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Abstract The complexity of tumors and the challenges associated with treatment often stem from the limitations of existing models in accurately replicating authentic tumors. Recently, organoid technology has emerged as an innovative platform for tumor research. This bioengineering approach enables researchers to simulate, in vitro, the interactions between tumors and their microenvironment, thereby enhancing the intricate interplay between tumor cells and their surroundings. Organoids also integrate multidimensional data, providing a novel paradigm for understanding tumor development and progression while facilitating precision therapy. Furthermore, advancements in imaging and genetic editing techniques have significantly augmented the potential of organoids in tumor research. This review explores the application of organoid technology for more precise tumor simulations and its specific contributions to cancer research advancements. Additionally, we discuss the challenges and evolving trends in developing comprehensive tumor models utilizing organoid technology.

Abstract To elucidate the mechanisms underlying photoperiodic responses, we investigated the genomic and metabolomic responses of two broomcorn millet (Panicum miliaceum L.) genotypes. For this purpose, light-insensitive (D32) and light-sensitive (M51) genotypes were exposed to a 16 h photoperiod (long-day (LD) conditions) and an 8 h photoperiod (short-day (SD) conditions), and various transcriptomic and metabolomic changes were investigated. A total of 1664, 2564, 13,017, and 15548 DEGs were identified in the SD-D, LD-D, LD-M, and SD-M groups, respectively. Furthermore, 112 common DEGs were identified as well. Interestingly, most DEGs in the different groups were associated with photosynthesis and phenylpropanoid and carotenoid biosynthesis. In addition, 822 metabolites were identified under different treatments. The main metabolites, including L-malic and fumaric acids, were identified in the negative mode, whereas brucine and loperamide were identified in the positive mode. KEGG analysis revealed that the metabolites in the different groups were enriched in the same metabolic pathway of the TCA cycle. Furthermore, in negative mode, the metabolites of M51 were mainly D-glucose, whereas those of D32 were mainly L-malic and fumaric acids. One photoperiod candidate gene (C2845_PM11G01290), annotated as ATP6B, significantly increased the levels of L-malic and fumaric acids. In conclusion, our study provides a theoretical basis for understanding the molecular mechanisms of photoperiodic response regulation and can be used as a reference for marker development and resource identification in Panicum miliaceum L..

Abstract Malignant tumors remain a primary cause of human mortality. Among the various treatment modalities for neoplasms, tumor vaccines have consistently shown efficacy and promising potential. These vaccines offer advantages such as specificity, safety, and tolerability, with mRNA vaccines representing promising platforms. By introducing exogenous mRNAs encoding antigens into somatic cells and subsequently synthesizing antigens through gene expression systems, mRNA vaccines can effectively induce immune responses. Katalin Karikó and Drew Weissman were awarded the 2023 Nobel Prize in Physiology or Medicine for their great contributions to mRNA vaccine research. Compared with traditional tumor vaccines, mRNA vaccines have several advantages, including rapid preparation, reduced contamination, nonintegrability, and high biodegradability. Tumor-targeted therapy is an innovative treatment modality that enables precise targeting of tumor cells, minimizes damage to normal tissues, is safe at high doses, and demonstrates great efficacy. Currently, targeted therapy has become an important treatment option for malignant tumors. The application of mRNA vaccines in tumor-targeted therapy is expanding, with numerous clinical trials underway. We systematically outline the targeted delivery mechanism of mRNA vaccines and the mechanism by which mRNA vaccines induce anti-tumor immune responses, describe the current research and clinical applications of mRNA vaccines in tumor-targeted therapy, and forecast the future development trends of mRNA vaccine application in tumor-targeted therapy.

The advent of cancer immunotherapy has imparted a transformative impact on cancer treatment paradigms by harnessing the power of the immune system. However, the challenge of practical and precise targeting of malignant cells persists. To address this, engineered nanoparticles (NPs) have emerged as a promising solution for enhancing targeted drug delivery in immunotherapeutic interventions, owing to their small size, low immunogenicity, and ease of surface modification. This comprehensive review delves into contemporary research at the nexus of NP engineering and immunotherapy, encompassing an extensive spectrum of NP morphologies and strategies tailored toward optimizing tumor targeting and augmenting therapeutic effectiveness. Moreover, it underscores the mechanisms that NPs leverage to bypass the numerous obstacles encountered in immunotherapeutic regimens and probes into the combined potential of NPs when co-administered with both established and novel immunotherapeutic modalities. Finally, the review evaluates the existing limitations of NPs as drug delivery platforms in immunotherapy, which could shape the path for future advancements in this promising field.

Abstract Antimicrobial proteins contribute to host-microbiota interactions and are associated with inflammatory bowel disease (IBD), but our understanding on antimicrobial protein diversity and functions remains incomplete. Ribonuclease 4 (Rnase4) is a potential antimicrobial protein with no known function in the intestines. Here we find that RNASE4 is expressed in intestinal epithelial cells (IEC) including Paneth and goblet cells, and is detectable in human and mouse stool. Results from Rnase4-deficient mice and recombinant protein suggest that Rnase4 kills Parasutterella to modulate intestinal microbiome, thereby enhancing indoleamine-2,3-dioxygenase 1 (IDO1) expression and subsequently kynurenic and xanthurenic acid production in IECs to reduce colitis susceptibility. Furthermore, deceased RNASE4 levels are observed in the intestinal tissues and stool from patients with IBD, correlating with increased stool Parasutterella. Our results thus implicate Rnase4 as an intestinal antimicrobial protein regulating gut microbiota and metabolite homeostasis, and as a potential diagnostic biomarker and therapeutic target for IBD.

This paper summarizes the application, review, and award of research funding in the Mining and Metallurgical Engineering discipline in the topics of petroleum engineering, mining engineering, safety science and engineering, and metallurgy and material processing engineering by the Department of Engineering and Materials Science of the National Natural Science Foundation of China in 2023. Additionally, this paper introduces the future development strategies in this discipline and proposes the next steps for continuous improvements.

