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ObjectivesThe hardness of silicon carbide is second only to those of diamond, cubic boron nitride, and boron carbide, making its processing very difficult. Compared with plastic metal materials, the brittle and hard nature of silicon carbide makes it prone to brittle fracture and edge fragmentation during processing, greatly affecting its superior performance. Therefore, it is crucial to carefully select appropriate cutting methods and establish reasonable cutting process conditions.MethodsThe finite element software Abaqus was used to establish a model of micro-cutting silicon carbide crystal with a diamond conical grain, and the selection range of micro-cutting depth and speed was determined by the pre-simulation model. Then, the main and secondary factors affecting the cutting force were analyzed, and the influence of a single cutting parameter on the cutting effect was studied. In addition, with the help of Hertzian contact stress, the influence of the loading force on the friction force, the morphology of the cutting edge, and the cutting depth was verified by the tip scratching experiment.Results(1) The cutting depth is a crucial factor that greatly impacts the quality of the cutting process. When the cutting depth is less than 1.50 μm, the removal of silicon carbide material primarily occurs through plastic removal. However, when the cutting depth exceeds 1.50 μm, cracks of varying lengths and pits of different sizes gradually form at the cutting edge of the workpiece. As the cutting depth increases, the length of cracks and the number of pits also increase. This type of removal is known as brittle removal. To ensure the integrity of the cutting edge and minimize damage to the silicon carbide workpiece, it is essential to control the cutting depth of the abrasive particles during stages I and III, keeping it below 1.50 μm. (2) Through variance and range analysis of the main cutting force, the relationship between the three factors and the magnitude of the main cutting force is V > W > U, meaning that cutting depth is the most important factor affecting cutting force. The optimal solution V1W1U2 and cutting parameters have been determined, namely a diamond abrasive cutting depth of 0.50 μm, a diamond abrasive cutting edge angle of 60°, and a cutting speed of 76 m/s. Cutting depth is the main factor affecting the magnitude of cutting force, while cutting speed and cutting edge angle are secondary factors. (3) As the cutting depth increases, the affected area surrounding the cut also expands, causing an increase in equivalent stress even in areas where the abrasive particles do not come into contact with the workpiece. This phenomenon is responsible for the development of cutting edge cracks and pits. Additionally, as the cutting depth increases, the main cutting force experiences greater fluctuations. To maintain cutting stability, it is important to control the cutting depth. In the high-speed cutting range of 60-106 m/s, the impact of cutting speed on cutting force is minimal. Therefore, increasing the cutting speed can be an effective method for improving cutting efficiency and ensuring high-quality cuts. For optimal results, a cutting depth of 0.50 μm and a cutting speed of 76 m/s are recommended. (4) The coefficient of friction is not only affected by the properties of the two materials in contact, but also by the depth of the diamond probe pressing into the workpiece. The greater the depth of pressing, the higher the coefficient of friction and the greater the frictional force. The surface of the microgrooves is clear and tidy, with relatively smooth edges. Under the same Hertz contact stress, the simulated depth values and experimental depth values show a consistent trend with the change in loading force.ConclusionsFinite element simulation has become a valuable tool for studying the interaction and removal of materials in the precision machining of crystal materials. The purpose of this article is to investigate the removal characteristics of silicon carbide and determine the optimal range of cutting parameters. The study analyzes cutting force, stress distribution, and removal mechanisms, and proposes effective methods for enhancing cutting efficiency. The findings of this research can contribute to improving the smoothness of the cutting edge and reducing subsurface damage to the workpiece. Furthermore, this research has significant implications for understanding the impact of process parameters on cutting accuracy and the removal mechanism of hard and brittle materials during cutting.

Abstract Background More than 50% of colorectal cancer(CRC) patients experience cancer-related psychological burden after radical surgery, which can seriously affect their physical wellness, quality of life and even survival outcomes. Our research team developed a six-week Traditional Chinese Medicine Combined Online Group Psychotherapy (TCM-eRhab) and proved its efficacy on relieving cancer-related anxiety, depression and fear of cancer recurrence though phase I single arm clinical trial (n = 40). Large sample size randomized controlled clinical trial(RCT) is necessary to further evaluate TCM-eRhab’s role on improving quality of life and survival outcomes among this population. Methods We design a phase II RCT study, in which 210 CRC patients who have received radical surgery (stage I-III) will be recruited. Eligible patients will be randomly assigned to TCM-eRhab group or usual care group by 2:1 ratio. Patients in the intervention group will receive the structured TCM-eRhab program for six weeks, while patients in control group will receive usual care only. The primary outcomes are quality of life, severity of anxiety, depression and fear of cancer recurrence. Cancer recurrence rate will also be calculated according to long term follow-up data. Discussion As one of the first RCTs to evaluate the impacts of TCM combined psychological therapy to improve CRC patients’ quality of life after surgery, the results from this study will provide innovative knowledge and evidence on integrating TCM into CRC survivorship care and mind–body intervention model.

Abstract Background To evaluate the clinical value of serum CEA levels and their implications on the diagnostic value of the conventional TNM staging system in the oldest-old patients with colorectal cancer (CRC). Methods The recruited subjects were colorectal cancer patients aged 85 and older. The cutoff value for normal CEA level is 5 ng/mL. Patients with elevated CEA levels were categorized as stage C1, and those with normal CEA levels as stage C0. A number of Cox proportional hazard regression models were established to evaluate the prognosis of different prognostic factors with hazard ratios (HRs) and 95% confidence intervals (CIs). The Kaplan–Meier method was utilized to display the disparate prognostic impact of multiple clinicopathological factors with the log-rank test. Results A total of 17,359 oldest-old patients diagnosed with CRC were recruited from the SEER database. The conditional survival of oldest-old patients with CRC was dismal with a 1-year conditional survival of only 11%, 18%, and 30% for patients surviving 1, 3, and 5 years, respectively. Patients with stage C1 exhibited a 48.5% increased risk of CRC-specific mortality compared with stage C0 (HR = 1.485, 95%CI = 1.393–1.583, using stage C0 patients as the reference, P

Abstract The mass and volume of Rosa roxburghii fruits are essential for fruit grading and consumer selection. Physical characteristics such as dimension, projected area, mass, and volume are interrelated. Image-based mass and volume estimation facilitates the automation of fruit grading, which can replace time-consuming and laborious manual grading. In this study, image processing techniques were used to extract fruit dimensions and projected areas, and univariate (linear, quadratic, exponential, and power) and multivariate regression models were used to estimate the mass and volume of Rosa roxburghii fruits. The results showed that the quadratic model based on the criterion projected area (CPA) estimated the best mass (R2 = 0.981) with an accuracy of 99.27%, and the equation is M = 0.280 + 0.940CPA + 0.071CPA 2. The multivariate regression model based on three projected areas (PA 1, PA 2, and PA 3) estimated the best volume (R2 = 0.898) with an accuracy of 98.24%, and the equation is V = − 8.467 + 0.657PA 1 + 1.294PA 2 + 0.628PA 3. In practical applications, cost savings can be realized by having only one camera position. Therefore, when the required accuracy is low, estimating mass and volume simultaneously from only the dimensional information of the side view or the projected area information of the top view is recommended.

Background: In patients with metastatic colorectal cancer (mCRC), Quxie Cap-sule (QX)—a combination of conventional therapy (including chemotherapy, targeted therapy or supportive care)—has shown a significant overall survival benefit compared with placebo and might have the property of dual effects of antitumor and immunity enhancement, both mediated by the microbiome. In preclinical models, QX has also shown activity against colorectal cancer. This study aimed to describe how the aforementioned effects of QX look after when focusing on the patients in third or above line setting. Methods: A Simon’s Minimax two-stage phase II design was used in this study, which enrolled mCRC patients who progressed after second-line treatment. Patients received conventional therapy plus QX until disease progression or unacceptable toxicity. Before and after 1-month intervention, we collected patients’ stool samples for microbiome analysis by 16s rRNA sequencing approaches. And the microbiome analysis before and after 1-month intervention was done through bioinformation analysis platform. Results: Fifteen patients were enrolled and gut microbiome were analyzed from 7 of 10 patients that with PFS over 3.7 months. Microbiome community analysis on genus level showed that the proportion of Lachnospiraceae_UCG-001 (0.04% vs 1.06%, P = .02249) significantly increased after conventional therapy plus QX while the proportion of Alistipes (2.96% vs 1.35%, P = .03461), Flavonifractor (0.04% vs 0.02%, P = .02249), Bifidobacterium (6.11% vs 1.14%, P = .02249) and Butyricimonas (0.24% vs 0.11%, P = .03603) significantly decreased after intervention . LEfSe analysis showed that after intervention, samples were highly related with unclassified-f-lachnospiraceae , Eubacterium and Lachnospiraceae_UCG-001 . Conclusions: Decrease of gut bacteria with potential roles in carcinogenesis of colorectal cancer and increase in the abundance of gut anticancer bacteria such as Lachnospiraceae may partly explain how conventional therapy combined with QX can influence carcinogenesis and tumor progression in colon cancer. Trial registration: Chinese Clinical Trial Registry (ChiCTR2100053874).

