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The longstanding notion that Pt(IV) complexes are inert under physiological conditions where there are limited reducing agents is facing a great challenge. Herein, we systematically investigated the hydrolytic stability of a wide range of unsymmetric Pt(IV) anticancer prodrugs built upon clinical Pt(II) drugs. The detailed structure–stability relationship shows that the hydrolytic stability of one certain axial ligand in Pt(IV) complexes can be dramatically affected by the other five ligands; both the coordination environment of equatorial ligands and the “trans influence” from one axial ligand affect the hydrolytic stability of the counter axial ligand, and the more electronegative axial ligand faces the higher possibility to detach. Inspiringly, this newly discovered structure–stability relationship has been successfully applied to improve the hydrolytic stability of Pt(IV) complexes that contain axial dichloroacetato ligands. Our discovery represents a significant advancement in the theory of the chemical inertness of Pt(IV) complexes toward ligand exchange reactions and provides a practical guide for the future design of Pt(IV) anticancer prodrugs.

Although silicon delivers outstanding charge storage capacity during its electrochemical oxidation, utilization of this process to the battery applications is fundamentally hindered by its propensity to form passivated oxide layer on surface. Here we report a copper catalysed electrochemistry and mechanics coupled route to retain the reactivity of silicon in acidic solution. The formation of wavy silicon oxide layer on silicon can be promoted by the inhomogeneous distributed copper catalyst and thus local strain is formed. The strain will induce the formation of highly defective oxide layer that can facilitate the electrolyte transport to silicon. Thus the combination of the catalytic reaction and the defective oxide structure causes the spontaneous and continuous electrochemical oxidation of silicon. Silicon acid batteries with high energy density, reduced electrolyte consumption and long shelf-life are built based on such reaction.

Selective activation of prodrugs at diseased tissue through bioorthogonal catalysis represents an attractive strategy for precision cancer treatment. Achieving efficient prodrug photoactivation in cancer cells, however, remains challenging. Herein, we report two Pt(iv) complexes, designated as rhodaplatins {rhodaplatin 1, [Pt(CBDCA-O,O)(NH3)2(RhB)OH]; rhodaplatin 2, [Pt(DACH)ox(RhB)(OH)], where CBDCA is cyclobutane-1,1-dicarboxylate, RhB is rhodamine B, DACH is (1R,2R)-1,2-diaminocyclohexane, and ox is oxalate}, that bear an internal photoswitch to realize efficient accumulation, significant co-localization, and subsequent effective photoactivation in cancer cells. Compared with the conventional platform of external photocatalyst plus substrate, rhodaplatins presented up to 4.8 104-fold increased photoconversion efficiency in converting inert Pt(iv) prodrugs to active Pt(ii) species under physiological conditions, due to the increased proximity and covalent bond between the photoswitch and Pt(iv) substrate. As a result, rhodaplatins displayed increased photocytotoxicity compared with a mixture of RhB and conventional Pt(iv) compound in cancer cells including Pt-resistant ones. Intriguingly, rhodaplatin 2 efficiently accumulated in the mitochondria and induced apoptosis without causing genomic DNA damage to overcome drug resistance. This work presents a new approach to develop highly effective prodrugs containing intramolecular photoswitches for potential medical applications., The newly developed Pt(iv) prodrugs, rhodaplatins, contain an internal photoswitch and present up to 4.8 104-fold increased photoconversion efficiency compared to the conventional photocatalyst plus Pt(iv) prodrug photocatalysis platform.

A new approach was applied to synthesize boron nanoplates based on layer exfoliation of etched MgB2 particles through a controlled decomposition and explosion of a widely used dipolar aprotic solvent: dimethyl sulfoxide (DMSO). These nanoplates are environmentally stable, surface-functionalized, and reveal excellent electrochemical performance as an anode material for lithium-ion batteries.

