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BackgroundStatic tumor features before initiating anti-tumor treatment were insufficient to distinguish responding from non-responding tumors under the selective pressure of immuno-therapy. Herein we investigated the longitudinal dynamics of peripheral blood inflammatory indexes (dPBI) and its value in predicting major pathological response (MPR) in non-small cell lung cancer (NSCLC).MethodsA total of 147 patients with NSCLC who underwent neoadjuvant immunochemotherapy were retrospectively reviewed as training cohort, and 26 NSCLC patients from a phase II trial were included as validation cohort. Peripheral blood inflammatory indexes were collected at baseline and as posttreatment status; their dynamics were calculated as their posttreatment values minus their baseline level. Least absolute shrinkage and selection operator algorithm was utilized to screen out predictors for MPR, and a MPR score was integrated. We constructed a model incorporating this MPR score and clinical predictors for predicting MPR and evaluated its predictive capacity via the area under the curve (AUC) of the receiver operating characteristic and calibration curves. Furthermore, we sought to interpret this MPR score in the context of micro-RNA transcriptomic analysis in plasma exosomes for 12 paired samples (baseline and posttreatment) obtained from the training cohort.ResultsLongitudinal dynamics of monocyte–lymphocyte ratio, platelet-to-lymphocyte ratio, platelet-to-albumin ratio, and prognostic nutritional index were screened out as significant indicators for MPR and a MPR score was integrated, which was further identified as an independent predictor of MPR. Then, we constructed a predictive model incorporating MPR score, histology, and differentiated degree, which discriminated MPR and non-MPR patients well in both the training and validation cohorts with an AUC value of 0.803 and 0.817, respectively. Furthermore, micro-RNA transcriptomic analysis revealed the association between our MPR score and immune regulation pathways. A significantly better event-free survival was seen in subpopulations with a high MPR score.ConclusionOur findings suggested that dPBI reflected responses to neoadjuvant immuno-chemotherapy for NSCLC. The MPR score, a non-invasive biomarker integrating their dynamics, captured the miRNA transcriptomic pattern in the tumor microenvironment and distinguished MPR from non-MPR for neoadjuvant immunochemotherapy, which could support the clinical decisions on the utilization of immune checkpoint inhibitor-based treatments in NSCLC patients.

To explore the accuracy of the calculation method of the jacking force of circular curved pipe jacking under different pipe-soil contact characteristics, in combination with the curved steel pipe jacking project of Gongbei Tunnel of Hong Kong-Zhuhai-Macao Bridge, this paper adopted several commonly used jacking force calculation formulas for the curved pipe jacking at home and abroad and jacking force finite element analysis model with consideration of grouting effect and the pipe-soil contact range established with ABAQUS to calculate the jacking force. It was found by contrast with the pipe jacking force data: ①The calculated value of jacking force: JMTA formula≫Shanghai normative formula>Shimada formula, where it was considered that the calculated value of the lower limit of Shimada formula of 1/3 pipe-soil contact was relatively close to the measured value. ②Through numerical simulation, it was found that the simulated jacking force of 1/3 pipe-soil contact characteristics was gradually close to the one of 1/2 pipe-soil contact characteristics; in the grouting state, the previously measured jacking force was close to the one of 1/2 pipe-soil contact characteristics. When the jacking force tended to be stable, the measured jacking force was close to the one of 1/3 pipe-soil contact characteristics. Therefore, the numerical model could predict the jacking force of the pipe jacking under the same working condition and had a certain guiding significance for actual construction.

