Overview of role of survivin in cancer: expression, regulation, functions, and its potential as a therapeutic target.

Survivin holds significant importance as a member of the inhibitor of apoptosis protein (IAP) family due to its predominant expression in tumours rather than normal terminally differentiated adult tissues. The high expression level of survivin in tumours is closely linked to chemotherapy resistance, heightened tumour recurrence, and increased tumour aggressiveness and serves as a negative prognostic factor for cancer patients. Consequently, survivin has emerged as a promising therapeutic target for cancer treatment. In this review, we delve into the various biological characteristics of survivin in cancers and its pivotal role in maintaining immune system homeostasis. Additionally, we explore different therapeutic strategies aimed at targeting survivin.

Cerium Methacrylate Assisted Preparation of Highly Thermally Conductive and Anticorrosive Multifunctional Coatings for Heat Conduction Metals Protection.

Preparing polymeric coatings with well corrosion resistance and high thermal conductivity (TC) to prolong operational life and ensure service reliability of heat conductive metallic materials has long been a substantive and urgent need while a difficult task. Here we report a multifunctional epoxy composite coating (F-CB/CEP) by synthesizing cerium methacrylate and ingeniously using it as a novel curing agent with corrosion inhibit for epoxy resin and modifier for boron nitride through "cation-π" interaction. The prepared F-CB/CEP coating presents a high TC of 4.29 W m-1 K-1, which is much higher than other reported anti-corrosion polymer coatings and thereby endowing metal materials coated by this coating with outstanding thermal management performance compared with those coated by pure epoxy coating. Meanwhile, the low-frequency impedance remains at 5.1 × 1011 Ω cm2 even after 181 days of immersion in 3.5 wt% NaCl solution. Besides, the coating also exhibits well hydrophobicity, self-cleaning properties, temperature resistance and adhesion. This work provides valuable insights for the preparation of high-performance composite coatings with potential to be used as advanced multifunctional thermal management materials, especially for heat conduction metals protection.

Surfactant-free emulsion of epoxy resin/sodium alginate for achieving robust underwater superoleophobic coating via a combination of phase separation and biomineralization.

Underwater superoleophobic coatings exhibit promising prospects in the field of oil contamination resistance. However, their poor durability, stemming from the fragile structures and unstable hydrophilicity, greatly restricted their development. In this report, we proposed a novel strategy of combination water-induced phase separation and biomineralization to prepare the robust underwater superoleophobic epoxy resin-calcium alginate (EP-CA) coating by utilizing a surfactant-free emulsion of epoxy resin/sodium alginate (EP/SA). The EP-CA coating not only exhibited excellent adhesion to various substrates, but also had remarkable resistance to the physical/chemical attacks such as abrasion, acid, alkali and salt. It could also protect the substrate (e.g., PET substrate) from the damage of organic solution and the fouling of crude oil. This report provides a new perspective to fabricate robust superhydrophilic coating with a facile way.

Na+ Migration Mediated Phase Transitions Induced by Electric Field in the Framework Structured Tungsten Bronze.

Framework structured tungsten bronzes serve as promising candidates for electrode materials in sodium-ion batteries (SIBs). However, the tungsten bronze framework structure changes drastically as mediated by the sodium ion concentration at high temperatures. While the three-dimensional ion channels facilitate fast ion storage and transport capabilities, the structural instability induced by Na+ migration is a big concern regarding the battery performance and safety, which unfortunately remains elusive. Here, we show the real-time experimental evidence of the phase transitions in framework structured Na0.36WO3.14 (triclinic phase) by applying different external voltages. The Na+-rich (Na0.48WO3, tetragonal phase) or -deficient (NaxWO3, x < 0.36, hexagonal phase) phase nucleates under the positive or negative bias, respectively. Combined with the theoretical calculations, the atomistic phase transition mechanisms associated with the Na+ migration are directly uncovered. Our work sheds light on the phase instability in sodium tungsten bronzes and paves the way for designing advanced SIBs with high-stability.

Lenvatinib plus immune checkpoint inhibitors or locoregional therapy in unresectable hepatocellular carcinoma: Lessons learned and moving forwards.

