Enhanced Electron Delocalization Induced by Ferromagnetic Sulfur doped C 3 N 4 Triggers Selective H 2 O 2 Production.

For the 2D metal-free carbon catalysts, the atomic coplanar architecture enables a large number of pz orbitals to overlap laterally, thus forming π-electron delocalization, and the delocalization degree of the central atom dominates the catalytic activity. Herein, designing sulfur-doped defect-rich graphitic carbon nitride (S-Nv-C3N4) materials as a model, we propose a strategy to promote localized electron polarization by enhancing the ferromagnetism of ultra-thin 2D carbon nitride nanosheets. The introduction of sulfur (S) further promotes localized ferromagnetic coupling, thereby inducing long-range ferromagnetic ordering and accelerating the electron interface transport. Meanwhile, the hybridization of sulfur atoms breaks the symmetry and integrity of the unit structure, promotes electron enrichment and stimulating electron delocalization at the active site. This optimization enhances the *OOH desorption, providing a favorable kinetic pathway for the production of hydrogen peroxide (H2O2). Consequently, S-Nv-C3N4 exhibits high selectivity (>95%) and achieves a superb H2O2 production rate, approaching 4374.8 ppm during continuous electrolysis over 300-hour. According to theoretical calculation and in-situ spectroscopy, the ortho-S configuration can provide ferromagnetic perturbation in carbon active centers, leading to the electron delocalization, which optimizes the OOH* adsorption during the catalytic process.

Dual-site segmentally synergistic catalysis mechanism: boosting CoFeSx nanocluster for sustainable water oxidation.

Efficient oxygen evolution reaction electrocatalysts are essential for sustainable clean energy conversion. However, catalytic materials followed the conventional adsorbate evolution mechanism (AEM) with the inherent scaling relationship between key oxygen intermediates *OOH and *OH, or the lattice-oxygen-mediated mechanism (LOM) with the possible lattice oxygen migration and structural reconstruction, which are not favorable to the balance between high activity and stability. Herein, we propose an unconventional Co-Fe dual-site segmentally synergistic mechanism (DSSM) for single-domain ferromagnetic catalyst CoFeSx nanoclusters on carbon nanotubes (CNT) (CFS-ACs/CNT), which can effectively break the scaling relationship without sacrificing stability. Co3+ (L.S, t2g6eg0) supplies the strongest OH* adsorption energy, while Fe3+ (M.S, t2g4eg1) exposes strong O* adsorption. These dual-sites synergistically produce of Co-O-O-Fe intermediates, thereby accelerating the release of triplet-state oxygen ( ↑ O = O ↑ ). As predicted, the prepared CFS-ACs/CNT catalyst exhibits less overpotential than that of commercial IrO2, as well as approximately 633 h of stability without significant potential loss.

Albumosomes formed by cytoplasmic pre-folding albumin maintain mitochondrial homeostasis and inhibit nonalcoholic fatty liver disease.

Hepatic mitochondrial dysfunction contributes to the progression of nonalcoholic fatty liver disease (NAFLD). However, the factors that maintain mitochondrial homeostasis, especially in hepatocytes, are largely unknown. Hepatocytes synthesize various high-level plasma proteins, among which albumin is most abundant. In this study, we found that pre-folding albumin in the cytoplasm is completely different from folded albumin in the serum. Mechanistically, endogenous pre-folding albumin undergoes phase transition in the cytoplasm to form a shell-like spherical structure, which we call the "albumosome". Albumosomes interact with and trap pre-folding carnitine palmitoyltransferase 2 (CPT2) in the cytoplasm. Albumosomes control the excessive sorting of CPT2 to the mitochondria under high-fat-diet-induced stress conditions; in this way, albumosomes maintain mitochondrial homeostasis from exhaustion. Physiologically, albumosomes accumulate in hepatocytes during murine aging and protect the livers of aged mice from mitochondrial damage and fat deposition. Morphologically, mature albumosomes have a mean diameter of 4µm and are surrounded by heat shock protein Hsp90 and Hsp70 family proteins, forming a larger shell. The Hsp90 inhibitor 17-AAG promotes hepatic albumosomal accumulation in vitro and in vivo, through which suppressing the progression of NAFLD in mice.

Emerging role of circRNAs in cancer under hypoxia.