Platinum(IV) complexes containing carboxylate and carbamate ligands at the axial position have been reported previously. A better understanding of the similarity and difference between the two types of ligands will provide us with new insights and more choices to design novel Pt(IV) complexes. In this study, we systematically investigated and compared the properties of Pt(IV) complexes bearing the two types of ligands. Ten pairs of unsymmetric Pt(IV) complexes bearing axial carbamate or carboxylate ligands were synthesized and characterized. The stability of these Pt(IV) complexes in a PBS buffer with or without a reducing agent was investigated, and most of these complexes exhibited good stability. Besides, most Pt(IV) prodrugs with carbamate axial ligands were reduced faster than the corresponding ones with carboxylate ligands. Furthermore, the aqueous solubilities and lipophilicities of these Pt(IV) complexes were tested. All the carbamate complexes showed better aqueous solubility and decreased lipophilicity as compared to those of the corresponding carboxylate complexes, due to the increased polarity of carbamate ligands. Biological properties of these complexes were also evaluated. Many carbamate complexes showed cytotoxicity similar to that of the carboxylate complexes, which may derive from the lower cellular accumulation but faster reduction of the former. Our research highlights the differences between the Pt(IV) prodrugs containing carbamate and carboxylate axial ligands and may contribute to the future rational design of Pt-based anticancer prodrugs.

Although ultrahigh theoretical capacity has long been predicted for boron-based lithium-ion battery anodes, experimentally, boron has exhibited only limited performance and its lithiation process remains elusive. The two-dimensional (2D) form of boron is believed to be an ideal model system to investigate the lithiation behavior of boron; however, unfortunately, most reported 2D boron structures are prone to oxidation under ambient conditions. In this contribution, through a simultaneous etching and in situ functionalization process, we synthesized for the first time methyl-functionalized boron nanosheets, which remain stable up to 250 °C. Combining experiments and theoretical calculations, we found that lithiation of boron is realized through the formation of alloys such as LiB3 and Li3B14, while alloys with higher Li content such as Li5B are thermodynamically less favored. In addition, detailed electrochemical analysis reveals that side reactions on the boron surface may also contribute to the unsatisfactory performance of boron-based electrodes. Our findings suggest that reducing the enthalpy of formation of high Li content alloys and the choice of a less nucleophilic electrolyte are key to developing high-performance anodes based on novel boron materials. Our demonstration of stable 2D boron structures also paves the way for their fundamental study and practical applications.

Pt(IV) complexes bearing axial carbonate linkages have drawn much attention recently. A synthetic method behind this allows the hydroxyl group of bioactive ligands to be attached to the available hydroxyl group of Pt(IV) complexes, and the rapid release of free drugs is achieved after the reduction of carbonate-linked Pt(IV) complexes. Further understanding on the properties of Pt(IV) carbonates such as hydrolytic stability and reduction profiles, however, is hindered by limited research. Herein, six mono-carbonated Pt(IV) complexes in which the carbonate axial ligands possess various electron-withdrawing powers were synthesized, and the corresponding mono-carboxylated analogues were also prepared as references to highlight the different properties. The influence of the coordination environment towards the hydrolysis and reduction rate of Pt(IV) carbonates and carboxylates was explored. The mono-carbonated Pt(IV) complexes are both less stable and reduced faster than the corresponding mono-carboxylated ones. Moreover, the hydrolysis and reduction profiles are dependent not only on the electron-withdrawing ability of the carbonates but also on the nature of the opposite axial ligands. Besides, the exploration of the hydrolytic pathway for Pt(IV) carbonates suggests that the process proceeds by an attack of OH