Abstract Artificial micro/nanomotors using active particles hold vast potential in applications such as drug delivery and microfabrication. However, upgrading them to micro/nanorobots capable of performing precise tasks with sophisticated functions remains challenging. Bubble microthruster (BMT) is introduced, a variation of the bubble‐driven microrobot, which focuses the energy from a collapsing microbubble to create an inertial impact on nearby target microparticles. Utilizing ultra‐high‐speed imaging, the microparticle mass and density is determined with sub‐nanogram resolution based on the relaxation time characterizing the microparticle's transient response. Master curves of the BMT method are shown to be dependent on the viscosity of the solution. The BMT, controlled by a gamepad with magnetic‐field guidance, precisely manipulates target microparticles, including bioparticles. Validation involves measuring the polystyrene microparticle mass and hollow glass microsphere density, and assessing the mouse embryo mass densities. The BMT technique presents a promising chip‐free, real‐time, highly maneuverable strategy that integrates bubble microrobot‐based manipulation with precise bioparticle mass and density detection, which can facilitate microscale bioparticle characterizations such as embryo growth monitoring.

Carbon materials/MXenes composite materials have gained widespread attention in the field of supercapacitors due to their excellent electrochemical performance. Carbon materials are considered ideal electrode materials for supercapacitors due to their high specific surface area, good conductivity, and outstanding electrochemical stability. MXenes, as a novel two-dimensional material, exhibit prominent conductivity, mechanical properties, and ionic conductivity, thereby showing great potential for applications in energy storage devices. The combination of carbon materials and MXenes is expected to fully leverage the advantages of both, optimizing electrode conductivity, enhancing the energy density and power density, and improving the charge–discharge performance. This article reviews the key research progress of carbon/MXenes composite materials in supercapacitors in recent years, including their synthesis methods, structural tuning, and improvements in their electrochemical performance. Finally, the article looks forward to future research directions and proposes potential strategies to enhance the overall performance of the composite materials and achieve large-scale applications. By addressing the existing challenges, carbon/MXenes composite materials are anticipated to achieve higher energy and power outputs for the supercapacitor field in the future, providing strong support for the development of new energy storage technologies such as electric vehicles and wearable devices.

BackgroundIn recent years, the incidence of abdominal obesity among the middle-aged and older adult population in China has significantly increased. However, the gender disparities in the spatial distribution of abdominal obesity incidence and its relationship with meteorological factors among this demographic in China remain unclear. This gap in knowledge highlights the need for further research to understand these dynamics and inform targeted public health strategies.MethodsThis study utilized data from the 2015 China Health and Retirement Longitudinal Study (CHARLS) to analyze the incidence of abdominal obesity among the middle-aged and older adult population in China. Additionally, meteorological data were collected from the National Meteorological Information Center. Using Moran’s I index and Getis-Ord Gi* statistical methods, the spatial distribution characteristics of abdominal obesity incidence were examined. The influence of various meteorological factors on the incidence of abdominal obesity in middle-aged and older adult males and females was investigated using the q statistic from the Geodetector method. Furthermore, Multi-Scale Geographically Weighted Regression (MGWR) analysis was employed to explore the impact of meteorological factors on the spatial heterogeneity of abdominal obesity incidence from a gender perspective.ResultsThe spatial distribution of abdominal obesity among middle-aged and older adult individuals in China exhibits a decreasing trend from northwest to southeast, with notable spatial autocorrelation. Hotspots are concentrated in North and Northeast China, while cold spots are observed in Southwest China. Gender differences have minimal impact on spatial clustering characteristics. Meteorological factors, including temperature, sunlight, precipitation, wind speed, humidity, and atmospheric pressure, influence incidence rates. Notably, temperature and sunlight exert a greater impact on females, while wind speed has a reduced effect. Interactions among various meteorological factors generally demonstrate bivariate enhancement without significant gender disparities. However, gender disparities are evident in the influence of specific meteorological variables such as annual maximum, average, and minimum temperatures, as well as sunlight duration and precipitation, on the spatial heterogeneity of abdominal obesity incidence.ConclusionMeteorological factors show a significant association with abdominal obesity prevalence in middle-aged and older adults, with temperature factors playing a prominent role. However, this relationship is influenced by gender differences and spatial heterogeneity. These findings suggest that effective public health policies should be not only gender-sensitive but also locally adapted.

Abstract After undergoing metabolic reprogramming, tumor cells consume additional glutamine to produce amino acids, nucleotides, fatty acids, and other substances to facilitate their unlimited proliferation. As such, the metabolism of glutamine is intricately linked to the survival and progression of cancer cells. Consequently, targeting the glutamine metabolism presents a promising strategy to inhibit growth of tumor cell and cancer development. This review describes glutamine uptake, metabolism, and transport in tumor cells and its pivotal role in biosynthesis of amino acids, fatty acids, nucleotides, and more. Furthermore, we have also summarized the impact of oncogenes like C-MYC, KRAS, HIF, and p53 on the regulation of glutamine metabolism and the mechanisms through which glutamine triggers mTORC1 activation. In addition, role of different anti-cancer agents in targeting glutamine metabolism has been described and their prospective applications are assessed.

The digital economy now drives China’s new economic growth. However, with various industries’ digital transformation (DT), the consequent environmental pollution problems must be addressed. To achieve a better balance between economic growth and environmental protection, digitalization and carbon dioxide (CO2) emissions reduction targets should be achieved. In promoting the DT of manufacturing, it is essential to consider the industry’s CO2 emissions and the CO2 emission spillover effects (CO2SE). This paper first constructs a model of CO2SE generated and suffered in the DT of industries using input–output techniques, i.e., the perpetrator and victim effects, and measures these effects. Then, the cross-sectional inter-industry differences and vertical time-series characteristics are analyzed based on the measurement results. Finally, the convergence test of CO2 emission spillover effects in the digital transformation (CO2SE-DT) of China’s manufacturing industry is conducted, and the test results are analyzed. The research results show that (1) digital infrastructure-dependent and technology-intensive manufacturing have the largest CO2SE-DT, followed by capital-intensive and labor-intensive manufacturing in that order. (2) The whole victim effect in the DT of China’s manufacturing industry shows an “N” trend. In addition, according to the time-series changes of the perpetrator effect in the DT of China’s manufacturing industry between 2000 and 2014, China’s manufacturing industry can be classified into three types: stable, fluctuating downward, and fluctuating upward, among which the fluctuating upward type is the key industry of concern for CO2 emissions. (3) There is no gradual decrease in the industry differences in CO2SE-DT of China’s manufacturing industry, but manufacturing industries with low CO2SE-DT levels have faster growth rates compared with high-level manufacturing industries and eventually achieve convergence of CO2SE-DT rate of change. However, there is a significant difference in the results of the industry difference analysis for different types of manufacturing industries.