Circular RNA (circRNA), a recently identified type of non-coding RNAs (ncRNAs), forms a covalently closed loop with neither a 5' cap structure nor a 3' polyadenylated tail. Due to their lack of free ends, circRNAs are not easily cleaved by RNase R, thus avoiding degradation and being more stable than linear RNAs. Recent studies have suggested that circRNAs play a crucial role in regulating gene expression by acting as microRNAs sponges, RNA binding protein sponges and translational regulators. Currently, circRNAs are hot research topics due to their close association with the development of cancer and other diseases. Hypoxia is the most common microenvironment during tumor growth, and hypoxia-inducible factors have different effects on tumor growth and influence important cancer characteristics, including cell proliferation, apoptosis, differentiation, vascularization/angiogenesis, genetic instability, tumor metabolism, tumor immune response, invasion and metastasis. The present review aimed to study the biogenesis and mechanisms of gene regulation of circRNAs in hypoxia, to summarize the latest studies on circRNAs as potential diagnostic and prognostic biomarkers in hypoxia, and to understand the role of circRNAs in the process of tumor drug resistance under hypoxia.

Vertically growing nanowall-like N-doped NiP/NF electrocatalysts for the oxygen evolution reaction.

Developing low-cost, high-performance and corrosion-resistant catalysts for water splitting is anticipated, but it will also be a big challenge. In this study, nanowall-like N-Ni5P4/Ni2P/NF (N-NiP/NF) was synthesized by a simple two-step method involving hydrothermal treatment and phosphorylation. The catalyst has good catalytic activity for the OER, and only 160 mV is required to achieve a current density of 10 mA cm-2 in 1 M KOH, which is even better than RuO2, with good corrosion resistance. In addition, N-Co2P/Ni2P/NF (N-CoP/NF) was synthesized by the same method with good electrocatalytic properties and good conductivity towards the HER. N-NiP/NF was used as the anode and N-CoP/NF was used as the cathode to form the N-NiP//N-CoP double electrode system, which showed excellent electrolytic performance for water splitting, requiring only 1.48 V to reach 10 mA cm-2. This is mainly due to the strong electronegativity of N that makes the N doping induce the electron transfer process, which results in a high catalytic activity of the adjacent transition metal atoms and thus promotes the electrolysis of water, as well as the unique vertical nanowall-like structure, which gives the material a large surface area and accessibility to active sites, facilitating the adsorption of water molecules and catalytic reactions. In addition, the unique structure favors the diffusion of water molecules and the release of gaseous products, ensuring close contact between the catalyst and the electroactive material. This simple non-metallic N doping strategy provides a new way to produce efficient non-precious metal catalysts.

A Cr-FeOOH@Ni-P/NF binder-free electrode as an excellent oxygen evolution reaction electrocatalyst.

Refining the size of nanoparticles to exhibit larger specific surface areas and expose much more active sites is of great significance for enhancing the oxygen evolution reaction (OER) activity of the electrocatalyst, but still a tremendous challenge. Herein, a Cr-FeOOH@Ni2P-Ni5P4/NF (Cr-FeOOH@Ni-P/NF) catalyst was constructed by electrodepositing a layer of CrFe oxyhydroxides on the self-grown Ni-P nanoparticles, which exhibits ultrafine nanoparticles and thus superexcellent electrocatalytic OER performance. The final catalyst affords ultra-low overpotentials of 144 mV and 210 mV to achieve current densities of 10 and 50 mA cm-2, respectively. Meanwhile, it demonstrates robust stability for at least 80 hours with no activity decay. This strategy of refining nanoparticles on a three-dimensional electrode has once again been further demonstrated to be feasible and highly effective and opens a new door for the exploration of electrocatalysts with excellent comprehensive properties.

Self-supported Ni3S2@Ni2P/MoS2 heterostructures on nickel foam for an outstanding oxygen evolution reaction and efficient overall water splitting.

