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Summary: Over the past decades, researchers have continuously investigated the potential functions of long-chain polyunsaturated fatty acids (LCPUFAs) in cancers, including lung cancer. The ω-3 LCPUFAs, primarily consisting of eicosapentaenoic acid and docosahexaenoic acid, were found to modify inflammatory tumor microenvironment, induce cancer cell apoptosis and autophagy, and suppress tumor development when administered alone or with other therapeutical strategies. Although the precise anti-tumor mechanism has not been elucidated yet, ω-3 LCPUFAs are often used in the nutritional treatment of patients with cancer due to their ability to significantly improve patient’s nutritional status, increase the sensitivity of tumor cells to treatments, and alleviate cancer-related complications. Here we present the key roles of ω-3 LCPUFAs as dietary supplementations in lung cancer, comprehensively review the recent progress on the underlying mechanisms of cancer cell regulation by ω-3 LCPUFAs, and introduce the application of ω-3 LCPUFAs in the clinical management of lung cancer and its malignant complications.

Vesicular vehicles have been one of the most potential platforms for therapeutic delivery. Here, we commentate on recent advances in the development of therapeutic vesicular delivery platforms, emphasizing two intriguing works, namely, the chimeric nanobody-decorated immunoliposomes (Wan et al.) and the retrovirus-like capsids incorporated extracellular vesicles (Jiang et al.). In the work of Wan et al., the researchers proposed a novel strategy for antitumor immunoliposome construction by the one-step self-assembly of lipids with rationally designed chimeric nanobody that comprises a nanobody against human epidermal growth factor receptor 2, a flexible peptide linker, and a human single transmembrane domain. By leveraging the natural cell systems (e.g., E coli.) to synthesize the chimeric nanobody, this technique provides a facile and robust strategy for producing immunoliposome platforms, ensuring suitability for industrial manufacturing and distribution, regulatory compliance, and clinical use. In the work of Jiang et al., taking advantage of the natural extracellular vesicle biogenesis system, the researchers introduced the activity-regulated cytoskeleton-associated protein inside the vesicle lumen and thus constructed endogenous retrovirus-like vesicles for mRNA drug delivery to neurons. This technique offers a significative strategy for developing sophisticated delivery platforms, manifesting broad application potential for different disease therapeutics. Overall, these two works have represented two typical paradigms for the artificial construction of vesicular vesicles. Considering their complementary merits, in the future, the integration of artificial engineering technologies and natural biosynthesis systems is anticipated to be a promising strategy to expedite the development of potent delivery systems.

This study investigates the impact of wind shear on the flight dynamics of commercial aircraft where C* and C*U control laws are employed during the approach phase. Given the high incidence of flight accidents during takeoff and landing attributed to wind shear, this research aims to enhance aviation safety by analyzing control law behavior under varying wind shear conditions. A nonlinear flight simulation model was developed, utilizing aerodynamic and engine data from a B737, to explore the aircraft’s response to different wind shear intensities. The simulation analysis was used to compare the response of the aircraft with C* and C*U controllers, respectively, under different wind shear, and to evaluate the effectiveness of its stability enhancement in wind shear. It was found that in most cases, the controller can achieve a good stabilization effect, but in some cases of wind fields, the aircraft suffered more significant oscillation.

Generative artificial intelligence (GAI) shocked the world with its unprecedented ability and raised significant tensions in the education field. Educators inevitably transition to an educational future that embraces GAI rather than shuns it. Understanding the mechanism between students interacting with GAI tools and their achievement is important for educators and schools, but relevant empirical evidence is relatively lacking. Due to the characteristics of personalization and real-time interactivity of GAI tools, we propose that the students–GAI interaction would affect their learning achievement through serial mediators of self-efficacy and cognitive engagement. Based on questionnaire surveys that include 389 participants as the objective, this study finds that: (1) in total, there is a significantly positive relationship between student–GAI interaction and learning achievement. (2) This positive relationship is mediated by self-efficacy, with a significant mediation effect value of 0.015. (3) Cognitive engagement also acts as a mediator in the mechanism between the student–GAI interaction and learning achievement, evidenced by a significant and relatively strong mediating effect value of 0.046. (4) Self-efficacy and cognitive engagement in series mediate this positive association, with a serial mediating effect value of 0.011, which is relatively small in comparison but also shows significance. In addition, the propensity score matching (PSM) method is applied to alleviate self-selection bias, reinforcing the validity of the results. The findings offer empirical evidence for the incorporation of GAI in teaching and learning.