BackgroundCINV is a frequent adverse response to cancer treatment. There is still much to learn about the pathophysiology and initiating event of CINV, which necessitates continued research despite decades of effort. Identifying the current foci of the complex disease and assessing the scientific impact of pertinent study are made more difficult by the abundance of publications on CINV. Therefore, our goals in this article are to evaluate developments in this field, examine patterns in research domains, and gauge the expansion of CINV research production globally.MethodsArticles about CINV published between 2012 and 2022 were found by searching the Web of Science Core Collection of Clarivate Analytics. The number of publications over time was visualized using Microsoft Office Excel 2019. CiteSpace and VOSviewer were utilized to create knowledge maps that analyzed collaborations between nations, organizations, and writers. They also presented the history of CINV research and highlighted its current areas of focus.ResultsIn this study, 846 papers in all were assessed. Most publications (237, 28.01%) came from the United States. University of Toronto was the most productive institution (34, 4.01%). With 25 articles published, or 2.96% of the total, Aapro Matti published the most. The most frequently published journal was found to be Supportive Care (158, 18.68%). “Palonosetron,” “Moderately emetogenic chemotherapy,” “5-HT3 receptor antagonist,” and “Neurokinin 1 receptor antagonists” were considered the hot topics. It can be seen that the research focus is on the drug treatment of chemotherapy-induced nausea and vomiting.ConclusionThrough bibliometric analysis, we were able to gain profound insights into CINV research for the first time. Researchers looking to uncover research frontiers and comprehend important information in this discipline may find the study’s findings useful.

Abstract The immune response holds a pivotal role in cardiovascular disease development. As multifunctional cells of the innate immune system, macrophages play an essential role in initial inflammatory response that occurs following cardiovascular injury, thereby inducing subsequent damage while also facilitating recovery. Meanwhile, the diverse phenotypes and phenotypic alterations of macrophages strongly associate with distinct types and severity of cardiovascular diseases, including coronary heart disease, valvular disease, myocarditis, cardiomyopathy, heart failure, atherosclerosis and aneurysm, which underscores the importance of investigating macrophage regulatory mechanisms within the context of specific diseases. Besides, recent strides in single-cell sequencing technologies have revealed macrophage heterogeneity, cell–cell interactions, and downstream mechanisms of therapeutic targets at a higher resolution, which brings new perspectives into macrophage-mediated mechanisms and potential therapeutic targets in cardiovascular diseases. Remarkably, myocardial fibrosis, a prevalent characteristic in most cardiac diseases, remains a formidable clinical challenge, necessitating a profound investigation into the impact of macrophages on myocardial fibrosis within the context of cardiac diseases. In this review, we systematically summarize the diverse phenotypic and functional plasticity of macrophages in regulatory mechanisms of cardiovascular diseases and unprecedented insights introduced by single-cell sequencing technologies, with a focus on different causes and characteristics of diseases, especially the relationship between inflammation and fibrosis in cardiac diseases (myocardial infarction, pressure overload, myocarditis, dilated cardiomyopathy, diabetic cardiomyopathy and cardiac aging) and the relationship between inflammation and vascular injury in vascular diseases (atherosclerosis and aneurysm). Finally, we also highlight the preclinical/clinical macrophage targeting strategies and translational implications.

Abstract Background While de novo cholesterol biosynthesis plays a crucial role in chemotherapy resistance of colorectal cancer (CRC), the underlying molecular mechanism remains poorly understood. Methods We conducted cell proliferation assays on CRC cells with or without depletion of squalene epoxidase (SQLE), with or without 5-fluorouracil (5-FU) treatment. Additionally, a xenograft mouse model was utilized to explore the impact of SQLE on the chemosensitivity of CRC to 5-FU. RNA-sequencing analysis and immunoblotting analysis were performed to clarify the mechanism. We further explore the effect of SQLE depletion on the ubiquitin of NF-κB inhibitor alpha (IκBα) and (S)-2,3-epoxysqualene on the binding of IκBα to beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) by using immunoprecipitation assay. In addition, a cohort of 272 CRC patients were selected for our clinical analyses. Results Mechanistically, (S)-2,3-epoxysqualene promotes IκBα degradation and subsequent NF-κB activation by enhancing the interaction between BTRC and IκBα. Activated NF-κB upregulates the expression of baculoviral IAP repeat containing 3 (BIRC3), sustains tumor cell survival after 5-FU treatment and promotes 5-FU resistance of CRC in vivo. Notably, the treatment of terbinafine, an inhibitor of SQLE commonly used as antifungal drug in clinic, enhances the sensitivity of CRC to 5-FU in vivo. Additionally, the expression of SQLE is associated with the prognosis of human CRC patients with 5-FU-based chemotherapy. Conclusions Thus, our finding not only demonstrates a new role of SQLE in chemoresistance of CRC, but also reveals a novel mechanism of (S)-2,3-epoxysqualene-dependent NF-κB activation, implicating the combined potential of terbinafine for 5-FU-based CRC treatment.

Background: Reishi, a medicinal mushroom, is increasingly used for symptom control by cancer patients worldwide. However, data around patients' experiences with Reishi in oncology are lacking, limiting safe, effective clinical applications. We thus sought to evaluate patient reported benefits and harms of using Reishi. Methods: We conducted a cross-sectional survey among Chinese cancer patients using Reishi products, probing for symptom improvements and/or adverse events (AEs) after taking Reishi. Multivariable logistic regression models assessed whether socio-demographic or clinical factors, as well as duration of Reishi use or combination with other TCM herbs, were associated with being a “responder” – reporting “quite a bit” or “very much” symptom improvement. Results: Among 1374 participants, more than half of participants reported that nausea (55 %), fatigue (52 %), poor appetite (51 %), and depression (50 %) improved quite a bit or very much after taking Reishi. In multivariate analyses, age 5 years: AOR = 2.07, p < 0.001) were significantly associated with higher responder rates for symptom improvement. However, 125 (9.1 %) also reported a range of AEs, including dry mouth (5 %), constipation (4 %), insomnia (3 %), pruritus (3 %) and vertigo (3 %). Conclusion: While majority of cancer patients using Reishi reported symptom improvements, some reported adverse effects. This information can assist clinicians in advising cancer patients on safe and effective use of Reishi and help identify specific outcomes for assessment in future prospective clinical trials.

ABSTRACTMany biological processes related to cell function and fate begin with chromatin alterations, and many factors associated with the efficacy of immune checkpoint inhibitors (ICIs) are actually downstream events of chromatin alterations, such as genome changes, neoantigen production, and immune checkpoint expression. However, the influence of genes as chromatin regulators on the efficacy of ICIs remains elusive, especially in gastric cancer (GC). In this study, thirty out of 1593 genes regulating chromatin associated with a favorable prognosis were selected for GC. CHAF1A, a well-defined oncogene, was identified as the highest linkage hub gene. High CHAF1A expression were associated with microsatellite instability (MSI), high tumor mutation burden (TMB), high tumor neoantigen burden (TNB), high expressions of PD-L1 and immune effector genes, and live infiltration of immune cells. High CHAF1A expression indicated a favorable response and prognosis in immunotherapy of several cohorts, which was independent of MSI, TMB, TNB, PD-L1 expression, immune phenotype and transcriptome scoring, and improved patient selection based on these classic biomarkers. In vivo, CHAF1A knockdown alone inhibited tumor growth but it impaired the effect of an anti-PD-1 antibody by increasing the relative tumor proliferation rate and decreasing the survival benefit, potentially through the activation of TGF-β signaling. In conclusion, CHAF1A may be a novel biomarker for improving patient selection in immunotherapy.

BackgroundThe demand for fertility-sparing surgery (FSS) is increasing among patients with early-stage cervical cancer (CC). This study aimed to evaluate the feasibility of local excision as an alternative to hysterectomy in stage I CC patients aged 15–39 years—commonly referred to as adolescents and young adults (AYAs)—with varying clinicopathological characteristics.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database, we identified patients diagnosed between 2000 and 2020. We examined treatment interventions across different age groups, degrees of histological types, tumor differentiation, and tumor stages. The effect of local excision vs. hysterectomy was assessed by comparing overall survival (OS) and disease-specific survival (DSS) rates.ResultsA total of 10,629 stage I AYA cervical cancer patients were included in this study. Among these patients, 24.5% underwent local excision for fertility preservation, while 67.3% underwent radical hysterectomy. For patients with cervical squamous cell carcinoma (SCC), long-term outcomes favored local excision over hysterectomy, and a similar trend was observed in those with adenosquamous cell carcinoma (ASCC). However, the prognosis was comparable among patients with cervical adenocarcinoma (AC). In patients with well- and moderate- differentiated tumors, local excision demonstrated superior OS compared to hysterectomy. No significant differences in prognosis were found between the two surgical interventions for patients with poorly differentiated and undifferentiated tumors. In stage IA patients, local excision was considered a viable alternative to hysterectomy. In stage IB1–IB2, FSS yielded prognostic outcomes comparable to those of hysterectomy. Conversely, patients with stage IB3 exhibited significantly shorter 5-year OS and DSS following local excision than those who underwent hysterectomy.ConclusionIn stage IA–IB2 (diameter ≤4 cm) AYA patients, local excision may serve as a viable option for fertility preservation. The histological type of SCC, AC, and ASCC, along with differentiation, should not serve as restrictive factors in determining fertility preservation strategies for these patients. Patients with early-stage, well- or moderately-differentiated SCC may benefit from local excision surgery, even when fertility preservation is not the primary objective.

