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We propose a facile boron-assisted strategy to prepare NiFe LDHs with rich grain boundaries, which originate from imperfect oriented attachment between primary LDH particles. The grain-boundary-rich NiFe LDHs exhibit excellent OER activity.

The interfacial stability is highly responsible for the longevity and safety of sodium ion batteries (SIBs). However, the continuous solid-electrolyte interphase(SEI) growth would deteriorate its stability. Essentially, the SEI growth is associated with the electron leakage behavior, yet few efforts have tried to suppress the SEI growth, from the perspective of mitigating electron leakage. Herein, we built two kinds of SEI layers with distinct growth behaviors, via the additive strategy. The SEI physicochemical features (morphology and componential information) and SEI electronic properties (LUMO level, band gap, electron work function) were investigated elaborately. Experimental and calculational analyses showed that, the SEI layer with suppressed growth delivers both the low electron driving force and the high electron insulation ability. Thus, the electron leakage is mitigated, which restrains the continuous SEI growth, and favors the interface stability with enhanced electrochemical performance.

Huangjinya is a light-sensitive mutant tea cultivar that produces fresh leaves with a yellow phenotype, and the leaves also be used to produce black tea with special sensory characteristics. To thoroughly explore the chemical changes that occur during the processing of Huangjinya black tea, tea samples were collected from each processing step to perform quantitative and qualitative analyses by high-performance liquid chromatography and ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS). Compared to fresh tea leaves, only approximately 20% of the catechins remained at the end of processing, while theaflavins levels peaked at the rolling step and were slightly reduced in the fermentation and drying processes. The levels of amino acids derived from protein hydrolysis increased significantly in the withering and rolling processes. Altogether, 620 differential metabolites were identified from 11 subclasses using widely targeted metabolomics based on UPLC-HRMS for the four steps used to process Huangjinya black tea. Flavonoids, phenolic acids, and lipids were the three major classes of differential metabolites, accounting for 52.4% of the differential compounds. The greatest changes in the metabolite profile occurred during the rolling step, with 292 metabolites showing increases or decreases. Two glycoconjugates of the amino acid were first identified in tea, which was sharply increased in the drying stage. The present study provides comprehensive information on the chemical changes during the processing of Huangjinya black tea, and this information is valuable for optimizing manufacturing process and utilization of the Huangjinya tea plant.

Pyridostatin (PDS) is a well-known G-quadruplex (G4) inducer and stabilizer, yet its target genes have remained unclear. Herein, applying MS proteomics strategy, we revealed PDS significantly downregulated 22 proteins but upregulated 16 proteins in HeLa cancer cells, of which the genes both contain a number of G4 potential sequences, implying that PDS regulation on gene expression is far more complicated than inducing/stabilizing G4 structures. The PDS-downregulated proteins consequently upregulated 6 proteins to activate cyclin and cell cycle regulation, suggesting that PDS itself is not a potential anticancer agent, at least toward HeLa cancer cells. Importantly, SUB1, which encodes human positive cofactor and DNA lesion sensor PC4, was downregulated by 4.76-fold. Further studies demonstrated that the downregulation of PC4 dramatically promoted the cytotoxicity of trans-[PtCl2(NH3)(thiazole)] (trans-PtTz) toward HeLa cells to a similar level of cisplatin, contributable to retarding the repair of 1,3-trans-PtTz crosslinked DNA lesion mediated by PC4. These findings not only provide new insights into better understanding on the biological functions of PDS but also implicate a strategy for the rational design of novel multi-targeting platinum anticancer drugs via conjugation of PDS as a ligand to the coordination scaffold of transplatin for battling drug resistance to cisplatin.

Smart hydrogels with good flexibility and biocompatibility have been widely used. The common near-infrared (NIR) photothermal agents are facing a trade-off between good photothermal-conversion efficiency and high biocompatibility. Therefore, developing new metal-free photothermal agents with low cost, high biocompatibility and excellent phase stability is still in urgent need. In this study, we successfully combined poly(N-isopropylacrylamide) (PNIPAM) with the two-dimensional (2D) silicene nanosheets via the in situ polymerization method. Attributed to the thermal-responsive nature of PNIPAM and the excellent photothermal properties of 2D silicene, the obtained silicene/PNIPAM composite hydrogels exhibited dual thermal and NIR responsive properties. This smart hydrogel showed rapid, reversible and repeatable NIR light-responsive behaviors. The volume of this smart hydrogels can shrink significantly under NIR irradiation and recover to its original size without the NIR irradiation. Remote near-infrared light-controlled microfluidic pipelines and electronic switches based on obtained silicene/PNIPAM composite hydrogels were also demonstrated. This work significantly broadens the application prospects of silicene-based hydrogels in remote light-controlled devices.

