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Abstract Background Broussonetia papyrifera (L.) L’Hér. ex Vent. has the characteristics of strong stress resistance, high crude protein content, and pruning tolerance. It is an ecological, economic, and medicinal plant. Polyploid plants usually perform better than their corresponding diploid plants in terms of nutrients, active substances, and stress resistance. Results In this study, the leaves, calli, and seeds of diploid B. papyrifera were used for tetraploid induction by colchicine. The induction effect of colchicine on B. papyrifera was summarized through the early morphology, chromosome count and flow cytometry. It was concluded that the best induction effect (18.6%) was obtained when the leaves of B. papyrifera were treated in liquid MS (Murashige and Skoog) medium containing 450 mg·L-1 colchicine for 3 d. The comparative analysis of the growth characteristics of diploid and tetraploid B. papyrifera showed that tetraploid B. papyrifera has larger ground diameter, larger stomata, thicker palisade tissue and thicker sponge tissue than diploid B. papyrifera. In addition, the measurement of photosynthetic features also showed that tetraploids had higher chlorophyll content and higher photosynthetic rates. Conclusion This study showed that tetraploid B. papyrifera could be obtained by treating leaves, callus and seeds with liquid and solid colchicine, but the induction efficiency was different. Moreover, there were differences in stomata, leaf cell structure and photosynthetic features between tetraploid B. papyrifera and its corresponding diploid. The induced tetraploid B. papyrifera can provide a technical basis and breeding material for the creation of B. papyrifera germplasm resources in the future.

Heavy metal poisoning of soil from oil spills causes serious environmental problems worldwide. Various causes and effects of heavy metal pollution in the soil environment are discussed in this article. In addition, this study explores new approaches to cleaning up soil that has been contaminated with heavy metals as a result of oil spills. Furthermore, it provides a thorough analysis of recent developments in remediation methods, such as novel nano-based approaches, chemical amendments, bioremediation, and phytoremediation. The objective of this review is to provide a comprehensive overview of the removal of heavy metals from oil-contaminated soils. This review emphasizes on the integration of various approaches and the development of hybrid approaches that combine various remediation techniques in a synergistic way to improve sustainability and efficacy. The study places a strong emphasis on each remediation strategy that can be applied in the real-world circumstances while critically evaluating its effectiveness, drawbacks, and environmental repercussions. Additionally, it discusses the processes that reduce heavy metal toxicity and improve soil health, taking into account elements like interactions between plants and microbes, bioavailability, and pollutant uptake pathways. Furthermore, the current study suggests that more research and development is needed in this area, particularly to overcome current barriers, improve our understanding of underlying mechanisms, and investigate cutting-edge ideas that have the potential to completely transform the heavy metal clean up industry.

Summary: Background: The triglyceride-glucose (TyG) index has been recognized as a crucial risk factor for cardiovascular diseases. However, the association between the TyG index and mortality in the general population remains elusive. Methods: Participants were enrolled from the China Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART), a nationwide prospective cohort study. The outcomes of interest were all-cause, cardiovascular, and cancer mortality. Restricted cubic splines and Cox regression models were used to assess the associations between the TyG index and outcomes. Findings: In total, 3,524,459 participants with a median follow-up of 4.6 (IQR, 3.1–5.8) years were included. The associations of the TyG index with all-cause and cardiovascular mortality were reverse L-shaped, with cut-off values of 9.75 for all-cause mortality and 9.85 for cardiovascular mortality. For each 1-unit increase in the TyG index, when below the cut-off values, the TyG index was not significantly associated with all-cause mortality (HR = 1.02, 95% CI: 1.00–1.03) and was only modestly associated with cardiovascular mortality (HR = 1.09, 95% CI: 1.06–1.11). Conversely, when the cut-off values were exceeded, the HRs (95% CI) were 2.10 (1.94–2.29) for all-cause mortality and 1.99 (1.72–2.30) for cardiovascular mortality. However, the association between the TyG index and cancer mortality was linearly negative (HR = 0.97, 95% CI: 0.94–0.99). Interpretation: The associations of the TyG index with all-cause and cardiovascular mortality displayed reverse L-shaped patterns, while an elevated TyG index showed a slight negative association with cancer mortality. We suggest that