Abstract Background Notch signaling plays important roles in regulating innate immunity. However, little is known about the role of Notch in mesenchymal stromal/stem cell (MSC)-mediated immunomodulation during liver inflammatory response. Methods Notch activation in human umbilical cord-derived MSCs was performed by a tissue culture plate coated with Notch ligand, recombinant human Jagged1 (JAG1). Mice were given intravenous injection of Notch-activated MSCs after acetaminophen (APAP)-induced acute liver injury. Liver tissues were collected and analyzed by histology and immunohistochemistry. Results MSC administration reduced APAP-induced hepatocellular damage, as manifested by decreased serum ALT levels, intrahepatic macrophage/neutrophil infiltration, hepatocellular apoptosis and proinflammatory mediators. The anti-inflammatory activity and therapeutic effects of MSCs were greatly enhanced by Notch activation via its ligand JAG1. However, Notch2 disruption in MSCs markedly diminished the protective effect of MSCs against APAP-induced acute liver injury, even in the presence of JAG1 pretreatment. Strikingly, Notch-activated MSCs promoted AMP-activated protein kinase (AMPKα) phosphorylation, increased the sirtuins 1 (SIRT1) deacetylase expression, but downregulated spliced X-box-binding protein 1 (XBP1s) expression and consequently reduced NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation. Furthermore, SIRT1 disruption or XBP1s overexpression in macrophages exacerbated APAP-triggered liver inflammation and augmented NLRP3/caspase-1 activity in MSC-administrated mice. Mechanistic studies further demonstrated that JAG1-pretreated MSCs activated Notch2/COX2/PGE2 signaling, which in turn induced macrophage AMPK/SIRT1 activation, leading to XBP1s deacetylation and inhibition of NLRP3 activity. Conclusions Activation of Notch2 is required for the ability of MSCs to reduce the severity of APAP-induced liver damage in mice. Our findings underscore a novel molecular insights into MSCs-mediated immunomodulation by activating Notch2/COX2/AMPK/SIRT1 pathway and thus provide a new strategy for the treatment of liver inflammatory diseases.

In order to get a better tradeoff between the long lifetime and high performances of cesium beam atomic clocks, we proposed a design scheme of compact optically pumped cesium beam tube (OPCBT) based on hexapole magnetic focusing (HMF) system for the confinement of cesium. A practical optically pumped cesium beam tube without HMF system has been implemented and tested with high-stability laser by modulation transfer spectroscopy (MTS), and a signal-to-noise ratio (SNR) of 18,000 in 1 Hz bandwidth and Allan deviation of 2×10−12/τ were obtained. Based on this test, the simulation analysis results of the newly designed tube with HMF show that the predicted lifetime can reach over 20 years without degradation of the performances, and the expected frequency stability of the clock can be 6.5×10−13/τ with a lifetime of 10 years.

Abstract Objective To evaluate the effect of medial posterior tibial slope (PTS) on mid-term postoperative range of motion (ROM) and functional improvement of the knee after medial unicompartmental knee arthroplasty (UKA). Methods Medical records of 113 patients who had undergone 124 medial UKAs between April 2009 through April 2014 were reviewed retrospectively. The mean follow-up lasted 7.6 years (range, 6.2–11.2 years). Collected were demographic data, including gender, age, height, weight of the patients. Anteroposterior (AP) and lateral knee radiographs of the operated knees were available in all patients. The knee function was evaluated during office follow-up or hospital stay. Meanwhile, postoperative PTS, ROM, maximal knee flexion and Hospital for Special Surgery (HSS) knee score (pre−/postoperative) of the operated side were measured and assessed. According to the size of the PTS, patients were divided into 3 groups: group 1 (7°). The association between PTS and the knee function was investigated. Results In our cohort, the average PTS was 2.7° ± 0.6° in group 1, 5.6° ± 0.9° in group 2 and 8.7° ± 1.2° in group 3. Pairwise comparisons showed significant differences among them (p