Decoding motor imagery (MI) using deep learning in cortical level has potential in brain computer interface based intelligent rehabilitation. However, a mass of dipoles is inconvenient to extract the personalized features and requires a more complex neural network. In consideration of the structural and functional similarity of the neurons in a neuroanatomical region, i.e., a region of interest (ROI), we propose that the comprehensive performance of each ROI may be reflected by a specific representative dipole (RD), and the time-frequency spectrums of all RDs are applied simultaneously to Random Forest algorithm to give a quantitative metric of each ROI importance (RI). Then, the more divided sub-band spectral powers are reinforced by RI, and they are interpolated to a 2-dimensional (2D) plane transformed from 3D space of all RDs, yielding an ensemble representation of RD feature image sequences (ERDFIS). Furthermore, a lightweight network, including 2D separable convolution and gated recurrent unit (2DSCG), is developed to extract and classify the frequency-spatial and temporal features from ERDFIS, forming a novel MI decoding method in cortical level (called ERDFIS-2DSCG). Based on two public datasets, the decoding accuracies of ten-fold cross-validation are 89.89% and 94.35%, respectively. The results suggest that RD can embody the overall property of ROI in time-frequency-space domains, and ROI importance is helpful to highlight the subject-based characteristics of MI-EEG. Meanwhile, 2DSCG is matched well with ERDFIS, jointly improving the decoding performance.

Abstract Background Novel biomarkers are required in gastric cancer (GC) treated by immunotherapy. Epstein-Barr virus (EBV) infection induces an immune-active tumor microenvironment, while its association with immunotherapy response is still controversial. Genes underlying EBV infection may determine the response heterogeneity of EBV + GC. Thus, we screened hub genes associated with EBV infection to predict the response to immunotherapy in GC. Methods Prognostic hub genes associated with EBV infection were screened using multi-omic data of GC. EBV + GC cells were established and confirmed by EBV-encoded small RNA in situ hybridization (EBER-ISH). Immunohistochemistry (IHC) staining of the hub genes was conducted in GC samples with EBER-ISH assay. Infiltrating immune cells were stained using immunofluorescence. Results CHAF1A was identified as a hub gene in EBV + GC, and its expression was an independent predictor of overall survival (OS). EBV infection up-regulated CHAF1A expression which also predicted EBV infection well. CHAF1A expression also predicted microsatellite instability (MSI) and a high tumor mutation burden (TMB). The combined score (CS) of CHAF1A expression with MSI or TMB further improved prognostic stratification. CHAF1A IHC score positively correlated with the infiltration of NK cells and macrophages M1. CHAF1A expression alone could predict the immunotherapy response, but its CS with EBV infection, MSI, TMB, or PD-L1 expression showed better effects and improved response stratification based on current biomarkers. Conclusions CHAF1A could be a novel biomarker for immunotherapy of GC, with the potential to improve the efficacy of existing biomarkers.

Abstract Background UTX (encoded by KDM6A), a histone demethylase for H3K27me2/3, is frequently mutated in human cancers. However, its functional and regulatory mechanisms in colorectal cancer (CRC) remain unclear. Methods Immunohistochemistry staining was used to investigate the clinical relevance of UTX in CRC. Additionally, we generated a spontaneous mouse CRC model with conditional Utx knockout to explore the role of UTX in the colorectal tumorigenesis. Post-translational regulation of UTX was determined by co-immunoprecipitation and immunoblot analyses. Results Herein, we identify that downregulation of UTX, mediated by the Cullin 4B-DNA Damage Binding Protein-1-Constitutive Photomorphogenesis Protein 1 (CUL4B-DDB1-COP1) complex, promotes CRC progression. Utx deletion in intestinal epithelial cells enhanced the susceptibility to tumorigenesis in AOM/DSS-induced spontaneous mouse CRC model. However, this effect is primarily alleviated by GSK126, an inhibitor of histone methyltransferase EZH2. Mechanistically, EMP1 and AUTS2 are identified as putative UTX target genes mediating UTX functions in limiting intestinal tumorigenesis. Notably, the CUL4B-DDB1-COP1 complex is identified as the functional E3 ligase responsible for targeting UTX for degradation in CRC cells. Thus, Cop1 deficiency in mouse intestinal tissue results in UTX accumulation and restricts tumorigenesis. Furthermore, patient cohort analysis reveals that UTX expression is negatively correlated with clinical stage, favorable disease outcomes, and COP1 expression. Conclusions In the current study, the tumor suppressor function and regulation of UTX in CRC provide a molecular basis and the rationale to target EZH2 in UTX-deficient CRC.

The flying foxes optimization (FFO) algorithm stimulated by the strategy used by flying foxes for subsistence in heat wave environments has shown good performance in the single-objective domain. Aiming to explore the effectiveness and benefits of the subsistence strategy used by flying foxes in solving optimization challenges involving multiple objectives, this research proposes a decomposition-based multi-objective flying foxes optimization algorithm (MOEA/D-FFO). It exhibits a great population management strategy, which mainly includes the following features. (1) In order to improve the exploration effectiveness of the flying fox population, a new offspring generation mechanism is introduced to improve the efficiency of exploration of peripheral space by flying fox populations. (2) A new population updating approach is proposed to adjust the neighbor matrices to the corresponding flying fox individuals using the new offspring, with the aim of enhancing the rate of convergence in the population. Through comparison experiments with classical algorithms (MOEA/D, NSGA-II, IBEA) and cutting-edge algorithms (MOEA/D-DYTS, MOEA/D-UR), MOEA/D-FFO achieves more than 11 best results. In addition, the experimental results under different population sizes show that the proposed algorithm is highly adaptable and has good application prospects in optimization problems for engineering applications.

N6-methyladenosine (m6A) methylation modification is a ubiquitous RNA modification involved in the regulation of various cellular processes, including regulation of RNA stability, metabolism, splicing and translation. Gastrointestinal (GI) cancers are some of the world’s most common and fatal cancers. Emerging evidence has shown that m6A modification is dynamically regulated by a complex network of enzymes and that the catalytic subunit m6A-METTL complex (MAC)-METTL3/14, a core component of m6A methyltransferases, participates in the development and progression of GI cancers. Furthermore, it has been shown that METTL3/14 modulates immune cell infiltration in an m6A-dependent manner in TIME (Tumor immune microenvironment), thereby altering the response of cancer cells to ICIs (Immune checkpoint inhibitors). Immunotherapy has emerged as a promising approach for treating GI cancers. Moreover, targeting the expression of METTL3/14 and its downstream genes may improve patient response to immunotherapy. Therefore, understanding the role of MAC in the pathogenesis of GI cancers and its impact on immune cell infiltration may provide new insights into the development of effective therapeutic strategies for GI cancers.

Abstract The tumormicroenvironment (TME) plays a key role in tumor progression. Tumor-associated macrophages (TAMs), which are natural immune cells abundantin the TME, are mainly divided into the anti-tumor M1 subtype and pro-tumor M2 subtype. Due to the high plasticity of TAMs, the conversion of the M1 to M2 phenotype in hypoxic and hypoglycemic TME promotes cancer progression, which is closely related to lipid metabolism. Key factors of lipid metabolism in TAMs, including peroxisome proliferator-activated receptor and lipoxygenase, promote the formation of a tumor immunosuppressive microenvironment and facilitate immune escape. In addition, tumor cells promote lipid accumulation in TAMs, causing TAMs to polarize to the M2 phenotype. Moreover, other factors of lipid metabolism, such as abhydrolase domain containing 5 and fatty acid binding protein, have both promoting and inhibiting effects on tumor cells. Therefore, further research on lipid metabolism in tumors is still required. In addition, statins, as core drugs regulating cholesterol metabolism, can inhibit lipid rafts and adhesion of tumor cells, which can sensitize them to chemotherapeutic drugs. Clinical studies on simvastatin and lovastatin in a variety of tumors are underway. This article provides a comprehensive review of the role of lipid metabolism in TAMs in tumor progression, and provides new ideas for targeting lipid metabolism in tumor therapy.

