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Cadmium (Cd) is among the most available and most toxic heavy metals taken up by plants from soil. Compared to the classic plant-animal food chains, the host-parasitic plant food chains have, thus far, been largely overlooked in the studies of Cd trophic transfer. To investigate the pattern of Cd transfer during the infection of parasitic plants on Cd-contaminated hosts, we conducted a controlled experiment that grew soybeans parasitized by Chinese dodders (Cuscuta chinensis) in soil with different levels of Cd treatment, and examined the concentration, accumulation, allocation and transfer coefficients of Cd within this parasitic system. Results showed that among all components, dodders accounted for more than 40% biomass of the whole system but had the lowest Cd concentration and accumulated the least amount of Cd. The transfer coefficient of Cd between soybean stems and dodders was much lower than 1, and was also significantly lower than that between soybean stems and soybean leaves. All these features were continuously strengthened with the increase of Cd treatment levels. The results suggested no evidence of Cd biomagnification in dodders parasitizing Cd-contaminated hosts, and implied that the Cd transfer from hosts to dodders may be a selective process.

Seed dispersal plays critical roles in determining species survival and community structures. Since the dispersal is biologically under maternal control, it is hypothesized that intraspecific variation of dispersal potential and associated traits of seeds (diaspores) should be influenced by maternal habitat quality. We tested this hypothesis by examining the effects of maternal environmental light condition on morphological traits and descending performance of nearly 1800 wind-dispersed samaras collected from maple species Acer palmatum. Results showed that samaras produced by trees from shaded microhabitats had greater dispersal potential, in terms of slower terminal velocity of descent, than those produced in open microhabitats. This advantage was largely attributed to morphological plasticity. On average, samaras produced in shaded microhabitats, as compared to those produced in open habitats, had lower wing loading by only reducing weight but not area. In allometric details, in the large size range, samaras from shaded microhabitats had larger areas than those from open microhabitats; in the small size range, samaras from shaded microhabitats had wider wings. These findings suggest that greater dispersal potential of samaras in response to stressful maternal light environment reflected an active maternal control through the morphological allometry of samaras.

Abstract Recent studies have demonstrated that plants can determine the identity of neighbouring roots (e.g., self and non-self, kin and non-kin), but whether they can discriminate by sex remains an open question. Here, we predict that dioecious plants can modulate their root performance in response to local root conditions related to sex. Female and male Populus cathayana cuttings were planted in a greenhouse in root-owner (one individual without a root neighbour) or root-sharer pairs (two individuals with roots neighbouring each other) with equal amounts of nutrients and space per plant in three combinations (females–females, males–males or females–males); root morphology, biomass and allocation were investigated. P. cathayana root-sharers altered their root growth in same-sex but not in different-sex combinations. Females enhanced root growth and allocation but decreased root proliferation (greater diameter with reduced branching and specific root length) in the presence of a female root neighbour, while males reduced root growth but increased root morphological proliferation in contact with another male. Therefore, the effect of a neighbour of the same sex differed from that of a neighbour of the opposite sex, which suggests that these plants can recognize the sexual identity of their neighbours.

Plants can detect the presence of their neighbors belowground, often responding with changes in root growth for resource competition. Recent evidence also implies that perception of neighbors may also elicit defense responses, however, the associated metabolic activities are unclear. We investigated primary and defense-related secondary metabolisms and hormone expressions in tobaccos (Nicotiana rustica) grown either with own roots or roots of another conspecifics in hydroponic condition. The results showed that non-self root interaction significantly reduced photosynthetic activity and assimilate production, leading to a reduction of growth. Non-self interaction also modified plant phenylpropanoids metabolism, yielding higher lignin content (i.e., structural resistance) at whole plant level and higher phenolics accumulation (i.e., chemical defense) in roots. All these metabolic responses were associated with enhanced expressions of phytohormones, particularly jasmonic acid, salicylic acid and cytokinin in roots and abscisic acid in leaves, at the early stage of non-self interaction. Since the presence of neighbors often increase the probability of attacks from, e.g., pathogens and pests, this defense activation may act as an adaptation of plants to these possible upcoming attacks.

