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Highly efficient charge transfer is a critical factor to modulate the photocatalytic activity. However, the conscious modulation of charge transfer efficiency is still a great challenge. Herein, a novel interfacial Mo-N bond and appropriate oxygen vacancies (OVs) modulated S-scheme MoO

Developing photocatalysts with superior performance to generate hydrogen peroxide (H

Backgrounds Although kidney impairments have been reported following immune checkpoint inhibitors (ICIs) in clinical studies, there are few pharmacoepidemiology studies to compare the occurrences, clinical features, and prognosis of renal adverse effects. Methods Disproportionality and Bayesian analysis were used in data mining to screen the suspected renal adverse effects after the administration of different ICIs, based on FDA's Adverse Event Reporting System (FAERS) from January 2004 to September 2019. The time to onset, fatality and hospitalization rates of renal adverse effects were also investigated. Results We identified 1444 reports of renal adverse effects. Affected patients tended to be older than 65 years (52.7%). Renal effects were most commonly reported in nivolumab monotherapy (33.24%). Atezolizumab appeared the strongest association among six ICI monotherapies, based on the highest reporting odds ratio (ROR = 144.38, two‐sided 95% CI = 123.08 −169.37), proportional reporting ratio (PRR = 139.13, χ 2 = 21 425.38), and empirical Bayes geometric mean (EBGM = 131.75, one‐sided 95% CI = 115.28). The combination treatments showed higher RORs, PRRs, and EBGMs, compared with either nivolumab or pembrolizumab monotherapy. The median onset time of renal adverse effects was 48 (interquartile range [IQR] 18.75‐121.25) days after the monotherapies of ICI regimens. Patients treated with the combination of nivolumab plus ipilimumab were younger than receivers in nivolumab monotherapy (63.81 ± 12.03 vs 66.39 ± 11.53, P = .004); The fatality rate of renal adverse effects appeared lower in the combination group, compared to nivolumab monotherapy (18.53% vs 27.50%, P = .004). The top hospitalization rates due to renal effects occurred in patients with combination therapies. Conclusion Based on the FAERS database, we profiled renal adverse effects after various ICIs with real‐world data in occurrences, clinical characteristics, and prognosis. Renal effects should be tightly monitored, especially within the first several months after ICIs administration. Particular concern should be paid for patients with a tendency for kidney impairments, such as old age., This is the first and largest pharmacoepidemiology study until recently to compare the associations, timing, and prognosis of renal adverse effects following different immune checkpoint inhibitors (ICIs) in the real‐world practice based on the Food and Drug Administration's Adverse Event Reporting System (FAERS) pharmacovigilance database. Renal adverse effects related to various ICIs are profiled with real‐world data in occurrences, clinical characteristics, and prognosis. We suggest that particular concern should be paid for atezolizumab, nivolumab, and combination therapies when applied for patients with a tendency for renal effects.

Liver fibrosis leads to over one million deaths annually worldwide. Hepatic stellate cells (HSCs) have been identified as the main executors of liver fibrosis. Unfortunately, no drug has yet been approved for clinical use against liver fibrosis, largely because the tested drugs have been unable to access HSCs and efficiently remove the collagen accumulation involved in fibrogenesis. Here, we designed an efficient HSC-targeting lipid delivery system that carried dual siRNAs intended to both inhibit collagen synthesis and promote collagen degradation, with the goal of realizing enhanced anti-liver fibrosis by bidirectional regulation of collagen accumulation. The delivery system was constructed by using amphiphilic cationic hyperbranched lipoids (C15-PA) for siRNA complexation and helper lipoids (cholesterol-polyethylene glycol-vitamin A, Chol-PEG-VA) for HSCs targeting. The generated vitamin A-decorated and hyperbranched lipoid-based lipid nanoparticles (VLNPs) showed excellent gene-binding ability and transfection efficiency, and enhanced the delivery of siRNAs to HSCs. Fibrotic mice treated with dual siRNA-loaded VLNPs showed a great reduction in the collagen accumulation seen in this model; the enhanced effect of bidirectional regulation reduced the collagen accumulation level in treated mice to almost that seen in normal mice. There was no notable sign of toxicity or tissue inflammation in mice exposed to repeated intravenous administration of the dual siRNA-loaded VLNPs. In conclusion, our results indicate that biocompatible VLNPs designed to exploit precise targeting and an effective bidirectional regulation strategy hold promise for treating liver fibrosis.

