Dramatic Enhancement Enabled by Introducing TiN into Bread-like Porous Si-Carbon Anodes for High-Performance and Safe Lithium Storage.

Doping modifications and surface coatings are effective methods to slow volume dilatation and boost the conductivity in silicon (Si) anodes for lithium-ion batteries (LIBs). Herein, using low-cost ferrosilicon from industrial production as the energy storage material, a bread-like nitrogen-doped carbon shell-coated porous Si embedded with the titanium nitride (TiN) nanoparticle composite (PSi/TiN@NC) was synthesized by simple ball milling, etching, and self-assembly growth processes. Remarkably, the porous Si structure formed by etching the FeSi2 phase in ferrosilicon alloys can provide buffer space for significant volume expansion during lithiation. Highly conductive and stable TiN particles can act as stress absorption sites for Si and improve the electronic conductivity of the material. Furthermore, the nitrogen-doped porous carbon shell further helps to sustain the structural stability of the electrode material and boost the migration rate of Li-ions. Benefiting from its unique synergistic effect of components, the PSi/TiN@NC anode exhibits a reversible discharge capacity up to 1324.2 mAh g-1 with a capacity retention rate of 91.5% after 100 cycles at 0.5 A g-1 (vs fourth discharge). Simultaneously, the electrode also delivers good rate performance and a stable discharge capacity of 923.6 mAh g-1 over 300 cycles. This research can offer a potential economic strategy for the development of high-performance and inexpensive Si-based anodes for LIBs.

LncRNA lncLLM Facilitates Lipid Deposition by Promoting the Ubiquitination of MYH9 in Chicken LMH Cells.

The liver plays an important role in regulating lipid metabolism in animals. This study investigated the function and mechanism of lncLLM in liver lipid metabolism in hens at the peak of egg production. The effect of lncLLM on intracellular lipid content in LMH cells was evaluated by qPCR, Oil Red O staining, and detection of triglyceride (TG) and cholesterol (TC) content. The interaction between lncLLM and MYH9 was confirmed by RNA purification chromatin fractionation (CHIRP) and RNA immunoprecipitation (RIP) analysis. The results showed that lncLLM increased the intracellular content of TG and TC and promoted the expression of genes related to lipid synthesis. It was further found that lncLLM had a negative regulatory effect on the expression level of MYH9 protein in LMH cells. The intracellular TG and TC content of MYH9 knockdown cells increased, and the expression of genes related to lipid decomposition was significantly reduced. In addition, this study confirmed that the role of lncLLM is at least partly through mediating the ubiquitination of MYH9 protein to accelerate the degradation of MYH9 protein. This discovery provides a new molecular target for improving egg-laying performance in hens and treating fatty liver disease in humans.

Single nucleus/cell RNA-seq of the chicken hypothalamic-pituitary-ovarian axis offers new insights into the molecular regulatory mechanisms of ovarian development.

The hypothalamic-pituitary-ovarian (HPO) axis represents a central neuroendocrine network essential for reproductive function. Despite its critical role, the intrinsic heterogeneity within the HPO axis across vertebrates and the complex intercellular interactions remain poorly defined. This study provides the first comprehensive, unbiased, cell type-specific molecular profiling of all three components of the HPO axis in adult Lohmann layers and Liangshan Yanying chickens. Within the hypothalamus, pituitary, and ovary, seven, 12, and 13 distinct cell types were identified, respectively. Results indicated that the pituitary adenylate cyclase activating polypeptide (PACAP), follicle-stimulating hormone (FSH), and prolactin (PRL) signaling pathways may modulate the synthesis and secretion of gonadotropin-releasing hormone (GnRH), FSH, and luteinizing hormone (LH) within the hypothalamus and pituitary. In the ovary, interactions between granulosa cells and oocytes involved the KIT, CD99, LIFR, FN1, and ANGPTL signaling pathways, which collectively regulate follicular maturation. The SEMA4 signaling pathway emerged as a critical mediator across all three tissues of the HPO axis. Additionally, gene expression analysis revealed that relaxin 3 (RLN3), gastrin-releasing peptide (GRP), and cocaine- and amphetamine regulated transcripts (CART, also known as CARTPT) may function as novel endocrine hormones, influencing the HPO axis through autocrine, paracrine, and endocrine pathways. Comparative analyses between Lohmann layers and Liangshan Yanying chickens demonstrated higher expression levels of GRP, RLN3, CARTPT, LHCGR, FSHR, and GRPR in the ovaries of Lohmann layers, potentially contributing to their superior reproductive performance. In conclusion, this study provides a detailed molecular characterization of the HPO axis, offering novel insights into the regulatory mechanisms underlying reproductive biology.