BackgroundAberrant metabolism is a major hallmark of cancers and hereditary diseases. Genes associated with inborn metabolic errors may also play roles in cancer development. This study evaluated the overall impact of these genes on gastric cancer (GC).MethodsIn total, 162 genes involved in 203 hereditary metabolic diseases were identified in the Human Phenotype Ontology database. Clinical and multi-omic data were acquired from the GC cohort of the Affiliated Hospital of Jiangsu University and other published cohorts. A 4-gene and 32-gene signature was established for diagnosis and prognosis or therapeutic prediction, respectively, and corresponding abnormal metabolism scores (AMscores) were calculated.ResultsThe diagnostic AMscore showed high sensitivity (0.88-1.00) and specificity (0.89-1.00) to distinguish between GC and paired normal tissues, with area under the receiver operating characteristic curve (AUC) ranging from 0.911 to 1.000 in four GC cohorts. The prognostic or predictive AMscore was an independent predictor of overall survival (OS) in five GC cohorts and a predictor of the OS and disease-free survival benefit of postoperative chemotherapy or chemoradiotherapy in one GC cohort with such data. The AMscore adversely impacts immune biomarkers, including tumor mutation burden, tumor neoantigen burden, microsatellite instability, programmed death-ligand 1 protein expression, tumor microenvironment score, T cell receptor clonality, and immune cell infiltration detected by multiplex immunofluorescence staining. The AUC of the AMscore for predicting immunotherapy response ranging from 0.780 to 0.964 in four cohorts involving GC, urothelial cancer, melanoma, and lung cancer. The objective response rates in the low and high AMscore subgroups were 78.6% and 3.2%, 40.4% and 7%, 52.6% and 0%, and 72.7% and 0%, respectively (all p

Landslide susceptibility assessment is considered the first step in landslide risk assessment, but current studies mostly rely on GIS platforms or other software for data preprocessing. The modeling process is relatively complicated and multi-models cannot be integrated. With regard to this issue, this study develops a Python system for automatic assessment of regional landslide susceptibility. The Python system implements landslide susceptibility assessment through three modules: geographic data processing, machine learning modeling and result evaluation analysis. For geographic data processing, ten landslide influencing factors can be used to construct an evaluation factor dataset and reclassify the thematic maps based on the frequency ratio method. Four built-in machine learning models (logistic regression (LR), multi-layer perceptron (MLP), support vector machine (SVM) and extreme gradient boosting (XGBoost)) are integrated into the system to complete susceptibility modeling and calculation. Additionally, receiver operating characteristic (ROC) curves can be automatically generated to evaluate the accuracy. The system was then applied into Lantian County in Shaanxi Province as a demonstration example. The results show that the areas under the ROC curve (AUC) of the four models are 0.838 (LR)、0.882 (SVM)、0.809 (MLP) and 0.812 (XGBoost), respectively, indicating that the SVM model was the most suitable model for landslide susceptibility assessment in Lantian County in the Loess Plateau of China. The system has now been made open source on Github, which can effectively improve the efficiency of regional landslide susceptibility assessment, especially provide tools for data processing and modeling for non-professionals.

Solid waste produced by the nonferrous smelting industry has a significant number of notable differences. The lack of recognition of solid waste characteristics is the main factor restricting its disposal and utilization. In this study, we analyzed the main production processes of the nonferrous smelting industry; identified the key production nodes of solid waste; and clarified the characteristics, including the physical, chemical, and pollution characteristics of solid wastes, through a large sample statistical analysis. We found similarities among solid wastes from a common generation source as well as notable differences among the different generation sources: slags and sludges from waste acid treatment and wastewater treatment units had a water content of 27.43–52.71% and 51.14–68.27%, respectively, which were significantly higher than those of other metallurgy and dust collection units; the pH of slags from an electrorefining unit was strongly alkaline; the mineral phase of sludges from wastewater treatment was only calcite; slags from a waste acid treatment unit were mainly in phase of gypsum, claudetite, and anglesite; the chemical composition of slags from pyrometallurgy and hydrometallurgy units was mainly SiO2 and Fe2O3. In this paper, we discuss a new classification method based on a common generation source for the first time. These results are beneficial to guide the disposal, utilization, and management of solid waste.

With urban heat challenges increasingly severe, assessing heat health risk has become crucial for human settlements. Unfortunately, previous studies have not accurately identified the driving factors, posing a significant obstacle to translating assessment results into policymaking. Particularly, potential spatial heterogeneity of driving factors at the indicator-level may exist. Therefore, this study developed a systematic method to examine the spatial heterogeneity of driving factors for heat health risk in Chongqing. Based on this heterogeneity, an integrated framework linking heat health risk, driving factors, and response strategies was proposed, supporting specific solutions for different cities. The results indicate that driving factors exhibit strong heterogeneity at the indicator-level. Even within the same prevention zone and urban functional areas, the maximum differences in the number of driving factors and combination categories can reach four and five, respectively. Moreover, relying solely on the driving factors obtained through traditional methods to develop cooling measures is unreasonable. When these driving factors are consistent, there are still, on average, six combinations of driving factors at the indicator-level, and each combination includes an average of 2.9 indicators. The higher the level of the risk prevention zone, the more driving factors it contains. The average number of driving factors above the moderate risk level is 3.9, higher than the 1.1 and 2 found in moderate and below moderate risk levels. Overall, this study provides a reference for understanding spatial heterogeneity of driving factors for heat health risk and offers an approach to assist policymakers in formulating guided cooling strategies.

Background: Patients with colon cancer who receive chemotherapy usually experience various gastrointestinal adverse reactions, including nausea, vomiting, and diarrhea, which make it challenging for them to adhere to treatment. As an effective traditional Chinese medicine, the Jianpi Bushen formula has been widely used to alleviate the side effects of chemotherapy. Objective: To evaluate the efficacy and safety of Jianpi Bushen formulae for patients who undergo chemotherapy. This statistical analysis plan (SAP) is intended to enhance the transparency and research quality of our randomized controlled trial. Methods: Our study is a multicenter, double-blind, randomized controlled clinical trial. This trial aimed to compare the completion rate of chemotherapy in colon cancer patients who are using and not using Jianpi Bushen formula. To attenuate possible selection bias in the final report, we declared the overall trial design, outcome measures, subgroup analyses, and safety measures. Also, we described the data management and statistical analysis methods in detail. Conclusion: The SAP provides more detailed information than the trial protocol for data management and statistical analysis methods. Further post-hoc analyses can be performed by referring to the SAP, and possible selection bias can be attenuated.

Abstract Background Circular RNAs (circRNAs) generated by back‐splicing of precursor mRNAs (pre‐mRNAs) are often aberrantly expressed in cancer cells. Accumulating evidence has revealed that circRNAs play a critical role in the progression of several cancers, including colorectal cancer (CRC). However, the current understandings of the emerging functions of circRNAs in CRC lipid metabolism and the underlying molecular mechanisms are still limited. Here, we aimed to explore the role of circCAPRIN1 in regulating CRC lipid metabolism and tumorigenesis. Methods circRNA microarray was performed with three pairs of tumor and non‐tumor tissues from CRC patients. The expression of circRNAs were determined by quantitative PCR (qPCR) and in situ hybridization (ISH). The endogenous levels of circRNAs in CRC cells were manipulated by transfection with lentiviruses overexpressing or silencing circRNAs. The regulatory roles of circRNAs in the occurrence of CRC were investigated both in vitro and in vivo using gene expression array, RNA pull‐down/mass spectrometry, RNA immunoprecipitation assay, luciferase reporter assay, chromatin immunoprecipitation analysis, and fluorescence in situ hybridization (FISH). Results Among circRNAs, circCAPRIN1 was most significantly upregulated in CRC tissue specimens. circCAPRIN1 expression was positively correlated with the clinical stage and unfavorable prognosis of CRC patients. Downregulation of circCAPRIN1 suppressed proliferation, migration, and epithelial‐mesenchymal transition of CRC cells, while circCAPRIN1 overexpression had opposite effects. RNA sequencing and gene ontology analysis indicated that circCAPRIN1 upregulated the expressions of genes involved in CRC lipid metabolism. Moreover, circCAPRIN1 promoted lipid synthesis by enhancing Acetyl‐CoA carboxylase 1 (ACC1) expression. Further mechanistic assays demonstrated that circCAPRIN1 directly bound signal transducer and activator of transcription 2 (STAT2) to activate ACC1 transcription, thus regulating lipid metabolism and facilitating CRC tumorigenesis. Conclusions These findings revealed the oncogenic role and mechanism of circCAPRIN1 in CRC. circCAPRIN1 interacted with STAT2 to promote CRC tumor progression and lipid synthesis by enhancing the expression of ACC1. circCAPRIN1 may be considered as a novel potential diagnostic and therapeutic target for CRC patients.

