity. Finally, from the perspective of enterprises themselves, this study proposes strategies to promote green total factor productivity and sustainable development. It expands the existing literature and evidence on the impact of digitalization on green total factor productivity while providing recommendations for businesses striving to achieve sustainable development.

Structural and electrical remodeling within the atrium mediate the pathogenesis of atrial fibrillation (AF). Two key genes that sever a role in this remodeling are connexin 40 (Cx40) and potassium voltage-gated channel subfamily A member 5 (KCNA5), respectively. Electrical remodeling is considered to induce structural remodeling during AF. In the present study, the left atrial appendage section and atrial myocytes of patients with AF were evaluated. It was observed that Cx40 and KCNA5 mRNA (P<0.05) and protein (P<0.01) expression was significantly downregulated in AF compared with rheumatic heart disease. In addition, a positive correlation between the mRNA expression Cx40 and KCNA5 was observed in the atrial myocytes of patients with AF (P<0.05; r=0.42). The association between Cx40 and KCNA5 expression was subsequently investigated in primary cultured atrial myocytes using siRNA transfection. In atrial myocytes, downregulation of Cx40 inhibited the expression of KCNA5. Similarly, silencing of KCNA5 suppressed the expression of Cx40. These results indicate that synergistic regulation may occur between Cx40 and KCNA5 expression. Furthermore, the combined effects of electrical and structural remodeling in the atrial myocytes of patients with AF may contribute to the pathogenesis of AF. [ABSTRACT FROM AUTHOR]

Titanium alloy has the advantages of low thermal conductivity, a small expansion coefficient and being non-magnetic, making it an ideal low-temperature structural material. In this paper, the typical TC4 titanium alloy in industrial titanium alloy is selected as the research object. The microstructure deformation law and mechanical behavior of TC4 titanium alloy at liquid nitrogen temperature are mainly investigated, and compared with the microstructure and properties at room temperature. The macroscopic and microscopic deformation mechanism of the simultaneous increase in elongation and hardening index of titanium alloy at low temperature is revealed, which provides a basic basis for the low-temperature deformation mechanism and strengthening and toughening design of titanium alloy. Based on the uniaxial tensile tests at room temperature (298 K) and low temperature (77 K), the effects of low temperature on the yield strength, elongation, tensile strength and work hardening curve of titanium alloy were compared and analyzed. The strength/plasticity synergistic improvement of TC4 titanium alloy under low-temperature deformation was found. At low temperature, the yield strength, tensile strength and elongation of TC4 titanium alloy are improved compared with room temperature. The tensile strength increases from 847.93 MPa at 298 K to 1318.70 MPa at 77 K, and the elongation increases from 21.8% at 298 K to 24.9% at 77 K. The grain morphology, grain orientation, dislocation density and fracture morphology of titanium alloy under room temperature and low-temperature tensile conditions were studied by SEM and EBSD. The results of fracture morphology characterization at room temperature and low temperature show that TC4 titanium alloy exhibits ductile fracture characteristics and a large number of dimples are formed on the fracture surface. The dimple depth at low temperature is shallower than that at room temperature and the overall surface is more flat. Compared with room temperature deformation, the deformation process of TC4 titanium alloy in a low-temperature environment produces stronger dislocation pile-up and forms a large number of twins, but the grain rotation is more significant, which effectively alleviates the stress concentration and delays the initiation and propagation of cracks at grain boundaries.

Dense and enhanced mechanical properties (Zr, Ti)(C, N)-based composites were fabricated using ZrC, TiC0.5N0.5, and Si powders as the raw powders by reactive hot-pressing at 1500–1700 °C. At the low sintering temperature, both (Zr, Ti)(C, N) and (Ti, Zr)(C, N) solid solutions were formed in the composites by adjusting the ratio of ZrC to TiC0.5N0.5. During the sintering process, the Si added at a rate of 5 mol% reacted with ZrC and TiC0.5N0.5 to generate SiC. With the increase in Si addition, it was found that the residual β-ZrSi was formed, which greatly reduced the flexural strength of composites but improved their toughness. The reaction and solid-solution-driven inter-diffusion processes enhanced mass transfer and promote densification. The solid solution strengthening and grain refinement improved the mechanical properties. The ZrC–47.5 mol% TiC0.5N0.5–5 mol% Si (raw powder) composite possessed excellent comprehensive performance. Its flexural strength, Vickers hardness, and fracture toughness were 508 ± 33 MPa, 24.5 ± 0.7 GPa, and 3.8 ± 0.1 MPa·m1/2, respectively. These reached or exceeded the performance of most (Zr, Ti)(C, N) ceramics reported in previous studies. The lattice distortion, abundant grain boundaries, and fine-grained microstructure may make it possible for the material to be resistant to radiation.

Opioid-induced constipation (OIC) is one of the common adverse reactions of opioids, which may affect the quality of life and follow-up treatment compliance of patients. With the rise of number of cancer patients worldwide and the increase in the use of opioids in chronic non-cancerous pain, the number of OIC patients will increase accordingly. Therefore, how to achieve effective analgesia and balance the occurrence of analgesia and OIC is one of the clinical problems that need to be resolved urgently. At present, the main therapeutic drugs for OIC mainly include oral laxatives and peripheral μ-opioid receptor antagonists, secretagogues, traditional Chinese medicines, etc. This paper mainly analyzed the drug therapy of OIC, in order to provide a reference for the effective clinical prevention and treatment of OIC.

To promote the safe and efficient mining of intelligent comprehensive mining under complex geological conditions, taking the geological structure of 3124S intelligent comprehensive mining face of Longtan Coal Power Company as the background, the structural conditions and mining difficulties are comprehensively analyzed. A series of complete technical schemes are made, including the structural form of geological borehole detection, surrounding rock structure reinforcement by grouting borehole, optimization and transformation of roadway system, advance laying of high-rise false roof, supplement and strengthen of disaster management, intelligent mining of rock breaking by coal machine, etc. Through the field practice, the output of geological structural section for intelligent fully-mechanized mining does not reduced, and the safety is guaranteed.

Introduction: Perioperative inflammatory markers, including the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), are associated with oncological prognosis. However, their changes in colorectal cancer surgery for predicting the prognosis are rarely investigated., Aim: To compare perioperative changes to evaluate the prognostic significance of patients' survival., Material and Methods: Retrospective clinical data and baseline laboratory parameters of 183 colorectal cancer (CRC) patients who underwent curative surgery were collected between January 2007 and January 2013. The clinicopathological characteristics were compared. Statistical analysis was used to identify the predictive changes of perioperative NLR and PLR associated with survival prognosis., Results: ROC analysis indicated that perioperative NLR/PLR showed higher predictive accuracy for prognosis, and the optimal cut-off values of pre-NLR, post-NLR, pre-PLR, and post-PLR were 2.94, 4.32, 184.29, and 212.37, respectively. Kaplan-Meier analysis suggested that the four groups stratified by perioperative changes had significantly different recurrence-free survival and overall survival ( p < 0.05). Univariate and multivariable analysis revealed that patients with higher cancer stage, lymph node metastasis, and perioperative change of NLR/PLR (HH, LH) had significant association with poor prognosis of RFS and OS (all p < 0.05)., Conclusions: Perioperative NLR and PLR might be good predictors for prognosis in CRC patients who have undergone curative surgery, which could guide the customised therapeutic strategy. Furthermore, their assessment could contribute to accurately predicting oncologic outcomes and provide an in-depth understanding of the patients, which could guide the operational strategy., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2019 Termedia Sp. z o. o.)