The social currency, the existing potential resource in the social networks and communities of an individual, has become more significant in the era of information technology. Meanwhile, the rapid development of Internet service, especially its application on mobile devices, brings many new contents of prosocial behaviors (PBs), which benefits both individuals and communities. Specifically, social currency plays a positive role in promoting PB, forming positive personalities, promoting positive social adaptation, and contributing to human survival and social development. However, the theoretical research in this field still lags far behind the development of practice, and the research on the impact of social currency on PB remains exceedingly scarce. Grounded in the social exchange theory (SET), the present study collects a total of 497 WeChat user questionnaires, constructs a model for the influence mechanism of social currency on PB, and tests the hypothesis through hierarchical regression. According to the results obtained, it was found that the social currency is positively associated with PB, and users with a more social currency are more likely to act prosocially on their own. The PB of an individual is then influenced by the social currency generated through collective self-esteem (CS) so that the perception of CS can be considered as a mediating variable. Moreover, the communication network heterogeneity (CNH) moderates the above relationship, and the degree of heterogeneity will have different effects on the relationship of CS. The obtained conclusions enrich the previous theoretical results of PB and provided new insights for social managers to enhance the prosocial-related behaviors for the group, organization, and society.

In this study, a systematic and comprehensive meta-analysis of the relationship between thriving at work and its antecedents is conducted. The antecedents in terms of the characteristics of unit contextual features, the resources produced at work, agentic work behaviors, and personality traits are illustrated according to the socially embedded model of thriving described by Spreitzer and research. Additionally, we examine possible cultural influence on the relationship between thriving and its antecedents at different levels of individualistic culture. According to 67 independent samples (N = 28,097), our findings reveal the correlations between thriving at work and the antecedents such as those in the form of unit contextual features, the resources produced at work, agentic work behaviors, and personality traits. Furthermore, we find that individualism moderate the relationships between certain antecedents and thriving at work. Finally, we discuss the theoretical and practical implications of this study as well as the directions for future research.

Signal plays a significant role in the online retailing market, especially where the service quality of sellers is unobservable. In the current study, a game-theoretical model was formulated to help examine whether the new delivery service called distribution alliance in the electronic market can serve as a superior signal in revealing online seller’s service quality. Our results showed that the certification accuracy and the application fee are closely related to the signaling effect of the distribution alliance. Specifically, we found a concrete analytical boundary where a certain high level of certification accuracy is required to guarantee the existence of market equilibrium, and a corresponding application fee can convoy the signal’s effectiveness. In addition, the potential extensions and limitations of this research were also discussed.

Tissue engineering with 3D scaffold is a simple and effective method for bone healing after large-scale bone loss. So far, bone marrow-derived mesenchymal stem cells (BMSCs) are mostly used in the treatment of bone healing in animal models due to their self-renewal capability and osteogenic potential. Due to the fact that the main functional cells in promoting osteoid mineralization and bone remodeling were osteocytes, we chose an osteoblast-to-osteocyte transition cell line, IDG-SW3, which are not proliferative under physiological conditions, and compared the healing capability of these cells to that of BMSCs in bone defect. In vitro, IDG-SW3 cells revealed a stronger mineralization capacity when grown in 3D collagen gel, compared to that of BMSCs. Although both BMSC and IDG-SW3 can generate stable calcium-phosphate crystal similar to hydroxyapatite (HA), the content was much more enriched in IDG-SW3-mixed collagen gel. Moreover, the osteoclasts co-cultured with IDG-SW3-mixed collagen gel were easier to be activated, indicating that the IDG-SW3 grafting could promote the bone remodeling more efficiently in vivo. Last, in order to reduce the self-healing capability, we assessed the healing capability between the IDG-SW3 cells and BMSCs in osteoporotic mice. We found that the collagen hydrogel mixed with IDG-SW3 cells has a better healing pattern than what was seen in hydrogel mixed with BMSCs. Therefore, these results demonstrated that by promoting osteoblast-to-osteocyte transition, the therapeutic effect of BMSCs in bone defect repair could be improved.