Superhydrophobic fabrics were successfully prepared by modification of fibers with polymers containing polyhedral oligomeric silsesquioxane (POSS). The modification was conducted by chemical vapor deposition with mercapto silanes followed by click coupling with pentaerythritol tetrakis(3-mercaptopropionate) and octavinyl-POSS to form POSS-based polymers on the cotton fibers. The POSS-based polymers onto the fabric surfaces both increased the surface roughness and lowered the surface energy of the fabrics. The as-prepared superhydrophobic fabrics have excellent superhydrophobicity stability toward acid, base, salt, acetone, and N,N-dimethylformamide. In addition, the fabrics maintained superhydrophobicity under long time exposure to UV irradiation, and have better antifouling properties.

Determining optimal well locations is a challenging work because engineering and geologic variables affect reservoir performance which are often highly nonlinearly correlated and uncertain. Particle swarm optimization algorithm (PSO) could solve the well placement optimization problem, but it has the shortcomings such as low convergence speed and long computation time. This paper proposed a well placement optimization model based on PSO assisted by quality map (QM) and Gompertz-based grey model (GGM), and the well locations can be determined in the condition of use of numerical simulation in more fewer times. We conduct a numerical experiment which is developing an oil field by the four well placement arrangements namely the PSO+QM, PSO+QM+GGM, PSO, and original well placement plan (BASE) with the maximization of cumulative oil production as the objective function. It is shown that the PSO+QM method outperforms PSO+QM+GGM method, and PSO+QM+GGM method outperforms PSO and BASE method. The cumulative oil production of well placement generated by PSO+QM is 4.89 × 106 m3 which is 1.24% more than the PSO+QM+GGM based well placement plan (4.83 × 106 m3), but the cost time of PSO+QM is 11.25 h which is 47.64% more than the PSO+QM+GGM based well placement plan (7.62 h). Taken in total, the PSO+QM+GGM method has the superiority both in optimization results and computation time, which can provide a reliable basis for well placement optimization in real oil fields.

Liver fibrosis refers to excessive accumulation of hepatic collagen, which is primarily produced by activated hepatic stellate cells (HSCs). No effective drugs are clinically available to treat this condition, reflecting the fact that antifibrotic drugs do not specifically target activated HSCs. Here, we report the synthesis and evaluation of poly (lactide-co-glycolide)-polyspermine-poly (ethylene glycol)-vitamin A (PLGA-PSPE-PEG-VA), and activated HSC-targeted, biocompatible amphiphilic polymers for co-delivery of chemical (silibinin) and genetic (siCol1α1) drugs that synergistically suppress collagen I accumulation in fibrogenesis. PLGA-PSPE-PEG-VA self-assembled into core-shell polymeric micelles (PVMs) at low concentrations. After loading with silibinin and siCol1α1, the resulting chemical/genetic drug-loaded PVMs (CGPVMs) exhibited a small particle size and a slightly positive surface. CGPVMs had very low cytotoxicity and hemolytic activity in vitro and were well tolerated in mice, with no liver toxicity or inflammation. Importantly, CGPVMs effectively accumulated in fibrotic livers and specifically targeted activated HSCs. As expected CGPVMs more efficiently decreased collagen I production and ameliorated liver fibrosis compared with chemical drug (silibinin)-loaded PVMs (CPVMs) or genetic drug (siCol1α1)-loaded PVMs (GPVMs) only. These results indicate that CGPVMs are a promising tool for targeted delivery of chemogenes to activated HSCs in the treatment of liver fibrosis.