A considerable amount of secondary aluminum dross is generated in the aluminum refining process. Secondary aluminum dross (SAD) is hazardous waste because of its constituent pollutants, such as AlN, fluoride, chloride, and heavy metal pollutants. SAD treatment can be categorized into thermal and wet methods. The thermal process has attracted considerable research attention because of its simplicity and ability to prepare Al–Mg spinels, refractory materials, and ceramics and recover alumina during the treatment. However, at this stage, SAD pyrolysis processes are typically focused on the removal of single pollutants. Limited studies have explored the simultaneous removal of various pollutants and their interactions. This study focused on the pyroprocess in the SAD treatment process and investigated the SAD mechanism in the preparation of Al–Mg spinel, refractories, ceramics, and recycled alumina. Furthermore, the conversion of AlN, fluoride, chloride salts, and heavy metals, which are the main pollutants generated in the thermal reaction of SAD, and their control mechanisms were analyzed. The synergistic mechanism of SAD denitrification∖chlorine salt and fluoride fixation∖heavy metal was studied through the reaction mechanism of similar component minerals in the pyroprocess for improving the high-value utilization of SAD and scientific prevention and control of secondary pollution. Finally, the feasibility of preparing ceramic pellets from aluminum dross (AD) was evaluated. The results of the study can provide crucial development directions for SAD utilization.

Abstract Vortex electromagnetic wave (VEMW) carrying orbital angular momentum (OAM), which is expected to introduce additional degrees of freedom in inverse synthetic aperture radar(ISAR) imaging. However, the current research about maneuvering targets is based on the "stop go" hypothesis, which does not apply to high-speed motion scenarios due to the intrapulse movement of the target. To improve the imaging quality, this letter proposes a VEMW-based high-speed maneuvering targets imaging method. Firstly, the ISAR imaging scenario of high-speed target is established. According to the spatial geometric relationship between radar and maneuvering target, the vortex echo is deduced and its characteristics are analyzed. Subsequently, a frequency modulation rate estimation method considering both calculation efficiency and high precision is proposed to realize the accurate estimation of target speed. Then, an adaptive azimuth image compensation method based on minimum entropy is proposed. Through the setting of threshold, the number of component signals in linear frequency modulation (LFM) signal is determined and compensated successively. Finally, the range profile and azimuth profile are combined to reconstruct the three-dimensional information. The simulation results demonstrate that this work can effectively eliminate the influence of high-speed motion on range and azimuth profile, also benefit the development of ISAR imaging technique of high-speed maneuvering targets.

Lueyang black-bone chicken is a domestic breed in China. The genetic mechanism of the formation of important economic traits of this breed has not been studied systematically. Therefore, in this study, whole genome resequencing was used to systematically analyze and evaluate the genetic diversity of the black-feather and white-feather populations, and to screen and identify key genes related to phenotypes. The results of principal component analysis and population structure analysis showed that Lueyang black-feathered chickens and white-feathered chickens could be divided into 2 subgroups, and the genetic diversity of black-feathered chicken was richer than that of white-feathered chickens. Linkage disequilibrium analysis also showed that the selection intensity of black-feathered chickens was lower than for white-feathered chickens, which was mainly due to the small population size of white-feathered chickens and a certain degree of inbreeding. Fixation index (FST) analysis revealed that the candidate genes related to feather color traits were G-gamma, FA, FERM, Kelch, TGFb, Arf, FERM, and melanin synthesis-related gene tyrosinase (TYR). Based on Kyoto Encyclopedia of Genes and Genomes enrichment analysis, Jak-STAT, mTOR, and TGF-β signaling pathways were mainly related to melanogenesis and plume color. The findings of this study supported important information for the evaluation and protection of chicken genetic resources and help to analyze the unique genetic phenotypes such as melanin deposition and feather color of Lueyang black-bone chicken. Additionally, it could provide basic research data for the improvement and breeding of Lueyang black-bone chicken with characteristic traits.

Formaldehyde, a ubiquitous indoor air pollutant, plays a significant role in various biological processes, posing both environmental and health challenges. This comprehensive review delves into the latest advancements in electrochemical methods for detecting formaldehyde, a compound of growing concern due to its widespread use and potential health hazards. This review underscores the inherent advantages of electrochemical techniques, such as high sensitivity, selectivity, and capability for real-time analysis, making them highly effective for formaldehyde monitoring. We explore the fundamental principles, mechanisms, and diverse methodologies employed in electrochemical formaldehyde detection, highlighting the role of innovative sensing materials and electrodes. Special attention is given to recent developments in nanotechnology and sensor design, which significantly enhance the sensitivity and selectivity of these detection systems. Moreover, this review identifies current challenges and discusses future research directions. Our aim is to encourage ongoing research and innovation in this field, ultimately leading to the development of advanced, practical solutions for formaldehyde detection in various environmental and biological contexts.

Abstract The abnormal expression of long non-coding RNAs (LncRNAs) in platelet-derived microparticles (PMPs) is closely related to immune disorders and may lead to antiphospholipid antibody syndrome and recurrent miscarriage. To understand the association between the LncRNAs in PMPs and RM/APS, the differences in the expression of LncRNAs in RM/APS patients and healthy controls were analyzed. Microarray analysis and RT-qPCR detection proved that RM/APS patient exhibited high levels of LncNR_040117 expression. The lentiviral silent expression transfection of HTR-8/SVneo cells indicated that LncNR_040117 downregulation decreased the activity of HTR-8/SVneo cells and inhibited the MAPK signaling pathway, further confirming the biomarker proficiency of LncNR_040117 for RM/APS. After that, we proposed a β-In2S3@g-C3N4 nanoheterojunction-based photoelectrochemical (PEC) biosensor to achieve the ultrasensitive detection of LncNR_040117. The nanoheterojunction aids in the effective separation of photogenerated carriers and significantly improve the photocurrent response of the biosensor. The conjugation of LncNR_040117 onto the PEC biosensing platform increased the steric hindrance between electrolyte and electrode, subsequently decreasing the photocurrent signal. The PEC biosensor showed a wide detection range of 0.1–106 fM and a low limit of detection of 0.025 fM. For clinical sample testing, the results of the PEC and RT-qPCR were highly consistent. Overall, LncNR_040117 in PMPs was identified as an effective biomarker for RM/APS and could be accurately detected by the proposed PEC biosensor, which is expected to provide a reliable diagnostic platform for RM/APS.

Abstract Chemotherapy combined with or without targeted therapy is the fundamental treatment for metastatic colorectal cancer (mCRC). Due to the adverse effects of chemotherapeutic drugs and the biological characteristics of the tumor cells, it is difficult to make breakthroughs in traditional strategies. The immune checkpoint blockades (ICB) therapy has made significant progress in the treatment of advanced malignant tumors, and patients who benefit from this therapy may obtain a long-lasting response. Unfortunately, immunotherapy is only effective in a limited number of patients with microsatellite instability—high (MSI-H), and segment initial responders can subsequently develop acquired resistance. From September 4, 2014, the first anti-PD-1/PD-L1 drug Pembrolizumab was approved by the FDA for the second-line treatment of advanced malignant melanoma. Subsequently, it was approved for mCRC second-line treatment in 2017. Immunotherapy has rapidly developed in the past 7 years. The in-depth research of the ICB treatment indicated that the mechanism of colorectal cancer immune-resistance has become gradually clear, and new predictive biomarkers are constantly emerging. Clinical trials examining the effect of immune checkpoints are actively carried out, in order to produce long-lasting effects for mCRC patients. This review summarizes the treatment strategies for mCRC patients, discusses the mechanism and application of ICB in mCRC treatment, outlines the potential markers of the ICB efficacy, lists the key results of the clinical trials, and collects the recent basic research results, in order to provide a theoretical basis and practical direction for immunotherapy strategies.

The deployment of lithium metal batteries is forestalled by poor control over the deposition morphology of lithium. Here, the authors discover that high electrical resistance can be leveraged for controlling lithium morphology and enabling high-performing lithium metal batteries.

Abstract Chemodynamic therapy (CDT) based on Fenton or Fenton-like reactions is an emerging cancer treatment that can both effectively fight cancer and reduce side effects on normal cells and tissues, and it has made important progress in cancer treatment. The catalytic efficiency of Fenton nanocatalysts(F-NCs) directly determines the anticancer effect of CDT. To learn more about this new type of therapy, this review summarizes the recent development of F-NCs that are responsive to tumor microenvironment (TME), and detailedly introduces their material design and action mechanism. Based on the deficiencies of them, some effective strategies to significantly improve the anticancer efficacy of F-NCs are highlighted, which mainly includes increasing the temperature and hydrogen peroxide concentration, reducing the pH, glutathione (GSH) content, and the dependence of F-NCs on acidic environment in the TME. It also discusses the differences between the effect of multi-mode therapy with external energy (light and ultrasound) and the single-mode therapy of CDT. Finally, the challenges encountered in the treatment process, the future development direction of F-NCs, and some suggestions are analyzed to promote CDT to enter the clinical stage in the near future. Graphical Abstract

Abstract Background This study aims to develop an evidence-based clinical practice guideline of acupuncture in the treatment of patients with moderate and severe cancer pain. Methods The development of this guideline was triggered by a systematic review published in JAMA Oncology in 2020. We searched databases and websites for evidence on patient preferences and values, and other resources of using acupuncture for treatment of cancer pain. Recommendations were developed through a Delphi consensus of an international multidisciplinary panel including 13 western medicine oncologists, Chinese medicine/acupuncture clinical practitioners, and two patient representatives. The certainty of evidence, patient preferences and values, resources, and other factors were fully considered in formulating the recommendations. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was employed to rate the certainty of evidence and the strength of recommendations. Results The guideline proposed three recommendations: (1) a strong recommendation for the treatment of acupuncture rather than no treatment to relieve pain in patients with moderate to severe cancer pain; (2) a weak recommendation for the combination treatments with acupuncture/acupressure to reduce pain intensity, decrease the opioid dose, and alleviate opioid-related side effects in moderate to severe cancer pain patients who are using analgesics; and (3) a strong recommendation for acupuncture in breast cancer patients to relieve their aromatase inhibitor-induced arthralgia. Conclusion This proposed guideline provides recommendations for the management of patients with cancer pain. The small sample sizes of evidence limit the strength of the recommendations and highlights the need for additional research.