Through the use of recycled aggregates, the construction industry can mitigate its environmental impact. A key consideration for concrete structural engineers when designing and constructing concrete structures is compressive strength. This study aims to accurately forecast the compressive strength of recycled aggregate concrete (RAC) using machine learning techniques. We propose a simplified approach that incorporates a two-layer stacked ensemble learning model to predict RAC compressive strength. In this framework, the first layer consists of ensemble models acting as base learners, while the second layer utilizes a random forest (RF) model as the meta-learner. A comparative analysis with four other ensemble learning models demonstrates the superior performance of the proposed stacked model in effectively integrating predictions from the base learners, resulting in enhanced model accuracy. The model achieves a low mean absolute error (MAE) of 2.599 MPa, a root mean squared error (RMSE) of 3.645 MPa, and a high R-squared (R2) value of 0.964. Additionally, a Shapley (SHAP) additive explanation analysis reveals the influence and interrelationships of various input factors on the compressive strength of RAC, aiding design and construction professionals in optimizing raw material content during the RAC design and production process.

Unmanned aerial vehicles (UAVs) provide efficient and flexible means for maritime emergency rescue, with path planning being a critical technology in this context. Most existing unmanned device research focuses on land-based path planning in two-dimensional planes, which fails to fully leverage the aerial advantages of UAVs and does not accurately describe offshore environments. Therefore, this paper establishes a three-dimensional offshore environmental model. The UAV’s path in this environment is achieved through a novel swarm intelligence algorithm, which is based on the coati optimization algorithm (COA). New strategies are introduced to address potential issues within the COA, thereby solving the problem of UAV path planning in complex offshore environments. The proposed OCLCOA introduces a dynamic opposition-based search to address the population separation problem in the COA and incorporates a covariance search strategy to enhance its exploitation capabilities. To simulate the actual environment as closely as possible, the environmental model established in this paper considers three environmental factors: offshore flight-restricted area, island terrain, and sea winds. A corresponding cost function is designed to evaluate the path length and path deflection and quantify the impact of these three environmental factors on the UAV. Experimental results verify that the proposed algorithm effectively solves the UAV path planning problem in offshore environments.

Abstract Cell adhesion molecule (CAM) is an umbrella term for several families of molecules, including the cadherin family, integrin family, selectin family, immunoglobulin superfamily, and some currently unclassified adhesion molecules. Extracellular vesicles (EVs) are important information mediators in cell-to-cell communication. Recent evidence has confirmed that CAMs transported by EVs interact with recipient cells to influence EV distribution in vivo and regulate multiple cellular processes. This review focuses on the loading of CAMs onto EVs, the roles of CAMs in regulating EV distribution, and the known and possible mechanisms of these actions. Moreover, herein, we summarize the impacts of CAMs transported by EVs to the tumour microenvironment (TME) on the malignant behaviour of tumour cells (proliferation, metastasis, immune escape, and so on). In addition, from the standpoint of clinical applications, the significance and challenges of using of EV-CAMs in the diagnosis and therapy of tumours are discussed. Finally, considering recent advances in the understanding of EV-CAMs, we outline significant challenges in this field that require urgent attention to advance research and promote the clinical applications of EV-CAMs. Video Abstract

Livestock presence impacts plant biodiversity (species richness) in grassland ecosystems, yet extent and direction of grazing impacts on biodiversity vary greatly across inter-annual periods. In this study, an 8-year (2014-2021) grazing gradient experiment with sheep was conducted in a semi-arid grassland to investigate the impact of grazing under different precipitation variability on biodiversity. The results suggest no direct impact of grazing on species richness in semi-arid Stipa grassland. However, increased grazing indirectly enhanced species richness by elevating community dominance (increasing the sheltering effect of Stipa grass). Importantly, intensified grazing also regulates excessive community biomass resulting from increased inter-annual wetness (SPEI), amplifying the positive influence of annual humidity index on species richness. Lastly, we emphasize that, in water-constrained grassland ecosystems, intra-annual precipitation variability (PCI) was the most crucial factor driving species richness. Therefore, the water-heat synchrony during the growing season may alleviate physiological constraints on plants, significantly enhancing species richness as a result of multifactorial interactions. Our study provides strong evidence for how to regulate grazing intensity to increase biodiversity under future variable climate patterns. We suggest adapting grazing intensity according to local climate variability to achieve grassland biodiversity conservation.

Abstract Cancer stem cells(CSCs) play a key role in regulating tumorigenesis, progression, as well as recurrence, and possess typical metabolic characteristics. Autophagy is a catabolic process that can aid cells to survive under stressful conditions such as nutrient deficiency and hypoxia. Although the role of autophagy in cancer cells has been extensively studied, CSCs possess unique stemness, and their potential relationship with autophagy has not been fully analyzed. This study summarizes the possible role of autophagy in the renewal, proliferation, differentiation, survival, metastasis, invasion, and treatment resistance of CSCs. It has been found that autophagy can contribute to the maintenance of CSC stemness, facilitate the tumor cells adapt to changes in the microenvironment, and promote tumor survival, whereas in some other cases autophagy acts as an important process involved in the deprivation of CSC stemness thus leading to tumor death. Mitophagy, which has emerged as another popular research area in recent years, has a great scope when explored together with stem cells. In this study, we have aimed to elaborate on the mechanism of action of autophagy in regulating the functions of CSCs to provide deeper insights for future cancer treatment.

Objectives: Dog-mediated human rabies remains an important public health problem in China. In this study, we aimed to understand the spatiotemporal variation of rabies and examine its nonmedical ecological factors. Methods: In this study, we used the annual incidence data for rabies at the province level in China to describe the incidence trends for the period 2004-2019 and used a Bayesian hierarchical spatiotemporal model to determine the impacts of environmental, economic, and demographic factors. Results: From 2004 to 2019, there were 26,593 cases reported in 31 provinces in Mainland China, and the annual incidence increased from 0.02 per 100,000 in 2004 to 0.14 in 2007, substantially decreased in 2008, and was gradually declining thereafter. Guizhou, Guangxi, Hunan, and Hainan were four high-risk provinces, and Yunnan and Anhui provinces showed an increased risk in 2018 and 2019. Temperature and per capita gross domestic product were significantly positively correlated with the disease risk. The standardized morbidity ratio of rabies is likely to increase by 28% (relative risk: 1.28, 95% credible interval: 1.13-1.36) for every 1°C rise in temperature, and 17% (relative risk: 1.17, 95% credible interval: 1.01-1.34) for every 10,000 yuan increase in per capita gross domestic product. Conclusion: In most provinces in China, the risk of rabies has been reduced to a persistently low level. However, the progress of rabies control in six provinces have been less than satisfactory. The study highlights interventions, such as enhancing animal vaccination need to be implemented in these priority areas.

