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HighlightsAnalyzed the function of internal polarization field in Ni2P/FeP2 via hydroxyl spillover effect.From theoretical design to experimental verification, to optimize adsorption energy of oxygen intermediates on Ni active site, and further boost the xygen evolution reaction process.A hydroxyl spillover effect driven by internal polarization field in Ni2P/FeP2 can be amplified in low concentration alkaline electrolyte environment, and facilitate the application in anion exchange membrane water electrolyzer systems.The formation of multiple oxygen intermediates supporting efficient oxygen evolution reaction (OER) are affinitive with hydroxyl adsorption. However, ability of the catalyst to capture hydroxyl and maintain the continuous supply at active sits remains a tremendous challenge. Herein, an affordable Ni2P/FeP2 heterostructure is presented to form the internal polarization field (IPF), arising hydroxyl spillover (HOSo) during OER. Facilitated by IPF, the oriented HOSo from FeP2 to Ni2P can activate the Ni site with a new hydroxyl transmission channel and build the optimized reaction path of oxygen intermediates for lower adsorption energy, boosting the OER activity (242 mV vs. RHE at 100 mA cm–2) for least 100 h. More interestingly, for the anion exchange membrane water electrolyzer (AEMWE) with low concentration electrolyte, the advantage of HOSo effect is significantly amplified, delivering 1 A cm–2 at a low cell voltage of 1.88 V with excellent stability for over 50 h.

The corrosive acidic interfacial microenvironment caused by rapid multi-step deprotonation of alkaline oxygen evolution reaction in industrial high current water electrolysis is one of the key problems limiting its stability. Some functional anions derived from electrocatalysis exhibit special functionalities in modulating the interface microenvironment, but this matter has not received adequate attention in academic discussions. Here we show that the coordinate squaric acid undergoes a dissolve-re-intercalation process in alkaline oxygen evolution, leading to its stabilization within the Fe-doped NiOOH interlayer in the form of the squaric acid anions (NiFe-SQ/NF-R). These intercalated squaric acid anions stabilizes OH − through multiple hydrogen bond interactions, which is conducive to maintaining high catalytic interface alkalinity. Hence, the interfacial acidification of prepared NiFe-SQ/NF-R is inhibited, resulting in a tenfold prolong in its catalytic durability (from 65 to 700 h) when exposed to 3.0 A cm −2 , as opposed to NiFe-LDH/NF-R. This derived functional anion guarantees the enduring performance of the NiFe-derived electrocatalyst under high current densities by controlling the interfacial alkalinity. The local acidic interfacial environment limits oxygen evolution at high current densities. Here, the authors report that intercalating squaric acid anions into NiFe-based electrocatalysts stabilizes the interface, inhibiting acidification and achieving stability for 700 h at 3.0 A cm −2 .

The intelligent design of copper flotation processes is an important means for improving resource utilization and reducing costs in the current mining industry. In our previous study, the flotation process design is split into the backbone process design and the cleaning and scavenging process design. The copper flotation backbone process design was transformed into multi-label classification, and it was found that applying label correlation and domain knowledge to multi-label classification could significantly improve the precision of backbone process design. However, the above method cannot be used for cleaning and scavenging process design, which is a multi-label regression problem. This study improves on our previous work and proposes new methods that allow it to simultaneously handle multi-label classification and regression for the design of copper flotation processes. Moreover, further improves the prediction effect through the following methods: (1) Referencing adaboost algorithm, the training set samples with large prediction error in the previous iteration are set with higher weight; (2) To enhance robustness, the label uncertainty coefficient is introduced; (3) To alleviate the over fitting of small sample machine learning, bootstrap aggregating is introduced for each sub label. The experimental results demonstrate the significantly superiority of the proposed method in the copper flotation process design. The above research has significant implications for the engineering application of artificial intelligence. From the ablation experimental results, these improvements are effective.