Objective: To investigate the role of Traditional Chinese Medicine (TCM) syndrome type, gut microbiome distribution, and host immunity function in predicting the early and advanced clinical stages of colorectal cancer (CRC). Methods: A cross-sectional case-control study was performed which included 48 early stage and 48 advanced patients with CRC enrolled from March 2018 to December 2020. 16S rRNA gene sequencing was performed to analyze the gut microbiomes of the patients, while T and B lymphocyte subsets in peripheral blood were assessed using flow cytometry. TCM syndrome type was measured using the spleen deficiency syndrome (SDS) scale. Results: The abundance levels of Prevotella, Escherichia-Shigella , and Faecalibacterium in the gut microbiota were significantly increased in the advanced group, while Bacteroides was significantly decreased. Phascolarctobacterium was detectable only in the early metaphase group, whereas Alistipes was detectable only in the advanced group. The lymphocyte ( P = .006), T helper cell (TH) ( P = .002), cytotoxic T cell (TC) ( P = .003), double positive T cell (DPT) ( P = .02), and total T counts ( P = .001) were significantly higher in the early metaphase group than in the advanced metaphase group. Compared with patients with early stage CRC, the advanced group had a higher SDS score. After adjusting for clinical stage, Spearman’s correlation analysis showed interactions among gut microbiome abundance, T cell level, and SDS score. Multivariate logistic analysis showed that after controlling for the SDS score, abundance of Alistipes and Faecalibacterium , and double negative T cell (DNT) level, DPT was significantly associated with a lower risk of advanced-stage disease (hazard ratio, 0.918; P = .022). Conclusion: Our study suggested associations between clinical stage, SDS, gut microbiota, and T lymphocytes, which provided insights for a potential prediction model for the disease progression of CRC.

Background: Accurate motion tracking in head-mounted displays (HMDs) has been widely used in immersive VR interaction technologies. However, tracking the head motion of users at all times is not always desirable. During a session of HMD usage, users may make scene-irrelevant head rotations, such as adjusting the head position to avoid neck pain or responding to distractions from the physical world. To the best of our knowledge, this is the first study that addresses the problem of scene-irrelevant head movements. Methods: We trained a classifier to detect scene-irrelevant motions using temporal eyehead-coordinated information sequences. To investigate the usefulness of the detection results, we propose a technique to suspend motion tracking in HMDs where scene-irrelevant motions are detected. Results: /Conclusions Experimental results demonstrate that the scene-relevancy of movements can be detected using eye-head coordination information, and that ignoring scene-irrelevant head motions in HMDs improves user continuity without increasing sickness or breaking immersion.

Abstract Background Resistance to oxaliplatin is a major obstacle for the management of locally advanced and metastatic colon cancer (CC). Although long noncoding RNAs (lncRNAs) play key roles in CC, the relationships between lncRNAs and resistance to oxaliplatin have been poorly understood yet. Methods Chemo-sensitive and chemo-resistant organoids were established from colon cancer tissues of the oxaliplatin-sensitive or -resistant patients. Analysis of the patient cohort indicated that lnc-RP11-536 K7.3 had a potential oncogenic role in CC. Further, a series of functional in vitro and in vivo experiments were conducted to assess the effects of lnc-RP11-536 K7.3 on CC proliferation, glycolysis, and angiogenesis. RNA pull-down assay, luciferase reporter and fluorescent in situ hybridization assays were used to confirm the interactions between lnc-RP11-536 K7.3, SOX2 and their downstream target HIF-1α. Results In this study, we identified a novel lncRNA, lnc-RP11-536 K7.3, was associated with resistance to oxaliplatin and predicted a poor survival. Knockout of lnc-RP11-536 K7.3 inhibited the proliferation, glycolysis, and angiogenesis, whereas enhanced chemosensitivity in chemo-resistant organoids and CC cells both in vitro and in vivo. Furthermore, we found that lnc-RP11-536 K7.3 recruited SOX2 to transcriptionally activate USP7 mRNA expression. The accumulative USP7 resulted in deubiquitylation and stabilization of HIF-1α, thereby facilitating resistance to oxaliplatin. Conclusion In conclusion, our findings indicated that lnc-RP11-536 K7.3 could promote proliferation, glycolysis, angiogenesis, and chemo-resistance in CC by SOX2/USP7/HIF-1α signaling axis. This revealed a new insight into how lncRNA could regulate chemosensitivity and provide a potential therapeutic target for reversing resistance to oxaliplatin in the management of CC.

Aim: Quxie capsule (QX), a compound of 21 kinds of Traditional Chinese Medicine (TCM) herbs, has been used to treat patients with metastatic colorectal cancer (mCRC) and could suppress the growth of colon cancer. However, the mechanisms of QX inhibiting colorectal cancer remain unclear. In current study, we attempted to determine the anti-colorectal cancer (CRC) effects of QX and the mechanisms of QX in alleviating colorectal cancer. Methods: A colitis-associated colon cancer (CAC) model was established by intraperitoneally injecting mice with AOM followed by 3 cycles of 2% DSS in water. During establishment of CAC model, we orally gavaged mice with QX. Hematoxylin and eosin (H&E) and immunohistochemistry were performed to assess lesion of the colonic tumors. The expression of pro-inflammatory cytokines in colonic tumors was measured by qPCR. The proportion of immune cells in colonic tumors was analyzed by flow cytometry. Internal transcribed spacer (ITS) sequencing and 16S rRNA gene sequencing were performed to detect intestinal microbiota. The expression of glycolytic related enzymes, lactate production, and extracellular acidification rate (ECAR) were used to assess the level of aerobic glycolysis. Results: QX markedly inhibited intestinal tumorigenesis by decreasing the expression of pro-inflammatory cytokines and the proportion of myeloid-derived suppressor cells (MDSCs), and increasing the proportion of CD8 + T cells in colon tumors. Fecal microbiota sequencing revealed that QX increased the relative abundances of intestinal symbiotic probiotics, such as, Lactobacillus , Bifidobacterium and Faecalibacterium genera. What’s more, opportunistic pathogens, Bacteroides genera and Aspergillus - Aspergillus fumigatus , exhibited remarkably reduced abundances in mice treated with QX compared with untreated CAC mice. Further experiments showed that QX significantly reduced glycolysis of colon tumor and suppressed A. fumigatus -induced glycolytic metabolism of colon cancer cells. Conclusions: QX alleviates the development of CRC at least in part through modulating intestinal microbiota and reducing A. fumigatus -induced aerobic glycolysis of colon cancer cells.

Background: This study aimed to evaluate associations between physical activities, gut microbiome and survival outcomes among Chinese metastatic colorectal cancer (mCRC) patients. Methods: We conducted a secondary analysis nested in a randomized controlled clinical trial (RCT) of a traditional Chinese herbal medicine for mCRC patients (ChiCTR2000029599). After one-month intervention, we followed up patients every six months for survival outcomes and the last follow-up was in August 2022 (median follow-up time 28.6 months). We assessed patients’ physical activity (PA) through short form of the International Physical Activity Questionnaire (IPAQ-SF) and collected patients’ stool samples at baseline. Kaplan–Meier survival analyses and Cox regression models were used to evaluate the association between PA level and overall survival outcomes. 16S rRNA sequencing approaches were utilized for the gut microbiome analysis. Results: Among 40 mCRC patients enrolled in the original RCT, 15 patients were still alive at the time of the last follow-up. The mean IPAQ score was 2569.5 MET-min/week for all patients, indicating a moderate PA level. Specifically, there were 7 patients in high PA level group, 2 patients in low PA level group and the rest were in middle PA group. Gut microbiome community difference analysis showed that patients with high PA levels had a significantly higher alpha diversity than that of the middle PA group (131.53 vs. 98.12, p = 0.04), an increased abundance of Phascolarctobacterium and Ruminococcaceae and a decreased abundance of Megasphaera at the genus level. Cox regression model showed that after controlling for the original tumor site and TCM treatment, high PA level was independently associated with a lower risk of death (relative risk 0.13, p = 0.014). Conclusions: High PA level could be associated with survival benefits among Chinese mCRC patient through its potential role on modulating gut microbiome. Our results could be referred to patients’ education and future clinical study design.