Yunbin Xiao,1,* Zuan Tao Lin,2,* Yanmei Chen,1 He Wang,1 Ya Li Deng,2 D Elizabeth Le,3 Jianguo Bin,1 Meiyu Li,1 Yulin Liao,1 Yili Liu,1 Gangbiao Jiang,2 Jianping Bin1 1State Key Laboratory of Organ Failure Research, Division of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Pharmaceutical Engineering, South China Agricultural University, Guangzhou, People’s Republic of China; 3Cardiovascular Division, Oregon Health and Science University, Portland, OR, USA *These authors contributed equally to this work Abstract: Magnetic resonance imaging (MRI) contrast agents based on chitosan derivatives have great potential for diagnosing diseases. However, stable tumor-targeted MRI contrast agents using micelles prepared from high molecular weight chitosan derivatives are seldom reported. In this study, we developed a novel tumor-targeted MRI vehicle via superparamagnetic iron oxide nanoparticles (SPIONs) encapsulated in self-aggregating polymeric folate-conjugated N-palmitoyl chitosan (FAPLCS) micelles. The tumor-targeting ability of FAPLCS/SPIONs was demonstrated in vitro and in vivo. The results of dynamic light scattering experiments showed that the micelles had a relatively narrow size distribution (136.60±3.90 nm) and excellent stability. FAPLCS/SPIONs showed low cytotoxicity and excellent biocompatibility in cellular toxicity tests. Both in vitro and in vivo studies demonstrated that FAPLCS/SPIONs bound specifically to folate receptor-positive HeLa cells, and that FAPLCS/SPIONs accumulated predominantly in established HeLa-derived tumors in mice. The signal intensities of T2-weighted images in established HeLa-derived tumors were reduced dramatically after intravenous micelle administration. Our study indicates that FAPLCS/SPION micelles can potentially serve as safe and effective MRI contrast agents for detecting tumors that overexpress folate receptors. Keywords: superparamagnetic iron oxide, magnetic resonance imaging, polymeric micelles, folate receptors, tumor-targeted MRI, N-palmitoyl chitosan

High power short-pulse lasers presently reach peak powers of a few hundred Terawatts up to a Petawatt, and routinely reach focal intensities of 1018 - 1021 W/cm2 . These lasers are able to produce various secondary radiation, from relativistic electrons and multi-MeV/nucleon ions to high-energetic X-rays and γ-rays. In many laboratories world-wide large efforts are presently devoted to a rapid development of this novel tool of particle acceleration, targeting nuclear, fundamental and high-field physics studies as well as various applications. Based on the Radiation Pressure Acceleration mechanism, laser-accelerated ion beams can be generated with solid-state density, thus exceeding beams from conventional accelerators by about 14 orders of magnitudes. This opens the perspective of a novel reaction scheme called ’f ssion-fusion’, where in a first step f ssion is induced both in laser-accelerated f ssile projectiles from a ’production target’ and in a second ’reaction target’ again from f ssile material hit by the accelerated projectiles. Due to the unprecedented ion density, (neutron-rich) light f ssion fragments from projectile and target can fuse again, forming extremely exotic species approaching the region of the N = 126 waiting point of the r-process. Within the next 5 years a new EU-funded large-scale research infrastructure (ELI: Extreme Light Infrastructure) will be constructed, with one of its four pillars exclusively devoted to nuclear physics based on high intensity lasers (ELI-Nuclear Physics, to be built in Magurele/Bucharest). Studies of laser-induced nuclear reactions like the ’f ssion-fusion’ mechanism will be amongst the experimental f agship projects pursued there.

Magnetic Vortex Acceleration (MVA) from near critical density targets is one of the promising schemes of laser-driven ion acceleration. 3D particle-in-cell simulations are used to explore a more extensive laser-target parameter space than previously reported in the literature as well as to study the laser pulse coupling to the target, the structure of the fields, and the properties of the accelerated ion beam in the MVA scheme. The efficiency of acceleration depends on the coupling of the laser energy to the self-generated channel in the target. The accelerated proton beams demonstrate a high level of collimation with achromatic angular divergence, and carry a significant amount of charge. For petawatt-class lasers, this acceleration regime provides a favorable scaling of the maximum ion energy with the laser power for the optimized interaction parameters. The megatesla-level magnetic fields generated by the laser-driven coaxial plasma structure in the target are a prerequisite for accelerating protons to the energy of several hundred mega-electron-volts.