Background The purpose of this study is to analyze the impact of post-operative radiotherapy on the results in patients with intracranial hemangiopericytoma (HPC). Materials and methods We retrospectively reviewed 66 intracranial HPC patients between 1999 and 2019 including 29 with surgery followed by radiotherapy (11 with intensity-modulated radiotherapy (IMRT) and 18 with stereotactic radiosurgery (SRS)) and 37 with surgery alone. Chi-squared test was used to compare the clinical characteristic between the groups. The Kaplan-Meier method was used to analyze overall survival (OS) and recurrence-free survival (RFS). Multivariate Cox proportional hazards models were used to examine prognostic factors of survival. Results The crude local control rates were 58.6% in the surgery plus post-operative radiotherapy group (PORT) and 67.6% in the surgery alone group (p = 0.453). In the subgroup analysis of the PORT patients, local controls were 72.7% in the IMRT group and 50% in the SRS group (p = 0.228). The median OS in the PORT and surgery groups were 122 months and 98 months, respectively (p = 0.169). The median RFS was 96 months in the PORT group and 72 months in the surgery alone group (p = 0.714). The median OS and RFS of the SRS group were not significantly better than those in the IMRT group (p = 0.256, 0.960). The median RFS were 112 and 72 months for pathology grade II and III patients, respectively (p = 0.001). Conclusion PORT did not improve the local control rates nor the survivals. The local control rates after IMRT and SRS were similar even though the IMRT technique had a much higher biological dose compared with the SRS technique. PORT is not indicated for intracranial HPC patients with a complete resection margin.

Soft robots employ flexible and compliant materials to perform adaptive tasks and navigate uncertain environments. However, soft robots are often unable to achieve forces and precision on the order of rigid-bodied robots. In this paper, we propose a new class of mobile soft robots that can reversibly transition between compliant and stiff states without reconfiguration. The robot can passively conform or actively control its shape, stiffen in its current configuration to function as a rigid-bodied robot, then return to its flexible form. The robotic structure consists of passive granular material surrounded by an active membrane. The membrane is composed of interconnected robotic sub-units that can control the packing density of the granular material and exploit jamming behaviors by varying the length of the interconnecting cables. Each robotic sub-unit uses a differential drive system to achieve locomotion and self-reconfigurability. We present the robot design and perform a set of locomotion and object manipulation experiments to characterize the robot’s performance in soft and rigid states. We also introduce a simulation framework in which we model the jamming soft robot design and study the scalability of this class of robots. The proposed concept demonstrates the properties of both soft and rigid robots, and has the potential to bridge the gap between the two.

Background. sCD30 and sCD26 are correlated with autoimmune diseases. However, little research has been done on the relationship between them and primary immune thrombocytopenia (ITP). Methods. This study enrolled 47 patients diagnosed with ITP in the Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences (Tianjin, China), from January 2015 to August 2015. The peripheral blood of all subjects was collected. The mRNA expression of CD30 was quantified by RT-PCR, and concentrations of sCD30 and sCD26 were measured by ELISA. Patient characteristics, CD30 mRNA levels, and sCD30 and sCD26 concentrations were analyzed. Results. The concentration of sCD30 was higher in active ITP patients (median, 35.82 ng/mL) than in remission ITP patients (median, 23.12 ng/mL; P=0.021) and healthy controls (median, 25.11 ng/mL; P=0.002). Plasma sCD26 levels decreased in remission ITP patients compared with that in healthy controls (median, 599.4 ng/mL vs. 964.23 ng/mL; P=0.004). Ratios of sCD26/sCD30 in active ITP patients decreased compared with those in controls (P=0.005). Increased sCD30 was positively correlated with hemorrhage (r=0.493, P=0.017) in ITP patients while little relationship was identified between sCD26 and ITP. Conclusion. Since sCD30 levels and sCD26/sCD30 ratios may contribute to the activity of the disease, they may be used to assess ITP disease activity.