BackgroundTo construct prognostic model of colorectal cancer (CRC) recurrence and metastasis (R&M) with traditional Chinese medicine (TCM) factors based on different machine learning (ML) methods. Aiming to offset the defects in the existing model lacking TCM factors.MethodsPatients with stage I-III CRC after radical resection were included as the model data set. The training set and the internal verification set were randomly divided at a ratio of 7: 3 by the “set aside method”. The average performance index and 95% confidence interval of the model were calculated by repeating 100 tests. Eight factors were used as predictors of Western medicine. Two types of models were constructed by taking “whether to accept TCM intervention” and “different TCM syndrome types” as TCM predictors. The model was constructed by four ML methods: logistic regression, random forest, Extreme Gradient Boosting (XGBoost) and support vector machine (SVM). The predicted target was whether R&M would occur within 3 years and 5 years after radical surgery. The area under curve (AUC) value and decision curve analysis (DCA) curve were used to evaluate accuracy and utility of the model.ResultsThe model data set consisted of 558 patients, of which 317 received TCM intervention after radical resection. The model based on the four ML methods with the TCM factor of “whether to accept TCM intervention” showed good ability in predicting R&M within 3 years and 5 years (AUC value > 0.75), and XGBoost was the best method. The DCA indicated that when the R&M probability in patients was at a certain threshold, the models provided additional clinical benefits. When predicting the R&M probability within 3 years and 5 years in the model with TCM factors of “different TCM syndrome types”, the four methods all showed certain predictive ability (AUC value > 0.70). With the exception of the model constructed by SVM, the other methods provided additional clinical benefits within a certain probability threshold.ConclusionThe prognostic model based on ML methods shows good accuracy and clinical utility. It can quantify the influence degree of TCM factors on R&M, and provide certain values for clinical decision-making.

Background: Liu Jun An Wei formula (LJAW), derived from “Liu Jun Zi Decoction”, is a classical prescription of Tradition Chinese Medicine and has been used for the treatment of gastrointestinal reactions caused by chemotherapy for colorectal cancer (CRC) for many years. Its molecular mechanism remains to be further explored.Objective: To clarify the mechanism of LJAW in attenuating gastrointestinal reactions caused by chemotherapy for CRC.Methods: The 5-fluorouracil (5-FU) induced mouse and intestine organoid models were established to observe the effect of LJAW. The ingredients of LJAW were analyzed and identified by UPLC-Q-TOF-MS technology. Targets of LJAW and chemotherapy-induced gastrointestinal reactions were collected from several databases. “Ingredient-target” network and protein-protein interaction network were constructed based on network pharmacology. Then, gene ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Subsequently, molecular docking method was used to verify the interaction between the core ingredients and key targets. The results were validated by both in vivo experiments and organoid experiments. Western Blot was used to analyze the influence of LJAW on key targets including PI3K, AKT1, MAPK1, MAPK14 proteins and their phosphorylated proteins. RT-qPCR and Western Blot were used to detect the mRNA and protein levels of apoptosis-related gene PUMA.Results: Compared with the 5-FU group, the LJAW group had better morphology in mouse small intestine and intestine organoids. In total, 18 core ingredients and 19 key targets were obtained from 97 ingredients and 169 common targets. KEGG analysis showed that the common targets were involved in PI3K/Akt, MAPK, apoptosis and other signal pathways, which are closely related to gastrointestinal injury. Experiments confirmed that LJAW lowered the expressions of phosphorylated proteins including p-PI3K, p-AKT1, p-MAPK1, and p-MAPK14 and reduced the mRNA and protein levels of PUMA.Conclusion: LJAW shows protective effect on 5-FU induced small intestine and intestinal organoids injury. LJAW attenuates gastrointestinal reactions caused by chemotherapy for CRC probably by regulating apoptosis-related genes through PI3K/AKT and MAPK signaling pathways.

Positive circumferential resection margin (CRM) was associated with a higher recurrence rate and worse survival in rectal cancer. Predictors of CRM in rectal cancer have widely been investigated. Our study aims to determine the incidence, predictors and prognostic implications of positive CRM following colon cancer (CC) surgery in a Chinese high-volume cancer center. The clinicopathological features and oncological outcomes of CC patients undergoing surgery between January 2008 and December 2018 were identified from Fudan University Shanghai Cancer Center database. Positive CRM was defined as resection margin ≤1 mm. A total of 5268 stage I-IV CC patients were identified in our study, 108 (2.05%) of whom had positive CRM. Multivariate logistic analysis found that advanced N stage, distant metastases and poorly differentiated tumor had increased risk of positive CRM. After propensity score matching, the 5-year overall survival rates of the patients with positive and negative CRM were 33.2% and 39.8% (P=0.005), respectively. Multivariable COX regression model showed that positive CRM was an independent prognostic factor for OS in CC patients. The overall rate of positive CRM in our center is lower than that in western population. Several adverse pathological parameters deserve more attention to identify CC patients at a high risk of positive CRM. Adoption of appropriate surgical techniques and multidisciplinary treatment planning are expected to improve oncological outcomes for high selected CC patients with “high-risk” CRM involvement.

Transformed Luneburg lens has been widely employed to provide aberration-free imaging and high-gain antenna system, but whose focal plane and beam scanning range decrease correspondingly. In this paper, a two-dimensional compressed elliptical cylindrical Luneburg lens is presented based on transformation optics (TO) to achieve miniaturization and wide-angle beam steering. The Jacobian matrix and the permittivity tensor are calculated after supposing formulas to compress the focal plane, while maintaining the lens’ inherent performance. The gradient permittivity is achieved by two ring-type periodic unit cells on the basis of the Equivalent Medium Theory. The lens is then attached between a pair of parallel metal plates to further improve its gain and lower the side lobe level (SLL). To demonstrate this assumption, a prototype of this Luneburg lens is manufactured by isotropic material and 3D printing technique. The antenna operates at 3.3–5 GHz with a peak gain of 16.1/15.9 dBi. A 2D beam scanning range of ±50° and ± 20° can be implemented by merely five feeds, the side lobe level keeping less than -16.3/-16 dB. Measured results coincide well with theoretical predictions, offering a beneficial transformation mapping to both microwaves and optics.

Objective: Crohn’s disease (CD), a chronic recurrent illness, is a type of inflammatory bowel disease whose incidence and prevalence rates are gradually increasing. However, there is no universally accepted criterion for CD diagnosis. The aim of this study was to create a diagnostic prediction model for CD and identify immune cell infiltration features in CD.Methods: In this study, gene expression microarray datasets were obtained from the Gene Expression Omnibus (GEO) database. Then, we identified differentially expressed genes (DEGs) between 178 CD and 38 control cases. Enrichment analysis of DEGs was also performed to explore the biological role of DEGs. Moreover, the “randomForest” package was applied to select core genes that were used to create a neural network model. Finally, in the training cohort, we used CIBERSORT to evaluate the immune landscape between the CD and normal groups.Results: The results of enrichment analysis revealed that these DEGs may be involved in biological processes associated with immunity and inflammatory responses. Moreover, the top 3 hub genes in the protein-protein interaction network were IL-1β, CCL2, and CXCR2. The diagnostic model allowed significant discrimination with an area under the ROC curve of 0.984 [95% confidence interval: 0.971–0.993]. A validation cohort (GSE36807) was utilized to ensure the reliability and applicability of the model. In addition, the immune infiltration analysis indicated nine different immune cell types were significantly different between the CD and healthy control groups.Conclusion: In summary, this study offers a novel insight into the diagnosis of CD and provides potential biomarkers for the precise treatment of CD.

Abstract Background Although programmed cell death‐ligand 1 (PD‐L1) plays a well‐known function in immune checkpoint response by interacting with programmed cell death‐1 (PD‐1), the cell‐intrinsic role of PD‐L1 in tumors is still unclear. Here, we explored the molecular regulatory mechanism of PD‐L1 in the progression and metastasis of ovarian cancer. Methods Immunohistochemistry of benign tissues and ovarian cancer samples was performed, followed by migration, invasion, and angiogenesis assays in PD‐L1‐knockdown ovarian cancer cells. Immunoprecipitation, mass spectrometry, and chromatin immunoprecipitation were conducted along with zebrafish and mouse experiments to explore the specific functions and mechanisms of PD‐L1 in ovarian cancer. Results Our results showed that PD‐L1 induced angiogenesis, which further promoted cell migration and invasion in vitro and in vivo of ovarian cancer. Mechanistically, PD‐L1 was identified to directly interact with vascular endothelial growth factor receptor‐2 (VEGFR2) and then activated the FAK/AKT pathway, which further induced angiogenesis and tumor progression, leading to poor prognosis of ovarian cancer patients. Meanwhile, PD‐L1 was found to be regulated by the oncogenic transcription factor c‐JUN at the transcriptional level, which enhanced the expression of PD‐L1 in ovarian cancer. Furthermore, we demonstrated that PD‐L1 inhibitor durvalumab, combined with the antiangiogenic drug, apatinib, could enhance the effect of anti‐angiogenesis and the inhibition of cell migration and invasion. Conclusion Our results demonstrated that PD‐L1 promoted the angiogenesis and metastasis of ovarian cancer by participating in the c‐JUN/VEGFR2 signaling axis, suggesting that the combination of PD‐L1 inhibitor and antiangiogenic drugs may be considered as a potential therapeutic approach for ovarian cancer patients.