Hepatocellular carcinoma is one of the deadliest neoplasms around the world, and a major proportion of patients are diagnosed in an advanced state not amenable to curative treatment. Lenvatinib, a promising first-line targeted therapy, has shown antitumour activity in both preclinical studies and clinical trials. Emerging evidence indicates that a combination of lenvatinib plus anti-PD-1 inhibitors or locoregional therapies exerts a stronger antitumour effect than monotherapy and even offers the possibility of long-term survival while maintaining acceptable tolerability. Several studies have also shown the superiority of lenvatinib over sorafenib in combination strategies. This review addresses the rationale behind lenvatinib-based combination therapies and comprehensively summarizes various clinical studies investigating lenvatinib in combination with immune checkpoint inhibitors (ICIs), locoregional therapies, and other systemic treatments. We discuss the unsatisfactory search for suitable biomarkers and key ongoing trials in this field.

SVM based imbalanced correction method for Power Systems Transient stability evaluation.

Due to the requirement of safety and reliability in power systems, unstable samples in the real system are rarely appeared. The evaluation results of the model trained by these imbalance samples have a certain preference. Generally, the imbalance in quantity is taken into account, while the imbalance in quality is ignored. Faced with such a problem, an imbalanced correction method based on support vector machine (SVM) is proposed. Firstly, the classification hyperplane trained by SVM and the normalized Euclidean distance between each sample and the classification hyperplane are calculated so as to obtain their fault severity. Based on this, training samples can be grouped to multilevel sets. Then, the original stacked sparse auto-encoder (SSAE) are pretrained to quantify the imbalance between two classes of samples in multilevel sets. Subsequently, in order to improve the imbalance of training samples, a cost-sensitive correction matrix is generated according to the imbalanced information of multilevel sets. Finally, the loss function of SSAE is modified by cost-sensitive correction matrix to establish the final classifier. Simulation results in IEEE 39-bus system and the realistic regional power system of Eastern China show the high performance of the proposed imbalanced correction method.

Efficacy of immune checkpoint inhibitors plus molecular targeted agents after the progression of lenvatinib for advanced hepatocellular carcinoma.

Background: Lenvatinib is a standard first-line systemic therapy in advanced hepatocellular carcinoma (aHCC) and is widely used in all lines. However, the efficacy and safety of immune checkpoint inhibitors (ICIs) plus molecular targeted agents (MTAs) after the progression of lenvatinib treatment are unclear. Objective: The aim of this study was to evaluate the anticancer effects of ICI plus MTA in patients with aHCC who progressed after lenvatinib. Methods: We retrospectively included aHCC patients treated with ICI plus MTA after the progression of lenvatinib from two medical centers. Participants who continued lenvatinib treatment were classified into the "ICI+Lenva" group, while the "ICI+Others" group included patients receiving other MTAs. The efficacy endpoints were progression-free survival (PFS), post-progression survival (PPS), overall survival (OS), and tumor response following RECIST v1.1. Safety was evaluated according to Common Terminology Criteria for Adverse Events v5.0. Results: In this study, 85 eligible aHCC patients were enrolled, including 58 in the ICI+Lenva group and 27 in the ICI+Others group. At a median follow-up time of 22.8 months, the median PPS and PFS were 14.0 (95% CI: 9.0-18.2) and 4.5 months (95% CI: 3.5-8.3), respectively. The objective response and disease control rates were 10.6% and 52.9%, respectively. No significant differences were observed in any of the efficacy endpoints between the two groups. Prolonged PPS was associated with Child-Pugh grade A, AFP < 400 IU/ml, and concomitant locoregional treatment. All patients experienced adverse events (AEs), but no fatal AEs were observed. Conclusion: ICI plus MTA in aHCC patients after the progression of lenvatinib presented high antitumor activity and safety. Patients could continue lenvatinib treatment and receive ICIs as well as locoregional treatment to achieve better OS.

Prognostic analysis of patients with combined hepatocellular-cholangiocarcinoma after radical resection: A retrospective multicenter cohort study.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a form of rare primary liver cancer that combines intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma. AIM: To investigate overall survival (OS) and recurrence-free survival (RFS) after radical resection in patients with cHCC-CCA, and the clinicopathological factors affecting prognosis in two center hospitals of China. METHODS: We reviewed consecutive patients with cHCC-CCA who received radical resection between January 2005 and September 2021 at Peking Union Medical College and the 5th Medical Center of the PLA General Hospital retrospectively. Regular follow-up and clinicopathological characteristics were systematic collected for baseline and prognostic analysis. RESULTS: Our study included 95 patients who received radical resection. The majority of these patients were male and 82.7% of these patients were infected with HBV. The mean tumor size was 4.5 cm, and approximately 40% of patients had more than one lesion. The median OS was 26.8 (95%CI: 18.5-43.0) mo, and the median RFS was 7.27 (95%CI: 5.83-10.3) mo. Independent predictors of OS were CA19-9 ≥ 37 U/mL (HR = 8.68, P = 0.002), Child-Pugh score > 5 (HR = 5.52, P = 0.027), tumor number > 1 (HR = 30.85, P = 0.002), tumor size and transarterial chemoembolization (TACE) after surgery (HR = 0.2, P = 0.005). CONCLUSION: The overall postoperative survival of cHCC-CCA patients is poor, and most patients experience relapse within a short period of time after surgery. Preoperative tumor biomarker (CA19-9, alpha-fetoprotein) levels, tumor size, and Child-Pugh score can significantly affect OS. Adjuvant TACE after surgery prolongs RFS, suggesting that TACE is a possible option for postoperative adjuvant therapy in patients with cHCC-CCA.