SIRT7 protects against liver fibrosis by suppressing stellate cell activation via TGF-ß/SMAD2/3 pathway.

BACKGROUND: SIRT7 is a class III HDACs deacetylase which plays critical roles in various biological processes. Aberrant SIRT7 expression is associated with tumorigenesis and disease progression while role of SIRT7 in hepatic fibrosis remain elusive. METHODS: SIRT7 expression was examined in fibrotic liver sample via WB and IHC. Myeloid cell-specific knockout (SIRT7MKO) mice were generated by crossing SIRT7flox/flox mice with LysM-Cre mice. Primary hepatic stellate cells (HSCs) was isolated to examine stellate cells activation. SIRT7 and SMAD2/3 interaction were analyzed by immunoprecipitation. SB525334 was used to prevent SMAD2/3 phosphorylation. RESULTS: SIRT7 expression was decreased during chronic liver disease progression but was increased in liver cancer. IHC staining indicated that SIRT7 was primarily expressed in non-parenchymal cells in both fibrotic and cirrhotic liver. Knockout SIRT7 in myeloid cells resulted in significant elevation of serum ALT and liver fibrosis, but mildly affected hepatic inflammation after CCl4 treatment. We further observed significant elevation of elevation of stellate cell activation and SMAD2/3 activation in SIRT7MKO mice. By using primary HSCs and stellate cell line, we confirmed that SIRT7 interacted with SMAD2/3, induced its deacetylation and was critical in regulation of SMAD2/3 activation and stellate cell activation upon TGF-ß stimulation. Pharmacological inhibition of SMAD2/3 reversed the hyperactivation of SIRT7MKO HSCs after TGF-ß stimulation, and abolished stellate cell activation and liver fibrosis in SIRT7MKO mice. CONCLUSION: Our findings revealed previously unidentified role of SIRT7 in regulating HSCs activation via modulating TGF-ß/SMAD2/3 signaling pathway. Targeting SIRT7 might offer novel therapeutic option against liver fibrosis.

VT-3DCapsNet: Visual tempos 3D-Capsule network for video-based facial expression recognition.

Facial expression recognition(FER) is a hot topic in computer vision, especially as deep learning based methods are gaining traction in this field. However, traditional convolutional neural networks (CNN) ignore the relative position relationship of key facial features (mouth, eyebrows, eyes, etc.) due to changes of facial expressions in real-world environments such as rotation, displacement or partial occlusion. In addition, most of the works in the literature do not take visual tempos into account when recognizing facial expressions that possess higher similarities. To address these issues, we propose a visual tempos 3D-CapsNet framework(VT-3DCapsNet). First, we propose 3D-CapsNet model for emotion recognition, in which we introduced improved 3D-ResNet architecture that integrated with AU-perceived attention module to enhance the ability of feature representation of capsule network, through expressing deeper hierarchical spatiotemporal features and extracting latent information (position, size, orientation) in key facial areas. Furthermore, we propose the temporal pyramid network(TPN)-based expression recognition module(TPN-ERM), which can learn high-level facial motion features from video frames to model differences in visual tempos, further improving the recognition accuracy of 3D-CapsNet. Extensive experiments are conducted on extended Kohn-Kanada (CK+) database and Acted Facial Expression in Wild (AFEW) database. The results demonstrate competitive performance of our approach compared with other state-of-the-art methods.

Autophagy in hematopoietic stem cell development of the embryo.

