Tiliroside disrupted iron homeostasis and induced ferroptosis via directly targeting calpain-2 in pancreatic cancer cells.

BACKGROUND: Tiliroside (TIL) is a flavonoid compound that exists in a variety of edible plants. These dietary plants are widely used as food and medicine to treat various diseases. However, the effect of TIL on pancreatic cancer (PC) and its underlying mechanisms are unclear. PURPOSE: This study aims to reveal the anti-PC effect of TIL and clarify its mechanism. METHODS: The inhibitory effects of TIL on PC growth were studied both in vitro and in vivo. Flow cytometry, transmission electron microscopy, immunofluorescence, biochemical analyses, RT-qPCR, genetic ablation, and western blotting were employed to evaluate ferroptosis, autophagy, and iron regulation. Additionally, RNA sequencing (RNA-seq), biomolecular layer interferometry (BLI), and molecular simulation analysis were combined to identify TIL molecular targets. The clinicopathological significance of Calpain-2 (CAPN2) was determined through immunohistochemistry (IHC) on a PC tissue microarray. RESULTS: Herein, we showed that TIL was an effective anti-PC drug. CAPN2 was involved in the TIL - induced elevation of the labile iron pool (LIP) in PC cells. TIL directly bound to and inhibited CAPN2 activity, resulting in AKT deactivation and decreased expression of glucose transporters (GLUT1 and GLUT3) in PC cells. Consequently, TIL impaired ATP and NADPH generation, inducing autophagy and ROS production. The accumulation of TIL-induced ROS combined with LIP iron causes the Fenton reaction, leading to lipid peroxidation. Meanwhile, TIL-induced reduction of free iron ions promoted autophagic degradation of ferritin to regulate cellular iron homeostasis, which further exacerbated the death of PC cells by ferroptosis. As an extension of these in vitro findings, our murine xenograft study showed that TIL inhibited the growth of PANC-1 cells. Additionally, we showed that CAPN2 expression levels were related to clinical prognoses in PC patients. CONCLUSION: We identify TIL as a potent bioactive inhibitor of CAPN2 and an anti-PC candidate of natural origin. These findings also highlight CAPN2 as a potential target for PC treatment.

Potential Effects of Orally Ingesting Polyethylene Terephthalate Microplastics on the Mouse Heart.

Polyethylene terephthalate microplastics (PET MPs) are widespread in natural environment, and can enter organisms and accumulate in the body, but its toxicity has not been well studied. Therefore, in order to investigate the toxic effects of PET microplastics on mammals, this study investigated the toxic effects of PET MPs on ICR mice and H9C2 cells by different treatment groups. The results indicated the cardiac tissue of mice in the PET-H (50 µg/mL) group showed significant capillary congestion, myocardial fiber breakage, and even significant fibrosis compared to the PET-C (control) group (P < 0.01). Results of the TUNEL assay demonstrated significant apoptosis in myocardial tissue in the PET-H and PET-M (5 µg/mL) groups (P < 0.01). Meanwhile, Western blotting showed increased expression of the apoptosis-related protein Bax and decreased expression of PARP, caspase-3, and Bcl-2 proteins in both myocardial tissues and H9C2 cells. In addition, flow cytometry confirmed that PET MPs decreased the mitochondrial membrane potential and apoptosis in H9C2 cells; however, this trend was reversed by N-acetylcysteamine application. Moreover, PET MP treatment induced the accumulation of reactive oxygen species (ROS) in H9C2 cells, while the MDA level in the myocardial tissue was elevated, and the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were decreased (P < 0.01), indicating a change in the redox environment. In conclusion, PET MPs promoted cardiomyocyte apoptosis by inducing oxidative stress and activating mitochondria-mediated apoptotic processes, ultimately leading to myocardial fibrosis. This study provides ideas for the prevention of PET MP toxicity and promotes thinking about enhancing plastic pollution control.

Irreversible Electroporation Mediates Glioma Apoptosis via Upregulation of AP-1 and Bim: Transcriptome Evidence.

The heat-sink effect and thermal damage of conventional thermal ablative technologies can be minimized by irreversible electroporation (IRE), which results in clear ablative boundaries and conservation of blood vessels, facilitating maximal safe surgical resection for glioblastoma. Although much comparative data about the death forms in IRE have been published, the comprehensive genetic regulatory mechanism for apoptosis, among other forms of regulatory cell death (RCD), remains elusive. We investigated the electric field intensity threshold for apoptosis/necrosis (YO-PRO-1/PI co-staining) of the U251 human malignant glioma cell line with stepwise increased uniform field intensity. Time course samples (0-6 h) of apoptosis induction and sham treatment were collected for transcriptome sequencing. Sequencing showed that transcription factor AP-1 and its target gene Bim (Bcl2l11), related to the signaling pathway, played a major role in the apoptosis of glioma after IRE. The sequencing results were confirmed by qPCR and Western blot. We also found that the transcription changes also implicated three other forms of RCD: autophagy, necroptosis, and immunogenic cell death (ICD), in addition to apoptosis. These together imply that IRE possibly mediates apoptosis by the AP-1-Bim pathway, causes mixed RCD simultaneously, and has the potential to aid in the generation of a systemic antitumor immune response.