Photocatalysis is considered to be an effective way to remove organic pollutants, but the key to photocatalysis is finding a high-efficiency and stable photocatalyst. 2D materials-based heterojunction has aroused widespread concerns in photocatalysis because of its merits in more active sites, adjustable band gaps and shorter charge transfer distance. Among various 2D heterojunction systems, 2D/2D heterojunction with a face-to-face contact interface is regarded as a highly promising photocatalyst. Due to the strong coupling interface in 2D/2D heterojunction, the separation and migration of photoexcited electron-hole pairs are facilitated, which enhances the photocatalytic performance. Thus, the design of 2D/2D heterojunction can become a potential model for expanding the application of photocatalysis in the removal of organic pollutants. Herein, in this review, we first summarize the fundamental principles, classification, and strategies for elevating photocatalytic performance. Then, the synthesis and application of the 2D/2D heterojunction system for the removal of organic pollutants are discussed. Finally, the challenges and perspectives in 2D/2D heterojunction photocatalysts and their application for removing organic pollutants are presented.

Safe and efficient drug delivery systems have received great attention for cancer therapy due to their enhanced cancer-targeting efficiency and reduced undesirable side effects. Administration, safety, and effectiveness are the main issues for clinical trials in nanomedicine. Here, we develop a series of poly(lactic-co-glycolic acid)-co-polyspermine (PLGA-PSPE) copolymers via a simple polymerization reaction between activated carboxyl groups of poly(lactic-co-glycolic acid) (PLGA) and amine groups of polyspermine (PSPE) with different molecular weights (Mw) for safe and efficient lung cancer drug delivery. PLGA-PSPE can self-assemble into polymeric micelles with a low critical micelle concentration. PLGA-PSPE had very low cytotoxicity and hemolytic activity. In addition, PLGA-PSPE also had no potential systemic toxicity after aerosol delivery to mice. Dihydroergotamine tartrate (DHE), which could suppress lung cancer cell survival by induction of apoptosis and mitophagy in the latest study, was employed as the model hydrophobic drug and encapsulated into PLGA-PSPE polymeric micelles (PLGA-PSPE/DHE). PLGA-PSPE/DHE could be stored at 25 °C for 7 days, and showed a controlled and sustained drug release, and time and dose dependent cellular uptake. Moreover, PLGA-PSPE/DHE efficiently increased apoptosis and mitophagy in A549 lung cancer cells. Furthermore, PLGA-PSPE/DHE significantly reduced tumor sizes and numbers, and efficiently suppressed lung tumorigenesis in K-rasLA1 lung cancer model mice after aerosol delivery. These results indicate that PLGA-PSPE polymeric micelles have a potential as an anticancer drug delivery carrier for lung cancer therapy.

As hepatic stellate cells (HSCs) are essential for hepatic fibrogenesis, HSCs targeted nano-drug delivery system is a research hotspot in liver fibrosis therapy. However, the excessive deposition of fibrosis collagen (mainly collagen I) in the space of Disse associated with hepatic fibrogenesis would significantly hinder nano-formulation delivery to HSCs. Here, we have prepared a collagenase I and retinol co-decorated polymeric micelle that possess nanodrill-like and HSCs-target function based on poly-(lactic-co-glycolic)-b-poly (ethylene glycol)-maleimide (PLGA-PEG-Mal) (named CRM) for liver fibrosis therapy. Upon encountering collagen I barrier, CRM exerted a nanodrill-like function, efficiently degrading pericellular collagen I and showing greater uptake by human HSCs than other micelle formulations. Besides, CRM could realize excellent accumulation in the fibrotic liver and accurate targeting to activated HSCs in mouse hepatic fibrosis model. Moreover, CRM loaded with nilotinib (CRM/NIL), a second-generation tyrosine kinase inhibitor used in the treatment of liver fibrosis, showed optimal antifibrotic activity. This work suggests that CRM with dual function is an efficient carrier for liver fibrosis drug delivery and collagenase I decorating could be a new strategy for building more efficient HSCs targeted nano-drug delivery system.