Manganese-enhanced MRI (MEMRI) is a powerful tool to study neuronal activity and microarchitecture in vivo. Yet the influence of exogenous manganese on the brain of the Parkinson's disease (PD) model mouse is poorly understood. Laser ablation connected to inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging for tissue section is an ideal tool to simultaneously analyze the metabolism of endogenous metal ions. In this study, DJ-1 knockout PD model mice were subjected to an MnCl

Tetrathiomolybdate (TM) is used in the clinic for the treatment of Wilson’s disease by targeting the cellular copper efflux protein ATP7B (WLN). Interestingly, both TM and WLN are associated with the efficacy of cisplatin, a widely used anticancer drug. Herein, we show that TM induces dimerization of the metal-binding domain of ATP7B (WLN4) through a unique sulfur-bridged Mo2S6O2 cluster. TM expels copper ions from Cu-WLN4 and forms a copper-free dimer. The binding of Mo to cysteine residues of WLN4 inhibits platination of the protein. Reaction with multi-domain proteins indicates that TM can also connect two domains in the same molecule, forming Mo-bridged intramolecular crosslinks. These results provide structural and chemical insight into the mechanism of action of TM against ATPase, and reveal the molecular mechanism by which TM attenuates the cisplatin resistance mediated by copper efflux proteins., Tetrathiomolybdate (TM) and Cu-ATPases, e.g. Wilson (WLN) protein, affect the efficacy of common anticancer drug cisplatin. Here, the authors show that TM generates a protein dimer with a WLN domain by expelling copper and provide insight into the synergy of TM and cisplatin in cancer chemotherapy.

Background: Kidney renal clear cell carcinoma (KIRC) has the highest incidence rate in renal cell carcinoma (RCC). Although bioinformatics is widely used in cancer, few reliable biomarkers of KIRC have been found. Therefore, continued efforts are required to elucidate the potential mechanism of the biogenesis and progression of KIRC.Methods: We evaluated the expression of tumor necrosis factor (TNF) family genes in KIRC, and constructed a prognostic signature. We validated the signature by another database and explored the relationship between the signature and progression of KIRC. We assessed the prognostic value, immune infiltration, and tumor mutation burden (TMB) of the signature in KIRC.Results: We selected four key genes (TNFSF14, TNFRSF19, TNFRSF21, and EDA) to construct the TNF-related signature. We divided the KIRC patients into high- and low-risk groups based on the signature. Patients with higher risk scores had shorter overall survival and worse prognosis. With another database, we validated the value of the signature. The signature was considered as an independent risk factor. A higher level of risk score was relevant to higher level of immune infiltration, especially T regulatory cells, CD8+ T cells, and macrophages. The signature was also associated with TMB scores, and it may have an effect on assessing the efficacy of immunotherapy.Conclusion: This is the first TNF-family-related signature of KIRC and we demonstrated its effectiveness. It played a significant role in predicting the prognosis of patients with KIRC. It also has the potential to become a powerful tool in guiding the immunotherapy of KIRC patients in clinical practice.

Cisplatin is a DNA targeting anticancer drug, yet its damaged gene loci have remained unclear. In the present work, combining affinity isolation and high throughput sequencing, we genome-widely mapped 17729 gene loci containing platination lesions, which mainly function as enzymes, transcription regulators, transporters and kinases, and of which 445 genes account for 71% of potential gene targets for cancer therapy reported in the literature. The most related core signaling pathway, disease and tissue toxicity of 7578 genes with an enrichment fold (EFG) of >12, where EFG refers to the ratio of total read counts of a gene detected in cells with and without cisplatin treatment, are sperm motility, cancer and hepatotoxicity with association P values of < 1×10−22. Among 616 kinase genes damaged by cisplatin, 427 are protein kinases which account for 82% of putative protein kinases, suggesting that cisplatin may act as broad-spectrum protein kinase inhibitor. Western Blot assays verified that expression of 8 important protein kinase genes was significantly reduced due to cisplatin damage. SPAG9 is closely related to 147 of 361 cancer diseases which the cisplatin damaged genes are associated with and was severely damaged by cisplatin. Given SPAG9 abundantly expresses JIP-4, a upstream mediator of protein kinase signaling, in testis, it may be responsible for the high sensitivity of testicular cancer to cisplatin, thus being a potential therapeutic target for precise treatment of testicular cancer. These findings provide novel insights into better understanding in molecular mechanism of anticancer activity and toxicity of cisplatin, more importantly inspire further studies in prioritizing gene targets for precise treatment of cancers.