The molecular mechanisms underlying the metabolic shift toward increased glycolysis observed in pulmonary artery smooth muscle cells (PASMC) during the pathogenesis of pulmonary arterial hypertension (PAH) are not fully understood. Here we show that the glycolytic enzyme α-enolase (ENO1) regulates the metabolic reprogramming and malignant phenotype of PASMC. We show that ENO1 levels are elevated in patients with associated PAH and in animal models of hypoxic pulmonary hypertension (HPH). The silencing or inhibition of ENO1 decreases PASMC proliferation and de-differentiation, and induces PASMC apoptosis, whereas the overexpression of ENO1 promotes a synthetic, de- differentiated, and apoptotic-resistant phenotype via the AMPK-Akt pathway. The suppression of ENO1 prevents the hypoxia-induced metabolic shift from mitochondrial respiration to glycolysis in PASMC. Finally, we find that pharmacological inhibition of ENO1 reverses HPH in mice and rats, suggesting ENO1 as a regulator of pathogenic metabolic reprogramming in HPH.

Dielectric materials with large energy storage density and power density has been a sought-after goal. Here, we report new ceramic system (1-x) [0.5(Bi0.5Na0.5)TiO3-0.5SrTiO3]-x NaNbO3 exhibiting an excellent energy storage property (Wrec = 2.34 J/cm3, η = 74.6%). It is found that NaNbO3 incorporation can not only enhance the breakdown strength but also induce the formation of ergodic relaxation state, both benefitting the energy storage performance. Meanwhile, further research shows that the ceramic has excellent charge and discharge performance with high power density PD of 58.52 MW/cm3 and fast discharge speed t0.9 of 227 ns. Moreover, corresponding energy storage performance shows good cycle stability (1–10,000) and frequency stability (5–200 Hz), while the discharge performance exhibits excellent temperature stability (20–120 °C). These aforementioned merits reveal that of the relaxor ferroelectric 0.5BNT-0.5ST-0.03NN ceramic has great potential in practical pulse power dielectric capacitor applications.

A model of cellular neural networks with mixed delays is proposed. Applying contraction mapping fixed point theorem and differential inequality technique, several sufficient conditions are derived to ensure the existence and exponential stability of weighted pseudo anti-periodic solutions for the proposed neural networks. Finally, a numerical simulation example is given to illustrate the effectiveness of the obtained results.

Many clinical trials using combinations of platinum drugs and PARP-1 inhibitors (PARPi) have been carried out, with the hope that such combinations will lead to enhanced therapeutic outcomes against tumors. Herein, we obtained seven potential PARPi with structural diversity and then conjugated them with cisplatin-based platinum(IV) complexes. Both the synthesized PARPi ligands and PARPi-Pt conjugates [PARPi-Pt(IV)] show inhibitory effects against PARP-1's catalytic activity. The PARPi-Pt(IV) conjugates are cytotoxic in a panel of human cancer cell lines, and the leading ones display the ability to overcome cisplatin resistance. A mechanistic investigation reveals that the representative PARPi-Pt(IV) conjugates efficiently enter cells, bind to genomic DNA, disturb cell cycle distribution, and induce apoptotic cell death in both cisplatin-sensitive and -resistant cells. Our study provides a strategy to improve the cytotoxicity of platinum(IV)-based anticancer complexes and overcome cisplatin resistance by using a small-molecule anticancer complex that simultaneously damages DNA and inhibits PARP.

In this paper, we consider the p-Laplacian equations with hereditary effects and the nonlinear term f satisfying the polynomial growth of arbitrary order q − 1 (q ≥ 2). We analyze the well-posedness of solutions and establish the existence of the (CL2(Ω),CL2(Ω)) and (CL2(Ω),CLq(Ω))-pullback attractors by applying the idea of the bi-spaces and the asymptotic a priori estimate method.