Background Wnt1-inducible signaling pathway protein 1 (WISP1) is upregulated in several types of human cancer, and has been implicated in cancer progression. However, its clinical implications in gastric cancer (GC) remain unclear. Aim To explore the expression pattern and clinical significance of WISP1 in GC. Methods Public data portals, including Oncomine, The Cancer Genome Atlas database, Coexpedia, and Kaplan-Meier plotter, were analyzed for the expression and clinical significance of WISP1 mRNA levels in GC. One hundred and fifty patients who underwent surgery for GC between February 2010 and October 2012 at the Affiliated Hospital of Jiangnan University were selected for validation study. WISP1 levels were measured at both the mRNA and protein levels by RT-qPCR, Western blot analysis, and immunohistochemistry (IHC). In addition, the in situ expression of WISP1 in the GC tissues was determined by IHC, and the patients were accordingly classified into high- and low-expression groups. The correlation of WISP1 expression status with patient prognosis was then determined by univariate and multivariate Cox regression analyses. WISP1 was knocked down by RNA interference. The 50% inhibitory concentration of oxaliplatin was detected by CellTiter-Blue assay. Results WISP1 levels at both the mRNA and protein levels were remarkably upregulated in GC tissues compared to normal tissues. Moreover, IHC revealed that WISP1 expression was associated with T stage and chemotherapy outcome, but not with lymph node metastasis, age, gender, histological grade, or histological type. GC patients with high WISP1 expression showed a poor overall survival. Multivariate survival analysis indicated that WISP1 was an important prognostic factor for GC patients. Mechanistically, knock-down of WISP1 expression enhanced sensitivity to oxaliplatin by reducing DNA repair and enhancing DNA damage. Conclusion Significantly upregulated WISP1 expression is associated with cancer progression, chemotherapy outcome, and prognosis in GC. Mechanistically, knock-down of WISP1 expression enhances oxaliplatin sensitivity by reducing DNA repair and enhancing DNA damage. WISP1 may be a potential therapeutic target for GC treatment or a potential biomarker for diagnosis and prognosis.

Flexible and wearable sensors are of extreme importance for various practical applications in complex environments, such as electronic skin, body motion detection, etc. However, preparation of cost-effective and superhydrophobic wearable sensors with excellent flexibility, anti-corrosion, outstanding sensitivity and environmental adaptability remains challenging. Herein, a superhydrophobic flexible film is fabricated by spray-coating thermoplastic elastomer (TPE) solution on the upside of a multi-walled carbon nanotube (MWCNTs) sheet formed at the air/water interface, followed by treating the downside of MWCNTs sheet with polydimethylsiloxane (PDMS) pumped into the water. In the process, the covering of TPE on the MWCNTs made the sheet shrunk and increased the density of the conductive network. PDMS coating enhanced superhydrophobicity of the film, and binding fastness of the MWCNTs. The obtained sandwich-like TPE/MWCNTs/PDMS film had superior conductive sensitivity, large strain range (80%), fast and stable response time (60–80 ms) with great stability over 1000 stretching-relaxing cycles. Benefiting from the favorable superhydrophobic property, the fabricated film was capable of being put into liquid environment for quantifying the resistance under humid environments including moisture, acid, basic and salt conditions. It can be effectively used to measure wrist pulse and monitor various movements associated with different human body joints, such as finger, wrist, elbow. Moreover, the sensing film was able to capture the continuous signals in diverse atmosphere such as the area change of film, and the real-time stress response of drop impact. This study affords an innovative and promising track for multifunctional wearable sensors with wide applications in a harsh environment.