Abstract A 3D nanostructured scaffold as the host for zinc enables effective inhibition of anodic dendrite growth. However, the increased electrode/electrolyte interface area provided by using 3D matrices exacerbates the passivation and localized corrosion of the Zn anode, ultimately bringing about the degradation of the electrochemical performance. Herein, a nanoscale coating of inorganic–organic hybrid (α‐In2Se3‐Nafion) onto a flexible carbon nanotubes (CNTs) framework (ISNF@CNTs) is designed as a Zn plating/stripping scaffold to ensure uniform Zn nucleation, thus achieving a dendrite‐free and durable Zn anode. The introduced inorganic–organic interfacial layer is dense and sturdy, which hinders the direct exposure of deposited Zn to electrolytes and mitigates the side reactions. Meanwhile, the zincophilic nature of ISNF can largely reduce the nucleation energy barrier and promote the ion‐diffusion transportation. Consequently, the ISNF@CNTs@Zn electrode exhibits a low‐voltage hysteresis and a superior cycling life (over 1500 h), with dendrite‐free Zn‐plating behaviors in a typical symmetrical cell test. Additionally, the superior feature of ISNF@CNTs@Zn anode is further demonstrated by Zn‐MnO2 cells in both coin and flexible quasi‐solid‐state configurations. This work puts forward an inspired remedy for advanced Zn‐ion batteries.

Ovarian cancer is a common tumor among women. It is often asymptomatic in the early stages, with most cases already at stage III to IVE at the time of diagnosis. Direct spread and lymphatic metastasis are the primary modes of metastasis, whereas hematogenous spread is rare. An initial diagnosis of ovarian cancer that has metastasized to the stomach is also uncommon. Therefore, clear treatment methods and prognostic data for such metastasis are lacking. In our hospital, we encountered a patient with an initial imaging diagnosis of a gastric tumor and a history of an ovarian tumor with endoscopic abdominal metastasis. Based on the characteristics of the case, the two tumors were considered to be the same. After chemotherapy, a partial response was observed in the stomach and pelvic lesions, suggesting the effectiveness of the treatment. Through three treatments of recurrence, gastroscopy confirmed the stomach to be a metastatic site. Therefore, determining the primary source of advanced tumors is crucial in guiding treatment decisions. Clinicians must approach this comprehensively, relying on thorough evaluation and personal experience.

Abstract Toll‐like receptors (TLRs) are an important family of pattern‐recognition receptors that recognize a series of pathogen‐associated molecular patterns to trigger the host immune response. In the present study, we identified three TLR13 genes (i.e., LcLTR13a, LcTLR13b, and LcTLR13c) in American bullfrogs, Lithobates catesbeianus, and explored their constitutive and pathogen‐induced expression profile in different tissues. The open reading frames of LcLTR13a, LcTLR13b and LcTLR13c are 2811, 2844, and 2814 bp long, encoding 955, 947, and 933 amino acids, respectively. Phylogenetic analysis showed that three LcTLR13 genes grouping in different subclades indicate the gene duplication of bullfrog TLR13 as in teleost. The three LcTLR13 genes were expressed in all the tissues examined, with the liver and spleen expressing the higher levels. Moreover, the expression levels of LcLTR13a, LcTLR13b, and LcTLR13c were significantly induced in the liver and spleen after bullfrogs were challenged with bacterial (i.e., Citrobacter freundii, Aeromonas hydrophila, and Edwardsiella tarda) pathogens. These results indicate that LcTLR13 genes play an essential role in the bullfrog antibacterial innate immune response, providing new insights into immune mechanisms of bullfrogs.