Access to finance is perceived as one of the major problems facing businesses in Sub-Saharan Africa, as well as the structures that support them in their development. This paper aims to measure the probability that a support structure with given characteristics, specific services to entrepreneurs and some technical capacities will face large-scale financial problems. We estimate a multinomial logistic model using a pool of disaggregated data collected by the Nkafu Policy Institute in a survey of 80 business support structures in Burkina Faso, Cameroon and Ghana in 2021. Our results show that the financial health of a business support structure is not fundamentally dependent on the duration of support, but rather on other factors related to the quality of services offered to entrepreneurs. [ABSTRACT FROM AUTHOR]

We report on a target system supporting automated positioning of nano-targets with a precision resolution of in three dimensions. It relies on a confocal distance sensor and a microscope. The system has been commissioned to position nanometer targets with 1Â Hz repetition rate. Integrating our prototype into the table-top ATLAS 300 TW-laser system at the Laboratory for Extreme Photonics in Garching, we demonstrate the operation of a 0.5Â Hz laser-driven proton source with a shot-to-shot variation of the maximum energy about 27% for a level of confidence of 0.95. The reason of laser shooting experiments operated at 0.5Â Hz rather than 1Â Hz is because the synchronization between the nano-foil target positioning system and the laser trigger needs to improve.

Abstract Acute-on-chronic liver failure (ACLF) is a syndrome characterized by the acute decompensation of chronic liver disease, resulting in organ failure and high short-term mortality. The progression of ACLF is dynamic and reversible in a considerable proportion of patients during hospitalization. Early detection and accurate assessment of ACLF are essential; however, ideal methods for this purpose are still lacking. Therefore, this study aimed to develop a new score for predicting the onset of ACLF in patients with various chronic liver diseases.A total of 6,188 patients with various chronic liver diseases were included in the study. Clinical and laboratory data were collected, and the occurrence of ACLF within 28 days was recorded. The Lasso-Cox regression method was employed to develop prediction models for the onset of ACLF at 7, 14, and 28 days. Among 5,221 patients without ACLF, 477 progressed to ACLF within 28 days. Seven predictors were identified as significantly associated with the occurrence of ACLF at 7, 14, and 28 days. A new scoring system was developed as follows: [NEUT ≥ 7, 109/L; 1 or 0] × 0.49 + [PLT 7, mmol/L; 1 or 0] × 0.51 + Ln[INR] × 0.87 + 3.40. This new score demonstrated superior discrimination, with the C-indexes of 0.958, 0.944, and 0.938 at 7, 14, and 28 days, respectively, outperforming those of four other scores (CLIF-C-ACLF-Ds, MELD, MELD-Na, and CLIF-C-ADs score; all P

Abstract Embryonal carcinoma (EC), characterized by a high degree of stemness similar to that of embryonic stem cells, is the most malignant subtype within non-seminomatous testicular germ cell tumors (TGCTs). However, the mechanisms underlying its malignancy remain unknown. In this study, we employed single-cell RNA sequencing to analyze four non-seminoma samples. Our differential expression analysis revealed high expression of SERPINB9 in metastatic EC cells. We conducted in vitro experiments to further investigate SERPINB9’s role in the progression of EC. Functionally, the knockdown of SERPINB9 in NCCIT and NTERA-2 leads to a diminished migratory capability and decreased cis-platin resistance, as demonstrated by Transwell migration assay and drug sensitivity assay. Moreover, embryoid bodies showed reduced size and lower OCT4 expression, alongside heightened expression of differentiation markers AFP, ACTA2, and CD57 in shSERPINB9 cells. In vivo, the role of SERPINB9 in maintaining cancer stemness was validated by the limiting dilution assay. Mechanistically, Bulk RNA-seq further showed downregulation of ERK1/2 signaling and WNT signaling pathways with concomitant upregulation of differentiation pathways subsequent to SERPINB9 knockdown. Additionally, the analysis indicated increased levels of cytokines linked to tertiary lymphoid structures (TLS), such as IL6, IL11, IL15, CCL2, CCL5, and CXCL13 in shSERPINB9 cells, which were further validated by ELISA. Our research indicates that SERPINB9 plays a key role in driving tumor progression by enhancing tumor stemness and suppressing TLS. This study stands as the first to elucidate the molecular signature of non-seminomas at a single-cell level, presenting a wealth of promising targets with substantial potential for informing the development of future therapeutic interventions.

