Enabling High Reversibility of Zn anode via Interfacial Engineering Induced by Amino acid Electrolyte Additive.

Despite possessing substantial benefits of enhanced safety and cost-effectiveness, the aqueous zinc ion batteries (AZIBs) still suffers with the critical challenges induced by inherent instability of Zn metal in aqueous electrolytes. Zn dendrites, surface passivation, and corrosion are some of the key challenges governed by water-driven side reactions in Zn anodes. Herein, a highly reversible Zn anode is demonstrated via interfacial engineering of Zn/electrolyte driven by amino acid D-Phenylalanine (DPA) additions. The preferential adsorption of DPA and the development of compact SEI on the Zn anode suppressed the side reactions, leading to controlled and uniform Zn deposition. As a result, DPA added aqueous electrolyte stabilized Zn anode under severe test environments of 20.0 mA cm-2 and 10.0 mAh cm-2 along with an average plating/stripping Coulombic efficiency of 99.37%. Under multiple testing conditions, the DPA-incorporated electrolyte outperforms the control group electrolyte, revealing the critical additive impact on Zn anode stability. This study advances interfacial engineering through versatile electrolyte additive(s) toward development of stable Zn anode, which may lead to its practical implementation in aqueous rechargeable zinc batteries.

Zn-In Alloying Powder Solvent Free Electrode Toward High-Load Ampere-Hour Aqueous Zn-Mn Secondary Batteries.

Aqueous Zn-ion batteries (ZIBs) are promising candidates for large-scale energy storage due to high safety, abundant reserves, low-cost, and high energy density. However, the reversibility of the metallic Zn anode in the mild electrolyte is still unsatisfactory, due to the Zn dendrite growth, hydrogen evolution, and corrosion passivation. Herein, a Zn-In alloying powder solvent free electrode is proposed to replace the Zn foil in ZIBs. The novel Zn anodes are constructed by a solvent-free manufacturing process with carbons, forming a 3D Zn deposition network and providing uniformly electric field distribution. The In on the Zn powder surface can increase the overpotential for hydrogen evolution and further improve the morphology of Zn deposition against dendrite growth. The Zn solvent-free electrodes enable the Zn-MnO2 batteries with high cathode loading mass of 10-20 mg cm-2 to achieve >380 stable cycles. Furthermore, the assembled soft package batteries of 2.4 Ah (52 Wh kg-2 ) is evaluated and the capacity retention is maintained at 80% after 200 cycles at a high areal capacity of 5 mAh cm-2 without gas evolution. This work offers a workable strategy to develop a durable Zn anode for the eventually commercial applications of aqueous Zn-Mn secondary batteries.

Rotation and separation of chiral active particles in a ring-shaped channel.

Transport of chiral active particles is numerically investigated in a two-dimensional ring-shaped channel. The ring-shaped channel is transversal asymmetric and can induce the directed transport (rotation) of chiral active particles. For the particles with small chirality, they slide along the outer boundary of the channel. For the particles with large chirality, the particles move along some small local circular orbits and can also exhibit directed rotation. Moreover, the rotation effect can be strongly enhanced by modifying the inner boundary geometry. Based on the study of particle rotation, we further study the separation of active particles with different chiralities. It is found that the particles with different chiralities may be distributed in different regions of the ring-shaped channel. Interestingly, these particles can be completely separated by shifting the channel's inner boundary or adding a blocking plate in the channel. Our results may be useful for understanding relevant experimental phenomena and provide a scheme for the separation of binary mixtures.

PARP5B is required for nonhomologous end joining during tumorigenesis in vivo.