Cisplatin is a widely used anticancer drug in clinic, and ammonium tetrathiomolybdate ([(NH4)2MoS4], TM) is a copper chelator used in clinic for the treatment of Wilson's disease. Recently, TM has been found to enhance the therapeutic effect of cisplatin; however, the origin of this effect is not clear. Here we found that TM can inhibit the reaction of cisplatin with Cu-Atox1 and prevent the protein unfolding and aggregation induced by cisplatin. Although Ag(i) binds to Atox1 in a way similar to Cu(i)-Atox1, TM does not prevent the reaction of Ag-Atox1 with cisplatin. This result indicates that the formation of a Mo-centered trimeric protein cluster in the TM-Cu-Atox1 system plays a role in the inhibitory effect. This work provides new insights into the mechanism by which TM enhances the cytotoxic efficacy of cisplatin and helps to circumvent cisplatin resistance of tumor cells.

Platinum anti-tumor drugs are widely used in cancer chemotherapy. These compounds are believed to induce apoptosis in tumor cells by DNA crosslinking, which causes DNA damage and suppresses DNA replication. However, recent studies indicate that platinum drugs can react with a large variety of intracellular and extracellular proteins before binding to the nuclear DNA. These protein interactions can alter the transportation and metabolism of platinum drugs as well as their interactions with the DNA target, which have significant influence on the efficacy and resistance of platinum drugs. On the other hand, platinum reactions can alter the function of proteins, which contributes to the drug efficacy and side-effects of platinum drugs. In this article, we review the recent progress in the protein interaction of platinum drugs. The influence of small molecules on the reaction, the reaction of non-cancer target proteins, and the research methods for the investigation are also discussed.

Efficient and safe intracellular delivery of proteins is highly desired in the development of protein therapeutics. Current methods of protein delivery commonly suffer from low loading efficiency, low stability in serum, and lack of versatility for different proteins. Here, we developed a platform for efficient protein delivery using mesoporous silica nanoparticles (MSN) with lipid fusion. By different surface modifications on MSN, the positively charged MSN (MSN+) and the negatively charged MSN (MSN–), were generated for loading different proteins. The cargo proteins, based on the surface charges, can be selectively loaded in very high efficiency. The protein-loaded MSNs were fused with liposomes to form a protocell-like delivery system (MSN-LP) in order to prevent burst release of proteins. The lipid fusion significantly increases the stability of the nanosystem in physiological conditions, and the MSN-LP protocell can efficiently deliver proteins into cells. The cargo proteins can be released in cells ...

Prostate cancer (PCa) is a leading cause of cancer-related deaths among men. The anthracycline doxorubicin (DOX) is used for the treatment of this disease, but its considerable side effects and non-selectivity are major drawbacks. Simvastatin (Sim), a lipid-lowering agent, holds great promise as a cancer therapeutic, and thus could be used in combination with DOX. Targeted drug-loaded nano-carriers with antibodies for receptors that are overexpressed on tumor cells are promising strategies for decreasing toxicity to normal tissues and enhancing the efficacy of chemotherapies in cancer treatment. Specifically, human epidermal growth factor 2 is overexpressed and constitutively activated in the PC-3 cell line. Within this context, we designed a co-delivery system coated with Herceptin for PCa, performed physicochemical characterizations, and tested the formulations for cytotoxicity and uptake. The targeted liposomes had a mean particle size of 134 nm, and the drug encapsulation efficiency of both Sim and DOX were greater than 80%. We discovered that the drug combination led to the strong inhibition of PCa both in vitro and in vivo, with inhibitory rates of tumor volumes corresponding to 80.36% and 68.77% of Herceptin-coated liposomes and non-targeted liposomes, respectively. We also found that the anti-tumor mechanisms of the DOX and Sim combination were possibly attributed to synergistic anti-angiogenesis. These results reveal that Herceptin-conjugated liposomes co-loaded with DOX and Sim are a potential novel therapeutic strategy for overcoming PCa.

A new biomimetic catalytic oxidation system which employs 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as the catalyst, molecular oxygen as the terminal oxidant and iron(II) phthalocyanine (FeIIPc) as the electron-transfer mediator has been developed. This system can be applied for oxidative deprotection of PMB ethers, alcohol oxidation, aromatization and α,β-unsaturated aldehyde formation. After immobilizing FeIIPc on multi-walled carbon nanotubes, it can be reused without loss of activity.