Hematopoietic stem cells (HSC) emerge from hemogenic endothelial cells (HEC) in the aorta-gonad-mesonephros (AGM) region of embryos, which go through the pre-HSC process. Various intrinsic and extrinsic factors are involved in this process. We recently discovered that the existence of distinct macroautophagic/autophagic statuses in hematopoietic precursors is related to the hematopoietic potential of pre-HSCs and the depletion of the Atg5 (autophagy related 5) gene specifically in endothelial cells impaired in the transition of endothelial to pre-HSCs, by hampering the autophagic process, likely via the NCL (nucleolin) pathway.Abbreviation: Atg5: autophagy related 5; EGFP: enhanced green fluorescent protein; EHT: endothelial-to-hematopoietic transition; HEC: hemogenic endothelial cell; HSC: hematopoietic stem cell; NCL: nucleolin; RFP: red fluorescent protein.

A subset of megakaryocytes regulates development of hematopoietic stem cell precursors.

Understanding the regulatory mechanisms facilitating hematopoietic stem cell (HSC) specification during embryogenesis is important for the generation of HSCs in vitro. Megakaryocyte emerged from the yolk sac and produce platelets, which are involved in multiple biological processes, such as preventing hemorrhage. However, whether megakaryocytes regulate HSC development in the embryonic aorta-gonad-mesonephros (AGM) region is unclear. Here, we use platelet factor 4 (PF4)-Cre;Rosa-tdTomato+ cells to report presence of megakaryocytes in the HSC developmental niche. Further, we use the PF4-Cre;Rosa-DTA (DTA) depletion model to reveal that megakaryocytes control HSC specification in the mouse embryos. Megakaryocyte deficiency blocks the generation and maturation of pre-HSCs and alters HSC activity at the AGM. Furthermore, megakaryocytes promote endothelial-to-hematopoietic transition in a OP9-DL1 coculture system. Single-cell RNA-sequencing identifies megakaryocytes positive for the cell surface marker CD226 as the subpopulation with highest potential in promoting the hemogenic fate of endothelial cells by secreting TNFSF14. In line, TNFSF14 treatment rescues hematopoietic cell function in megakaryocyte-depleted cocultures. Taken together, megakaryocytes promote production and maturation of pre-HSCs, acting as a critical microenvironmental control factor during embryonic hematopoiesis.

Autophagy regulates the maturation of hematopoietic precursors in the embryo.

An understanding of the mechanisms regulating embryonic hematopoietic stem cell (HSC) development would facilitate their regeneration. The aorta-gonad-mesonephros region is the site for HSC production from hemogenic endothelial cells (HEC). While several distinct regulators are involved in this process, it is not yet known whether macroautophagy (autophagy) plays a role in hematopoiesis in the pre-liver stage. Here, we show that different states of autophagy exist in hematopoietic precursors and correlate with hematopoietic potential based on the LC3-RFP-EGFP mouse model. Deficiency of autophagy-related gene 5 (Atg5) specifically in endothelial cells disrupts endothelial to hematopoietic transition (EHT), by blocking the autophagic process. Using combined approaches, including single-cell RNA-sequencing (scRNA-seq), we have confirmed that Atg5 deletion interrupts developmental temporal order of EHT to further affect the pre-HSC I maturation, and that autophagy influences hemogenic potential of HEC and the formation of pre-HSC I likely via the nucleolin pathway. These findings demonstrate a role for autophagy in the formation/maturation of hematopoietic precursors.

TRIM21 is critical in regulating hepatocellular carcinoma growth and response to therapy by altering the MST1/YAP pathway.

Liver cancer is the sixth most common cancer and the third leading cause of cancer-related death globally. Despite efforts being made in last two decades in cancer diagnosis and treatment, the 5-year survival rate of liver cancer remains extremely low. TRIM21 participates in cancer metabolism, glycolysis, immunity, chemosensitivity and metastasis by targeting various substrates for ubiquitination. TRIM21 serves as a prognosis marker for human hepatocellular carcinoma (HCC), but the mechanism by which TRIM21 regulates HCC tumorigenesis and progression remains elusive. In this study, we demonstrated that TRIM21 protein levels were elevated in human HCC. Elevated TRIM21 expression was associated with HCC progression and poor survival. Knockdown of TRIM21 in HCC cell lines significantly impaired cell growth and metastasis and enhanced sorafenib-induced toxicity. Mechanistically, we found that knockdown of TRIM21 resulted in cytosolic translocation and inactivation of YAP. At the molecular level, we further identified that TRIM21 interacted and induced ubiquitination of MST1, which resulted in MST1 degradation and YAP activation. Knockdown of MST1 or overexpression of YAP reversed TRIM21 knockdown-induced impairment of HCC growth and chemosensitivity. Taken together, the current study demonstrates a novel mechanism that regulates the Hippo pathway and reveals TRM21 as a critical factor that promotes growth and chemoresistance in human HCC.