Poly(ADP-ribose) polymerases (PARP) act as DNA damage sensors that produce poly(ADP-ribose) (PAR) chains at double-strand breaks, facilitating the recruitment of repair factors. Cancers with homologous recombination defects are sensitive to small molecule PARP inhibitors. Despite PARP5B gene copy number changes in many cancers, the effects of this genetic alteration on tumor phenotype are largely unknown. To better understand this clinical finding, we characterized a PARP5B null mutation in a carcinogen-induced in vivo head and neck squamous cell carcinoma (SCC) model. Reduced PARP5B expression inhibited tumor growth, induced primary tumor differentiation and apoptosis, and inhibited cell proliferation and metastasis. Loss of PARP5B expression-induced ataxia telangiectasia and Rad3 related (ATR) activation and depleted the cancer stem cell fraction. PARP5B null tumor cells lacked 53BP1+ double-strand break foci, ATM activation, and p53 induction compared to PARP5B+/+ cancers. PARP5B null SCC expresses a multiprotein complex containing PML, pRPA, Rad50, Rad51, XRCC1, proliferating cell nuclear antigen (PCNA), and Mcm2, suggesting an HR-mediated repair mechanism at DNA replication foci. Low doses of etoposide combined with the PARP5B inhibitor XAV939 induced senescence and apoptosis in human SCC lines. NBS1 overexpression in these cells inhibited the effects of low-dose etoposide/XAV939 treatment. Our results indicate that PARP5B inhibition is new targeted cancer therapy.

Absolute negative mobility of active polymer chains in steady laminar flows.

We investigate the transport of active polymer chains in steady laminar flows in the presence of thermal noise and an external constant force. In the model, the polymer chain is worm-like and is propelled by active forces along its tangent vectors. Compared with inertial Brownian particles, active polymer chains in steady laminar flows exhibit richer movement patterns due to their specific spatial structures. The simulation results show that the velocity-force relation is strongly dependent on the system parameters such as the chain length, bending rigidity, active force and so on. The polymer chain may move in some preferential movement directions and exhibits absolute negative mobility within appropriate parameter regimes, i.e., the polymer chain can move in a direction opposite to the external constant force. In particular, we can observe giant negative mobility in a broad range of parameter regimes.

Integrating Network Pharmacology, Molecular Docking, and Experimental Validation to Investigate the Mechanism of (-)-Guaiol Against Lung Adenocarcinoma.

BACKGROUND Lung adenocarcinoma (LUAD) is the most common type of lung cancer, which poses a serious threat to human life and health. -(-)Guaiol, an effective ingredient of many medicinal herbs, has been shown to have a high potential for tumor interference and suppression. However, knowledge of pharmacological mechanisms is still lacking adequate identification or interpretation. MATERIAL AND METHODS The genes of LUAD patients collected from TCGA were analyzed using limma and WGCNA. In addition, targets of (-)-Guaiol treating LUAD were selected through a prediction network. Venn analysis was then used to visualize the overlapping genes, which were further condensed using the PPI network. GO and KEGG analyses were performed sequentially, and the essential targets were evaluated and validated using molecular docking. In addition, cell-based verification, including the CCK-8 assay, cell death assessment, apoptosis analysis, and western blot, was performed to determine the mechanism of action of (-)-Guaiol. RESULTS The genes included 959 differentially-expressed genes, 6075 highly-correlated genes, and 480 drug-target genes. Through multivariate analysis, 23 hub genes were identified and functional enrichment analyses revealed that the PI3K/Akt signaling pathway was the most significant. Experiment results showed that -(-)Guaiol can inhibit LUAD cell growth and induce apoptosis. Additional evidence suggested that the PI3K/Akt signaling pathway established an inseparable role in the antitumor processes of -(-)Guaiol, which is consistent with network pharmacology results. CONCLUSIONS Our results show that the effect of (-)-Guaiol in LUAD treatment involves the PI3K/Akt signaling pathway, providing a useful reference and medicinal value in the treatment of LUAD.

A Novel Predictive Model Incorporating Ferroptosis-Related Gene Signatures for Overall Survival in Patients with Lung Adenocarcinoma.