Abstract Clinical proteomics analysis is of great significance for analyzing pathological mechanisms and discovering disease-related biomarkers. Using computational methods to accurately predict disease types can effectively improve patient disease diagnosis and prognosis. However, how to eliminate the errors introduced by peptide precursor identification and protein identification for pathological diagnosis remains a major unresolved issue. Here, we develop a powerful end-to-end deep learning model, termed “MS1Former”, that is able to classify hepatocellular carcinoma tumors and adjacent non-tumor (normal) tissues directly using raw MS1 spectra without peptide precursor identification. Our model provides accurate discrimination of subtle m/z differences in MS1 between tumor and adjacent non-tumor tissue, as well as more general performance predictions for data-dependent acquisition, data-independent acquisition, and full-scan data. Our model achieves the best performance on multiple external validation datasets. Additionally, we perform a detailed exploration of the model’s interpretability. Prospectively, we expect that the advanced end-to-end framework will be more applicable to the classification of other tumors.

V and Cr bimetals are utilized as interlayers in the vacuum diffusion bonding of TA2 Ti and 20# steel to prevent the formation of Ti–Fe intermetallic compounds and improve the interface compatibility. The microstructure and mechanical properties of the diffusion-bonded joints are investigated using optical microscopy, scanning electron microscopy combined with energy dispersive spectroscopy, transmission electron microscopy, X-ray diffraction, nanoindentation, and tensile testing. The results indicate that the V/Cr bimetallic interlayer effectively inhibits the formation of Ti–Fe intermetallic compounds, with solid solutions without these compounds present at the Ti/V and steel/Cr interfaces. However, a 1–3-μm-thick continuous, hard, brittle vanadium carbide layer with hardness and elastic modulus value of 6.66 GPa and 201.55 GPa is unexpectedly discovered at the interface between V and Cr. The fracture morphology analysis reveals that the continuous carbide layer at the V/Cr interface is the primary cause of joint failure. The tensile strength of the joint remains relatively stable with an increase in the bonding temperature, whereas the elongation gradually decreases. A maximum tensile strength of 252 MPa is achieved with an elongation of 4.3%.

The AlN particles reinforced Mg-10Gd-3Y–1Zn (GWZ) composites were prepared by mixing AlN/Al particles using ball milling followed by stirring casting method. The influence of AlN/Al particles on the microstructural evolution and high-temperature mechanical properties of GWZ alloys were revealed and discussed. With AlN/Al particles added into the as-cast alloys, the Mg3RE phase was transformed into lamellar LPSO phase, while the content of Al2RE and LPSO phase increased. Since the Al2RE and AlN were effective nucleation sites for α-Mg, the grain size of AlN/Al-GWZ composites was reduced obviously from 126.1 to 39.8 μm. After homogenization, due to the coherent lattice matching relationships between 18R-LPSO phase and Al2RE or AlN particles, the 18R-LPSO phase nucleated on the Al2RE and AlN particles. After ageing treatment, the 2AlN/Al-GWZ composite showed the optimum mechanical properties at 250 °C, with the yield strength, ultimate tensile strength and elongation of 247.1 MPa, 265.5 MPa and 4.0%, respectively. The strengthening effect was primarily originated from the AlN particles, Al2RE and LPSO phases in the 2AlN/Al-GWZ composite. Besides, the composites can achieve the enhancement of high-temperature strength without the sacrifice of plasticity due to the coordinated deformation of AlN particles as well as the refinement of grains.

