Latest ArticlesProtein glycosylation and phosphorylation, as two of the most important protein post-translational modifications (PTMs), play key roles in living organisms. However, glycopeptides and phosphopeptides have low abundance in biological samples. In addition, the low ionization efficiency and the severe signal interference in the presence of other peptides present great difficulties for their direct mass spectrometry (MS) analysis. Therefore, it is important to develop feasible enrichment strategies to pretreat glycopeptides and phosphopeptides in complex samples before MS detection. This paper reviews the application of various magnetic nanomaterials (MNMs) in glycopeptides and phosphopeptides in the last decade, with emphasis on the enrichment principles, the design and synthesis process of the materials, and the effectiveness of the application in biological samples. In addition, possible future trends and potential challenges are presented.
TiO2 has been widely studied as one of the most promising anode materials for lithium-ion batteries (LIBs) due to good structural stability and small volume changes. However, its applications are still greatly affected by its poor electrical conductivity. In this work, ultrasmall TiO2 quantum dots (QDs) are firmly grown onto 2D Ti3C2Tx nanosheets (A-TiO2/Ti3C2Tx), benefiting from the positive regulation of (3-aminopropyl)triethoxysilane (APTES). Interestingly, SiO2 nanoparticles produced by the hydrolysis of APTES can strengthen the strong coupling of TiO2 QDs with Ti3C2Tx, thereby enhancing the structural integrity of the composite. As expected, the A-TiO2/Ti3C2Tx composite demonstrates an exceptional lithium storage performance, achieving a high capacity of 425.4 mAh/g for 400 cycles at 0.1 A/g, and an outstanding long-term cycling stability. In-situ electrochemical impedance spectroscopy and theoretical analysis unconver that the superior lithium storage performance is attributed to its unique heterostructure and in-situ N doping derived from APTES, which not only reduces the Li+ adsorption energy, but also gives the fast charge transfer dynamics.
As a kind of emerging energy storage devices, Aqueous zinc ion batteries possess the characteristics of safety, low cost and environmental friendliness. However, their further application is restricted by the sluggish electrochemical reaction kinetics and low conductivity. In this work, we prepare two H3.78V6O13 electrode materials with many active sites, which promotes the kinetics of ion diffusion and then improves the capacity of the cell. The as-obtained HVO-PVP electrode possess a capacity of 393.2 and 285.9 mAh/g at 0.2 and 5.0 A/g, respectively. Moreover, the assembled Zn//HVO-PVP cells also indicate excellent specific capacity and cycle stability at different operating temperatures (0–60 ℃).
Sulfide solid electrolytes with an ultrahigh ionic conductivity are considered to be extremely promising alternatives to liquid electrolytes for next-generation lithium batteries. However, it is difficult to obtain a thin solid electrolyte layer with good mechanical properties due to the weak binding ability between their powder particles, which seriously limits the actual energy density of sulfide all-solid-state lithium batteries (ASSLBs). Fortunately, the preparation of sulfide-polymer composite solid electrolyte (SPCSE) membranes by introducing polymer effectively reduces the thickness of solid electrolytes and guarantees high mechanical properties. In this review, recent progress of SPCSE membranes for ASSLBs is summarized. The classification of components in SPCSE membranes is first introduced briefly. Then, the preparation methods of SPCSE membranes are categorized according to process characteristics, in which the challenges of different methods and their corresponding solutions are carefully reviewed. The energy densities of the full battery composed of SPCSE membranes are further given whenever available to help understanding the device-level performance. Finally, we discuss the potential challenges and research opportunities for SPCSE membranes to guide the future development of high-performance sulfide ASSLBs.
Mesoporous silica nanoparticles (MSNs) are thought to be an attractive drug delivery material because of their advantages including high specific surface area, tunable pore size and morphology, easy surface modification and good biocompatibility. However, as a result of the poor biodegradability of MSNs, their biomedical applications are limited. To break the bottleneck of limited biomedical applications of MSNs, more and more researchers tend to design biodegradable MSNs (b-MSNs) nanosystems to obtain biodegradable as well as safe and reliable drug delivery carriers. In this review, we focused on summarizing strategies to improve the degradability of MSNs and innovatively proposed a series of advantages of b-MSNs, including controlled cargo release behavior, multifunctional frameworks, nano-catalysis, bio-imaging capabilities and enhanced therapeutic effects. Based on these advantages, we have innovatively summarized the applications of b-MSNs for enhanced tumor theranostics, including enhanced chemotherapy, delivery of nanosensitizers, gas molecules and biomacromolecules, initiation of immune response, synergistic therapies and image-guided tumor diagnostics. Finally, the challenges and further clinical translation potential of nanosystems based on b-MSNs are fully discussed and prospected. We believe that such b-MSNs delivery carriers will provide a timely reference for further applications in tumor theranostics.
Natural phytoconstituents exhibit distinct advantages in the management and prevention of inflammatory bowel disease (IBD), attributed to their robust biological activity, multi-target effects, and elevated safety profile. Although promising, the clinical application of phytoconstituents have been impeded by poor water solubility, low oral bioavailability, and inadequate colonic targeting. Recent advancements in nanotechnology has offered prospective avenues for the application of phytoconstituents in the treatment of IBD. A common strategy involves encapsulating or conjugating phytoconstituents with nanocarriers to enhance their stability, prolong intestinal retention, and facilitate targeted delivery to colonic inflammatory tissues. Furthermore, drawing inspiration from the self-assembling nanostructures that emerge during the decoction process of Chinese herbs, a variety of natural active compounds-based nanoassemblies have been developed for the treatment of IBD. They exhibit high drug-loading capacities and surmount the challenges posed by poor water solubility and low bioavailability. Notably, phyto-derived nanovesicles, owing to their unique structure and biological functions, can serve as therapeutic agents or novel delivery vehicles for the treatment of IBD. Consequently, this review provides an extensive overview of emerging phytoconstituent-derived nano-medicines/vesicles for the treatment of IBD, intending to offer novel insights for the clinical management of IBD.