BACKGROUND Lung adenocarcinoma (LUAD) is the predominant histological type of lung cancer with high morbidity and mortality. Ferroptosis is regarded as a new pattern of programmed cell death concerned with the progression of lung cancer characterized by lipid peroxidation. Nevertheless, the prognostic role of ferroptosis-related genes for LUAD warrant to be explored. MATERIAL AND METHODS RNA sequencing and relevant clinical patient data were obtained from public-access databanks. A prognostic model was constructed through the LASSO Cox regression in the cancer genome atlas cohort. The diagnostic value of the prognostic model was further evaluated in the gene expression omnibus cohort. RESULTS Most of the ferroptosis-related genes (69.9%) were differentially expressed between tumor and adjacent non-cancerous tissues. 43 differentially expressed genes showed a close association with the prognosis of LUAD patients (adjusted p-value <0.05). An 18-gene signature was built and applied to assign patients into high vs low-risk groups. Compared with the high-risk group, patients defined as the low-risk group suffered significantly prolonged OS. Both uni- and multivariate analyses demonstrated that the signature-based score served as a crucial role in influencing the OS of LUAD patients (hazard ratio >1, p<0.001). The immunity-related signaling pathway was enriched in the functional analysis and the infiltration of the immune cells showed a great difference between groups. CONCLUSIONS The predictive model could be applied for prognostic prediction for LUAD. Targeting ferroptosis could be a possible curative strategy against LUAD, and immunomodulation may be one of the potential mechanisms.

Polyphenylene Sulfide-Based Solid-State Separator for Limited Li Metal Battery.

The urgent need for high energy batteries is pushing the battery studies toward the Li metal and solid-state direction, and the most central question is finding proper solid-state electrolyte (SSE). So far, the recently studied electrolytes have obvious advantages and fatal weaknesses, resulting in indecisive plans for industrial production. In this work, a thin and dense lithiated polyphenylene sulfide-based solid state separator (PPS-SSS) prepared by a solvent-free process in pilot stage is proposed. Moreover, the PPS surface is functionalized to immobilize the anions, increasing the Li+ transference number to 0.8-0.9, and widening the electrochemical potential window (EPW > 5.1 V). At 25 °C, the PPS-SSS exhibits high intrinsic Li+ diffusion coefficient and ionic conductivity (>10-4 S cm-1 ), and Li+ transport rectifying effect, resulting in homogenous Li-plating on Cu at 2 mA cm-2 density. Based on the limited Li-plated Cu anode or anode-free Cu, high loadings cathode and high voltage, the Li-metal batteries (LMBs) with polyethylene (PE) protected PPS-SSSs deliver high energy and power densities (>1000 Wh L-1 and 900 W L-1 ) with >200 cycling life and high safety, exceeding those of state-of-the-art Li-ion batteries. The results promote the Li metal battery toward practicality.

Particle separation induced by triangle obstacles in a straight channel.

Efficient separation of particles has ever-growing importance in both fundamental research and nanotechnological applications. However, such particles usually suffer from some fluctuations from external surroundings and outside intervention from unknown directions. Here, we numerically investigate the transport of Brownian particles in a straight channel with regular arrays of equilateral triangle obstacles. The particles can be rectified by the triangle obstacles under the action of an oscillating (square wave) force. At the given amplitude and frequency of the oscillating force, the transport is sensitively dependent on the force direction and particle size. In the cases of longitudinal and transversal oscillating force, the particles with different sizes exhibit different transport behaviors. Interestingly, under a constant force in the longitudinal direction, the phenomenon of particle separation is observed, where the particles with different radii will move in different directions. Furthermore, we also study the transport of Brownian particles driven by a tilt oscillating force. By choosing proper force directions, we can observe the gating phenomenon and transport reversal. Under different driving conditions, we can separate particles of different sizes and make them move in opposite directions.

Molecular and cellular basis of mammary gland fibrosis and cancer risk.

Mammary gland luminal cells are maintained by the proliferation of ER- luminal progenitor (LP) cells. Human breast LP cells exhibit telomere DNA damage, which is associated with mammographic density and increased cancer risk. Telomeric repeat factor 2 (TRF2) protects telomeres from DNA damage response. TRF2 expression is reduced in human breast cancers. We deleted TRF2 expression in mammary gland epithelium. Mammary glands lacking TRF2 expression exhibited increased telomere DNA damage response, histopathological and functional degeneration, and prominent ductal fibrosis. TRF2-deficient mammary tumors exhibited rapid onset and increased proliferation. Tumor derived LP cells failed to form tumors after transplantation. The MSC population was highly tumorigenic and maintained telomeres via the ALT mechanism. Telomere DNA damage response in mammary tumors resulted in p53 dependent ER+ cellular differentiation and sensitivity to anti-estrogen therapy. Our results provide a new in vivo model of mammographic density, stem cell differentiation, cancer risk, and therapeutic sensitivity.