Nonlinear vectorial holography with quad-atom metasurfaces.

Vectorial optical holography represents a solution to control the polarization and amplitude distribution of light in the Fourier space. While vectorial optical holography has been experimentally demonstrated in the linear optical regime, its nonlinear counterpart, which can provide extra degrees of freedom of light-field manipulation through the frequency conversion processes, remains unexplored. Here, we experimentally demonstrate the nonlinear vectorial holography through the second harmonic generation process on a quad-atom plasmonic metasurface. The quad-atom metasurface consists of gold meta-atoms with threefold rotational symmetry. Based on the concept of nonlinear geometric phase, we can simultaneously manipulate the phase and amplitude of the left and right circularly polarized second harmonic waves generated from the quad-atom metasurface. By superposing the two orthogonal polarization components, the quad-atom metasurface can produce nonlinear holographic images with vectorial polarization distributions. The proposed metasurface platform may have important applications in vectorial polarization nonlinear optical source, high-capacity optical information storage, and optical encryption.

Efficiently Integrated Desulfurization from Natural Gas over Zn-ZIF-Derived Hierarchical Lamellar Carbon Frameworks.

Selective removal of carbonyl sulfide (COS) and hydrogen sulfide (H2S) is the key step for natural gas desulfurization due to the highly toxic and corrosive features of these gaseous sulfides, and efficient and stable desulfurizers are urgently needed in the industry. Herein, we report a class of nitrogen-functionalized, hierarchically lamellar carbon frameworks (N-HLCF-xs), which are obtained from the structural transformation of Zn zeolitic imidazolate frameworks via controllable carbonization. The N-HLCF-xs possess the desirable characteristics of large Brunauer-Emmett-Teller surface areas (645-923 m2/g), combined primary three-dimensional microporosity and secondary two-dimensional lamellar microstructure, and high density of nitrogen base sites with enhanced pyridine ratio (17.52 wt %, 59.91%). The anchored nitrogen base sites in N-HLCF-xs show improved accessibility, which boosts their interaction with acidic COS and H2S. As expected, N-HLCF-xs can be employed as multifunctional and efficient desulfurizers for selective removal of COS and H2S from natural gas. COS was first transformed into H2S via catalytic hydrolysis, and the produced H2S was then captured and separated and catalyzed oxidation into elemental sulfur. The above continuous processes can be achieved with solo N-HLCF-xs, giving extremely high efficiencies and reusability. Their integrated desulfurization performance was better than many desulfurizers used in the area, such as activated carbon, ß zeolite, MIL-101(Fe), K2CO3/γ-Al2O3, and FeOx/TiO2.

Spin-orbit interactions of transverse sound.

Spin-orbit interactions (SOIs) endow light with intriguing properties and applications such as photonic spin-Hall effects and spin-dependent vortex generations. However, it is counterintuitive that SOIs can exist for sound, which is a longitudinal wave that carries no intrinsic spin. Here, we theoretically and experimentally demonstrate that airborne sound can possess artificial transversality in an acoustic micropolar metamaterial and thus carry both spin and orbital angular momentum. This enables the realization of acoustic SOIs with rich phenomena beyond those in conventional acoustic systems. We demonstrate that acoustic activity of the metamaterial can induce coupling between the spin and linear crystal momentum k, which leads to negative refraction of the transverse sound. In addition, we show that the scattering of the transverse sound by a dipole particle can generate spin-dependent acoustic vortices via the geometric phase effect. The acoustic SOIs can provide new perspectives and functionalities for sound manipulations beyond the conventional scalar degree of freedom and may open an avenue to the development of spin-orbit acoustics.

Efficiently Selective Oxidation of H2S to Elemental Sulfur over Covalent Triazine Framework Catalysts.