BackgroundSarcopenia, common in the elderly, often linked to chronic diseases, correlates with inflammation.The association between SII and mortality in sarcopenia patients is underexplored, this study investigates this relationship in a U.S. adult cohort.MethodsWe analyzed 1999–2018 NHANES data, focusing on 2,974 adults with sarcopenia. Mortality outcomes were determined by linking to National Death Index (NDI) records up to December 31, 2019. Using a weighted sampling design, participants were grouped into three groups by the Systemic Immune-Inflammation Index (SII). We used Cox regression models, adjusting for demographic and clinical variables, to explore SII’s association with all-cause and cause-specific mortality in sarcopenia, performing sensitivity analyses for robustness.ResultsOver a median follow-up of 9.2 years, 829 deaths occurred. Kaplan-Meier analysis showed significant survival differences across SII groups. The highest SII group showed higher hazard ratios (HRs) for all-cause and cause-specific mortality in both crude and adjusted models. The highest SII group had a higher HR for all-cause(1.57, 1.25–1.98), cardiovascular(1.61, 1.00–2.58), cancer(2.13, 1.32–3.44), and respiratory disease mortality(3.21, 1.66–6.19) in fully adjusted models. Subgroup analyses revealed SII’s association with all-cause mortality across various demographics, including age, gender, and presence of diabetes or cardiovascular disease. Sensitivity analyses, excluding participants with cardiovascular diseases, those who died within two years of follow-up, or those under 45 years of age, largely reflected these results, with the highest SII group consistently demonstrating higher HRs for all types of mortality in both unadjusted and adjusted models.ConclusionOur study is the first to demonstrate a significant relationship between SII and increased mortality risks in a sarcopenia population.

Drought is a misfortune for crops. Wheat is a staple crop and its sustainability and adequate supply are vital to food security around the world. The development of drought-tolerant cultivars in wheat is a major challenge to breeders, therefore there is dire need of time to determine the genetic components of drought tolerance in wheat crop. To overcome intense drought stress, wheat plants undergo certain morphological and physiological changes and develop certain genetically adaptive mechanisms. Since wheat is an allotriploid with three sub-genomes, its adaptability molecular mechanisms to drought, particularly needs scientific attention. Here, we systematically and comprehensively reviewed the causes of wheat drought tolerance and the consequences for wheat physiology and genetics. The quantitative trait loci (QTL), which be function on the control of wheat drought tolerance, were comprehensively summarized by a meta-analysis and total 75 meta-QTLs (MQTLs) were identified. In addition, we summarized the genes tightly involved in wheat drought tolerance, and several important genes were selected to elucidate signaling networks related to the wheat drought tolerance. This review is integral to growing suitable strains in the worldwide arid regions to improve wheat yields under recent global climate change scenarios.

The oligomerization of light olefins is an alternative for generating clean liquid fuels. In this study, the MCM-22 zeolite featuring a partially disordered layered structure with framework combined 10 membered ring (10 MR) was discussed for 1-hexene oligomerization. MCM-22 and Y zeolite were compared to investigate the influences of the framework and acidity strength on the activity and yield in the 1-hexene oligomerization. The results indicated that the MCM-22 zeolite was an efficient catalyst for oligomerization compared to Y zeolite. The MCM-22 zeolite was characterized in detail by NMR, Py-FTIR, and TG analyses. The catalytic performance and deactivation properties of MCM-22 zeolite in the oligomerization reaction of 1-hexene were investigated. Structure–activity relationships were established through the kinetic study. Although the density of strong acid sites was essential for the oligomerization of 1-hexene, the presence of low pressure was also necessary for the formation of dimers. Thus, MCM-22 zeolite demonstrates a substantial improvement in initial conversion and catalyst lifespan for 1-hexene oligomerization.