Abstract Background Thymoma is a primary tumor of the thymus, commonly located in the anterior mediastinum. Most thymomas are benign or low‐grade malignant, but they can invade surrounding organs or metastasize. The primary treatment for thymoma is surgical resection. Traditional methods involve open thoracotomy, but it is traumatic, with slow recovery and many complications. In recent years, with the development of thoracoscopic techniques, thoracoscopic total thymectomy has gradually become the preferred method for small size thymomas due to its minimally invasive, safe, and effective. Methods This paper introduces a thoracoscopic extend thymectomy technique, the subxiphoid video–assisted thoracoscopic extend thymectomy with sternal suspension. This method involves placing hooks at the upper and lower ends of the sternum to suspend the sternum upward, increasing the thoracic cavity space and facilitating thoracoscopic operations. This research reviews the clinical data of 59 patients with early‐stage thymomas treated with this technique at our center since 2020 and analyzes the perioperative therapeutic efficacy and safety. It also compares the outcomes with those of 17 patients who underwent thoracoscopic approaches. Results The results show that subxiphoid video–assisted thoracoscopic total thymectomy with sternal suspension is an innovative and effective surgical method, achieving the same tumor eradication as other thoracic surgeries. The flexible switching of observation ports provides a more comprehensive surgical field, reduces surgical trauma and complications, and improves the surgical outcomes and quality of life for patients.

Solubility enhancement of poorly aqueous-soluble drugs, like Terbinafine (TBN), is a critical challenge in formulating effective dosage forms. This study focused on developing β-cyclodextrin (β-CD) and polyacrylamide (PAM)-based microgels to address the solubility issue of TBN, classified as a biopharmaceutics classification system class II drug. The microgels were crafted through free radical polymerization, employing methylene bisacylamide as a cross-linker and methacrylic acid as a monomer, initiated by ammonium persulfate. Comprehensive characterizations, including Fourier transform infrared, thermo-gravimetric analysis, differential scanning calorimetry, scanning electron microscopy, powder X-ray diffractometry analysis, Zeta size, and Zeta potential, were conducted. In vitro studies, such as drug release and swelling, were performed at pH 1.2. Toxicity analysis in rabbits revealed zero toxicity. These β-CD/PAM microgels successfully enhanced the solubility of TBN.

Androgen‐regulated DNA damage response (DDR) is one of the essential mechanisms in prostate cancer (PCa), a hormone‐sensitive disease. The heterogeneous nuclear ribonucleoprotein K (hnRNPK)‐homology splicing regulatory protein known as far upstream element‐binding protein 2 (KHSRP) is an RNA‐binding protein that can attach to AU‐rich elements in the 3′ untranslated region (3′‐UTR) of messenger RNAs (mRNAs) to mediate mRNA decay and emerges as a critical regulator in the DDR to preserve genome integrity. Nevertheless, how KHSRP responds to androgen‐regulated DDR in PCa development remains unclear. This study found that androgen can significantly induce acetylation of KHSRP, which intrinsically drives tumor growth in xenografted mice. Moreover, enhanced KHSRP acetylation upon androgen stimuli impedes KHSRP‐regulated DDR gene expression, as seen by analyzing RNA sequencing (RNA‐seq) and Gene Set Enrichment Analysis (GSEA) datasets. Additionally, NAD‐dependent protein deacetylase sirtuin‐7 (SIRT7) is a promising deacetylase of KHSRP, and androgen stimuli impairs its interaction with KHSRP to sustain the increased KHSRP acetylation level in PCa. We first report the acetylation of KHSRP induced by androgen, which interrupts the KHSRP‐regulated mRNA decay of the DDR‐related genes to promote the tumorigenesis of PCa. This study provides insight into KHSRP biology and potential therapeutic strategies for PCa treatment, particularly that of castration‐resistant PCa.