Hydrogen production by electrocatalytic water splitting is a pollution-free, energy-saving, and efficient method. The low efficiency of hydrogen production, high overpotentials and expensive noble-metal catalysts have limited the development of hydrogen production from electrocatalytic water splitting. Therefore, the exploration of bifunctional electrocatalysts for water overall splitting to produce hydrogen is of profound significance. Herein, Ni3S2@Ni2P/MoS2 heterostructure electrocatalysts were synthesized on Ni foam through an environmentally friendly hydrothermal method and low-temperature phosphating method. The synergistic effects between different components and the mutual substitution principle between sulfur atoms and phosphorus atoms greatly improve the OER performance of the electrocatalyst. It is also an effective strategy to optimize the adsorption energies of intermediates by the design of heterostructured catalysts composed of multiple substances. Ni3S2@Ni2P/MoS2 only requires a low overpotential (η10) of 175 mV at a current density of 10 mA cm-2 in 1.0 M KOH solution and the stable duration exceeds 40 h. In addition, this heterogeneous structure is assembled into an electrolytic cell for overall water splitting, which exhibits a low cell voltage of 1.61 volts and retains the robust stability over 30 h at 10 mA cm-2. The Ni3S2@Ni2P/MoS2 heterostructure prepared in this research provides a strategy for exploring other heterostructured electrocatalysts with different components.

An Mn-doped NiCoP flower-like structure as a highly efficient electrocatalyst for hydrogen evolution reaction in acidic and alkaline solutions with long duration.

The exploration of efficient non-noble metal electrocatalysts for hydrogen evolution reaction has received considerable attention to replace commercial Pt catalyst. It is known that the cooperative coupling of appropriate non-noble metals exhibits excellent HER performance than a single component. Herein, an Mn-doped NiCoP flower-like electrocatalyst with self-assembled nanosheets on a nickel foam is synthesized via successive hydrothermal methods, followed by low temperature phosphidation. The as-synthesized Mn-NiCoP presents extraordinarily high catalytic activity and robust chemical stability towards the hydrogen evolution reaction in both acidic and alkaline electrolytes. Benefiting from the dual modulation of the morphology structure and chemical compositions, Mn-NiCoP/NF achieves a current density of 10 mA cm-2 at a low overpotential of 37 mV for HER in a 0.5 M H2SO4 solution. Moreover, it only requires overpotentials of 67 mV and 142 mV to deliver current densities of 10 mA cm-2 and 50 mA cm-2 in a 1 M KOH solution, respectively. Remarkably, it holds enhanced stability in 1 M KOH, maintaining HER activity for at least 120 h with negligible overpotential decay. The highly efficient and stable Mn-NiCoP electrocatalyst is valuable in applications relevant to energy storage.

Mutant p53 Drives Cancer Metastasis via RCP-Mediated Hsp90α Secretion.

Mutant p53 (mutp53) loses its tumor suppressor properties but gains oncogenic functions of driving malignancy. However, it remains largely unknown how mutp53 drives cancer metastasis. Here, we show that wild-type p53 (WTp53) suppresses the secretion of heat shock protein 90-alpha (Hsp90α), whereas mutp53 enhances Hsp90α vesicular trafficking and exosome-mediated secretion. Long-term delivery of an antibody that blocks extracellular Hsp90α (eHsp90α) function extends the survival of p53-/- mice and attenuates the invasiveness of p53 mutant tumors. Furthermore, mass spectrometry and functional analysis identified a critical role for Rab coupling protein (RCP) in mutp53-induced Hsp90α secretion. RCP knockdown decreases eHsp90α levels and inhibits malignant progression. Notably, recombinant Hsp90α re-introduction markedly rescues the impaired migration and invasion abilities caused by RCP depletion. Taken together, these findings elucidate the molecular mechanisms by which mutp53 executes oncogenic activities via its downstream RCP-mediated Hsp90α secretion and a strategy to treat human cancers expressing mutp53 proteins.

Contrallable synthesis of peony-like porous Mn-CoP nanorod electrocatalyst for highly efficient hydrogen evolution in acid and alkaline.