Abstract Introduction Fungal communities are key players in the soil biogeochemical processes of forest ecosystems. Although it has been illustrated that soil fungi are susceptible to environmental changes, little is known about the interactive effects of nitrogen (N) and phosphorus (P) enrichment on the soil fungal functional guild. Materials and Methods Here, a 5‐year N and P addition manipulation experiment was conducted in two growing stages (i.e., tree ages 80 years) of a subtropical forest, in which soil fungal diversity and functional guilds were investigated using a multiple‐time sampling strategy. Results Fungal species richness and Shannon indices were significantly different across sampling times. Fungal community composition was significantly affected by both N and P addition but not by forest age. Old forest had a higher fungal network complexity than young forest, and fertilisation decreased soil fungal network complexity and generated looser and more random networks in comparison with the control. The community composition of symbiotrophic and saprotrophic fungi was significantly impacted by N and P addition and correlated with soil available P and total P contents and soil C:P and N:P. Conclusions Our findings highlight that soil P availability has a strong effect on soil fungal communities and their functional guild composition in the subtropical forest.

Abstract Developing efficient metal‐nitrogen‐carbon (M‐N‐C) single‐atom catalysts for oxygen reduction reaction (ORR) is significant for the widespread implementation of Zn‐air batteries, while the synergic design of the matrix microstructure and coordination environment of metal centers remains challenges. Herein, a novel salt effect‐induced strategy is proposed to engineer N and P coordinated atomically dispersed Fe atoms with extra‐axial Cl on interlinked porous carbon nanosheets, achieving a superior single‐atom Fe catalyst (denoted as Fe‐NP‐Cl‐C) for ORR and Zn‐air batteries. The hierarchical porous nanosheet architecture can provide rapid mass/electron transfer channels and facilitate the exposure of active sites. Experiments and density functional theory (DFT) calculations reveal the distinctive Fe‐N2P2‐Cl active sites afford significantly reduced energy barriers and promoted reaction kinetics for ORR. Consequently, the Fe‐NP‐Cl‐C catalyst exhibits distinguished ORR performance with a half‐wave potential (E1/2) of 0.92 V and excellent stability. Remarkably, the assembled Zn‐air battery based on Fe‐NP‐Cl‐C delivers an extremely high peak power density of 260 mW cm−2 and a large specific capacity of 812 mA h g−1, outperforming the commercial Pt/C and most reported congeneric catalysts. This study offers a new perspective on structural optimization and coordination engineering of single‐atom catalysts for efficient oxygen electrocatalysis and energy conversion devices.

Long noncoding RNA small nucleolar RNA host gene 1 (lncRNA SNHG1) plays a crucial role in the occurrence and progression of various tumors. This study investigates the function of lncRNA SNHG1 in hepatocellular carcinoma (HCC). We discovered that lncRNA SNHG1 is significantly upregulated in HCC and markedly enhances cell proliferation, migration, and invasion, while simultaneously suppressing apoptosis in HCC cells. Furthermore, lncRNA SNHG1 was found to downregulate miR-7-5p expression. Overexpression of lncRNA SNHG1 counteracted the suppression of HCC cell migration, proliferation, and invasion caused by miR-7-5p mimics, and reversed the miR-7-5p mimics' enhancement of apoptosis in HCC cells. Additionally, miR-7-5p was shown to negatively regulate IGF2BP2, with the silencing of IGF2BP2 diminishing the abilities of HCC cells to proliferate, migrate, and invade, and increasing their propensity for apoptosis. Overexpression of lncRNA SNHG1 negated these effects. Thus, lncRNA SNHG1 fosters HCC progression by upregulating IGF2BP2 expression through targeting miR-7-5p.