Maritime UAV path planning is a key link in realizing the intelligence of maritime emergency transportation, providing key support for fast and flexible maritime accident disposal and emergency material supply. However, most of the current UAV path planning methods are designed for land environments and lack the ability to cope with complex marine environments. In order to achieve effective path planning for UAV in marine environments, this paper proposes a Directional Drive-Rotation Invariant Quadratic Interpolation White Shark Optimization algorithm (DD-RQIWSO). First, the directional guidance of speed is realized through a directional update strategy based on the fitness value ordering, which improves the speed of individuals approaching the optimal solution. Second, a rotation-invariant update mechanism based on hyperspheres is added to overcome the tracking pause phenomenon in WSO. In addition, the quadratic interpolation strategy is added to enhance the utilization of local information by the algorithm. Then, a wind simulation environment based on the Lamb–Oseen vortex model was constructed to better simulate the real scenario. Finally, DD-RQIWSO was subjected to a series of tests in 2D and 3D scenarios, respectively. The results show that DD-RQIWSO is able to realize path planning under wind environments more accurately and stably.

Background: Selenium (Se) has been reported to have an antagonistic effect on heavy metals in animals. Nevertheless, there is a lack of epidemiological research examining whether Se can mitigate the adverse effects of cadmium (Cd) and lead (Pb) on hand grip strength (HGS) in middle-aged and elderly individuals.Methods: This study used data from the 2011–2014 National Health and Nutrition Examination Survey (NHANES). HGS measurements were conducted by trained examiners with a dynamometer. Concentrations of Se, Cd, and Pb in blood were determined via inductively coupled plasma mass spectrometry. We employed linear regression, restricted cubic splines, and quantile g-computation (qgcomp) to assess individual and combined associations between heavy metals and HGS. The study also explored the potential influence of Se on these associations.Results: In both individual metal and multi-metal models adjusted for confounders, general linear regression showed Se’s positive association with HGS, while Cd and Pb inversely related to it. At varying Se-Cd and Se-Pb concentrations, high Se relative to low Se can attenuate Cd and Pb’s HGS impact. An inverted U-shaped correlation exists between Se and both maximum and combined HGS, with Se’s benefit plateauing beyond approximately 200 μg/L. Stratified analysis by Se quartiles reveals Cd and Pb’s adverse HGS effects diminishing as Se levels increase. Qgcomp regression analysis detected Se alleviating HGS damage from combined Cd and Pb exposure. Subsequent subgroup analyses identified the sensitivity of women, the elderly, and those at risk of diabetes to HGS impairment caused by heavy metals, with moderate Se supplementation beneficial in mitigating this effect. In the population at risk for diabetes, the protective role of Se against heavy metal toxicity-induced HGS reduction is inhibited, suggesting that diabetic individuals should particularly avoid heavy metal-induced handgrip impairment.Conclusion: Blood Cd and Pb levels are negatively correlated with HGS. Se can mitigate this negative impact, but its effectiveness plateaus beyond 200 μg/L. Women, the elderly, and those at risk of diabetes are more vulnerable to HGS damage from heavy metals. While Se supplementation can help, its protective effect is limited in high diabetes risk groups.

BackgroundHypertension has now developed into a major public health problem worldwide. Under the existing antihypertensive drug treatment paradigm, problems such as decreasing drug resistance and increasing drug side effects can occur for elderly patients. Acupuncture, a core technique in the non-pharmacological treatment of Chinese medicine, plays an important role in the treatment of elevated blood pressure.ObjectiveThis study aimed to systematically evaluate the effect of acupuncture alone or in combination with antihypertensive drugs on the efficiency of reducing blood pressure and controlling blood pressure in elderly patients with hypertension.MethodsArticles of randomized controlled trials of acupuncture for hypertension in the elderly published before November 2022 were searched in 7 databases. The methodological quality of the literature was evaluated using the Cochrane Risk of Bias Assessment Tool. The primary outcome was the efficiency rate of blood pressure reduction, and the secondary outcome was the change in blood pressure after treatment.ResultsThis study conducted a systematic review and meta-analysis of 12 randomized controlled trials with a total of 1,466 subjects. Among the primary outcome—efficiency rate, acupuncture-only treatment (RR = 1.11, 95% CI: 1.03–1.20, P

Abstract Hepatocellular carcinoma (HCC), one of the most malignant tumors, is characterized by its stubborn immunosuppressive microenvironment. As one of the main members of the tumor microenvironment (TME) of HCC, tumor-associated macrophages (TAMs) play a critical role in its occurrence and development, including stimulating angiogenesis, enhancing immunosuppression, and promoting the drug resistance and cancer metastasis. This review describes the origin as well as phenotypic heterogeneity of TAMs and their potential effects on the occurrence and development of HCC and also discusses about various adjuvant therapy based strategies that can be used for targeting TAMs. In addition, we have highlighted different treatment modalities for TAMs based on immunotherapy, including small molecular inhibitors, immune checkpoint inhibitors, antibodies, tumor vaccines, adoptive cellular immunotherapy, and nanocarriers for drug delivery, to explore novel combination therapies and provide feasible therapeutic options for clinically improving the prognosis and quality of life of HCC patients.