As a kind of solid waste, using Prestressed High-Strength Concrete Pile Waste Concrete (PPWC) as the replacement for limestone filler in asphalt concrete can not only reduce the accumulation of PPWC and increase its utilization but also avoid the increased road construction costs and environmental degradation associated with limestone mining. This study aims to investigate the effect of using PPWC filler to replace limestone filler on the road performance of asphalt concrete. Firstly, PPWC was ground into filler particles with a diameter less than 0.075 mm. The particle characteristics such as surface morphology, particle size distribution and chemical composition of PPWC filler and limestone filler were compared. Then, PPWC filler was used to replace limestone filler with different volume fractions to prepare asphalt concrete, and the water damage resistance, high-temperature rutting resistance, low-temperature crack resistance, fatigue resistance and adhesion performance of asphalt concrete were tested. The results showed that PPWC filler has a smaller particle size and rougher surface than limestone filler, and it contains Ca(OH)2 produced by hydration. The addition of PPWC filler can effectively improve the mechanical properties of asphalt concrete without reducing its water damage resistance. PPWC filler can improve the high-temperature rutting resistance and low-temperature crack resistance of asphalt concrete, but reduce its low-temperature fatigue resistance. The low content of PPWC filler will enhance the adhesion between asphalt mortar and aggregate. However, when the content of PPWC filler exceeds 50%, Ca (OH)2 in PPWC will reduce the adhesion between acid asphalt mortar and alkaline basalt aggregate. Therefore, the use of PPWC as filler in asphalt mixtures provides a reliable solution for the sustainable development of road materials.

In this paper, a novel dual-three-phase dual-rotor flux-switching permanent magnet (PM) (DRFSPM) machine, building upon conventional FSPM machines, is proposed, where the stator is equipped with dual PMs and dual armature windings, enabling it to operate in various working modes and provide fault tolerance in the event of PM or armature winding faults. Depending on the magnetization directions of the PMs, the proposed DRFSPM machine’s structure can be categorized as 6N-DRFSPM or NS-DRFSPM. In order to assess the electromagnetic performance of the proposed DRFSPM machines with two different magnetizing modes, the topology and operating principle of the two DRFSPM machines are introduced first. Then, the no-load air-gap flux density of the two proposed machines is investigated for a more optimized and purposeful design. Finally, a comparison of the electromagnetic performance between the two proposed DRFSPM machines is conducted by finite-element analysis (FEA), and the FEA-predicted results indicate that the proposed 6N-DRFSPM machine outperforms the NS-DRFSPM machine, as it exhibits a larger back-EMF and average torque and a smaller cogging torque and torque ripple.

Jacking force is one of the most important parameters in the design and construction of pipe jacking. The accuracy of the jacking force will directly affect the success or failure of the pipe jacking project. Pipe jacking is increasingly applied to rock formations, but there are few calculation models for the jacking force in rock formations. To calculate the head-on resistance in the rock formation more accurately, a new calculation formula of the construction face resistance during pipe jacking is derived. The pipe jacking face is assumed to be stable; the rock pipe jacking force is analyzed by consideration of the rock breaking mechanism, force model and influence law of the rock pipe jacking machine cutter head hob. The results show that in rock pipe jacking, the compressive and shear strengths of the rock and the depth of the pipe jacking hob cut into the rock directly determine the value of the head-on resistance; after determining the appropriate hob spacing, the number of tools is not blindly increased; otherwise, the rock breaking effect of each hob will be affected. Moreover, the measured head-on resistance in engineering practice is consistent with the predicted value of the formula, which proves its applicability.

Background: The ciliary muscle plays a role in changing the shape of the crystalline lens to maintain the clear retinal image during near work. Studying the dynamic changes of the ciliary muscle during accommodation is necessary for understanding the mechanism of presbyopia. Optical coherence tomography (OCT) has been frequently used to image the ciliary muscle and its changes during accommodation in vivo . However, the segmentation process is cumbersome and time-consuming due to the large image data sets and the impact of low imaging quality. Objectives: This study aimed to establish a fully automatic method for segmenting and quantifying the ciliary muscle on the basis of optical coherence tomography (OCT) images. Design: A perspective cross-sectional study. Methods: In this study, 3500 signed images were used to develop a deep learning system. A novel deep learning algorithm was created from the widely used U-net and a full-resolution residual network to realize automatic segmentation and quantification of the ciliary muscle. Finally, the algorithm-predicted results and manual annotation were compared. Results: For segmentation performed by the system, the total mean pixel value difference (PVD) was 1.12, and the Dice coefficient, intersection over union (IoU), and sensitivity values were 93.8%, 88.7%, and 93.9%, respectively. The performance of the system was comparable with that of experienced specialists. The system could also successfully segment ciliary muscle images and quantify ciliary muscle thickness changes during accommodation. Conclusion: We developed an automatic segmentation framework for the ciliary muscle that can be used to analyze the morphological parameters of the ciliary muscle and its dynamic changes during accommodation.