Identification of a novel FOXO3 agonist that protects against alcohol induced liver injury.

Alcohol-related liver disease (ALD) is a global healthcare concern which caused by excessive alcohol consumption with limited treatment options. The pathogenesis of ALD is complex and involves in hepatocyte damage, hepatic inflammation, increased gut permeability and microbiome dysbiosis. FOXO3 is a well-recognized transcription factor which associated with longevity via promoting antioxidant stress response, preventing senescence and cell death, and inhibiting inflammation. We and many others have reported that FOXO3-/- mice develop more severe liver injury in response to alcohol. In the present study, we aimed to develop compounds that activate FOXO3 and further investigate their effects in alcohol induced liver injury. Through virtual screening, we discovered series of small molecular compounds that showed high affinity to FOXO3. We confirmed effects of compounds on FOXO3 target gene expression, as well as antioxidant and anti-apoptotic effects in vitro. Subsequently we evaluated the protective efficacy of compounds in alcohol induced liver injury in vivo. As a result, the leading compound we identified, 214991, activated downstream target genes expression of FOXO3, inhibited intracellular ROS accumulation and cell apoptosis induced by H2O2 and sorafenib. By using Lieber-DeCarli alcohol feeding mouse model, 214991 showed protective effects against alcohol-induced liver inflammation, macrophage and neutrophil infiltration, and steatosis. These findings not only reinforce the potential of FOXO3 as a valuable target for therapeutic intervention of ALD, but also suggested that compound 214991 as a promising candidate for the development of innovative therapeutic strategies of ALD.

A multi-objective optimization evaluation model for seismic performance of slopes reinforced by pile-anchor system.

The significance means of the seismic reinforcement effect of a pile-anchor system for slope reinforcement has been widely recognized. However, cases of deformation failure and instability sliding of the pile-anchor system itself and the reinforced slope under seismic action continue to be recorded. Therefore, it is crucial to evaluate the seismic performance of slopes reinforced by a pile-anchor system to prevent the system's failure. Current evaluation models of a slope reinforced by a pile-anchor system mainly focus on slope stability; however, the safety of the pile-anchor system itself is not sufficiently considered in these models. Consequently, in this study, we propose a multi-objective optimization evaluation (MOE) model for evaluating the seismic performance of slopes reinforced by a pile-anchor system that considers slope stability, safety of the pile-anchor system, and dynamic response of the slope. This model considers slope displacement, acceleration amplification factor of a slope, pile displacement, and anchor displacement as negative indexes, and anti-slide pile bending moment, shear force, and anchor axial force as intermediate indexes. The comprehensive weight of relevant indexes is obtained by combining subjective and objective weights, and the seismic reinforcement effect of the pile-anchor system is evaluated subsequently. In conclusion, the MOE model proposed in this study provides a novel solution for the optimization evaluation of a slope reinforced by a pile-anchor system in forthcoming projects.

SIRT7 promotes Hippo/YAP activation and cancer cell proliferation in hepatocellular carcinoma via suppressing MST1.

