Reactions of Cisplatin with Thioredoxin-1 Regulate Intracellular Redox Homeostasis.

Cisplatin is a widely used anticancer drug. In addition to inducing DNA damage, increased levels of reactive oxygen species (ROS) play a significant role in cisplatin-induced cell death. Thioredoxin-1 (Trx1), a redox regulatory protein that can scavenge ROS, has been found to eliminate cisplatin-induced ROS, while elevated Trx1 levels are associated with cisplatin resistance.

Enhancing Tumor Immunotherapy by Multivalent Anti-PD-L1 Nanobody Assembled via Ferritin Nanocage.

Increasing immunotherapy response rate and durability can lead to significant improvements in cancer care. To address this challenge, a novel multivalent immune checkpoint therapeutic platform is constructed through site-specific ligation of anti-PD-L1 nanobody (Nb) on ferritin (Ftn) nanocage. Nb-Ftn blocks PD-1/PD-L1 interaction and downregulates PD-L1 levels via endocytosis-induced degradation.

Mutual promotion of co-condensation of KRAS G-quadruplex and a well-folded protein HMGB1.

Liquid-liquid phase separation (LLPS) of G-quadruplex (GQ) is involved in many crucial cellular processes, while the quadruplex-folding and their functions are typically modulated by specific DNA-binding proteins. However, the regulatory mechanism of binding proteins, particularly the well-folded proteins, on the LLPS of GQs is largely unknown. Here, we investigated the effect of HMGB1 on the condensation of a G-quadruplex of KRAS promoter (GQKRAS).

Peroxide-Simulating and GSH-Depleting Nanozyme for Enhanced Chemodynamic/Photodynamic Therapy via Induction of Multisource ROS.

Reactive oxygen species (ROS) generation, using photodynamic therapy (PDT) and chemodynamic therapy (CDT), is a promising strategy for cancer treatment. However, the production of ROS in tumor cells is often limited by hypoxia, insufficient substrates, and high level of ROS scavengers in a tumor microenvironment, which seriously affects the efficacy of ROS-related tumor therapies. Herein, we report a lipid-supported manganese oxide nanozyme, MLP@DHA&Ce6, by decorating a MnO nano-shell on the liposome loaded with dihydroartemisinin (DHA) and photosensitizer Ce6 for generating multisource ROS to enhance cancer therapy.

Cellular uptake of nickel by NikR is regulated by phase separation.

Bacterial cells were long thought to be "bags of enzymes" with minimal internal structures. In recent years, membrane-less organelles formed by liquid-liquid phase separation (LLPS) of proteins or nucleic acids have been found to be involved in many important biological processes, although most of them were studied on eukaryotic cells. Here, we report that NikR, a bacterial nickel-responsive regulatory protein, exhibits LLPS both in solution and inside cells.

Cisplatin reacts with the RING finger domain of RNF11 and interferes with the protein functions.

Protein reactions play important roles in the mechanism of action of cisplatin. In this work, we found that cisplatin is highly reactive to the RING finger domain of RNF11, a key protein involved in tumorigenesis and metastasis. The results show that cisplatin binds to RNF11 at the zinc coordination site and leads to zinc ejection from the protein.

Metabolite profiling and identification in living cells by coupling stable isotope tracing and induced electrospray mass spectrometry.

Direct observation of metabolites in living cells by mass spectrometry offers a bright future for biological studies but also suffers a severe challenge to untargeted peak assignment to tentative metabolite candidates. In this study, we developed a method combining stable isotope tracing and induced electrospray mass spectrometry for living-cells metabolite measurement and identification. By using C-glucose and ammonium chloride-N as the sole carbon and nitrogen sources for cell culture, Escherichia coli synthesized metabolites with N and C elements.

Native Mass Spectrometry for Peptide-Metal Interaction in Picoliter Cell Lysate.

Native mass spectrometry, which takes a high concentration of ammonium acetate (NHOAc) for ionization, coupled with tedious and solvent-consuming purification, which separates proteins from complicated environments, has shown great potential for proteins and their complexes. A high level of nonvolatile salts in the endogenous intracellular environment results in serious ion suppression and has been one of the bottlenecks for native mass spectrometry, especially for protein complexes. Herein, an integrated protocol utilizing the inner surface of a micropipette for rapid purification, desorption, and ionization of peptide-metal interaction at subfemtomole level in cell lysate was demonstrated for native mass spectrometry.

Polymer Composite with Enhanced Thermal Conductivity and Insulation Properties through Aligned AlO Fiber.

Thermoplastic polyolefins, such as polyethylene (PE), are traditionally one of the most widely used polymer classes with applications in the electric industry, and their nanocomposites have caught the interest of researchers. The linear filler is shown to be beneficial in decreasing the charge injection and hindering the formation of charge packs. So, we demonstrate a novel composite with excellent properties.

Differentiation of renal cell carcinoma subtypes through MRI-based radiomics analysis.

Objectives: To explore whether clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC), and chromophobe renal cell carcinoma (cRCC) can be distinguished using radiomics features extracted from magnetic resonance (MR) images.