ObjectivesIn recent years, there has been an increase in the number of randomized clinical trials of BTX-A combined with ESWT for the treatment of post-stroke spasticity. This has made it possible to observe the benefits of combination therapy in clinical practice. Therefore, this paper reviews the effectiveness of BTX-A in combination with ESWT for the treatment of post-stroke spasticity.MethodsBy October 2023, a systematic review was conducted in the databases PubMed, Cochrane, Embase, Medline, Web of Science, China National Knowledge Infrastructure, Wan Fang Database, China Biology Medicine disc and China Science and Technology Journal Database were systematically searched. We included randomized controlled trials that reported outcome metrics such as MAS, FMA, and MBI score. Studies were excluded if MAS was not reported. The quality of the included studies was assessed by the Cochrane Collaboration’s tool for assessing risk of bias, and the AMSTAR quality rating scale was selected for self-assessment.ResultsA total of 70 articles were included in the initial search, and six were ultimately included. The results of the included studies showed that the combination therapy was effective in reducing MAS scores and improving FMA and MBI scores in patients with spasticity compared to the control group. Combination therapy has also been shown to improve joint mobility and reduce pain in spastic limbs.ConclusionCumulative evidence from clinical randomized controlled trial studies suggests that the combination therapy is effective in reducing lower limb spasticity and improving mobility after stroke. However, more clinical trials are still needed to corroborate the evidence regarding the efficacy of BTX-A combined with shockwave therapy.Systematic Review RegistrationThe system review can be searched in the PROSPERO database (CRD42023476654).

Neuronal damage resulting from traumatic brain injury (TBI) causes disruption of neuronal projections and neurotransmission that contribute to behavioral deficits. Cellular generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) is an early event following TBI. ROS often damage DNA, lipids, proteins, and carbohydrates while RNS attack proteins. The products of lipid peroxidation 4-hydroxynonenal (4-HNE) and protein nitration 3-nitrotyrosine (3-NT) are often used as indicators of oxidative and nitrosative damages, respectively. Increasing evidence has shown that striatum is vulnerable to damage from TBI with a disturbed dopamine neurotransmission. TBI results in neurodegeneration, oxidative stress, neuroinflammation, neuronal apoptosis, and autophagy in the striatum and contribute to motor or behavioral deficits. Pomalidomide (Pom) is a Food and Drug Administration (FDA)-approved immunomodulatory drug clinically used in treating multiple myeloma. We previously showed that Pom reduces neuroinflammation and neuronal death induced by TBI in rat cerebral cortex. Here, we further compared the effects of Pom in cortex and striatum focusing on neurodegeneration, oxidative and nitrosative damages, as well as neuroinflammation following TBI. Sprague–Dawley rats subjected to a controlled cortical impact were used as the animal model of TBI. Systemic administration of Pom (0.5 mg/kg, intravenous [i.v.]) at 5 h post-injury alleviated motor behavioral deficits, contusion volume at 24 h after TBI. Pom alleviated TBI-induced neurodegeneration stained by Fluoro-Jade C in both cortex and striatum. Notably, Pom treatment reduces oxidative and nitrosative damages in cortex and striatum and is more efficacious in striatum (93% reduction in 4-HNE-positive and 84% reduction in 3-NT-positive neurons) than in cerebral cortex (42% reduction in 4-HNE-positive and 55% reduction in 3-NT-positive neurons). In addition, Pom attenuated microgliosis, astrogliosis, and elevations of proinflammatory cytokines in cortical and striatal tissue. We conclude that Pom may contribute to improved motor behavioral outcomes after TBI through targeting oxidative/nitrosative damages and neuroinflammation.

BackgroundAsthma has become one of the most common chronic conditions worldwide, especially among children. Recent findings show that the prevalence of childhood asthma has increased by 12.6% over the past 30 years, with >262 million people currently affected globally. The reasons for the growing asthma epidemic remain complex and multifactorial. ObjectiveThis study aims to provide an up-to-date analysis of the changing global and regional asthma prevalence, mortality, disability, and risk factors among children aged

Kinesin motors are a large family of molecular motors that walk along microtubules to fulfill many roles in intracellular transport, microtubule organization, and chromosome alignment. Kinesin-7 CENP-E (Centromere protein E) is a chromosome scaffold-associated protein that is located in the corona layer of centromeres, which participates in kinetochore-microtubule attachment, chromosome alignment, and spindle assembly checkpoint. Over the past 3 decades, CENP-E has attracted great interest as a promising new mitotic target for cancer therapy and drug development. In this review, we describe expression patterns of CENP-E in multiple tumors and highlight the functions of CENP-E in cancer cell proliferation. We summarize recent advances in structural domains, roles, and functions of CENP-E in cell division. Notably, we describe the dual functions of CENP-E in inhibiting and promoting tumorigenesis. We summarize the mechanisms by which CENP-E affects tumorigenesis through chromosome instability and spindle assembly checkpoints. Finally, we overview and summarize the CENP-E-specific inhibitors, mechanisms of drug resistances and their applications.