To investigate the effects of marketing days and genders on the bearded chicken’s quality, in this study, bearded chickens (roosters, 80, 90, 100, and 110 days of age; hens, 100, 120, 140, and 160 days of age) were slaughtered, and their slaughter performance, chicken skin microstructure, muscles color, breast muscle pH45 min, myofiber characteristics and water retention capacities were evaluated. The results showed the live weight, feathers weight, and blood weight of the bearded chicken from the same gender groups increased along with the increase of age (P0.05) for chickens which had not reached sexual maturity (roosters of 80~90 d and hens of 100~120 d), and significant differences (P

Abstract Fabricating engineered vasculature within biological scaffolds is one of the most common strategies to maintain high cell viability before implantation. Many studies have been conducted from the aspects of the manufacturing process, materials science, and cell biology to fabricate engineered vasculature with the aim of enhancing the integration between scaffold and host. Among them, the method of combining three‐dimensional (3D) printing and sacrifice‐based technique has attracted extensive attention. Taking advantage of 3D printing, the method of separating the printed sacrificial template from the biological scaffold to form a 3D channel has become a widely used approach to advance the engineered vasculature. With the development of 3D printing techniques and material science, numerous sacrificial materials have shown their potential in fabricating engineered vasculature. However, several issues remain in this multimethod design, including, but not limited to, the printing process, removal method of sacrificial material, and cell seeding method. This review aims to summarize recent strategies for 3D printing sacrificial templates for fabricating engineered vasculature. The pros and cons of sacrificial materials used in these studies are analyzed. Future perspectives are proposed to fabricate biomimetic‐engineered vasculature. Flexible fabrication processes and materials should be advanced to support the 3D printing of sacrificial templates.

Abstract Mesenchymal/stromal stem cells (MSCs) are a crucial component of the tumour microenvironment (TME). They can be recruited from normal tissues into the TME and educated by tumour cells to transform into tumour-associated MSCs, which are oncogenic cells that promote tumour development and progression by impacting or transforming into various kinds of cells, such as immune cells and endothelial cells. Targeting MSCs in the TME is a novel strategy to prevent malignant processes. Exosomes, as communicators, carry various RNAs and proteins and thus link MSCs and the TME, which provides options for improving outcomes and developing targeted treatment.

The hydrophilic polysaccharides (PS) were isolated and purified from the tuberous roots of Pseudostellaria heterophylla. The extraction process of PS from Pesudostellariae radix was optimized by single–factor experiments and orthogonal design. The extract was purified by DEAE cellulose column to obtain the pure polysaccharide PHP. Then PHP was treated with different intensities of sonication to study the effect of sonication on PHP’s characteristics and its biological activity in vitro and in vivo. The results of this study revealed that ultrasound treatment did not significantly change the properties of PHP. Further, with the increase of ultrasound intensity, PHP enhanced the proliferation and phagocytosis of macrophage RAW264.7. Meanwhile, it could also significantly improve the body’s antioxidant activity and immune function. The results of this study demonstrated that PHP has the potential as a food additive with enhanced antioxidant and immune functions, and its biological activities could be enhanced by sonication.

Abstract A high intratumoral nerve density is correlated with poor survival, high metastasis, and high recurrence across multiple solid tumor types. Recent research has revealed that cancer cells release diverse neurotrophic factors and exosomes to promote tumor innervation, in addition, infiltrating nerves can also mediate multiple tumor biological processes via exosomes and neurotransmitters. In this review, through seminal studies establishing tumor innervation, we discuss the communication between peripheral nerves and tumor cells in the tumor microenvironment (TME), and revealed the nerve-tumor regulation mechanisms on oncogenic process, angiogenesis, lymphangiogenesis, and immunity. Finally, we discussed the promising directions of ‘old drugs newly used’ to target TME communication and clarified a new line to prevent tumor malignant capacity.

To clarify the effect of copper powder morphology on the microstructure and properties of copper matrix bulk composites reinforced with Ni-doped graphene, spherical and dendritic copper powders were selected to fabricate the Ni-doped graphene reinforced copper matrix bulk composites. The Ni-doped graphene were synthesized by hydrothermal reduction method, followed by mixing with copper powders, and then consolidated by spark plasma sintering. It is found that the Ni-doped graphene are well bonded with the dendritic copper powder, whereas Ni-doped graphene are relatively independent on the spherical copper powder. The copper base bulk composite prepared by the dendritic copper powder has better properties than that prepared by spherical copper powder. At 0.5wt.% Ni-doped graphene, the dendritic copper base bulk composite has a good combination of hardness, electrical conductivity and yield strength, which are 81.62 HV, 87.93% IACS and 164 MPa, respectively.

Abstract Autophagy is a conserved method of quality control in which cytoplasmic contents are degraded via lysosomes. Lipophagy, a form of selective autophagy and a novel type of lipid metabolism, has recently received much attention. Lipophagy is defined as the autophagic degradation of intracellular lipid droplets (LDs). Although much remains unknown, lipophagy appears to play a significant role in many organisms, cell types, metabolic states, and diseases. It participates in the regulation of intracellular lipid storage, intracellular free lipid levels (e.g., fatty acids), and energy balance. However, it remains unclear how intracellular lipids regulate autophagy. Impaired lipophagy can cause cells to become sensitive to death stimuli and may be responsible for the onset of a variety of diseases, including nonalcoholic fatty liver disease and metabolic syndrome. Like autophagy, the role of lipophagy in cancer is poorly understood, although analysis of specific autophagy receptors has helped to expand the diversity of chemotherapeutic targets. These studies have stimulated increasing interest in the role of lipophagy in the pathogenesis and treatment of cancer and other human diseases.

BackgroundAs a common clinical symptom, insomnia has a high incidence of combined mental illness and it is also a risk factor for the development of depression, anxiety and suicide. As a new concept in the field of health in recent years, mindfulness therapy can improve insomnia, anxiety and depression, which is a new way to solve such diseases.ObjectiveThis study aims to systematically evaluate the effects of mindfulness compared with conventional treatment on scores of the Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) in people with insomnia and anxiety-depressive symptoms.MethodsArticles published before October 2022 were searched from seven databases and included in randomized controlled trials (RCTs) to evaluate mindfulness therapy. The assessment tool of Cochrane bias risk was used to evaluate the methodological quality of the literature. The main outcome indicators were HAMD and HAMA scores, and the secondary outcome indicators were SDS and SAS scores.ResultsTen randomized controlled trials including 1,058 subjects were systematically evaluated and meta-analyzed in this study. In the main outcome indicators, there was a significant difference between mindfulness therapy and conventional treatment in reducing HAMD score (MD: −3.67, 95% CI: −5.22–2.11, p

The complex curved boundary of the topology optimization model is not conducive to industrial manufacturing hence the necessity to reconstruct the geometrical model. This study presents a general method for the boundary regularization fitting reconstruction of a topological optimization model based on the Freeman code. This method is performed as follows: the unit vector is defined; the vectorized expression of the Freeman code boundary is established; through the concept of the boundary bending parameter, determination of the bending degree of the Freeman code boundary is established; an elemental structure analysis method is proposed, and the logic of the automatic extraction of the control points of the Freeman code boundary fitting is achieved. This method proposes a series of innovative technical methods, such as unit vector definition, boundary bending matrix, and elemental structure analysis method, and designs a complete set of structural analysis logic for a Freeman code type boundary, which can automatically analyze the structure feature of the 8-connected Freeman code boundary, extract the fitting control points on the boundary, and complete the automatic fitting and reconstruction of the boundary. This method is robust and applicable to all Freeman code boundaries. The entire process is automated.