A dual-fluorescent nanocarrier was synthesized by coating human serum albumin (HSA) on lanthanide-doped upconversion nanoparticles (UCNPs). The HSA coating makes the particles highly biocompatible and well dispersed in aqueous solutions. This nanocarrier demonstrates two types of fluorescence: the blue upconversion fluorescence under excitation with a 980 nm light of the UCNP core, and the green fluorescence under the excitation with a 450 nm light of the polymerized HSA layer. This dual-fluorescence property makes the material more applicable in bio-imaging. A photo-sensitive ruthenium complex ([Ru(bpy)2(dmbpy)2]Cl2, Ru-1) was loaded to generate the light-responsive Ru-HSA-UCNPs. This conjugate showed very low inhibitory effect on cell proliferation in the dark, while light irradiation significantly enhanced its cytotoxicity to cancer cells. Further investigations showed that irradiation activated Ru-1 and the product became highly reactive to DNA. This result suggests the potential application of this conjugate in the controlled release of active anticancer agents in tumor sites.

In this research, a fast, accurate, and stable system of lung cancer detection based on novel deep learning techniques is proposed. A convolutional neural network (CNN) structure akin to that of GoogLeNet was built using a transfer learning approach. In contrast to previous studies, Median Intensity Projection (MIP) was employed to include multi-view features of three-dimensional computed tomography (CT) scans. The system was evaluated on the LIDC-IDRI public dataset of lung nodule images and 100-fold data augmentation was performed to ensure training efficiency. The trained system produced 81% accuracy, 84% sensitivity, and 78% specificity after 300 epochs, better than other available programs. In addition, a t-based confidence interval for the population mean of the validation accuracies verified that the proposed system would produce consistent results for multiple trials. Subsequently, a controlled variable experiment was performed to elucidate the net effects of two core factors of the system - fine-tuned GoogLeNet and MIPs - on its detection accuracy. Four treatment groups were set by training and testing fine-tuned GoogLeNet and Alexnet on MIPs and common 2D CT scans, respectively. It was noteworthy that MIPs improved the network's accuracy by 12.3%, and GoogLeNet outperformed Alexnet by 2%. Lastly, remote access to the GPU-based system was enabled through a web server, which allows long-distance management of the system and its future transition into a practical tool.

The Menkes (MNK) and Wilson (WLN) disease proteins are two P-type ATPases responsible for active Cu efflux. These ATPases are also associated with resistance to cisplatin. In this work, different metal-binding domains (MBDs) of ATPases (9 out of 12 domains) were compared based on their reactivity towards cisplatin. The reaction rates of the MBDs can be largely different; the reaction of MNK6 is about six times faster than that of WLN2. Copper coordination favors the platination of the MBDs to different extents. The rate of platination was generally greater for holo-MBDs than for apo-MBDS (particularly in the case of WLN4 and WLN2); however, it was negligibly affected in the case of MNK6. Interestingly, the platinum binding weakens the CuI coordination, but does not expel the copper ion from MBDs. The latter results nicely explain the inhibitory effect of Cu upon the cisplatin translocation promoted by Cu-ATPases and can help in understanding how copper levels can modulate the sensitivity of cancer cells to platinum chemotherapy.

A facile and efficient protocol for direct transformation of p-methoxybenzyl (PMB) ethers to aldehydes or ketones via a catalytic aerobic oxidation process has been developed. The reaction was performed with the combination of catalytic amounts of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), 2,2,6,6-tetramethylpiperidine N-oxy (TEMPO), and tert-butyl nitrite (TBN), with molecular oxygen as terminal oxidant. A variety of PMB ether substrates derived from benzylic alcohols, heteroaromatic alcohols, and aliphatic alcohols, were converted to their corresponding carbonyl compounds in good conversions and selectivities.

Polyimides are widely used in electronic, semiconductor industry, however, with the wide application, the degradation of the polymer has become a serious problem people have to face. In this work, a series of new fast degradable polyimides were synthesized from diamine p -phenylenedioxybis(5-amino-2-pyridine) with various commercially available aromatic dianhydrides via a conventional two-stage process. The resulting polyimides could degrade at room temperature under a certain condition, and we proposed a degradation mechanism by analyzing the degradation products. Compared with the traditional method, here, we provided a facile and effective method for polyimide degradation. The result suggested that introducing a phenyl-2-pyridyl ether structure into polymer chains may become a class of new method for polymer degradation.

A facile and efficient protocol is presented for the direct transformation of Pmb-ether substrates derived from benzylic and aliphatic alcohols into their corresponding carbonyl compounds.