Abstact: Objective: To examine the joint association of healthy lifestyles and statin use with all-cause and cardiovascular mortality in high-risk individuals, and evaluate the survival benefits by life expectancy. Methods: During 2015–2021, participants aged 35–75 years were recruited by the China Health Evaluation And risk Reduction through nationwide Teamwork. Based on number of healthy lifestyles related to smoking, alcohol drinking, physical activity, and diet, we categorized them into: very healthy (3–4), healthy (2), and unhealthy (0–1). Statin use was determined by self-report taking statin in last two weeks. Results: Among the 265,209 included participants at high risk, 6979 deaths were observed, including 3236 CVD deaths during a median 3.6 years of follow-up. Individuals taking statin and with a very healthy lifestyle had the lowest risk of all-cause (HR: 0.70; 95 %CI: 0.57–0.87) and cardiovascular mortality (0.56; 0.40–0.79), compared with statin non-users with an unhealthy lifestyle. High-risk participants taking statin and with a very healthy lifestyle had the highest years of life gained (5.90 years at 35-year-old [4.14–7.67; P < 0.001]) compared with statin non-users with an unhealthy lifestyle among high-risk people. And their life expectancy was comparable with those without high risk but with a very healthy lifestyle (4.49 vs. 4.68 years). Conclusion: The combination of preventive medication and multiple healthy lifestyles was associated with lower risk of all-cause and cardiovascular mortality and largest survival benefits. Integrated strategy to improve long-term health for high-risk people was urgently needed.

Acute lymphocytic leukemia is a hematological malignancy that primarily affects children. Long-term chemotherapy is effective, but always causes different toxic side effects. With the application of a chemotherapy-free treatment strategy, we intend to demonstrate the most recent results of using one type of epigenetic drug, histone deacetylase inhibitors, in ALL and to provide preclinical evidence for further clinical trials. In this review, we found that panobinostat (LBH589) showed positive outcomes as a monotherapy, whereas vorinostat (SAHA) was a better choice for combinatorial use. Preclinical research has identified chidamide as a potential agent for investigation in more clinical trials in the future. In conclusion, histone deacetylase inhibitors play a significant role in the chemotherapy-free landscape in cancer treatment, particularly in acute lymphocytic leukemia.

Lung cancer remains the leading cause of cancer-related mortality, with 1.8 million deaths per year. Small cell lung cancer and non-small cell lung cancer (NSCLC) are the main cancer types. Approximately 85% of cases are NSCLC, including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. In this reported treatment case, the tumor histological type changed after targeted therapy, which has not been previously well documented. The patient was a 67-year-old woman diagnosed with squamous cell carcinoma via bronchoscopy. She received five neoadjuvant immune monotherapies. The lesion shrank but then progressed, with a diagnosis of small cell carcinoma via bronchoscopy. This finding suggests that tumor acquisition of resistance as manifested by cancer-type changes needs consideration and study in the application of this particular type of immunotherapy.