Mg–3Y/Al composites were produced through accumulated rolling bonding. During annealing, Al–Y precipitates were synthesized in-situ within the Mg–3Y/Al composites through solid diffusion reactions. In these composites, the volume fraction of the interface layer containing abundant Al–Y precipitates can reach approximately 74% after three passes of accumulated rolling bonding and diffusion annealing. At room temperature, the Mg–3Y/Al composite exhibits increased strength (∼273.9 MPa) but reduced ductility (∼3.5%) compared to the base Mg–3Y alloy (∼191.0 MPa, ∼30%), due to the presence of numerous Al–Y precipitates and residual dislocations. These Al–Y precipitates display remarkable thermal stability, maintaining their size without significant coarsening even after annealing at 400 °C for 1–4 h, thereby contributing to the exceptional thermal stability observed in Mg–3Y/Al samples. After annealing at 400 °C for 4 h, the tensile strength of the Mg–3Y/Al samples remained unchanged, while the ductility increased to 8.5%. At 300 °C, the Mg–3Y/Al composite demonstrates exceptional high-temperature strength (179.9 MPa), significantly surpassing that of the original Mg–3Y alloy (110.6 MPa). Moreover, compared to the original Mg–3Y alloy and magnesium alloys reported in the literature, the Mg–3Y/Al composite exhibits a higher RE-equivalent strength at 300 °C. This enhanced strength is primarily attributed to precipitation strengthening induced by fine Al–Y precipitates. These findings underscore that introducing fine Al–Y precipitates through a solid diffusion reaction is an effective approach for achieving outstanding high-temperature strength in magnesium alloys.

Abstract The Omicron subvariants of SARS-CoV-2, especially for BA.2.86 and JN.1, have rapidly spread across multiple countries, posing a significant threat in the ongoing COVID-19 pandemic. Distinguished by 34 additional mutations on the Spike (S) protein compared to its BA.2 predecessor, the implications of BA.2.86 and its evolved descendant, JN.1 with additional L455S mutation in receptor-binding domains (RBDs), are of paramount concern. In this work, we systematically examine the neutralization susceptibilities of SARS-CoV-2 Omicron subvariants and reveal the enhanced antibody evasion of BA.2.86 and JN.1. We also determine the cryo-EM structures of the trimeric S proteins from BA.2.86 and JN.1 in complex with the host receptor ACE2, respectively. The mutations within the RBDs of BA.2.86 and JN.1 induce a remodeling of the interaction network between the RBD and ACE2. The L455S mutation of JN.1 further induces a notable shift of the RBD–ACE2 interface, suggesting the notably reduced binding affinity of JN.1 than BA.2.86. An analysis of the broadly neutralizing antibodies possessing core neutralizing epitopes reveals the antibody evasion mechanism underlying the evolution of Omicron BA.2.86 subvariant. In general, we construct a landscape of evolution in virus-receptor of the circulating Omicron subvariants.

Abstract Head pose estimation is an especially challenging task due to the complexity nonlinear mapping from 2D feature space to 3D pose space. To address the above issue, this paper presents a novel and efficient head pose estimation framework based on particle swarm optimized contrastive learning and multimodal entangled graph convolution network. Firstly, a new network, the region and difference‐aware feature pyramid network (RD‐FPN), is proposed for 2D keypoints detection to alleviate the background interference and enhance the feature expressiveness. Then, particle swarm optimized contrastive learning is constructed to alternatively match 2D and 3D keypoints, which takes the multimodal keypoints matching accuracy as the optimization objective, while considering the similarity of cross‐modal positive and negative sample pairs from contrastive learning as a local contrastive constraint. Finally, multimodal entangled graph convolution network is designed to enhance the ability of establishing geometric relationships between keypoints and head pose angles based on second‐order bilinear attention, in which point‐edge attention is introduced to improve the representation of geometric features between multimodal keypoints. Compared with other methods, the average error of our method is reduced by 8.23%, indicating the accuracy, generalization, and efficiency of our method on the 300W‐LP, AFLW2000, BIWI datasets.

Aluminum alloys have been widely used in engineering due to their high strength and low density. However, their poor corrosion and wear resistance have largely limited their application in marine equipment. This study successfully improved the corrosion and wear resistance of a typical 7075 Al alloy by depositing a high-performance TC4 titanium alloy coating using in-house annular laser cladding equipment. Microstructural investigations revealed that the defect-free TC4 coating is metallurgically bonded to the 7075 Al alloy substrate along with excellent bond strength. Electrochemical test results showed that compared to the hot-forged 7075 Al alloy and hot-forged double-phase TC4 bulk alloy, the TC4 coating exhibits superior corrosion resistance due to its net-basket α-single-phase microstructure. Further, wear testing results showed that the coefficient of friction and wear volume of the TC4 coating are far lower than that of 7075 Al alloy. The enhanced wear resistance is closely related to the high hardness of the TC4 coating and its excellent fatigue-wear resistance. Therefore, this work can serve as a reference to improve Aluminum alloys' corrosion and wear resistance by depositing Titanium alloy coatings using the annular laser cladding process, which shall widen the potential applications of Aluminum alloys in marine equipment.