In order to obtain high specific power, high specific capacity and highly reliable power supply, a combined power supply system is often used. As one of the main loads to the combined power supply system, the servo system can adjust the trajectory and attitude of the aerospace vehicles in real-time. However, a sudden change of the load to the servo system can have adverse effects on the DC bus voltage output, which will reduce the performance of the electrical equipment on the aerospace vehicles. Firstly, this paper theoretically deduces and analyzes the influence of servo loading conditions on the DC bus voltage of aerospace combined power supply. Secondly, in the field of aerospace combined power system, the mechanism of regulating DC bus voltage by combining bidirectional DC-DC converter and ultracapacitor is proposed, and its effectiveness and enforceability are verified by simulation and experiment. Finally, aiming at the strong nonlinear and time-varying characteristics of bidirectional DC-DC converter, a fuzzy predictive control algorithm which can effectively adjust the DC bus voltage is proposed, and a good regulation control effect is achieved.

Abstract Hypoxia is a remarkable trait of the tumor microenvironment (TME). When facing selective pressure, tumor cells show various adaptive characteristics, such as changes in the expression of cancer hallmarks (increased proliferation, suppressed apoptosis, immune evasion, and so on) and more frequent cell communication. Because of the adaptation of cancer cells to hypoxia, exploring the association between cell communication mediators and hypoxia has become increasingly important. Exosomes are important information carriers in cell-to-cell communication. Abundant evidence has proven that hypoxia effects in the TME are mediated by exosomes, with the occasional formation of feedback loops. In this review, we equally focus on the biogenesis and heterogeneity of cancer-derived exosomes and their functions under hypoxia and describe the known and potential mechanism ascribed to exosomes and hypoxia. Notably, we call attention to the size change of hypoxic cancer cell-derived exosomes, a characteristic long neglected, and propose some possible effects of this size change. Finally, jointly considering recent developments in the understanding of exosomes and tumors, we describe noteworthy problems in this field that urgently need to be solved for better research and clinical application.

Abstract Programmed cell death 1 ligand 1 (PD-L1) is the ligand for programmed death protein-1 (PD-1), is associated with immunosuppression. Signaling via PD-1/PD-L1 will transmits negative regulatory signals to T cells, inducing T-cell inhibition, reducing CD8+ T-cell proliferation, or promoting T-cell apoptosis, which effectively reduces the immune response and leads to large-scale tumor growth. Accordingly, many antibody preparations targeting PD-1 or PD-L1 have been designed to block the binding of these two proteins and restore T-cell proliferation and cytotoxicity of T cells. However, these drugs are ineffective in clinical practice. Recently, numerous of studies have shown that, in addition to the surface of tumor cells, PD-L1 is also found on the surface of extracellular vesicles secreted by these cells. Extracellular vesicle PD-L1 can also interact with PD-1 on the surface of T cells, leading to immunosuppression, and has been proposed as a potential mechanism underlying PD-1/PD-L1-targeted drug resistance. Therefore, it is important to explore the production, regulation and tumor immunosuppression of PD-L1 on the surface of tumor cells and extracellular vesicles, as well as the potential clinical application of extracellular vesicle PD-L1 as tumor biomarkers and therapeutic targets. Video Abstract

IntroductionThe erythrocyte membranes used in nanovaccines include high membrane stability, long circulation life, adaptability and extremely good bio compatibility. Nanoparticles encapsulated by erythrocyte membranes are widely used as ideal drug delivery vehicles because of their high drug loading, long circulation time, and excellent biocompatibility. The mannose modification of delivery materials can help target mannose receptors (MRs) to deliver antigens to antigen-presenting cells (APCs).MethodsIn this study, the antigen gene gp90 of avian reticuloendotheliosis virus (REV) was encapsulated with carboxymethyl chitosan (CS) to obtain CSgp90 nanoparticles, which were coated with mannose-modied fowl erythrocyte membranes to yield CS-gp90@M-M nanoparticles. The physicochemical characterization and immune response of the CS-gp90@M-M nanoparticles were investigated in vitro and in vivo.ResultsCS-gp90@M-M nanoparticles were rapidly phagocytized in vitro by macrophages to induce the production of cytokines and nitric oxide. In vivo, CS-gp90@M-M nanoparticles increased cytokine levels, the CD4+/8+ ratio, REV-specific antibodies in the peripheral blood of chicks, and the mRNA levels of immune-related genes in the spleen and bursa of immunized chicks. CS-gp90@M-M nanoparticles could be targeted to lymphoid organs to prolong the retention time of the nanoparticles at the injection site and lymphatic organs, leading to a strong, sustained immune response. Moreover, the CS-gp90@M-M nano-vaccine showed a lasting immunoprotective effect and improved the body weight of chicks after the challenge.ConclusionOverall, CS-gp90@M-M nanoparticles can be used in vaccine designs as an effective delivery carrier with immune response-enhancing effects.

Abstract Background Tumor cells are known to release large numbers of exosomes containing active substances that participate in cancer progression. Abnormally expressed long noncoding RNAs (lncRNAs) have been confirmed to regulate multiple processes associated with tumor progression. However, the mechanism by which lncRNAs affect exosome secretion remains unclear. Methods The underlying mechanisms of long noncoding RNA LINC00511 (LINC00511) regulation of multivesicular body (MVB) trafficking, exosome secretion, invadopodia formation, and tumor invasion were determined through gene set enrichment analysis (GSEA), immunoblotting, nanoparticle tracking analysis, confocal colocalization analysis, electron microscopy, and invasion experiments. Results We revealed that the tumorigenesis process is associated with a significant increase in vesicle secretion in hepatocellular carcinoma (HCC). Additionally, LINC00511 was significantly more highly expressed in HCC tissues and is related to vesicle trafficking and MVB distribution. We also found that in addition to the formation of invadopodia in HCC progression, abnormal LINC00511 induces invadopodia formation in HCC cells by regulating the colocalization of vesicle associated membrane protein 7 (VAMP7) and synaptosome associated protein 23 (SNAP23) to induce the invadopodia formation, which are key secretion sites for MVBs and control exosome secretion. Finally, we revealed that LINC0051-induced invadopodia and exosome secretion were involved in tumor progression. Conclusions Our experiments revealed novel findings on the relationship between LINC00511 dysregulation in HCC and invadopodia production and exosome secretion. This is a novel mechanism by which LINC00511 regulates invadopodia biogenesis and exosome secretion to further promote cancer progression.