Abnormal activation of the oncogene YAP in the Hippo pathway is a major feature in liver cancer and inactivation of MST1/2 has been shown to be responsible for the overactivation of YAP that led to tumorigenesis. However, mechanisms underlying MST1/2 dysregulation remain poorly understood. RNA-seq analysis and genome (KEGG) pathway enrichment analysis were used to identify genes and pathways that were regulated by SIRT7. qRT-PCR, ChIP, and luciferase assay were used to investigate transcriptional regulation. Mass spectrometry, co-immunoprecipitation and immunoprecipitation were used to exam protein-protein interaction and post-transcriptional modification. A xenograft mouse model was used to confirm the effect of SIRT7 and SIRT7 inhibitors on hepatocellular carcinoma (HCC) proliferation in vivo. We found that SIRT7 suppresses MST1 by both transcriptional regulation and post-transcriptional modification, which in turn promotes YAP nuclear localization and transcriptional activation in liver cancer. Mechanistically, we revealed that SIRT7 suppresses MST1 transcription by binding to the MST1 promoter and inducing H3K18 deacetylation in its promoter region. In addition, SIRT7 directly binds to and deacetylates MST1, which primes acetylation-dependent MST1 ubiquitination and protein degradation. In clinical samples, we confirmed a negative correlation between SIRT7 and MST1 protein levels, and high SIRT7 expression correlated with elevated YAP expression and nuclear localization. In addition, SIRT7 specific inhibitor 2800Z sufficiently inhibited HCC growth by disrupting the SIRT7/MST1/YAP axis. Our data thus revealed the previously undescribed function of SIRT7 in regulating the Hippo pathway in HCC and further proved that targeting SIRT7 might provide novel therapeutic options for the treatment of liver cancer.

Dual immobilization of porous Si by graphene supported anatase TiO2/carbon for high-performance and safe lithium storage.

Smart surface coatings have been proven to be an effective strategy to significantly enhance the electronic conductivity and cycling stability of silicon-based anode materials. However, the single/conventional coatings face critical challenges, including low initial Coulomb efficiency (ICE), poor cyclability, and kinetics failure, etc. Hence, we proposed a dual immobilization strategy to synthesize graphene supported anatase TiO2/carbon-coated porous silicon composite (denoted as PSi@TiO2@C/Graphene) using industrial-grade ferrosilicon as lithium storage raw materials through the simple etching, combined with sol-gel and hydrothermal coating processes. In this work, the dual immobilization from the "confinement effect" of the inner TiO2 shell and the "synergistic effect" of the outer carbon shell, improves the kinetics of the electrochemical reaction and ensures the integrity of the electrode material structure during lithiation. Furthermore, the introduction of the graphene substrate offers ample space for dispersing and anchoring the Si-based granules, which in turn provides a stable 3D conductive network between the particles. As a result, the PSi@TiO2@C/Graphene electrode delivers high reversible capacity of 1605.4 mAh g-1 with 93.65% retention at 0.5 A g-1 after 100 cycles (vs. 4th discharge), high initial Coulomb efficiency (82.30%), and superior cyclability of 1159.9 mAh g-1 after 250 cycles. The above results suggest that the particle structure has great potential for applications in Si-based anode and may provide some inspiration for the design of other energy storage materials.

Ultrathin Van der Waals Lanthanum Oxychloride Dielectric for 2D Field-Effect Transistors.

Downsizing silicon-based transistors can result in lower power consumption, faster speeds, and greater computational capacity, although it is accompanied by the appearance of short-channel effects. The integration of high-mobility 2D semiconductor channels with ultrathin high dielectric constant (high-κ) dielectric in transistors is expected to suppress the effect. Nevertheless, the absence of a high-κ dielectric layer featuring an atomically smooth surface devoid of dangling bonds poses a significant obstacle in the advancement of 2D electronics. Here, ultrathin van der Waals (vdW) lanthanum oxychloride (LaOCl) dielectrics are successfully synthesized by precisely controlling the growth kinetics. These dielectrics demonstrate an impressive high-κ value of 10.8 and exhibit a remarkable breakdown field strength (Ebd ) exceeding 10 MV cm-1 . Remarkably, the conventional molybdenum disulfide (MoS2 ) field-effect transistor (FET) featuring a dielectric made of LaOCl showcases an almost negligible hysteresis when compared to FETs employing alternative gate dielectrics. This can be attributed to the flawlessly formed vdW interface and excellent compatibility established between LaOCl and MoS2 . These findings will motivate the further exploration of rare-earth oxychlorides and the development of more-than-Moore nanoelectronic devices.

WGX50 mitigates doxorubicin-induced cardiotoxicity through inhibition of mitochondrial ROS and ferroptosis.