Spontaneous rectification and absolute negative mobility of inertial Brownian particles induced by Gaussian potentials in steady laminar flows.

We study the transport of inertial Brownian particles in steady laminar flows in the presence of two-dimensional Gaussian potentials. Through extensive numerical simulations, it is found that the transport is sensitively dependent on the external constant force and the Gaussian potential. Within tailored parameter regimes, the system exhibits a rich variety of transport behaviors. There exists the phenomenon of spontaneous rectification (SR), where the directed transport of particles can occur in the absence of any external driving forces. It is found that SR of the particles can be manipulated by the spatial position of the Gaussian potential. Moreover, when the potential lies at the center of the cellular flow, the system exhibits absolute negative mobility (ANM), i.e., the particles can move in a direction opposite to the constant force. More importantly, the phenomenon of ANM induced by Gaussian potentials is robust in a wide range of system parameters and can be further strengthened with the optimized parameters, which may pave the way to the implementation of related experiments.

Great Enhancement of Carbon Energy Storage through Narrow Pores and Hydrogen-Containing Functional Groups for Aqueous Zn-Ion Hybrid Supercapacitor.

The proton transfer mechanism on the carbon cathode surface has been considered as an effective way to boost the electrochemical performance of Zn-ion hybrid supercapacitors (SCs) with both ionic liquid and organic electrolytes. However, cheaper, potentially safer, and more environmental friendly supercapacitor can be achieved by using aqueous electrolyte. Herein, we introduce the proton transfer mechanism into a Zn-ion hybrid supercapacitor with the ZnSO4 aqueous electrolyte and functionalized activated carbon cathode materials (FACs). We reveal both experimentally and theoretically an enhanced performance by controlling the micropores structure and hydrogen-containing functional groups (-OH and -NH functions) of the activated carbon materials. The Zn-ion SCs with FACs exhibit a high capacitance of 435 F g-1 and good stability with 89% capacity retention over 10,000 cycles. Moreover, the proton transfer effect can be further enhanced by introducing extra hydrogen ions in the electrolyte with low pH value. The highest capacitance of 544 F g-1 is obtained at pH = 3. The proton transfer process tends to take place preferentially on the hydroxyl-groups based on the density functional theory (DFT) calculation. The results would help to develop carbon materials for cheaper and safer Zn-ion hybrid SCs with higher energy.

Modulation the crosstalk between tumor-associated macrophages and non-small cell lung cancer to inhibit tumor migration and invasion by ginsenoside Rh2.

BACKGROUND: Tumor-associated macrophages (TAMs) play a critical role in modulating the tumor microenvironment and promote tumor metastases. Our studies have demonstrated that ginsenoside Rh2 (G-Rh2), a monomeric compound extracted from ginseng, is a promising anti-tumor agent in lung cancer cells. However, it remains unclear whetherG-Rh2 can modulate the differentiation of TAMs and its interaction with tumor microenvironment. In this study, we investigated how G-Rh2 regulates the phenotype of macrophages and affects the migration of non-small cell lung cancer (NSCLC) cells. METHODS: Murine macrophage-like RAW264.7 cells and human THP-1 monocyte were differentiated into M1 and M2 subsets of macrophages with different cytokines combination, which were further identified by flow cytometry with specific biomarkers. M2 macrophages were sorted out to co-culture with NSCLC cell lines, A549 and H1299. Wound healing assay was performed to examine the cell migration. Expression levels of matrix metalloproteinases 2 and 9 (MMP-2, - 9) and vascular endothelial growth factor-C (VEGF-C) were measured by RT-qPCR and western blot, and the release of VEGF in the supernatant was measured by a VEGF ELISA kit. Finally, modulation of TAMs phenotype and VEGF expression by G-Rh2 was examined in vivo. RESULTS: We demonstrated that M2 subset of macrophages alternatively differentiated from RAW264.7 or THP-1cells promote migration of NSCLC cells. Further examinations revealed that NSCLC significantly increased the release of VEGF to the media and elevated the expression levels of VEGF at mRNA and protein levels after being co-cultured with M2 macrophages. Similar alterations in MMP-2 and MMP-9 were observed in NSCLC after being co-cultured. Of note,G-Rh2 had a potential to effectively convert M2 phenotype to M1 subset of macrophages. Importantly, G-Rh2 had a preference to decrease the expression levels of VEGF, MMP2, and MMP9 in co-cultured lung cancer cells, over than those in lung cancer cells without co-culturing. Consistently, G-Rh2 reduced M2 macrophage marker CD206 and VEGF expression levels in vivo. CONCLUSIONS: All of these results suggested that M2 subset macrophages drive lung cancer cells with more aggressive phenotypes. G-Rh2 has a potential to convert TAMs from M2 subset to M1 in the microenvironment and prevents lung cancer cell migration, suggesting the therapeutic effects of G-Rh2onlung cancer.