Environmental change is a crucial driver shaping grassland biodiversity and stability. Both environmental change and stability contain multiple dimensions. Nonetheless, few studies examined multiple dimensions of stability in response to environmental change, especially under the combined effects of climatic variability and grazing intensity. Here, we conducted a 7-year field sheep grazing experiment, and we evaluated the impacts of grazing intensity (GI) and climate variability (temperature and precipitation variability) on plant community diversity and productivity and multi-dimensional stability using linear and structural equation models. Our results show that increasing grazing intensity significantly decreased temporal stability but did not affect resistance stability. Compared with the non-grazing (NG) treatment, grazing reduced temporal stability by 35.78%. The decline is primarily attributed to the grazing-induced reduction in evenness and weakening of species asynchrony, which in turn impairs insurance effects. The insignificant change in resistance stability was attributed to a trade-off between reduced interspecific competition and direct negative effects. Furthermore, temperature variability and precipitation variability exacerbate and mitigate the effects of grazing on temporal stability (negative) and resistance stability (positive), respectively. Overall, temporal stability is mainly influenced by temperature variability and GI, while resistance stability is mainly affected by GI. Our findings highlight the importance of considering the dimensions of stability and disturbance. Different dimensions of stability may respond differently to disturbance. Multiple disturbances may also interact synergistically or antagonistically on plant community stability.

The battery is an important part of the new energy electric vehicle, and the control of the flatness of its side plate/bottom plate is the key to quality improvement in mass production. However, there are few pieces of research on the flatness distribution form at present, and the distribution form is often assumed to be a normal distribution, which leads to a significant deviation between the tolerance design and quality control of the flatness and the reality. This paper establishes a statistical model of flatness distribution, its theoretical distribution form is deduced as a normal range distribution, and then the experimental data of the flatness distribution are collected to verify this conclusion. Determining the flatness distribution form has practical effects on improving manufacturing quality and reducing costs in battery manufacturing.

A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

Recent advances in computer and data sciences have made artificial intelligence techniques a useful tool in tackling the problems in petroleum exploration and production [...]

Abstract Molecular oxygen (O2) is a universal electron acceptor that is eventually synthesized into ATP in the mitochondrial respiratory chain of all metazoans. Therefore, hypoxia biology has become an organizational principle of cell evolution, metabolism and pathology. Hypoxia-inducible factor (HIF) mediates tumour cells to produce a series of glucose metabolism adaptations including the regulation of glucose catabolism, glycogen metabolism and the biological oxidation of glucose to hypoxia. Since HIF can regulate the energy metabolism of cancer cells and promote the survival of cancer cells, targeting HIF or HIF mediated metabolic enzymes may become one of the potential treatment methods for cancer. In this review, we summarize the established and recently discovered autonomous molecular mechanisms that can induce cell reprogramming of hypoxic glucose metabolism in tumors and explore opportunities for targeted therapy.

Hepatocellular carcinoma is one of the most common gastrointestinal malignancies. Anti-angiogenesis therapies have recently demonstrated promise in the treatment of malignancies, although early treatment benefits may be accompanied by metastasis over time. Additional and more effective anti-angiogenic treatment modalities are therefore needed. We previously found that Yes-associated protein 1 (YAP1) expression is increased in hepatocellular carcinoma (HCC), particularly around tumor-associated blood vessels, suggesting a role in angiogenesis. The YAP1 inhibitor verteporfin is presently in anti-angiogenic clinical trials for the treatment of various cancers. Depleted YAP1 from vascular endothelial cells effectively reduced proliferation and tube formation, validating its utility as an anti-angiogenesis target. We also showed that YAP1 depletion or inhibition in vascular endothelial cells leads to increased release of exosomes containing the long non-coding RNA (lncRNA) MALAT1 into the tumor microenvironment. Direct exosomal transfer of MALAT1 to hepatic cells leads to increased hepatic cell invasion and migration via activation of extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. These observations may explain the occurrence of distant tumor metastasis with YAP1-associated anti-angiogenic therapy over time. It provides insight into new pathways and treatment paradigms that may be targeted to increase the long-term success of anti-angiogenic therapies.

Abstract Multivesicular bodies (MVBs) are endosome organelles that are gradually attracting research attention. Initially, MVBs were considered as important components of the endosomal-lysosomal degradation pathway. In recent years, with an increase in extracellular vesicle (EV) research, the biogenesis, fate, and pathological effects of MVBs have been increasingly studied. However, the mechanisms by which MVBs are sorted to the lysosome and plasma membrane remain unclear. In addition, whether the trafficking of MVBs can determine whether exosomes are released from cells, the factors are involved in cargo loading and regulating the fate of MVBs, and the roles that MVBs play in the development of disease are unknown. Consequently, this review focuses on the mechanism of MVB biogenesis, intraluminal vesicle formation, sorting of different cargoes, and regulation of their fate. We also discuss the mechanisms of emerging amphisome-dependent secretion and degradation. In addition, we highlight the contributions of MVBs to the heterogeneity of EVs, and their important roles in cancer. Thus, we attempt to unravel the various functions of MVBs in the cell and their multiple roles in tumor progression. Video Abstract

Abstract Background Various methods for differential expression analysis have been widely used to identify features which best distinguish between different categories of samples. Multiple hypothesis testing may leave out explanatory features, each of which may be composed of individually insignificant variables. Multivariate hypothesis testing holds a non-mainstream position, considering the large computation overhead of large-scale matrix operation. Random forest provides a classification strategy for calculation of variable importance. However, it may be unsuitable for different distributions of samples. Results Based on the thought of using an ensemble classifier, we develop a feature selection tool for differential expression analysis on expression profiles (i.e., ECFS-DEA for short). Considering the differences in sample distribution, a graphical user interface is designed to allow the selection of different base classifiers. Inspired by random forest, a common measure which is applicable to any base classifier is proposed for calculation of variable importance. After an interactive selection of a feature on sorted individual variables, a projection heatmap is presented using k-means clustering. ROC curve is also provided, both of which can intuitively demonstrate the effectiveness of the selected feature. Conclusions Feature selection through ensemble classifiers helps to select important variables and thus is applicable for different sample distributions. Experiments on simulation and realistic data demonstrate the effectiveness of ECFS-DEA for differential expression analysis on expression profiles. The software is available at http://bio-nefu.com/resource/ecfs-dea.