In this paper, based on the conventional flux-switching permanent magnet (PM) (FSPM) machine, a novel dual-three-phase dual-rotor FSPM machine with PMs of NS layout (NS-DRFSPM) is proposed. The stator of the proposed NS-DRFSPM machine is equipped with dual PMs and dual armature windings to operate in a variety of operating modes and to handle the case of PMs or armature windings failure. Firstly, the topological structure and eight fault operating states of the NS-DRFSPM machine are introduced, and the key design parameters of the NS-DRFSPM machine are optimized by genetic algorithm (GA) optimization and finite element analysis (FEA). Then, the operation principle of the NS-DRFSPM machine is analyzed in detail. Finally, the finite element method is used to analyze the performances of the NS-DRFSPM machine under eight fault operating states, which is mainly analyzed from two aspects: no-load performance and torque performance. The results show that the NS-DRFSPM machine has good electromagnetic performance under different fault conditions, including large back-electromotive force (EMF) amplitude, sinusoidal EMF waveform, high average torque, small torque ripple, and strong anti-saturation ability.

There is still no ideal predictive biomarker for immunotherapy response among patients with non-small cell lung cancer. Costimulatory molecules play a role in anti-tumor immune response. Hence, they can be a potential biomarker for immunotherapy response. The current study comprehensively investigated the expression of costimulatory molecules in lung squamous carcinoma (LUSC) and identified diagnostic biomarkers for immunotherapy response. The costimulatory molecule gene expression profiles of 627 patients were obtained from the The Cancer Genome Atlas, GSE73403, and GSE37745 datasets. Patients were divided into different clusters using the k-means clustering method and were further classified into two discrepant tumor microenvironment (TIME) subclasses (hot and cold tumors) according to the immune score of the ESTIMATE algorithm. A high proportion of activated immune cells, including activated memory CD4 T cells, CD8 T cells, and M1 macrophages. Five CMGs (FAS, TNFRSF14, TNFRSF17, TNFRSF1B, and TNFSF13B) were considered as diagnostic markers using the Least Absolute Shrinkage and Selection Operator and the Support Vector Machine-Recursive Feature Elimination machine learning algorithms. Based on the five CMGs, a diagnostic nomogram for predicting individual tumor immune microenvironment subclasses in the TCGA dataset was developed, and its predictive performance was validated using GSE73403 and GSE37745 datasets. The predictive accuracy of the diagnostic nomogram was satisfactory in all three datasets. Therefore, it can be used to identify patients who may benefit more from immunotherapy.

Silicon (Si) has been considered to be one of the most promising anode materials for high energy density lithium−ion batteries (LIBs) due to its high theoretical capacity, low discharge platform, abundant raw materials and environmental friendliness. However, the large volume changes, unstable solid electrolyte interphase (SEI) formation during cycling and intrinsic low conductivity of Si hinder its practical applications. Various modification strategies have been widely developed to enhance the lithium storage properties of Si−based anodes, including cycling stability and rate capabilities. In this review, recent modification methods to suppress structural collapse and electric conductivity are summarized in terms of structural design, oxide complexing and Si alloys, etc. Moreover, other performance enhancement factors, such as pre−lithiation, surface engineering and binders are briefly discussed. The mechanisms behind the performance enhancement of various Si−based composites characterized by in/ex situ techniques are also reviewed. Finally, we briefly highlight the existing challenges and future development prospects of Si−based anode materials.