Transport of active particles induced by wedge-shaped barriers in straight channels with hard and soft walls.

The transport of active particles in straight channels is numerically investigated. The periodic wedge-shaped barriers can produce the asymmetry of the system and induce the directed transport of the active particles. The direction of the transport is determined by the apex angle of the wedge-shaped barriers. By confining the particles in channels with hard and soft walls, the transport exhibits similar behaviors. The average velocity is a peaked function of the translational diffusion, while it decreases monotonously with the increase of the rotational diffusion. Moreover, the simulation results show that the transport is sensitive to the parameters of the confined structures, such as the pore width, the intensity of potential, and the channel period.

Silencing of NRAGE induces autophagy via AMPK/Ulk1/Atg13 signaling pathway in NSCLC cells.

NRAGE has been reported to be overexpressed in cancer cells, especially in lung cancer cells. To determine the role of NRAGE in non-small-cell lung cancer cells, we investigated the effects of NRAGE on autophagy in non-small-cell lung cancer cells. Human A549 and H1299 cells were transfected with NRAGE-specific small-interfering RNA. The Cell Counting Kit-8 and plate clone assay showed that downregulation of NRAGE could induce the proliferation in A549 and H1299 cells. In addition, our data suggested that downregulation of NRAGE enhances autophagosome formation by immunofluorescence. We found that knockdown of NRAGE induced autophagy, together with downregulation of P62 and upregulation of LC3-II protein. Furthermore, to elucidate the mechanism of NRAGE in suppressing autophagy, the protein expressions of AMPK, Ulk1, and Atg13 were assessed. Collectively, these results demonstrate the effective anti-autophagic of NRAGE in non-small-cell lung cancer cells through AMPK/Ulk1/Atg13 autophagy signaling pathways. Therefore, NRAGE could be used as a potential therapeutic target for lung cancer.

Construction and application of a lung cancer stem cell model: antitumor drug screening and molecular mechanism of the inhibitory effects of sanguinarine.

Lung cancer is a neoplasm with a 5-year survival rate of less than 15 % and a leading cause of death worldwide, despite recent progress in treatment and diagnostic methods. Lung cancer stem-like cells (CSCs) are pivotal in lung cancer metastasis and drug resistance. This study aimed to develop lung CSCs that stably express stem cell properties through transfection to further screen traditional Chinese herbal compounds. Lung adenocarcinoma stem cells, which include various phenotypic subgroups, are normally characterized by high expression levels of pluripotent stem cell genes, particularly Nanog and OCT4. Plasmids containing Nanog and OCT4 were constructed and transfected into cells, and lung CSCs were identified not only in vitro using RT-PCR, Western blotting, plate cloning, sphere formation, drug resistance, and transwell migration but also in vivo using a nude mouse tumorigenicity assay. Subsequently, sanguinarine, which is derived from the whole leaves of the traditional Chinese medicine celandine, was identified through the high-throughput screening of a small-molecule compound library. Investigation of the molecular mechanisms of the effects of sanguinarine revealed that it significantly inhibited lung CSC proliferation, invasion, and apoptosis, possibly via downregulation of the Wnt/ß-catenin signaling pathway. Our results indicate that lung CSCs established by gene transfection may provide a stable and effective method of constructing CSCs to effectively screen potential antitumor drugs. Furthermore, these results suggest that sanguinarine may be a natural antitumor compound that targets lung CSCs, laying a foundation for further clinical study.