As a highly toxic and corrosive waste gas in the industry, hydrogen sulfide (H2S) usually originates from the utilization of coal, petroleum, and natural gas. The selective catalytic elimination of H2S shows great significance to ensure the safety of industrial processes and health of human beings. Herein, we report efficiently selective oxidation of H2S to elemental sulfur over covalent triazine framework (CTF-1-x, x = 400, 500, 600, 400-600 °C) catalysts. CTF-1-x samples were prepared from polymerization of 1,4-dicyanobenzene to form polyaryl triazine networks under ion solidothermal conditions in the presence of ZnCl2, which acts as both an initiator and a porogen. The resultant CTF-1-x samples possess abundant micro-mesoporosity, large Brunauer-Emmett-Teller (BET) surface areas, and tunable structural base sites with edge amine and graphitic nitrogen characteristics, which were homogeneously decorated onto their frameworks. As a result, CTF-1-x samples act as efficient and long-lived catalysts in selective oxidation of H2S to sulfur under ambient conditions (100% H2S conversion, 100% sulfur selectivity at 180 °C, 12 000 mL/(g·h)), and their activities were superior to those of commercial Fe2O3 and g-C3N4 desulfurization catalysts. Abundant nitrogen structural base sites of CTF-1-x effectively activate the reactants, and abundant micro-mesoporosity facilitates mass transfer in and out of CTF-1-x. The improved design of the nitrogen-doped carbon material for H2S activation and conversion could enhance the development of more active and robust nitrogen-doped carbon catalysts.

Engineering of crystal phase over porous MnO2 with 3D morphology for highly efficient elimination of H2S.

In the present work, we report a facile oxalate-derived hydrothermal method to fabricate α-, ß- and δ-MnO2 catalysts with hierarchically porous structure and study the phase-dependent behavior for selective oxidation of H2S over MnO2 catalysts. It was disclosed that the oxygen vacancy, reducibility and acid property of MnO2 are essentially determined by the crystalline phase. Systematic experiments demonstrate that δ-MnO2 is superior in active oxygen species, activation energy and H2S adsorption capacity among the prepared catalysts. As a consequence, δ-MnO2 nanosphere with a hierarchically porous structure shows high activity and stability with almost 100% H2S conversion and sulfur selectivity at 210 °C, better than majority of reported Mn-based materials. Meanwhile, hierarchically porous structure of δ-MnO2 nanosphere alleviates the generation of by-product SO2 and sulfate, promoting the adoptability of Mn-based catalysts in industrial applications.

Multi-dimensional wave steering with higher-order topological phononic crystal.

The recent discovery and realizations of higher-order topological insulators enrich the fundamental studies on topological phases. Here, we report three-dimensional (3D) wave-steering capabilities enabled by topological boundary states at three different orders in a 3D phononic crystal with nontrivial bulk topology originated from the synergy of mirror symmetry of the unit cell and a non-symmorphic glide symmetry of the lattice. The multitude of topological states brings diverse possibilities of wave manipulations. Through judicious engineering of the boundary modes, we experimentally demonstrate two functionalities at different dimensions: 2D negative refraction of sound wave enabled by a first-order topological surface state with negative dispersion, and a 3D acoustic interferometer leveraging on second-order topological hinge states. Our work showcases that topological modes at different orders promise diverse wave steering applications across different dimensions.

Autophagy in tumorigenesis and cancer treatment.

Autophagy is a self-digestion process, wrapping cytoplasmic proteins or organelles to form vesicles for degradation in lysosomes. The process plays an important role in the maintenance of intracellular homostasis. Here we overview articles on autophagy and cancer/tumors in Pubmed and found 327 articles. Autophagy exists in many tumors and is involved in cell malignant transformation and tumor cell growth. In early phases of tumorigenesis, autophagy clears the abnormally folded proteins and dysfunctional organelles such as mitochondria. Autophagy can also inhibit cell stress responses and prevent genetic damage. When a tumor develops, autophagy helps tumor cells survive nutritional deficiencies and hypoxic conditions. Studies of autophagy in the occurrence and progression of tumors should provide new therapeutic strategies for tumors.

Facile preparation of highly luminescent CdTe quantum dots within hyperbranched poly(amidoamine)s and their application in bio-imaging.

A new strategy for facile preparation of highly luminescent CdTe quantum dots (QDs) within amine-terminated hyperbranched poly(amidoamine)s (HPAMAM) was proposed in this paper. CdTe precursors were first prepared by adding NaHTe to aqueous Cd2+ chelated by 3-mercaptopropionic sodium (MPA-Na), and then HPAMAM was introduced to stabilize the CdTe precursors. After microwave irradiation, highly fluorescent and stable CdTe QDs stabilized by MPA-Na and HPAMAM were obtained. The CdTe QDs showed a high quantum yield (QY) up to 58%. By preparing CdTe QDs within HPAMAM, the biocompatibility properties of HPAMAM and the optical, electrical properties of CdTe QDs can be combined, endowing the CdTe QDs with biocompatibility. The resulting CdTe QDs can be directly used in biomedical fields, and their potential application in bio-imaging was investigated.