With global climate change, atmospheric nitrogen (N) deposition and drought have been well documented to cause substantial challenges for tropical and subtropical evergreen broad-leaved forests. Here, we conducted an experiment that measured the physiological responses of the seedlings of three dominant tree species (Tabebuia chrysantha, Elaeocarpus sylvestris, and Bischofia javanica) of the evergreen broad-leaved forests in South China under control (CT), drought stress (D), N addition (N), and drought stress plus N addition (N+D). We found that N addition significantly decreased malondialdehyde (MDA) content, abscisic acid (ABA) content, total antioxidant capacity (T-AOC), but significantly increased the content of proline (PRO), and the activities of ribulose-1, 5-bisphosphate carboxylase/oxygenase (Rubisco), nitrate reductase (NR), nitrite reductase (NiR), and glutamine synthetase (GS) in the three species under D. Meanwhile, we also found that under drought conditions, N addition promoted the leaf transpiration rate (E), stomatal conductance (gs), and light-saturated net photosynthetic rate (Amax) of the three species. These results indicate that N addition can enhance the drought tolerance of the three species by osmotic adjustment and protecting the photosystem. However, the enhancement in Amax and E will cause plants to face more severe drought conditions, especially B. javanica (large tree species). This study helps to explain why the evergreen broad-leaved forests in South China are gradually degrading to shrublands in recent decades.

Abstract Background To quantitatively assess anterior chamber angle (ACA) structure by anterior segment optical coherence tomography (AS-OCT) and develop a model to evaluate angle width as defined by gonioscopy. Methods The ACAs of each quadrant were evaluated by gonioscopy, classified by the Scheie grading system, and assigned into one of the three grades: small angle (SA), moderate angle (MA), and large angle (LA). The eyes were imaged by AS-OCT, and ACA structural parameters including angle opening distance at the scleral spur (AODSS) and at 750 μm anterior to the scleral spur (AOD750), trabecular-iris space area at 750 μm anterior to the scleral spur (TISA750), and a newly defined parameter “light intersection distance” (LID), were measured. The ACA structural data were used to construct an ordered logistic regression model for assignment of ACAs to one of the three angle grades. The validity of the model was then tested. Results A total of 169 quadrants from 53 subjects were included in the analysis, of which 111 quadrants were included in the modeling data and 58 in the testing data. In pairwise comparisons of SA, MA, and LA by ANOVA, the measured parameters were as follows: AOD750 (0.174 ± 0.060 vs. 0.249 ± 0.068 vs. 0.376 ± 0.114 mm; P

The main pathophysiological abnormalities in type 2 diabetes (T2D) include pancreatic β-cell dysfunction and insulin resistance. Due to hyperglycemia, patients receive long-term treatment. However, side effects and drug tolerance usually lead to treatment failure. GuaLouQuMaiWan (GLQMW), a common traditional Chinese medicine (TCM) prescription, has positive effects on controlling blood sugar and improving quality of life, but the mechanism is still unclear. To decipher their molecular mechanisms, we used a novel computational systems pharmacology-based approach consisting of bioinformatics analysis, network pharmacology, and drug similarity comparison. We divided the participants into nondisease (ND), impaired glucose tolerance (IGT), and type 2 diabetes groups according to the WHO’s recommendations for diabetes. By analyzing the gene expression profile of the ND-IGT-T2D (ND to IGT to T2D) process, we found that the function of downregulated genes in the whole process was mainly related to insulin secretion, while the upregulated genes were related to inflammation. Furthermore, other genes in the ND-IGT (ND to IGT) process are mainly related to inflammation and lipid metabolic disorders. We speculate that 17 genes with a consistent trend may play a key role in the process of ND-IGT-T2D. We further performed target prediction for 50 compounds in GLQMW that met the screening criteria and intersected the differentially expressed genes of the T2D process with the compounds of GLQMW; a total of 18 proteins proved potential targets for GLQMW. Among these, RBP4 is considerably related to insulin resistance. GO/KEGG enrichment analyses of the target genes of GLQMW showed enrichment in inflammation- and T2D therapy-related pathways. Based on the RDKit tool and the DrugBank database, we speculate that (-)-taxifolin, dialoside A_qt, spinasterol, isofucosterol, and 11,14-eicosadienoic acid can be used as potential drugs for T2D via molecular docking and drug similarity comparison.