Studies show that traditional Chinese medicine (TCM), such as Liujunanwei (LJAW) decoction, can play important roles in alleviating side effects of chemotherapy. The purpose of this study was to understand how LJAW can counter chemotherapy-induced emesis via alteration of gut microbiota. We evaluated the effect of LJAW on cisplatin (DDP)-induced nausea and vomiting using a rat-pica model. Rats react to emetic-producing stimuli with increased kaolin consumption, a phenomenon called pica. The rats were injected with cisplatin and then randomly assigned to the control (DDP), Ondansetron or LJAW. The intake of kaolin and chow diet as well as body weights were recorded every 24 hours. Fecal samples were collected prior to, after three and seven days of treatment. The expression of proteins was measured by western blot. The concentration of cytokines and serotonin was evaluated using ELISA assay kits. Kaolin consumption in rats induced by cisplatin was reduced by 16.5%, 22.5%, and 30.1% in the LJAW group compared to the DDP group at 24 hours, 48 hours and 72 hours, respectively (p>0.05). LJAW significantly increased the food intake of the rats (13.94 ± 4.73 g) during the first 24 hours as opposed to the DDP (9.23 ± 3.77 g) (p

Chimeric antigen receptor (CAR) T cell therapy has revolutionized the therapeutic landscape of haematological malignancies. However, resistance and relapse remain prominent limitations, and they are related to the limited persistence and efficacy of CAR T cells, downregulation or loss of tumour antigens, intrinsic resistance of tumours to death signalling, and immune suppressive microenvironment. Rational combined modality treatments are regarded as a promising strategy to further unlock the antitumor potential of CAR T cell therapy, which can be applied before CAR T cell infusion as a conditioning regimen or in ex vivo culture settings as well as concomitant with or after CAR T cell infusion. In this review, we summarize the combinatorial strategies, including chemotherapy, radiotherapy, haematopoietic stem cell transplantation, targeted therapies and other immunotherapies, in an effort to further enhance the effectiveness of this impressive therapy and benefit more patients.

The applications of three-dimensional materials combined with two-dimensional materials are attractive for constructing high-performance electronic and photoelectronic devices because of their remarkable electronic and optical properties. However, traditional preparation methods usually involve mechanical transfer, which has a complicated process and cannot avoid contamination. In this work, chemical vapor deposition was proposed to vertically synthesize self-assembly oriented hexagonal boron nitride on gallium nitride directly. The material composition, crystalline quality and orientation were investigated using multiple characterization methods. Thermal conductivity was found to be enhanced twofold in the h-BN incorporated sample by using the optothermal Raman technique. A vertical-ordered (VO)h-BN/GaN heterojunction photodetector was produced based on the synthesis. The photodetector exhibited a high ultraviolet photoresponsivity of up to 1970.7 mA/W, and detectivity up to 2.6 × 1013 Jones, and was stable in harsh high temperature conditions. Our work provides a new synthesis method to prepare h-BN on GaN-based materials directly, and a novel vertically oriented structure of VO-h-BN/GaN heterojunction, which has great application potential in optoelectronic devices.

Satisfying various constraints and multiple objectives simultaneously is a significant challenge in solving constrained multi-objective optimization problems. To address this issue, a new approach is proposed in this paper that combines multi-population and multi-stage methods with a Carnivorous Plant Algorithm. The algorithm employs the ϵ-constraint handling method, with the ϵ value adjusted according to different stages to meet the algorithm’s requirements. To improve the search efficiency, a cross-pollination is designed based on the trapping mechanism and pollination behavior of carnivorous plants, thus balancing the exploration and exploitation abilities and accelerating the convergence speed. Moreover, a quasi-reflection learning mechanism is introduced for the growth process of carnivorous plants, enhancing the optimization efficiency and improving its global convergence ability. Furthermore, the quadratic interpolation method is introduced for the reproduction process of carnivorous plants, which enables the algorithm to escape from local optima and enhances the optimization precision and convergence speed. The proposed algorithm’s performance is evaluated on several test suites, including DC-DTLZ, FCP, DASCMOP, ZDT, DTLZ, and RWMOPs. The experimental results indicate competitive performance of the proposed algorithm over the state-of-the-art constrained multi-objective optimization algorithms.

Research on turbulent drag reduction has been limited owing to the limitations of existing parameters used for the identification of vortex structures. As a new and more suitable vortex parameter, Liutex provides a novel research method for turbulence control. We used a channel with a transverse groove structure as the research model and employed large-eddy simulation method based on Liutex to study the influence and mechanism of the transverse groove structure on the watershed. The analysis revealed that the transverse groove structure significantly inhibited the vortex intensity, and this effect diminished with the increase of the normal height. Moreover, the transverse groove structure could maintain the stability of the flow vortex and restrain the hairpin vortex. The fundamental action mechanism of the groove structure pertained to slip condition of the bottom surface along the flow direction, which was essential for conveying the bottom fluid. Furthermore, the transverse groove structure could significantly reduce the overall increase in the vortex intensity in the transition layer, and the fluctuation of the vortex intensity in the logarithmic layer was lower under the action of the groove structure. This case can guide the application of the new vortex identification method in turbulence drag reduction.

Background: The immunotherapy efficacy in gastric cancer (GC) is limited. Cancer-associated fibroblasts (CAFs) induce primary resistance to immunotherapy. However, CAF infiltration in tumors is difficult to evaluate due to the lack of validated and standardized quantified methods. This study aimed to investigate the impact of infiltrating CAFs alternatively using fibroblast-associated mutation scoring (FAMscore).Methods: In a GC cohort from Affiliated Hospital of Jiangsu University (AHJU), whole exon sequencing of genomic mutations, whole transcriptome sequencing of mRNA expression profiles, and immunofluorescence staining of tumor-infiltrating immune cells were performed. GC data from The Cancer Genome Atlas were used to identify genetic mutations which were associated with overall survival (OS) and impacted infiltrating CAF abundance determined by transcriptome-based estimation. FAMscore was then constructed through a least absolute shrinkage and selection operator Cox regression model and further validated in AHJU. The predictive role of FAMscore for immunotherapy outcomes was tested in 1 GC, one melanoma, and two non-small-cell lung cancer (NSCLC-1 and -2) cohorts wherein participants were treated by immune checkpoint inhibitors.Results: FAMscore was calculated based on a mutation signature consisting of 16 genes. In both TCGA and AHJU, a high FAMscore was an independent predictor for poor OS of GC patients. FAMscore was associated with immune-associated genome biomarkers, immune cell infiltration, and signaling pathways of abnormal immunity. Importantly, patients with high FAMscore presented inferiority in the objective response rate of immunotherapy compared to those with low FAMscore, with 14.6% vs. 66.7% (p

Polybrominated dibenzo-p-dioxins and dibenzofurans (PBDD/Fs) are highly toxic and persistent compounds that provoke a wave of publicity. Bromophenols are important precursors for forming PBDD/Fs, and their reaction path has always been a research hotspot. In this study, the formation characteristic of PBDD/Fs from 2,4,6-TBP were studied. The yields of 2,3,7,8-substituted PBDD/Fs and 2,4,6,8-TBDF for the different thermal products ranged from 0.067 to 10.3 ng/g and 0.207–9.68 ng/g, respectively. The effects of adding Cu, Fe, and Sb2O3 were investigated and found to be more inclined to accelerate the formation of ortho-substituted PBDD/Fs than 2,3,7,8-PBDD/Fs. The formation pathways of 2,3,7,8-substituted PBDD/Fs and 2,4,6,8-TBDF were also proposed. 2,4,6,8-TBDF is generated in the C-C coupling reactions of some radical intermediates from the debromination of 2,4,6-TBP. The 2,3,7,8-PBDD/Fs are produced through more complex debromination, bromine substitution, and bromine rearrangement reactions. In addition, various catalytic effects on PBDD/F formation pathways were found, and the catalytic effect of Cu by the Ullmann reaction was the highest, while bromophenol oxidation by Fe was the highest. These results proved that both 2,3,7,8-substituted and non-2,3,7,8-substituted PBDD/Fs would be generated from 2,4,6-TBP, and the effects of the catalyst on the Br substituted position of 2,3,7,8-substituted PBDD/Fs were much lower than the Br-substituted position on bromophenol.