A model of shunting inhibitory cellular neural networks with mixed delays is proposed. Applying appropriate differential inequality techniques, several sufficient conditions are derived to ensure the existence and exponential stability of weighted pseudo-anti-periodic solutions for the proposed neural networks. Moreover, numerical examples are provided to show the validity and the advantages of the obtained results

We have reported that von Hippel-Lindau protein (pVHL) expression is elevated in human and mouse fibrotic lungs and that overexpression of pVHL stimulates fibroblast proliferation. We sought to determine whether loss of pVHL in fibroblasts prevents injury and fibrosis in mice that are treated with bleomycin. We generated heterozygous fibroblast-specific pVHL (Fsp-VHL) knockdown mice (Fsp-VHL(+/-)) and homozygous Fsp-VHL knockout mice (Fsp-VHL(-/-)) by crossbreeding vhlh 2-lox mice (VHL(fl/fl)) with Fsp-Cre recombinase mice. Our data show that Fsp-VHL(-/-) mice, but not Fsp-VHL(+/-) mice, have elevated red blood cell counts, hematocrit, hemoglobin content, and expression of hypoxia-inducible factor (HIF) targets, indicating HIF activation. To examine the role of pVHL in bleomycin-induced lung injury and fibrosis in vivo, we administered PBS or bleomycin to age-, sex-, and strain-matched 8-week-old VHL(fl/fl), Fsp-VHL(+/-), and Fsp-VHL(-/-) mice. In Fsp-VHL(+/-) and Fsp-VHL(-/-) mice, bleomycin-induced collagen accumulation, fibroblast proliferation, differentiation, and matrix protein dysregulation were markedly attenuated. Suppression of pVHL also decreased bleomycin-induced Wnt signaling and prostaglandin E2 signaling but did not affect bleomycin-induced initial acute lung injury and lung inflammation. These results indicate that pVHL has a pivotal role in bleomycin-induced pulmonary fibrosis, possibly via an HIF-independent pathway. Paradoxically, pVHL does not affect bleomycin-induced lung injury and inflammation, indicating a separation of the mechanisms involved in injury/inflammation from those involved in pulmonary fibrosis.

This paper is concerned with the anti-periodic solutions for a class of cellular neural network model with oscillating coefficients in leakage terms. By applying contraction mapping fixed point theorem and differential inequality techniques, we establish some sufficient conditions to guarantee the existence and exponential stability of anti-periodic solutions for this model, which improve and supplement existing ones. Moreover, an example and its numerical simulations are given to support the theoretical results.

In this paper, we consider the problem of the scattering of in-plane waves at an interface between a homogeneous medium and a metamaterial. The relevant eigenmodes in the two regions are calculated by solving a recently described non self-adjoint eigenvalue problem particularly suited to scattering studies. The method efficiently produces all propagating and evanescent modes consistent with the application of Snell’s law and is applicable to very general scattering problems. In a model composite, we elucidate the emergence of a rich spectrum of eigenvalue degeneracies. These degeneracies appear in both the complex and real domains of the wave-vector. However, since this problem is non self-adjoint, these degeneracies generally represent a coalescing of both the eigenvalues and eigenvectors (exceptional points). Through explicit calculations of Poynting vector, we point out an intriguing phenomenon: there always appears to be an abrupt change in the sign of the refraction angle of the wave on two sides of an exceptional point. Furthermore, the presence of these degeneracies, in some cases, hints at fast changes in the scattered field as the incident angle is changed by small amounts. We calculate these scattered fields through a novel application of the Betti–Rayleigh reciprocity theorem. We present several numerical examples showing a rich scattering spectrum. In one particularly intriguing example, we point out wave behavior which may be related to the phenomenon of resonance trapping. We also show that there exists a deep connection between energy flux conservation and the biorthogonality relationship of the non self-adjoint problem. The proof applies to the general class of scattering problems involving elastic waves (under self-adjoint or non self-adjoint operators).