Bone-resorbing activities of osteoclasts (OCs) are highly dependent on actin cytoskeleton remodeling, plasma membrane reorganization, and vesicle trafficking pathways, which are partially regulated by ARF-GTPases. In the present study, the functional roles of Golgi brefeldin A resistance factor 1 (GBF1) are proposed. GBF1 is responsible for the activation of the ARFs family and vesicular transport at the endoplasmic reticulum–Golgi interface in different stages of OCs differentiation. In the early stage, GBF1 deficiency impaired OCs differentiation and was accompanied with OCs swelling and reduced formation of mature OCs, indicating that GBF1 participates in osteoclastogenesis. Using siRNA and the specific inhibitor GCA for GBF1 knockdown upregulated endoplasmic reticulum stress-associated signaling molecules, including BiP, p-PERK, p-EIF2α, and FAM129A, and promoted autophagic Beclin1, Atg7, p62, and LC3 axis, leading to apoptosis of OCs. The present data suggest that, by blocking COPI-mediated vesicular trafficking, GBF1 inhibition caused intense stress to the endoplasmic reticulum and excessive autophagy, eventually resulting in the apoptosis of mature OCs and impaired bone resorption function.

The metal chalcogenides (MCs) for sodium-ion batteries (SIBs) have gained increasing attention owing to their low cost and high theoretical capacity. However, the poor electrochemical stability and slow kinetic behaviors hinder its practical application as anodes for SIBs. Hence, various strategies have been used to solve the above problems, such as dimensions reduction, composition formation, doping functionalization, morphology control, coating encapsulation, electrolyte modification, etc. In this work, the recent progress of MCs as electrodes for SIBs has been comprehensively reviewed. Moreover, the summarization of metal chalcogenides contains the synthesis methods, modification strategies and corresponding basic reaction mechanisms of MCs with layered and non-layered structures. Finally, the challenges, potential solutions and future prospects of metal chalcogenides as SIBs anode materials are also proposed.

The low–temperature poly–Si oxide (LTPO) backplane is realized by monolithically integrating low–temperature poly–Si (LTPS) and amorphous oxide semiconductor (AOS) thin–film transistors (TFTs) in the same display backplane. The LTPO–enabled dynamic refreshing rate can significantly reduce the display’s power consumption. However, the essential hydrogenation of LTPS would seriously deteriorate AOS TFTs by increasing the population of channel defects and carriers. Hydrogen (H) diffusion barriers were comparatively investigated to reduce the H content in amorphous indium–gallium–zinc oxide (a–IGZO). Moreover, the intrinsic H–resistance of a–IGZO was impressively enhanced by plasma treatments, such as fluorine and nitrous oxide. Enabled by the suppressed H conflict, a novel AOS/LTPS integration structure was tested by directly stacking the H–resistant a–IGZO on poly–Si TFT, dubbed metal–oxide–on–Si (MOOS). The noticeably shrunken layout footprint could support much higher resolution and pixel density for next–generation displays, especially AR and VR displays. Compared to the conventional LTPO circuits, the more compact MOOS circuits exhibited similar characteristics.

With the rapid growth of the oil and gas storage, transportation, and pipeline industries, it is necessary to improve the construction process of oil and gas pipelines. By combining the technical advantages of horizontal directional drilling and pipe jacking construction, the direct pipe laying method is suitable for pipeline crossing in different strata in the oil and gas, water conservancy and hydropower, and municipal industries due to its advantages of less construction land, high speed, and reversibility. Using the rapid jacking and laying of pipelines crossing Nanjuma River in the ‘Jingshihan’ gas pipeline double line project as a case study, this paper investigates the application status of the direct pipe laying method, summarizes the project, and introduces the construction of the working well, equipment selection, guiding control technology, supporting equipment installation, and drag reduction measures, as well as analyzes the influencing factors of thrust force and trajectory deviation combined with formation information.