The effect of extracellular matrix (ECM) stiffness on embryonic trophoblast cells invasion during mammalian embryo implantation remains largely unknown. In this study, we investigated the effects of ECM stiffness on various aspects of human trophoblast cell behaviors during cell–ECM interactions. The mechanical microenvironment of the uterus was simulated by fabricating polyacrylamide (PA) hydrogels with different levels of stiffness. The human choriocarcinoma (JAR) cell lineage was used as the trophoblast model. We found that the spreading area of JAR cells, the formation of focal adhesions, and the polymerization of the F-actin cytoskeleton were all facilitated with increased ECM stiffness. Significantly, JAR cells also exhibited durotactic behavior on ECM with a gradient stiffness. Meanwhile, stiffness of the ECM affects the invasion of multicellular JAR spheroids. These results demonstrated that human trophoblast cells are mechanically sensitive, while the mechanical properties of the uterine microenvironment could play an important role in the implantation process.

We aimed to assess the potential of ultrasonic treatment on the processing of polysaccharides as functional foods or food additives. The polysaccharide from Sinopodophyllum hexandrum fruit (SHP, 52.46 kDa, 1.91 nm) was isolated and purified. SHP was treated with various levels of ultrasound (250 W and 500 W), resulting in the formation of two polysaccharides, SHP1 (29.37 kD, 1.40 nm) and SHP2 (36.91 kDa, 0.987 nm). Ultrasonic treatment was found to reduce the surface roughness and molecular weight of the polysaccharides, leading to thinning and fracturing. The effect of ultrasonic treatment on polysaccharide activity was evaluated in vitro and in vivo. In vivo experiments showed that ultrasonic treatment improved the organ index. Simultaneously, it enhanced the activity of superoxide dismutase, total antioxidant capacity, and decreased the content of malondialdehyde in the liver. In vitro experiments demonstrated that ultrasonic treatment also promoted proliferation, nitric oxide secretion, phagocytic efficiency, costimulatory factors (CD80+, CD86+) expression, and cytokine(IL-6, IL-1β) production of RAW264.7 macrophages.

In this study, the flexural behavior tests of steel fiber reinforced concrete beams with BFRP bars under static load are carried out by means of statics experiment and theoretical analysis. A total of seven beams were designed for this experiment, and the effects of two factors on the mid-span deflection of the beams were investigated with the steel fiber incorporation rate (0%, 0.5%, 1%, 1%/0.5%, 1.5%) and the height of steel fibers in the concrete layer in the compression zone (180 mm, 210 mm, 300 mm) as the main variables. In this study, based on the existing research results and combined with the actual test results, the formulae for calculating the cracking section moment of inertia applicable to BFRP reinforced steel fiber (full section/pressure zone reinforced) concrete beams are derived. At the same time, the results obtained from the formula and the results of the ACI code in the United States are compared with the data of the results obtained from this test, and the calculated results of this formula are in good agreement with the actual values.

In this paper, the nonlinear stiffness of a polyester rope under dynamic loads at different temperatures was experimentally investigated. The effects and evolution of the average load, load period and load amplitude on dynamic stiffness were studied. The experimental results show that the dynamic stiffness at 30 °C was greater than that at 20 °C and 40 °C. This is because the dynamic stiffness reduced as the temperature and humidity increased, while in the closed thermostat, humidity decreased with an increase in temperature. In response to this phenomenon, a new set of empirical equations was proposed to consider temperature, humidity, and dynamic load based on the existing empirical formulas, by combining the experimental results. A set of experiments was conducted at 25 °C to verify the accuracy and applicability of the formula. The experimental results and the predicted results are in good agreement.

PurposeSorafenib is a multi-kinase inhibitor that is used as a standard treatment for advanced hepatocellular carcinoma (HCC). However, the mechanism of sorafenib resistance in HCC is still unclear. It has been shown that CISD2 expression is related to the progression and poor prognosis of HCC. Here, we show a new role for CISD2 in sorafenib resistance in HCC.MethodsBioinformatic analysis was used to detect the expression of negative regulatory genes of ferroptosis in sorafenib-resistant samples. The concentration gradient method was used to establish sorafenib-resistant HCC cells. Western blot was used to detect the protein expression of CISD2, LC3, ERK, PI3K, AKT, mTOR, and Beclin1 in HCC samples. Quantitative real-time PCR (qPCR) was used to detect gene expression. CISD2 shRNA and Beclin1 shRNA were transfected to knock down the expression of the corresponding genes. Cell viability was detected by a CCK-8 assay. ROS were detected by DCFH-DA staining, and MDA and GSH were detected with a Lipid Peroxidation MDA Assay Kit and Micro Reduced Glutathione (GSH) Assay Kit, respectively. Flow cytometry was used to detect apoptosis and the levels of ROS and iron ions.ResultsCISD2 was highly expressed in HCC cells compared with normal cells and was associated with poor prognosis in patients. Knockdown of CISD2 promoted a decrease in the viability of drug-resistant HCC cells. CISD2 knockdown promoted sorafenib-induced ferroptosis in resistant HCC cells. The levels of ROS, MDA, and iron ions increased, but the change in GSH was not obvious. Knockdown of CISD2 promoted uncontrolled autophagy in resistant HCC cells. Inhibition of autophagy attenuated CISD2 knockdown-induced ferroptosis. The autophagy promoted by CISD2 knockdown was related to Beclin1. When CISD2 and Beclin1 were inhibited, the effect on ferroptosis was correspondingly weakened.ConclusionInhibition of CISD2 promoted sorafenib-induced ferroptosis in resistant cells, and this process promoted excessive iron ion accumulation through autophagy, leading to ferroptosis. The combination of CISD2 inhibition and sorafenib treatment is an effective therapeutic strategy for resistant HCC.