RAD51 regulates CHK1 stability via autophagy to promote cell growth in esophageal squamous carcinoma cells.

The serine/threonine protein kinase CHK1 has been reported to bind to the recombinase RAD51 and facilitates its assembly in DNA damage sites via phosphorylation. However, the role of RAD51 in regulating the expression of CHK1 has never been explored. Here, we show that RAD51 is highly upregulated in esophageal squamous tumor tissues and its DMC1 domain significantly promotes cell growth of esophageal cancer (EC) cells through CHK1. To gain the mechanistic insights, firstly, in the presence of 3-methyladenine (3MA), an autophagy inhibitor, we found that the reduction of CHK1 and the inhibition of cell growth in RAD51-deficient EC109 cells were strikingly restored. Subsequently, the autophagy-related experiments revealed that RAD51 negatively participated in autophagy. Moreover, results from in vitro clonogenic survival assays showed that RAD51 depletion greatly enabled EC cells to resist the autophagy inhibitors 3MA and hydroxychloroquine (HCQ) treatments. Above all, our studies firstly highlight a direct role of RAD51 in autophagy process and characterize its functional domain in cell growth regulation. Moreover, our data firstly shed insights into the possible application of autophagy inhibitors in treating RAD51 overexpressed EC patients.

NK Cell-Dependent Growth Inhibition of Lewis Lung Cancer by Yu-Ping-Feng, an Ancient Chinese Herbal Formula.

Little is known about Yu-Ping-Feng (YPF), a typical Chinese herbal decoction, for its antitumor efficacy in non-small-cell lung cancer (NSCLC). Here, we found that YPF significantly inhibited the growth of Lewis lung cancer, prolonged the survival of tumor-bearing mice, promoted NK cell tumor infiltration, increased the population of NK cells in spleen, and enhanced NK cell-mediated killing activity. The growth suppression of tumors by YPF was significantly reversed by the depletion of NK cells. Furthermore, we found that YPF significantly downregulated the expression of TGF-ß, indoleamine 2,3-dioxygenase, and IL-10 in tumor microenvironment. These results demonstrated that YPF has a NK cell-dependent inhibitory effect on Lewis lung cancer.

Anisotropic imprint of amorphization and phase separation in manganite thin films via laser interference irradiation.

Materials with mesoscopic structural and electronic phase separation, either inherent from synthesis or created via external means, are known to exhibit functionalities absent in the homogeneous counterparts. One of the most notable examples is the colossal magnetoresistance discovered in mixed-valence manganites, where the coexistence of nano- to micrometer-sized phase-separated domains dictates the magnetotransport. However, it remains challenging to pattern and process such materials into predesigned structures and devices. In this work, a direct laser interference irradiation (LII) method is employed to produce periodic stripes in thin films of a prototypical phase-separated manganite Pr0.65 (Ca0.75 Sr0.25 )0.35 MnO3 (PCSMO). LII induces selective structural amorphization within the crystalline PCSMO matrix, forming arrays with dimensions commensurate with the laser wavelength. Furthermore, because the length scale of LII modification is compatible to that of phase separation in PCSMO, three orders of magnitude of increase in magnetoresistance and significant in-plane transport anisotropy are observed in treated PCSMO thin films. Our results show that LII is a rapid, cost-effective and contamination-free technique to tailor and improve the physical properties of manganite thin films, and it is promising to be generalized to other functional materials.

Diffusion and mobility of anisotropic particles in tilted periodic structures.

We numerically investigated the transport of anisotropic particles in tilted periodic structures. The diffusion and mobility of the particles demonstrate distinct behaviors dependence on the shape of the particles. In two-dimensional (2D) periodic potentials, we find that the mobility is influenced a little by the anisotropy of the particle, while the diffusion increases monotonically with the increasing of the particle anisotropy for large enough biased force. However, due to the sensitivity of the channels for the particle anisotropy, the transport in smooth channels is obviously different from that in energy potentials. The mobility decreases monotonically with the increasing of the particle anisotropy, while the diffusion can be a non-monotonic function of the particle anisotropy with a peak under appropriate biased force.