Background The sesquiterpene germacrene D is a highly promising product due to its wide variety of insecticidal activities and ability to serve as a precursor for many other sesquiterpenes. Biosynthesis of high value compounds through genome mining for synthases and metabolic engineering of microbial factories, especially Saccharomyces cerevisiae , has been proven to be an effective strategy. However, there have been no studies on the de novo synthesis of germacrene D from carbon sources in microbes. Hence, the construction of the S. cerevisiae cell factory to achieve high production of germacrene D is highly desirable. Results We identified five putative sesquiterpene synthases (AcTPS1 to AcTPS5) from Acremonium chrysogenum and the major product of AcTPS1 characterized by in vivo, in vitro reaction and NMR detection was revealed to be (–)-germacrene D. After systematically comparing twenty-one germacrene D synthases, AcTPS1 was found to generate the highest amount of (–)-germacrene D and was integrated into the terpene precursor-enhancing yeast strain, achieving 376.2 mg/L of (–)-germacrene D. Iterative engineering was performed to improve the production of (–)-germacrene D, including increasing the copy numbers of AcTPS1 , tHMG1 and ERG20 , and downregulating or knocking out other inhibitory factors (such as erg9 , rox1 , dpp1 ). Finally, the optimal strain LSc81 achieved 1.94 g/L (–)-germacrene D in shake-flask fermentation and 7.9 g/L (–)-germacrene D in a 5-L bioreactor, which is the highest reported (–)-germacrene D titer achieved to date. Conclusion We successfully achieved high production of (–)-germacrene D in S. cerevisiae through terpene synthase mining and metabolic engineering, providing an impressive example of microbial overproduction of high-value compounds.

Background Prostate cancer (PCa), one of the common malignant tumors, is the second leading cause of cancer-related deaths in men. The circadian rhythm plays a critical role in disease. Circadian disturbances are often found in patients with tumors and enable to promote tumor development and accelerate its progression. Accumulating evidence suggests that the core clock gene NPAS2 (neuronal PAS domain-containing protein 2) has been implicated in tumors initiation and progression. However, there are few studies on the association between NPAS2 and prostate cancer. The purpose of this paper is to investigate the impact of NPAS2 on cell growth and glucose metabolism in prostate cancer. Methods Quantitative real-time PCR (qRT-PCR), immunohistochemical (IHC) staining, western blot, GEO (Gene Expression Omnibus) and CCLE (Cancer Cell Line Encyclopedia) databases were used to analyze the expression of NPAS2 in human PCa tissues and various PCa cell lines. Cell proliferation was assessed using MTS, clonogenic assays, apoptotic analyses, and subcutaneous tumor formation experiments in nude mice. Glucose uptake, lactate production, cellular oxygen consumption rate and medium pH were measured to examine the effect of NPAS2 on glucose metabolism. The relation of NPAS2 and glycolytic genes was analyzed based on TCGA (The Cancer Genome Atlas) database. Results Our data showed that NPAS2 expression in prostate cancer patient tissue was elevated compared with that in normal prostate tissue. NPAS2 knockdown inhibited cell proliferation and promoted cell apoptosis in vitro and suppressed tumor growth in a nude mouse model in vivo. NPAS2 knockdown led to glucose uptake and lactate production diminished, oxygen consumption rate and pH elevated. NPAS2 increased HIF-1A (hypoxia-inducible factor-1A) expression, leading to enhanced glycolytic metabolism. There was a positive correlation with the expression of NPAS2 and glycolytic genes, these genes were upregulated with overexpression of NPAS2 while knockdown of NPAS2 led to a lower level. Conclusion NPAS2 is upregulated in prostate cancer and promotes cell survival by promoting glycolysis and inhibiting oxidative phosphorylation in PCa cells.

Previous work has shown reduced expression levels of let-7 in lung tumors. But little is known about the expression or mechanisms of let-7a in prostate cancer. In this study, we used in vitro and in vivo approaches to investigate whether E2F2 and CCND2 are direct targets of let-7a, and if let-7a acts as a tumor suppressor in prostate cancer by down-regulating E2F2 and CCND2. Findings Real-time RT-PCR demonstrated that decreased levels of let-7a are present in resected prostate cancer samples and prostate cancer cell lines. Cellular proliferation was inhibited in PC3 cells and LNCaP cells after transfection with let-7a. Cell cycle analysis showed that let-7a induced cell cycle arrest at the G1/S phase. A dual-luciferase reporter assay demonstrated that the 3'UTR of E2F2 and CCND2 were directly bound to let-7a and western blotting analysis further indicated that let-7a down-regulated the expression of E2F2 and CCND2. Our xenograft models of prostate cancer confirmed the capability of let-7a to inhibit prostate tumor development in vivo. These findings help to unravel the anti-proliferative mechanisms of let-7a in prostate cancer. Let-7a may also be novel therapeutic candidate for prostate cancer given its ability to induce cell-cycle arrest and inhibit cell growth, especially in hormone-refractory prostate cancer.