As one of the most common gynecological malignancies, peritoneal metastasis is a common feature and cause of high mortality in ovarian cancer (OC). Currently, the standard treatment for OC and its peritoneal metastasis is maximal cytoreductive surgery (CRS) combined with platinum-based chemotherapy. Compared with intravenous chemotherapy, traditional intraperitoneal (IP) chemotherapy exhibits obvious pharmacokinetic (PK) advantages and systemic safety and has shown significant survival benefits in several clinical studies of OC patients. However, there remain several challenges in traditional IP chemotherapy, such as insufficient drug retention, a lack of tumor targeting, inadequate drug penetration, gastrointestinal toxicity, and limited inhibition of tumor metastasis and chemoresistance. Nanomedicine-based IP targeting delivery systems, through specific drug carrier design with tumor cells and tumor environment (TME) targeting, make it possible to overcome these challenges and maximize local therapy efficacy while reducing side effects. In this review article, the rationale and challenges of nanomedicine-based IP chemotherapies, as well as their in vivo fate after IP administration, which are crucial for their rational design and clinical translation, are firstly discussed. Then, current strategies for nanomedicine-based targeting delivery systems and the relevant clinical trials in IP chemotherapy are summarized. Finally, the future directions of the nanomedicine-based IP targeting delivery system for OC and its peritoneal metastasis are proposed, expecting to improve the clinical development of IP chemotherapy.
Small interfering RNA (siRNA), a promising revolutionary therapy, faces delivery obstacles due to its poor targeting, strong charge negativity and macromolecular nature. Clinical-approved siRNAs can now only be delivered to the liver mediated by the chemically conjugated N-acetylgalactosamine (GalNAc) ligand, the conjugate can be effectively uptaken into cells through interaction with asialoglycoprotein receptor (ASGPR) highly expressed on liver hepatocytes. To further explore an efficient non-hepatic targeted delivery strategy, in this study, we designed a delivery system that chemically conjugated p53 siRNA to renal tubular cell-targeting peptides for targeting the kidney, which was suitable for industrial transformation. Results showed that peptide-siRNA conjugate could specifically enter renal tubular epithelial cells and silence target genes. In cisplatin-induced acute kidney injury (AKI) mice, peptide-siRNA conjugate blocked the p53-mediated apoptotic pathway and alleviated renal damage. The innovative proposed system to conjugate kidney-targeting peptides with siRNA achieved the efficient kidney-targeted delivery of siRNA and provided a prospective choice for treating AKI.
Asperfilasin A (1), featuring a unique 5/5 cyclopenta[c]pyrrol-one bicyclic core, represents a newly discovered skeletal cytochalasan isolated from Aspergillus flavipes. The enantioselective total synthesis was efficiently accomplished from the key intermediate (S)-6 with three contiguous stereocenters in 5 steps and the synthetic 1 induced G2/M-phase cell cycle arrest of HT29 cells and apoptosis of HL60 and NB4 cells by activation of caspase-3 and degradation of PARP. (S)-6, bearing three contiguous chiral centers, was efficiently constructed by a novel Nazarov cyclization reaction containing basic nitrogen, which was less developed, primarily due to the incompatibility of basic nitrogen under acidic reaction conditions. This reaction allows a wide range of pentadienone substrates containing basic nitrogen to undergo Nazarov cyclization in a single regioselective and diastereoselective manner and is capable of generating three stereocenters simultaneously. Furthermore, the mechanism of the Nazarov cyclization and the origin of the regio- and diastereoselectivity were elucidated by DFT calculations and deuteration experiments, providing valuable insights into the reaction and serving as a guide for future applications involving substrates containing basic nitrogen.
Molecularly imprinted polymers (MIPs) are a kind of synthetic receptors possessing wide application prospects in proteins recognition. However, there are still great challenges in proteins imprinting due to their large size and easy conformation change. In this study, we explored epitope-oriented MIP based on host-guest interaction (hg-MIP) and constructed a novel hg-MIP-SERS (surface-enhanced Raman scatting) approach for efficiently recognizing the terminal epitopes of neuron-specific enolase (NSE), a well-known disease biomarker for small cell lung cancer, neuroblstom, and Alzheimer's disease. The C- and N-terminal epitopes of NSE were modified with 4-(phenylazo) benzoic acid, then they were used as the templates and immobilized on β-cyclodextrin-functionalized substrates. The imprinted layer was formed by polymerization of various functional monomers. Combined with SERS detection, an antibody-free sandwich assay based on hg-MIP was successfully used to detect the concentration of NSE in human serums, with the advantages of simple operation, small sample volume (5 µL), wide linear range (1–104 ng/mL) and a limit of detection as low as 0.01 ng/mL. The developed epitope-oriented hg-MIP-SERS approach can also be extended to other proteins, expanding the imprinting method of proteins, and has a broad development space in the field of protein separation and detection.
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