Siloxanes are a group of substances characterized by Si-O-Si functional group. Siloxanes can react with alcohols to form Si-O-C bond. Siloxanes have been widely used as crossing linking agents and graft copolymers as well as additives for plastics. Lignin contains both phenolic and aliphatic hydroxy groups which have the potential to instigate bonding with siloxane compounds. However, there has not been any attempt to apply siloxanes as crosslinking agents for biobased composite formation. This manuscript presents the first study of applying siloxanes compounds to lignin and Cellulose nanofibers (CNF) with respective PLA, PETG, and HDPE to prepare biocomposites. Both Tetramethyl Tetraphenyl Trisiloxane (TTT) and Tetraethoxysilane (TEOS) were used as cross-linking agents. We have successfully incorporated 20 wt% lignin and 10 wt% CNF into the biocomposite filaments. The tensile properties of ensuing biocomposite were investigated. The objective of this work is to demonstrate the potential of lignin and CNF as a sustainable co-polymer to improve the properties of PLA/PETG/HDPE-based materials for 3D printing. This paper will also discuss the challenges and opportunities associated with the use of lignin in 3D printing, including the effect of lignin and CNF content on the mechanical and thermal properties, the compatibility of lignin and CNF with PLA/PETG/HDPE, and the potential for further optimization of the cross-linking chemistry using TTT and TEOS.

The U-steel support structures of underground caverns are prone to instability and failure under blast loads. The purpose of the underground cavern reinforcement is to mobilise the self-supporting capacity of the surrounding rock to resist the blast. To better understand the mechanical performance and failure mechanism of the U-steel support, the fracture process and vibration behaviour of the support structure under blast loading are investigated by the microseismic monitoring experiment. The dynamic responses of the cavern support structures under blast loading are investigated, and the potentially hazardous sections of the U-steel support structure are revealed by the theoretical analysis. The microseismic monitoring results show that the blast induced microseismic events are concentrated in the arch shoulder of the small chainage, correspondingly the U-steel structures in this region have been partially extruded and deformed. The failure mechanism of the supporting structure is presented. In order to effectively inhibit the internal fracture evolution or macroscopic failure of the rock mass, the synergetic reinforcement scheme of the structures is proposed. The results of the research can be used as a reference for the design and control method of the U-steel support in similar projects.

Background: Small extracellular vesicles (sEVs) mediate intercellular communication in the tumor microenvironment (TME) and contribute to the malignant transformation of tumors, including unrestricted growth, metastasis, or therapeutic resistance. However, there is a lack of agents targeting sEVs to overcome or reverse tumor chemotherapy resistance through sEVs-mediated TME reprogramming.Methods: The paclitaxel (PTX)-resistant A549T cell line was used to explore the inhibitory effect of alpha-hederin on impeding the transmission of chemoresistance in non-small cell lung cancer (NSCLC) through the small extracellular vesicles (sEVs) pathway. This investigation utilized the CCK-8 assay and flow cytometry. Transcriptomics, Western blot, oil red O staining, and targeted metabolomics were utilized to evaluate the impact of alpha-hederin on the expression of signaling pathways associated with chemoresistance transmission in NSCLC cells before and after treatment. In vivo molecular imaging and immunohistochemistry were conducted to assess how alpha-hederin influences the transmission of chemoresistance through the sEVs pathway. RT-PCR was employed to examine the expression of miRNA and lncRNA in response to alpha-hederin treatment.Results: The resistance to PTX chemotherapy in A549T cells was overcome by alpha-hederin through its dependence on sEV secretion. However, the effectiveness of alpha-hederin was compromised when vesicle secretion was blocked by the GW4869 inhibitor. Transcriptomic analysis for 463 upregulated genes in recipient cells exposed to A549T-derived sEVs revealed that these sEVs enhanced TGFβ signaling and unsaturated fatty acid synthesis pathways. Alpha-hederin inhibited 15 types of unsaturated fatty acid synthesis by reducing the signaling activity of the sEVs-mediated TGFβ/SMAD2 pathway. Further, we observed that alpha-hederin promoted the production of three microRNAs (miRNAs, including miR-21-5p, miR-23a-3p, and miR-125b-5p) and the sorting to sEVs in A549T cells. These miRNAs targeted the TGFβ/SMADs signaling activity in sEVs-recipient cells and sensitized them to the PTX therapy.Conclusion: Our finding demonstrated that alpha-hederin could sensitize PTX-resistant NSCLC cells by sEV-mediated multiple miRNAs accumulation, and inhibiting TGFβ/SMAD2 pathways in recipient cells.