Hepatic fibrosis is characterized by the pathological accumulation of extracellular matrix (ECM) in the liver resulting from the persistent liver injury and wound-healing reaction induced by various insults. Although hepatic fibrosis is considered reversible after eliminating the cause of injury, chronic injury left unchecked can progress to cirrhosis and liver cancer. A better understanding of the cellular and molecular mechanisms controlling the fibrotic response is needed to develop novel clinical strategies. It is well documented that activated hepatic stellate cells (HSCs) is the most principal cellular players promoting synthesis and deposition of ECM components. In the current review, we discuss pathways of HSC activation, emphasizing emerging extra- and intra-cellular signals that drive this important cellular response to hepatic fibrosis. A number of cell types and external stimuli converge upon HSCs to promote their activation, including hepatocytes, liver sinusoidal endothelial cells, macrophages, cytokines, altered ECM, hepatitis viral infection, enteric dysbiosis, lipid metabolism disorder, exosomes, microRNAs, alcohol, drugs and parasites. We also discuss the emerging signaling pathways and intracellular events that individually or synergistically drive HSC activation, including TGFβ/Smad, Notch, Wnt/β-catenin, Hedgehog and Hippo signaling pathways. These findings will provide novel potential therapeutic targets to arrest or reverse fibrosis and cirrhosis.

In practical engineering, due to the lack of information, it is impossible to accurately determine the distribution of all variables. Therefore, time-variant reliability problems with both random and interval variables may be encountered. However, this kind of problem usually involves a complex multilevel nested optimization problem, which leads to a substantial computational burden, and it is difficult to meet the requirements of complex engineering problem analysis. This study proposes a decoupling strategy to efficiently analyze the time-variant reliability based on the mixed uncertainty model. The interval variables are treated with independent random variables that are uniformly distributed in their respective intervals. Then the time-variant reliability-equivalent model, containing only random variables, is established, to avoid multi-layer nesting optimization. The stochastic process is first discretized to obtain several static limit state functions at different times. The time-variant reliability problem is changed into the conventional time-invariant system reliability problem. First order reliability analysis method (FORM) is used to analyze the reliability of each time. Thus, an efficient and robust convergence hybrid time-variant reliability calculation algorithm is proposed based on the equivalent model. Finally, numerical examples shows the effectiveness of the proposed method.

Functional cross-talk between osteoblasts and osteoclasts is a key process for bone homeostasis. Although osteoblast hypoxia-inducible factor-1α (HIF-1α) pathway activation results in impaired osteoclastogenesis via the direct regulation of osteoprotegerin (OPG), it is unclear whether there are other efficient mediators are involved in osteoblast HIF-1α pathway activation-restrained osteoclast formation. In addition to upregulated OPG, we observed that osteoblast HIF-1α activation led to increased interleukin-33 (IL-33) expression, which was found to inhibit osteoclastogenesis. Mechanistically, HIF-1α facilitates IL-33 expression by binding to −1,504/−1,500 bp on the Il-33 promoter. IL-33, thereby, acts on bone marrow-derived monocytes (BMMs) to reduce their osteoclastic differentiation. Moreover, microRNA-34a-5p (miR-34a-5p)-inhibited Notch1 activation was observed to play a central role in this process. Thereby, the identification of IL-33-miR-34a-5p-Notch1 pathway in the inhibitory effect of osteoblast HIF-1α pathway on osteoclastogenesis uncovers a new mechanism for understanding the effects of HIF-1α on bone remodeling.