Near-infrared fluorescence (NIRF) imaging is an attractive modality for early cancer detection with high sensitivity and multi-detection capability. Due to convenient modification by conjugating with moieties of interests, NIRF probes are ideal candidates for cancer targeted imaging. Additionally, the combinatory application of NIRF imaging and other imaging modalities that can delineate anatomical structures extends fluorometric determination of biomedical information. Moreover, nanoparticles loaded with NIRF dyes and anticancer agents contribute to the synergistic management of cancer, which integrates the advantage of imaging and therapeutic functions to achieve the ultimate goal of simultaneous diagnosis and treatment. Appropriate probe design with targeting moieties can retain the original properties of NIRF and pharmacokinetics. In recent years, great efforts have been made to develop new NIRF probes with better photostability and strong fluorescence emission, leading to the discovery of numerous novel NIRF probes with fine photophysical properties. Some of these probes exhibit tumoricidal activities upon light radiation, which holds great promise in photothermal therapy, photodynamic therapy, and photoimmunotherapy. This review aims to provide a timely and concise update on emerging NIRF dyes and multifunctional agents. Their potential uses as agents for cancer specific imaging, lymph node mapping, and therapeutics are included. Recent advances of NIRF dyes in clinical use are also summarized.

Growth differentiation factor 15 (GDF15), a direct target gene of p53, is a multifunctional member of the TGF-β/BMP superfamily. GDF15 can be induced and is implicated as a key secretory cytokine in response to multiple cellular stimuli. Accumulating evidence indicates that GDF15 is associated with the development and prognosis of diabetes mellitus, while whether GDF15 can be induced by high glucose is unknown. In the present study, we revealed that high glucose could induce GDF15 expression and secretion in cultured human umbilical vein endothelial cells in a ROS- and p53-dependent manner. Inhibition of high glucose-induced GDF15 expression by siRNA demonstrated that adaptively induced GDF15 played a protective role against high glucose-induced human umbilical vein endothelial cell apoptosis via maintaining the active state of PI3K/Akt/eNOS pathway and attenuating NF-κB/JNK pathway activation. The protective effects of GDF15 were probably achieved by inhibiting ROS overproduction in high glucose-treated human umbilical vein endothelial cells in a negative feedback manner. Our results suggest that high glucose can promote GDF15 expression and secretion in human umbilical vein endothelial cells, which in turn attenuates high glucose-induced endothelial cell apoptosis.

Urologic cancers, particularly kidney, bladder, and prostate cancer, have a growing incidence and account for about a million annual deaths worldwide. Treatments, including surgery, chemotherapy, radiotherapy, hormone therapy, and immunotherapy are the main therapeutic options in urologic cancers. Immunotherapy is now a clinical reality with marked success in solid tumors. Immunological checkpoint blockade, non-specific activation of the immune system, adoptive cell therapy, and tumor vaccine are the main modalities of immunotherapy. Immunotherapy has long been used to treat urologic cancers; however, dose-limiting toxicities and low response rates remain major challenges in the clinic. Herein, nanomaterial-based platforms are utilized as the “savior”. The combination of nanotechnology with immunotherapy can achieve precision medicine, enhance efficacy, and reduce toxicities. In this review, we highlight the principles of cancer immunotherapy in urology. Meanwhile, we summarize the nano-immune technology and platforms currently used for urologic cancer treatment. The ultimate goal is to help in the rational design of strategies for nanomedicine-based immunotherapy in urologic cancer.

In this paper, we investigate the existence of positive solutions for an infinite system of fractional order boundary value problems in a Banach sequence space c. Our analysis relies on the Krasnosel’skii fixed point theorem in a cone in conjunction with the criterion of relative compactness in C1(J,c)\\(C^1(J, c)\\). Finally, an example is given to illustrate our abstract results.