BACKGROUND: Doxorubicin (DOX)-induced cardiotoxicity (DIC) is a major impediment to its clinical application. It is indispensable to explore alternative treatment molecules or drugs for mitigating DIC. WGX50, an organic extract derived from Zanthoxylum bungeanum Maxim, has anti-inflammatory and antioxidant biological activity, however, its function and mechanism in DIC remain unclear. METHODS: We established DOX-induced cardiotoxicity models both in vitro and in vivo. Echocardiography and histological analyses were used to determine the severity of cardiac injury in mice. The myocardial damage markers cTnT, CK-MB, ANP, BNP, and ferroptosis associated indicators Fe2+, MDA, and GPX4 were measured using ELISA, RT-qPCR, and western blot assays. The morphology of mitochondria was investigated with a transmission electron microscope. The levels of mitochondrial membrane potential, mitochondrial ROS, and lipid ROS were detected using JC-1, MitoSOX™, and C11-BODIPY 581/591 probes. RESULTS: Our findings demonstrate that WGX50 protects DOX-induced cardiotoxicity via restraining mitochondrial ROS and ferroptosis. In vivo, WGX50 effectively relieves doxorubicin-induced cardiac dysfunction, cardiac injury, fibrosis, mitochondrial damage, and redox imbalance. In vitro, WGX50 preserves mitochondrial function by reducing the level of mitochondrial membrane potential and increasing mitochondrial ATP production. Furthermore, WGX50 reduces iron accumulation and mitochondrial ROS, increases GPX4 expression, and regulates lipid metabolism to inhibit DOX-induced ferroptosis. CONCLUSION: Taken together, WGX50 protects DOX-induced cardiotoxicity via mitochondrial ROS and the ferroptosis pathway, which provides novel insights for WGX50 as a promising drug candidate for cardioprotection.

Long-Range Uniform SiCxOy Beaded Carbon Fibers for Efficient Microwave Absorption.

SiCxOy beaded carbon fibers were successfully fabricated for the first time using a facile and stable electrospinning and temperature process. The resulting fibers showcase a unique micro-nanocomposite structure, in which ß-SiC beads with a silica-enriched surface are strung together with defect carbon fibers, as confirmed by XRD, XPS, and HRTEM investigation. The SiCxOy beaded carbon fibers display efficient microwave absorption performance, with a minimum reflection loss of -58.53 dB and an effective absorption bandwidth of 5.92 GHz. A modified Drude-Lorentz model was developed for SiCxOy beaded carbon fibers to reveal the double-peaked feature of the permittivity of these fibers, which is in good agreement with experimental measurements. Moreover, simulations were performed to extract polarized electric fields and microwave energy volume losses within a typical distribution of SiCxOy beaded carbon fibers. It is concluded that the dipole relaxation and hopping migration of localized electrons give a superior contribution to the overall decay of the microwave energy. This study indicates that SiCxOy beaded carbon fibers with a unique micro-nanocomposite structure hold great promise for microwave absorption applications. Additionally, this fabrication strategy offers a unique approach to producing micro-nanocomposite structures and highlights their potential applications.

2D Ruddlesden-Popper Polycrystalline PerovskitePyro-Phototronic Photodetectors.

Two-dimensional (2D) Ruddlesden-Popper (RP) layered halide perovskite has attracted wide attentions due to its unique structure and excellent optoelectronic properties. With inserting organic cations, inorganic octahedrons are forced to extend in a certain direction, resulting in an asymmetric 2D perovskite crystal structure and causing spontaneous polarization. The pyroelectric effect resulted from spontaneous polarization exhibits a broad prospect in the application of optoelectronic devices. Herein, 2D RP polycrystalline perovskite (BA)2 (MA)3 Pb4 I13 film with excellent crystal orientation is fabricated by hot-casting deposition, and a class of 2D hybrid perovskite photodetectors (PDs) with pyro-phototronic effect is proposed, achieving temperature and light detection with greatly improved performance by coupling multiple energies. Because of the pyro-phototronic effect, the current is ≈35 times to that of the photovoltaic effect current under 0 V bias. The responsivity and detectivity are 12.7 mA W-1 and 1.73 × 1011 Jones, and the on/off ratio can reach 3.97 × 103 . Furthermore, the influences of bias voltage, light power density, and frequency on the pyro-phototronic effect of 2D RP polycrystalline perovskite PDs are explored. The coupling of spontaneous polarization and light facilitates photo-induced carrier dissociation and tunes the carrier transport process, making 2D RP perovskites a competitive candidate for next-generation photonic devices.