Bio-inspired robust superhydrophilic/underwater superoleophobic coating with lubrication, anti-crude oil fouling and anti-corrosion performances.

The crude oil spill accidents cause numerous crude oil contaminations and oily wastewater. Underwater superoleophobic coating has excellent ability to resist crude oil contamination and separate oily wastewater. But it's hard to keep stable performance against the physical or chemical attack. Herein, a robust underwater superoleophobic coating was fabricated by spraying the mixture of polyethyleneimine (PEI) and TiO2 on epoxy resin (E44) surface. Besides the good physical and chemical stability, the coating exhibited better drag reduction, anti-fouling performance and anti-corrosive performance in water compared with the commercially hydrophilic coating. The stainless steel mesh (SSM), coated by the E44/PEI/TiO2 coating, could separate different oil-water emulsions with a high oil rejection greater than 99.7%.

Millefeuille-Inspired Thermal Interface Materials based on Double Self-Assembly Technique for Efficient Microelectronic Cooling and Electromagnetic Interference Shielding.

Owing to the increasing power density of miniaturized and high-frequency electronic devices, flexible thermal interface materials (TIMs) with the electromagnetic interference (EMI) shielding property are in urgent demand to maintain the system performance and reliability. Recently, carbon-based TIMs receive considerable attention due to the ultrahigh intrinsic thermal conductivity (TC). However, the large-scale production of such TIMs is restricted by some technical difficulties, such as production-induced defects of graphite sheets, poor microstructure architecture within the matrix, and nonnegligible interfacial thermal resistance result from the strong phono scattering. In this work, inspired by the structure and production process of millefeuille cakes, a unique double self-assembly strategy for fabricating ultrahigh thermal conductive TIMs with superior EMI shielding performance is demonstrated. The percolating and oriented multilayered microstructure enables the TIM to exhibit an ultrahigh in-plane TC of 233.67 W m-1 K-1 together with an outstanding EMI shielding effectiveness of 79.0 dB (at 12.4 GHz). In the TIM evaluation system, a nearly 45 °C decrease is obtained by this TIM when compared to the commercial material. The obtained TIM achieves the desired balance between thermal conduction and EMI shielding performance, indicating broad prospects in the fields of military applications and next-generation thermal management systems.

Efficient CO2 electroreduction on facet-selective copper films with high conversion rate.

Tuning the facet exposure of Cu could promote the multi-carbon (C2+) products formation in electrocatalytic CO2 reduction. Here we report the design and realization of a dynamic deposition-etch-bombardment method for Cu(100) facets control without using capping agents and polymer binders. The synthesized Cu(100)-rich films lead to a high Faradaic efficiency of 86.5% and a full-cell electricity conversion efficiency of 36.5% towards C2+ products in a flow cell. By further scaling up the electrode into a 25 cm2 membrane electrode assembly system, the overall current can ramp up to 12 A while achieving a single-pass yield of 13.2% for C2+ products. An insight into the influence of Cu facets exposure on intermediates is provided by in situ spectroscopic methods supported by theoretical calculations. The collected information will enable the precise design of CO2 reduction reactions to obtain desired products, a step towards future industrial CO2 refineries.

Novel Environmentally Friendly Waterborne Epoxy Coating with Long-Term Antiscaling and Anticorrosion Properties.