Developing highly efficient and low-cost electrocatalysts with superior durability for hydrogen evolution reaction (HER) is a big challenge. Here, we design and fabricate a highly efficient electrocatalyst with unique three-dimensional (3D) porous peony-like micro-flower Mn-CoP nano-structure on flexible carbon cloth (Mn-CoP PMFs/CC), which exhibits high electrocatalytic activity toward the HER in both acid and alkaline circumstances. Remarkably, benefiting from the unique 3D porous structure with large surface areas, good electron conductivity for fast electron transport, and effective channels for the release of gas, the resultant catalyst exhibits an ultra-low overpotential of 28 and 90 mV to arrive the current density of 10 mA/cm2 in 0.5 M H2SO4 and 1.0 M KOH solutions, respectively. Meanwhile, the Mn-CoP PMFs/CC material shows small Tafel slopes and good long-term stability in acid and alkaline media. Density Functional Theory (DFT) calculations illustrate that Mn doping indeed improve electron transfer, and makes the thermo-neutral hydrogen adsorption free energy (ΔGH*) of CoP on the surface of (0 1 1) sharply close to zero, which is very conducive to the adsorption and desorption of hydrogen, thereby making Mn-CoP PMFs/CC with significant enhanced electrocatalytic HER performance. Our 3D porous electrocatalyst has greatly promoted the efficient electrolysis of water to produce hydrogen.

A Series of Organic-Inorganic Hybrid Compounds [(C2H5)4N]InCl4-xBrx (x = 0, 2, 4): Synthesis, Crystal Structure, and Nonlinear Optical Properties.

A series of noncentrosymmetric (NCS) tetraethylammonium tetrahalide indium hybrids, [(C2H5)4N]InCl4-xBrx (x = 0, 2, 4), was synthesized by a hydrothermal reaction. Their structures, thermal properties, and linear and nonlinear optical properties were identified. The crystals belong to an isomorphic hexagonal system and feature zero-dimensional structures containing isolated distorted InCl4-xBrx- tetrahedra with [N(C2H5)4]+ cations inserted as charge balance. On the basis of the powder second harmonic generation, the SHG levels of [(C2H5)4N]InCl4-xBrx (x = 0, 2, 4) were estimated to be approximately 0.5, 0.7, 0.8 × KDP, respectively. The relationship between halogen composition and band gap, optical anisotropy, and frequency doubling effects were evaluated by first-principles calculations, thus suggesting that halogen regulation favors the design of new organic-inorganic hybrid halides with excellent performances for many optoelectronic applications.

Secreted Pyruvate Kinase M2 Promotes Lung Cancer Metastasis through Activating the Integrin Beta1/FAK Signaling Pathway.

Cancer cell-derived secretomes have been documented to play critical roles in cancer progression. Intriguingly, alternative extracellular roles of intracellular proteins are involved in various steps of tumor progression, which can offer strategies to fight cancer. Herein, we identify lung cancer progression-associated secretome signatures using mass spectrometry analysis. Among them, PKM2 is verified to be highly expressed and secreted in lung cancer cells and clinical samples. Functional analyses demonstrates that secreted PKM2 facilitates tumor metastasis. Furthermore, mass spectrometry analysis and functional validation identify integrin ß1 as a receptor of secreted PKM2. Mechanistically, secreted PKM2 directly bound to integrin ß1 and subsequently activated the FAK/SRC/ERK axis to promote tumor metastasis. Collectively, our findings suggest that PKM2 is a potential serum biomarker for diagnosing lung cancer and that targeting the secreted PKM2-integrin ß1 axis can inhibit lung cancer development, which provides evidence of a potential therapeutic strategy in lung cancer.

Pb7F12Cl2: a promising infrared nonlinear optical material with high laser damage threshold.

This study reports, for the first time, the second-harmonic generation (SHG) property of Pb7F12Cl2 as a promising infrared nonlinear optical (NLO) material. Powder second-harmonic generation (SHG) indicates that the compound exhibits phase-matchable SHG properties, which are 1.6 times stronger than those of KH2PO4 (KDP). The infrared transmission range could reach 20 µm. The UV absorption indicated that the band gap was about 4.5 eV. A preliminary measurement of laser damage threshold (LDT) is about 80 MW cm-2, which is much higher than AgGaS2 (currently commercialized IR NLO material, 5.2 MW cm-2, measured in the same condition), indicating that Pb7F12Cl2 is a potential IR NLO material with high LDT. Theoretical calculations were also performed to elucidate its band structure, electronic configuration and second-order nonlinear coefficients. Particularly, the distinct role of different Pb atoms located in divergent coordinations has also been elaborated using orbital analysis.

Synthesis, crystal structures and nonlinear optical properties of ß-RbCdI3·H2O and CsCdI3·H2O.