Background/Aims: As a very common malignancy of the digestive system, the incidence and mortality rates of gastric cancer (GC) are increasing year by year. The critical role of ferroptosis in cancer development has been well-documented. The polyphenol compound curcumin shows prominent anti-tumor effects in multiple cancer types, including GC. However, whether curcumin participates in GC tumorigenesis by regulating ferroptosis remains unknown. Materials and Methods: Gastric cancer cells AGS and HGC-27 were treated with curcumin (0, 10, and 20 μM). Cell viability and death were evaluated through CCK-8 and LDH release assays. LC3B expression in cells was estimated through immunofluorescence staining. Intracellular ferrous iron (Fe2+), GSH, MDA, and lipid ROS levels were assessed by corresponding assay kits. The cellular levels of autophagy markers (ATG5, ATG7, Beclin 1, and LC3B), ferroptosis markers (ACSL4, SLC7A11, and GPX4), and phosphorylated (p)-PI3K, p-AKT, and p-mTOR were determined through western blotting. Results: Curcumin attenuated cell viability but stimulated cell death in GC cells. Curcumin enhanced autophagy in GC cells, as demonstrated by the increased levels of ATG5, ATG7, Beclin 1, and LC3B. Besides, curcumin upregulated iron, MDA, GSH, and ACSL4 levels while downregulated lipid ROS, SLC7A11, and GPX4 levels, suggesting its stimulation on ferroptosis in GC cells. Curcumin decreased p-PI3K, p-AKT, and p-mTOR levels in cells. Importantly, the ferroptosis inhibitor ferrostatin-1 overturned the impacts of curcumin on GC cell viability, death, and ferroptosis. Conclusion: Curcumin suppresses GC development by inducing autophagy-mediated ferroptosis by inactivating the PI3K/AKT/mTOR signaling.

Abstract Increased fatty acid synthesis benefits glioblastoma malignancy. However, the coordinated regulation of cytosolic acetyl-CoA production, the exclusive substrate for fatty acid synthesis, remains unclear. Here, we show that proto-oncogene tyrosine kinase c-SRC is activated in glioblastoma and remodels cytosolic acetyl-CoA production for fatty acid synthesis. Firstly, acetate is an important substrate for fatty acid synthesis in glioblastoma. c-SRC phosphorylates acetyl-CoA synthetase ACSS2 at Tyr530 and Tyr562 to stimulate the conversion of acetate to acetyl-CoA in cytosol. Secondly, c-SRC inhibits citrate-derived acetyl-CoA synthesis by phosphorylating ATP-citrate lyase ACLY at Tyr682. ACLY phosphorylation shunts citrate to IDH1-catalyzed NADPH production to provide reducing equivalent for fatty acid synthesis. The c-SRC-unresponsive double-mutation of ACSS2 and ACLY significantly reduces fatty acid synthesis and hampers glioblastoma progression. In conclusion, this remodeling fulfills the dual needs of glioblastoma cells for both acetyl-CoA and NADPH in fatty acid synthesis and provides evidence for glioma treatment by c-SRC inhibition.

Abstract The concept of Yin-Yang, originating in ancient Chinese philosophy, symbolizes two opposing but complementary forces or principles found in all aspects of life. This concept can be quite fitting in the context of extracellular vehicles (EVs) and inflammatory diseases. Over the past decades, numerous studies have revealed that EVs can exhibit dual sides, acting as both pro- and anti-inflammatory agents, akin to the concept of Yin-Yang theory (i.e., two sides of a coin). This has enabled EVs to serve as potential indicators of pathogenesis or be manipulated for therapeutic purposes by influencing immune and inflammatory pathways. This review delves into the recent advances in understanding the Yin-Yang sides of EVs and their regulation in specific inflammatory diseases. We shed light on the current prospects of engineering EVs for treating inflammatory conditions. The Yin-Yang principle of EVs bestows upon them great potential as, therapeutic, and preventive agents for inflammatory diseases. Graphical Abstract