Metal pipes in industrial production are exposed to various corrosive ions. The combined action of these ions with oxygen in water causes corrosion and contamination of the metal pipes and equipment. In addition, metallic ions in water react with anions to form scale on the surface of the metal, which significantly reduces the service life of the metal and equipment, resulting in safety hazards. Waterborne coatings have attracted tremendous attention due to the less negative impact on the environment, but their practical applications are severely restricted by poor barrier properties and poor mechanical durability. Herein, the barrier properties of water-based coatings are successfully improved by adding functional slow-release nanofillers, and the fillers also endow the coating with excellent antiscaling properties. A functional slow-release nanofiller (lecithin/SiO2/HEDP) was prepared using HEDP (etidronic acid) as the scale inhibitor active material and SiO2 as the carrier, combined with a phospholipid membrane with slow-release permeability. With the addition of slow-release fillers, compared with the EP coating, the impedance modulus of composite coatings increases about 1 order of magnitude, the scale inhibition rate is as high as 80.7%, and the antiscaling life is double that of the coating without the phospholipid-coated filler. Thus, this study is expected to provide a new perspective for the preparation of new slow-release fillers and high-efficiency scale inhibitor coatings.

Optimization of the Administration Strategy for the Armed Oncolytic Adenovirus ZD55-IL-24 in Both Immunocompromised and Immunocompetent Mouse Models.

ZD55-IL-24 is an armed oncolytic adenovirus similar but superior to ONYX-015. Virotherapeutic strategies using ZD55-IL-24 have been demonstrated to be effective against several cancer types. However, it is unclear whether the traditional administration strategy is able to exert the maximal antitumor efficacy of ZD55-IL-24. In this study, we sought to optimize the administration strategy of ZD55-IL-24 in both A375-bearing immunocompromised mouse model and B16-bearing immunocompetent mouse model. Although the underlying antitumor mechanisms are quite different, the obtained results are similar in these two mouse tumor models. We find that the antitumor efficacy of ZD55-IL-24 increases as injection times increase in both of these two models. However, no obvious increase of efficacy is observed as the dose of each injection increases. Our further investigation reveals that the administration strategy of sustained ZD55-IL-24 therapy can achieve a better therapeutic effect than the traditional administration strategy of short-term ZD55-IL-24 therapy. Furthermore, there is no need to inject every day; every 2 or 3 days of injection achieves an equivalent therapeutic efficacy. Finally, we find that the sustained rather than the traditional short-term ZD55-IL-24 therapy can synergize with anti-PD-1 therapy to reject tumors in B16-bearing immunocompetent mouse model. These findings suggest that the past administration strategy of ZD55-IL-24 is in fact suboptimal and the antitumor efficacy can be further enhanced through administration strategy optimization. This study might shed some light on the development of clinically applicable administration regimens for ZD55-IL-24 therapy.

Enhanced anti-melanoma efficacy through a combination of the armed oncolytic adenovirus ZD55-IL-24 and immune checkpoint blockade in B16-bearing immunocompetent mouse model.

Although the recent treatment in melanoma through the use of anti-PD-1 immunotherapy is successful, the efficacy of this approach remains to be improved. Here, we explore the feasibility of combination strategy with the armed oncolytic adenovirus ZD55-IL-24 and PD-1 blockade. We find that combination therapy with localized ZD55-IL-24 and systemic PD-1 blockade leads to synergistic inhibition of both local and distant established tumors in B16-bearing immunocompetent mouse model. Our further mechanism investigation reveals that synergistic therapeutic effect is associated with marked promotion of tumor immune infiltration and recognition in both local and distant tumors as well as spleens. PD-1 blockade has no obvious effect on promotion of tumor immune infiltration and recognition. Localized therapy with ZD55-IL-24, however, can help PD-1 blockade to overcome the limitation of relatively low tumor immune infiltration and recognition. This study provides a rationale for investigation of such combination therapy in the clinic.

Controllable Distribution of Oxygen Vacancies in Grain Boundaries of p-Si/TiO2 Heterojunction Photocathodes for Solar Water Splitting.

Silicon is a promising photocathode material in photoelectrochemical water splitting for hydrogen production, but it is primarily limited by photocorrosion in aqueous electrolytes. As an extensively used protective material, crystalline TiO2 could protect Si photoelectrode against corrosion. However, a large number of grain boundaries (GBs) in polycrystalline TiO2 would induce excessive recombination centers, impeding the carrier transport. This paper describes the introduction of oxygen vacancies (Ovac ) with controllable spatial distribution for GBs to promote carrier transport. Two kinds of Ovac distribution, Ovac along GBs and Ovac inside grains, are compared, where the latter one is demonstrated to facilitate carrier transport owing to the formation of tunneling paths across GBs. Consequently, a simple p-Si/TiO2 /Pt heterojunction photocathode with controllable Ovac distribution in TiO2 shows a +400 mV onset potential shift and yields an applied bias photon-to-current efficiency of 5.9 %, which is the best efficiency reported among silicon photocathodes except for silicon homojunction.