Abstract With the growth of the industrial aluminum smelting sector, and the increasing proportion of incineration treatment in the field of waste management and disposal, there has been a corresponding increase in the production of secondary aluminum dross (SAD) and municipal solid waste incineration fly ash (MSWIFA) annually. In this research, ceramsite is prepared using SAD, MSWIFA, and municipal solid waste incineration bottom ash (MSWIBA) as raw materials. This study explores the impact of various factors on the mechanical properties of ceramsite and their mechanisms under different conditions, including sintering temperature, raw material ball particle size, raw material silica-alumina ratio, and sintering time. Single-factor experiments demonstrate that the compressive strength of ceramsite initially follows a non-linear ascending trend with increasing sintering temperatures. Additionally, the strength is enhanced with reductions in particle size of the raw material balls, prolongation of the sintering time, and a reduction in the silica-to-alumina ratio of the raw materials. Orthogonal experiments reveal the ideal preparation conditions for ceramsite as follows: a preheating temperature of 400 °C, a preheating duration of 20 min, a sintering temperature of 1270 °C, and a duration of 30 min. Under these conditions, the optimal composition ratio of ceramsite is Si:Al = 3, and the ideal particle size is 0.5 cm. Analysis through X-ray diffraction and scanning electron microscopy revealed the formation of new mineral phases such as sodium feldspar and potassium feldspar in the ceramsite, which display a dense structure under microscopic observation. These contribute positively to the mechanical properties of the ceramsite. Fourier-transform infrared spectroscopy analysis indicates that at a sintering temperature of 1260 °C or when the raw material ball size is 2 cm, the [SiO4] tetrahedral bands shift to higher wavenumbers, enhancing the degree of polymerization of the glass network in the ceramsite, thereby strengthening its compressive strength. As the silica-alumina ratio of the raw materials decreases and the sintering duration extends, the [SiO4] tetrahedral bands continue to shift to higher wavenumbers, further enhancing the compressive strength of the ceramsite.

Generative artificial intelligence (GAI) shocked the world with its unprecedented ability and raised significant tensions in the education field. Educators inevitably transition to an educational future that embraces GAI rather than shuns it. Understanding the mechanism between students interacting with GAI tools and their achievement is important for educators and schools, but relevant empirical evidence is relatively lacking. Due to the characteristics of personalization and real-time interactivity of GAI tools, we propose that the students--GAI interaction would affect their learning achievement through serial mediators of self-efficacy and cognitive engagement. Based on questionnaire surveys that include 389 participants as the objective, this study finds that: (1) in total, there is a significantly positive relationship between student--GAI interaction and learning achievement. (2) This positive relationship is mediated by self-efficacy, with a significant mediation effect value of 0.015. (3) Cognitive engagement also acts as a mediator in the mechanism between the student--GAI interaction and learning achievement, evidenced by a significant and relatively strong mediating effect value of 0.046. (4) Self-efficacy and cognitive engagement in series mediate this positive association, with a serial mediating effect value of 0.011, which is relatively small in comparison but also shows significance. In addition, the propensity score matching (PSM) method is applied to alleviate self-selection bias, reinforcing the validity of the results. The findings offer empirical evidence for the incorporation of GAI in teaching and learning. [ABSTRACT FROM AUTHOR]

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.

BackgroundUnilateral pulmonary artery discontinuity (UPAD) is a rare fetal abnormality, for which a prenatal ultrasonographic diagnosis remains challenging. We report a case of left pulmonary artery discontinuity in association with Taussig–Bing syndrome, which has rarely been reported in the literature thus far.Case presentationA pregnant woman with a fetus with congenital heart disease (CHD) at 23 weeks gestation was referred to our center. She denied any familial history of genetic disorders in either spouse, and non-invasive prenatal testing (NIPT) also showed a low risk of CHD for the fetus. An ultrasound examination revealed a complex cardiac malformation indicative of left pulmonary artery discontinuity originating from the ductus arteriosus with Taussig–Bing syndrome. The family eventually chose to terminate the pregnancy and agreed to an autopsy, which confirmed that the prenatal echocardiographic diagnosis was correct. In addition, in this report, we review and analyze 17 reported cases of prenatal echocardiographic diagnoses of UPAD.ConclusionsUPAD is characterized by discontinuity between the proximal and distal pulmonary arteries, along with a ductal origin of the distal pulmonary artery. A discontinuous pulmonary artery originating from the ductus can be detected on prenatal sonography using ultrasound technology. The aim is to detect malformations earlier and carry out the necessary intervention measures as soon as possible.

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.

Many 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.

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.

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 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 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.

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.