In this paper, an atmospheric pressure argon plasma jet generated by sinusoidal power input of moderate frequency (kHz range) and designed with dual-power electrodes is characterized and studied. Particularly, the effect of driving frequency in the 60–130 kHz range on the argon plasma discharge characteristics is investigated based on the electrical and spectroscopic diagnostics. It is shown that at constant applied voltage and gas flow rate, the increase of driving frequency in the range of 60–100 kHz exerts no significant influences on discharge parameters. While once the driving frequency exceeds a certain value of about 100 kHz, the discharge becomes intense abruptly and the corresponding discharge parameters increase drastically with the driving frequency. Detailed analysis about the effect of driving frequency on discharge characteristics is presented and two different dominant electron loss mechanisms, namely transport-dominated loss and diffusion-dominated loss, are proposed to account for the distinct effects of the driving frequency on argon discharge characteristics.

In this paper, a cold atmospheric plasma (CAP) jet array is generated by a 2-D array device of seven CAP jets arranged in a honeycomb configuration and designed with single-electrode configuration as the elemental plasma jet. The work is motivated by the challenge of using inherently small atmospheric plasmas to address many large-scale processing applications. The discharge characteristics of the plasma jet array are investigated based on detailed electrical, spectroscopic, and imaging characterizations. The CAP jet array is shown to achieve good temporal jet-jet uniformity. Furthermore, the dynamic behavior of the jet discharges is studied particularly through two series of intensified-charge-coupled-device images taken at the end views. It has been found that the seven jets show a good temporal synchronization and jet-jet uniformity, as well as rich dynamics of jet-jet interactions such as a slight repulsion at surrounding jet heads, particularly for a small gas flow rate of helium. These dynamic features offer possible insights with which to better control the jet-jet interactions and further optimize the design of large-scale CAP sources.

Abrasive suspension jet is a new embranchment of abrasive jet. In the cutting process of this jet, the suspension concentration is constant, so the cutting quality is more stable. In this paper, a prediction model based on a back-propagation (BP) artificial neural network is presented for predicting the cutting depth generated by abrasive suspension jet. In the application of the BP neural network, the mean error of the output in the model training is 0.01, the relatively discrepancy is below 8.70%. The modeling method based on the BP neural network is much more convenient and exact compared with traditional methods, and can always achieve a much better prediction effect. It is verified with experiments to be reasonable and feasible, and it is the better foundation for the future study of abrasive suspension jet.

Diterpenes, present in many medicinal plants, have been the focus of continuous studies for the development of new anticancer agents. ZBB-006 is a new synthetic diterpenoid derivative which exhibited significant anti-proliferation activity against various cancer cell lines in our previous study. Here, we investigated the antitumor effect of ZBB-006 and its potential mechanisms in the human hepatocellular carcinoma cell line HepG2, both in vitro and in vivo. We found that oral administration of ZBB-006 effectively suppressed the growth of HepG2 xenograft tumor in nude mice without body weight decline as compared with the control group. Meanwhile, the growth inhibitory effect of ZBB-006 on HepG2 cells was observed with MTT assay. Apoptosis induced by ZBB-006 in HepG2 cells was evidenced by DAPI staining and Annexin V/PI double staining assay. ZBB-006 also dissipated the mitochondrial membrane potential (ΔΨm) apparently as revealed by JC-1 staining. Furthermore, the cleavage of PARP, activation of caspase-3 and caspase-9 but not caspase-8 was demonstrated by western blot assay both in vitro and in vivo. Additionally, the proapoptotic protein Bax was markedly elevated, while the antiapoptotic protein Bcl-2 was downregulated. Collectively, our data indicated that ZBB-006 exerted a strong antitumor effect on HepG2 cells by initiating the mitochondrial-dependent apoptosis, and it has potential to be explored as a new promising therapeutic agent against human hepatoma.

In this paper, a time-resolved study on the evolution process of the plasma channels in an atmospheric pressure plasma jet is performed by using a high-speed camera system and synchronous current-voltage measurement. We have succeeded in observing the plasma channels turn up at the same time, and propagate at the speed of about 4×103 m/s in the air. Once pattern formation is done, discharge channels are fixed at the same locations, even when the polarity of the applied voltage changes.