The armed oncolytic adenovirus ZD55-IL-24 eradicates melanoma by turning the tumor cells from the self-state into the nonself-state besides direct killing.

ZD55-IL-24 is similar but superior to the oncolytic adenovirus ONYX-015, yet the exact mechanism underlying the observed therapeutic effect is still not well understood. Here we sought to elucidate the underlying antitumor mechanism of ZD55-IL-24 in both immunocompetent and immunocompromised mouse model. We find that ZD55-IL-24 eradicates established melanoma in B16-bearing immunocompetent mouse model not through the classic direct killing pathway, but mainly through the indirect pathway of inducing systemic antitumor immunity. Inconsistent with the current prevailing view, our further results suggest that ZD55-IL-24 can induce antitumor immunity in B16-bearing immunocompetent mouse model in fact not due to its ability to lyse tumor cells and release the essential elements, such as tumor-associated antigens (TAAs), but due to its ability to put a "nonself" label in tumor cells and then turn the tumor cells from the "self" state into the "nonself" state without tumor cell death. The observed anti-melanoma efficacy of ZD55-IL-24 in B16-bearing immunocompetent mouse model was practically caused only by the viral vector. In addition, we also notice that ZD55-IL-24 can inhibit tumor growth in B16-bearing immunocompetent mouse model through inhibiting angiogenesis, despite it plays only a minor role. In contrast to B16-bearing immunocompetent mouse model, ZD55-IL-24 eliminates established melanoma in A375-bearing immunocompromised mouse model mainly through the classic direct killing pathway, but not through the antitumor immunity pathway and anti-angiogenesis pathway. These findings let us know ZD55-IL-24 more comprehensive and profound, and provide a sounder theoretical foundation for its future modification and drug development.

Robust Waterborne Superhydrophobic Coatings with Reinforced Composite Interfaces.

Waterborne superhydrophobic coatings have attracted tremendous attention recently, but their practical applications are severely limited by hydrophobic instability and poor mechanical durability. Herein, a novel robust waterborne PTFE-CP&MgO-AOP superhydrophobic coating was successfully fabricated by reinforcing composite interfaces. Combined with the self-polymerization of dopamine and the in situ grown MgO, CNTs-polydopamine&MgO (CP&MgO) particles with improved interfacial compatibility were obtained. Through the cross-linking and hydrogen bonding interactions, phosphate networks (CP&MgO-AOP) with the aluminum orthophosphate (AOP) binder were formed during dehydration polymerization. The phosphate networks not only enhanced the interfacial interaction among CP&MgO to form coral-like structures but also strengthened the interfacial binding force between the waterborne polytetrafluoroethylene (PTFE) coating and the substrate. With the enhanced composite interfacial strength, the waterborne PTFE-CP&MgO-AOP coating exhibited excellent wear-resistance, which can withstand more than 1.27 × 105 abrasion cycles. Moreover, the chemical bonding between the functional groups of phosphate networks and metal substrate improved the adhesion strength from grade 5 to 1. Furthermore, the prepared coating surface with the reticular/coral-like composite structures can lock the stable gas layer to maintain excellent hydrophobic stability, even under the conditions of strong acidic/alkaline, high-temperature, xenon lamp irradiation, and mechanical wear. Thus, this study is expected to open new insights into interfacial enhancement of robust waterborne superhydrophobic coatings.

A sustainable dynamic redox reaction passive film for long-term anti-corrosion of carbon steel surface.

CeO2 was used as the only oxidant for aniline polymerization, and polyaniline (PANI) was grown on CeO2 surface to form CeO2@PANI nanocomposites. SEM and TEM showed that the CeO2@PANI composites were nanorods in a core-shell structure. XPS indicated that CeO2-core was reduced by aniline into Ce3+, which was then captured by the PANI-shell. Then the passive ability of CeO2@PANI coating on steels was explored. EIS showed that the impedance modulus of the CeO2@PANI coating exceeded 108 Ω·cm2 after accelerated immersion. The SVET and XPS confirmed that PANI polarized the anodic reaction, Ce3+ suppressed the cathodic reaction, and PO43- formed complex precipitation. Some high-valent metal oxides can directly oxidize the aniline polymerization to form MO@PANI hybrid particles. The cations obtained by the metal oxide reduction can be captured by PANI and participate in passivation together with dopants. This study provides a new kind of nanocomposite fillers that can effectively passivate steel substrates within epoxy coatings for long-time protection.