Rationale Forkhead box M1 (FoxM1) is a transcription factor that promotes cell proliferation by regulating a broad spectrum of genes that participate in cell cycle regulation, such as Cyclin B, CDC25B, and Aurora B Kinase. We have shown that hypoxia, a well-known stimulus for pulmonary hypertension (PH), induces FoxM1 in pulmonary artery smooth muscle cells (PASMC) in a HIF-dependent pathway, resulting in PASMC proliferation, while the suppression of FoxM1 prevents hypoxia-induced PASMC proliferation. However, the implications of FoxM1 in the development of PH remain less known. Methods We determined FoxM1 levels in the lung samples of idiopathic PAH (pulmonary arterial hypertension) (IPAH) patients and hypoxia-induced PH mice. We generated constitutive and inducible smooth muscle cell (SMC)-specific FoxM1 knockdown or knockout mice as well as FoxM1 transgenic mice which overexpress FoxM1, and exposed them to hypoxia (10% O2, 90% N2) or normoxia (Room air, 21% oxygen) for four weeks, and measured PH indices. We also isolated mouse PASMC (mPASMC) and mouse embryonic fibroblasts (MEF) from these mice to examine the cell proliferation and expression levels of SMC contractile proteins. Results We showed that in hypertensive human lungs or mouse lungs, FoxM1 levels were elevated. Constitutive knockout of FoxM1 in mouse SMC caused early lethality, whereas constitutive knockdown of FoxM1 in mouse SMC prevented hypoxia-induced PH and PASMC proliferation. Inducible knockout of FoxM1 in SMC reversed hypoxia-induced pulmonary artery wall remodeling in existing PH. Overexpression of FoxM1 enhanced hypoxia-induced pulmonary artery wall remodeling and right ventricular hypertrophy in mice. Alteration of FoxM1 status did not affect hypoxia-induced hypoxia-inducible factor (HIF) activity in mice. Knockout of FoxM1 decreased PASMC proliferation and induced expression of SMC contractile proteins and TGF-β/Smad3 signaling. Conclusions Our studies provide clear evidence that altered FoxM1 expression in PASMC contributes to PH and uncover a correlation between Smad3-dependent signaling in FoxM1-mediated proliferation and de-differentiation of PASMC.

We have previously reported that miR-17~92 is critically involved in the pathogenesis of pulmonary hypertension (PH). We also identified two novel mR-17/20a direct targets, PDZ and LIM domain protein 5 (PDLIM5) and prolyl hydroxylase 2 (PHD2), and elucidated the signaling pathways by which PDLIM5 and PHD2 regulate functions of pulmonary artery smooth muscle cells (PASMCs). In addition, we have shown that plasminogen activator inhibitor-1 (PAI-1) is also downregulated in PASMCs that overexpress miR-17~92. However, it is unclear whether PAI-1 is a direct target of miR-17~92 and whether it plays a role in regulating the PASMC phenotype. In this study, we have identified PAI-1 as a novel target of miR-19a/b, two members of the miR-17~92 cluster. We found that the 3′-untranslated region (UTR) of PAI-1 contains a miR-19a/b binding site and that miR-19a/b can target this site to suppress PAI-1 protein expression. MiR-17/20a, two other members of miR-17~92, may also indirectly suppress PAI-1 expression through PDLIM5. PAI-1 is a negative regulator of miR-17~92-mediated PASMC proliferation. Silencing of PAI-1 induces Smad2/calponin signaling in PASMCs, suggesting that PAI-1 is a negative regulator of the PASMC contractile phenotype. We also found that PAI-1 is essential for the metabolic gene expression in PASMCs. Furthermore, although there is no significant change in PAI-1 levels in PASMCs isolated from idiopathic pulmonary arterial hypertension and associated pulmonary arterial hypertension patients, PAI-1 is downregulated in hypoxia/Sugen-induced hypertensive rat lungs. These results suggest that miR-17~92 regulates the PASMC contractile phenotype and proliferation coordinately and synergistically by direct and indirect targeting of PAI-1.

This paper is concerned with the existence of pseudo almost periodic solutions for shunting inhibitory cellular neural networks with leakage delays and complex deviating arguments. Applying the contraction mapping fixed point theorem and inequality techniques, some sufficient conditions are presented to ensure the existence of pseudo almost periodic solutions of this model, which are new and supplement some previously known ones.