Searching for new IR nonlinear optical (NLO) crystals with a high laser damage threshold (LDT) is still a challenge. In this paper, two new halides, ß-RbCdI3·H2O and CsCdI3·H2O, have been synthesized by a conventional solution reaction. Both of them crystallize in the monoclinic space group Pc (no. 7). In their crystal structures, all the corner-sharing [CdI4] tetrahedra connect with each other to form 1D chains, which further connect with [Rb(H2O)]+/[Cs(H2O)]+ complexes to form three-dimensional (3D) frameworks. All the polar [CdI4]2- groups align in such a way that results in a favorable net polarization. Powder second-harmonic generation (SHG) measurements indicate that ß-RbCdI3·H2O and CsCdI3·H2O show phase-matchable SHG responses of 2.7 and 2.6 times that of KH2PO4 (KDP). The infrared transmission range can reach 21 µm. The UV-vis diffuse reflectance spectra indicate that the band gaps of ß-RbCdI3·H2O and CsCdI3·H2O are about 3.26 and 3.54 eV, respectively. A preliminary measurement indicates that the LDT of their powders is about 90 and 100 MW cm-2, respectively, suggesting that ß-RbCdI3·H2O and CsCdI3·H2O are two new promising IR NLO materials. Their band structure and optical property calculations based on DFT methods are carried out.

Lysyl Oxidase-Like Protein 2 Promotes Tumor Lymphangiogenesis and Lymph Node Metastasis in Breast Cancer.

Tumor lymphangiogenesis has been previously documented to predict regional lymph node metastasis and promote the spread to distant organs. However, the underlying mechanism initiating tumor lymphangiogenesis remains unclear. Here we described a novel role of tumor cell-derived Lysyl Oxidase-like protein 2 (LOXL2) in promoting lymphangiogenesis and lymph node metastasis in breast cancer. Immunohistochemistry (IHC) analysis of samples from breast cancer patients showed that the expression of LOXL2 was positively correlated with lymphatic vessel density and breast cancer malignancy. In animal studies, LOXL2-overexpressing breast cancer cells significantly increased lymphangiogenesis and lymph node metastasis, whereas knockdown of LOXL2 suppressed both processes. In order to study the mechanisms of lymphangiogenesis progression, we performed further in vitro investigations and the data revealed that LOXL2 significantly enhanced lymphatic endothelial cells (LECs) invasion and tube formation through directly activation of the Akt-Snail and Erk pathways. Moreover, LOXL2 also stimulated fibroblasts to secrete high level of pro- lymphangiogenic factors VEGF-C and SDF-1α. Taken together, our study elucidates a novel function of tumor cell secreted LOXL2 in lymphangiogenesis and lymph node metastasis, demonstrating that LOXL2 serves as a promising target for anti-lymphangiogenesis and anti-metastasis therapies for breast cancer.

CXCR7 promotes melanoma tumorigenesis via Src kinase signaling.

Chemokine receptors have been documented to exert critical functions in melanoma progression. However, current drugs targeting these receptors have limited efficacy in clinical applications, suggesting the urgency to further explore the roles of chemokine receptors in melanoma. Here we found that C-X-C chemokine receptor 7 (CXCR7) was the most highly expressed chemokine receptor in murine melanoma cell lines. In addition, the expression level of CXCR7 was positively correlated with melanoma progression in the clinical samples. High CXCR7 expression was associated with shorter overall survival in melanoma patients. Increased expression of CXCR7 augmented melanoma proliferation in vitro and tumor growth in vivo, whereas knockout of CXCR7 exhibited significant inhibitory effects. Moreover, our data elucidated that CXCR7 activated Src kinase phosphorylation in a ß-arrestin2-dependent manner. The administration of the Src kinase inhibitor PP1 or siRNA specific for ß-arrestin2 abolished CXCR7-promoted cell proliferation. Importantly, CXCR7 also regulated melanoma angiogenesis and the secretion of vascular endothelial growth factor (VEGF). Subsequent investigations revealed a novel event that the activation of the CXCR7-Src axis stimulated the phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) to accelerate the translation of hypoxia-inducible factor 1α (HIF-1α), which enhanced the secretion of VEGF from melanoma cells. Collectively, our results illuminate the crucial roles of CXCR7 in melanoma tumorigenesis, and indicate the potential of targeting CXCR7 as new therapeutic strategies for melanoma treatment.