SLC3A2 promotes tumor-associated macrophage polarization through metabolic reprogramming in lung cancer.

Tumor-associated macrophages (TAMs) are one of the most abundant immunosuppressive cells in the tumor microenvironment and possess crucial functions in facilitating tumor progression. Emerging evidence indicates that altered metabolic properties in cancer cells support the tumorigenic functions of TAMs. However, the mechanisms and mediators the underly the cross-talk between cancer cells and TAMs remain largely unknown. In the present study, we revealed that high solute carrier family 3 member 2 (SLC3A2) expression in lung cancer patients was associated with TAMs and poor prognosis. Knockdown of SLC3A2 in lung adenocarcinoma cells impaired M2 polarization of macrophages in a coculture system. Using metabolome analysis, we identified that SLC3A2 knockdown altered the metabolism of lung cancer cells and changed multiple metabolites, including arachidonic acid, in the tumor microenvironment. More importantly, we showed that arachidonic acid was responsible for SLC3A2-mediated macrophage polarization in the tumor microenvironment to differentiate into M2 type both in vitro and in vivo. Our data illustrate previously undescribed mechanisms responsible for TAM polarization and suggest that SLC3A2 acts as a metabolic switch on lung adenocarcinoma cells to induce macrophage phenotypic reprogramming through arachidonic acid.

Sorafenib/2800Z Co-Loaded into Cholesterol and PEG Grafted Polylysine NPs for Liver Cancer Treatment.

The treatment of liver cancer remains challenging due to the low responsiveness of advanced cancer to therapeutic options. Sorafenib is the first line chemotherapeutic drug for advanced liver cancer but is frequently associated with severe side effects lead to discontinuation of chemotherapy. We previously developed a specific SIRT7 inhibitor 2800Z, which suppressed tumor growth and enhanced the chemosensitivity of sorafenib. In this study, we constructed polylysine polymer nanoparticles modified with cholesterol and GSH-sensitive PEG (mPssPC) to load sorafenib (SOR) and the SIRT7 inhibitor 2800Z to form dual-loaded NPs (S2@PsPCs) to reduce the toxicity and increase efficacy of sorafenib in liver cancer. The average size of S2@PsPC NPs was approximately 370 nm and the zeta potential was approximately 50-53 mV. We found that the release of the drugs exhibited pH sensitivity and was significantly accelerated in an acid release medium simulating the tumor environment. In addition, S2@PsPC NPs inhibited the proliferation and induced apoptosis of liver cancer cells in vitro. An in vivo study further revealed that S2@PsPCs showed high specificity to the liver cancer but low affinity and toxicity to the main organs including the heart, kidneys, lungs, and liver. Our data thus further approved the combination of a SIRT7 inhibitor and sorafenib for the treatment of liver cancer and provided new drug delivery system for targeted therapy.

CircEML1 facilitates the steroid synthesis in follicular granulosa cells of chicken through sponging gga-miR-449a to release IGF2BP3 expression.

Non-coding RNAs (ncRNAs) induced competing endogenous RNAs (ceRNA) play crucial roles in various biological process by regulating target gene expression. However, the studies of ceRNA networks in the regulation of ovarian ovulation processing of chicken remains deficient compared to that in mammals. Our present study revealed that circEML1 was differential expressed in hen's ovarian tissues at different ages (15 W/20 W/30 W/68 W) and identified as a loop structure from EML1 pre-mRNA, which promoted the expressions of CYP19A1/StAR and E2/P4 secretion in follicular granulosa cells (GCs). Furthermore, circEML1 could serve as a sponge of gga-miR-449a and also found that IGF2BP3 was targeted by gga-miR-449a to co-participate in the steroidogenesis, which possibly act the regulatory role via mTOR/p38MAPK pathways. Meanwhile, in the rescue experiment, gga-miR-449a could reverse the promoting role of circEML1 to IGF2BP3 and steroidogenesis. Eventually, this study suggested that circEML1/gga-miR-449a/IGF2BP3 axis exerted an important role in the steroidogenesis in GCs of chicken.