Methods: Seventy-seven patients (ccRCC = 32, pRCC = 23, cRCC = 22) underwent MRI before surgery between May 2013 and August 2018 in this retrospective study. Thirty-nine radiomics features were extracted from tumor volumes on three sequences (T2WI, EN-T1WI CMP, and EN-T1WI NP).

Cisplatin binds to the MDM2 RING finger domain and inhibits the ubiquitination activity.

Cisplatin can directly bind to the RING finger domain of MDM2, leading to the zinc-release and protein unfolding. Consequently, cisplatin inhibits the MDM2-mediated ubiquitination, which is the molecular basis of p53 activation. This work provides insight into the cisplatin-induced p53-elevation that is involved in cell apoptosis.

A dual functional ruthenium arene complex induces differentiation and apoptosis of acute promyelocytic leukemia cells.

Human acute promyelocytic leukemia (APL) is the most malignant form of acute leukemia. The fusion of PML and RARα genes is responsible for over 98% of cases of APL. In this work, we found that a Ru(ii) arene complex, [(η--bip)Ru(en)Cl][PF] (), can selectively react with PML, leading to zinc-release and protein unfolding.

Covalent versus Noncovalent Binding of Ruthenium η -p-Cymene Complexes to Zinc-Finger Protein NCp7.

Ruthenium-arene complexes are a unique class of organometallic compounds that have been shown to have prominent therapeutic potencies. Here, we have investigated the interactions of Ru-cymene complexes with a zinc-finger protein NCp7, aiming to understand the effects of various ligands on the reaction. Five different binding modes were observed on selected Ru-complexes.

Computed tomographic characteristics of gastric schwannoma.

Objective: This study aimed to characterize the computed tomographic (CT) features of gastric schwannoma (GS).

Methods: We retrospectively reviewed CT images of 19 cases of histologically proven GS between January 2010 and December 2015. Tumor location, size, contour, margin, growth pattern, and degree and pattern of enhancement, perigastric lymph nodes, ulceration, necrosis, and calcification were evaluated.

Charge-Selective Delivery of Proteins Using Mesoporous Silica Nanoparticles Fused with Lipid Bilayers.

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.

Selective Targeting of the Zinc Finger Domain of HIV Nucleocapsid Protein NCp7 with Ruthenium Complexes.

Nucleocapsid protein 7 (NCp7) is an attractive target for anti-HIV drug development. Here we found that ruthenium complexes are reactive to NCp7 and various Ru-agents exhibit significantly different reactivity. Interestingly, the zinc-finger domains of NCp7 also demonstrate different affinity to Ru-complexes; the C-terminal domain is much more reactive than the N-terminal domain.

Arsenic trioxide preferentially binds to the ring finger protein PML: understanding target selection of the drug.

Arsenic trioxide (ATO) is used in the clinic for the treatment of acute promyelocytic leukemia by targeting the protein PML. However, many zinc-finger proteins could also be reactive to arsenic in cells. Here we found that ATO preferentially binds to the ring-finger domain of PML in a protein mixture with zinc-finger domains.

TSA1 interacts with CSN1/CSN and may be functionally involved in Arabidopsis seedling development in darkness.

The COP9 signalosome (CSN) is a multiprotein complex which participates in diverse cellular and developmental processes. CSN1, one of the subunits of CSN, is essential for assembly of the multiprotein complex via PCI (proteasome, COP9 signalosome and initiation factor 3) domain in the C-terminal half of CSN1. However, the role of the N-terminal domain (NTD) of CSN1, which is critical for the function of CSN, is not completely understood.

Endogenous protein mono-ADP-ribosylation in Arabidopsis thaliana.

Protein mono-ADP-ribosylation post-translationally transfers the ADP-ribose moiety from the β-NAD+ donor to various protein acceptors. This type of modification has been widely characterized and shown to regulate protein activities in animals, yeast and prokaryotes, but has never been reported in plants. In this study, using [³²P]NAD+ as the substrate, ADP-ribosylated proteins in Arabidopsis were investigated.

MULTIPOLAR SPINDLE 1 (MPS1), a novel coiled-coil protein of Arabidopsis thaliana, is required for meiotic spindle organization.

The spindle is essential for chromosome segregation during meiosis, but the molecular mechanism of meiotic spindle organization in higher plants is still not well understood. Here, we report on the identification and characterization of a plant-specific protein, MULTIPOLAR SPINDLE 1 (MPS1), which is involved in spindle organization in meiocytes of Arabidopsis thaliana. The homozygous mps1 mutant exhibits male and female sterility.

Regulation of COP1 nuclear localization by the COP9 signalosome via direct interaction with CSN1.

COP1 and COP9 signalosome (CSN) are key regulators of plant light responses and development. Deficiency in either COP1 or CSN causes a constitutive photomorphogenic phenotype. Through coordinated actions of nuclear- and cytoplasmic-localization signals, COP1 can respond to light signals by differentially partitions between nuclear and cytoplasmic compartments.

Transformation by T-DNA integration causes highly sterile phenotype independent of transgenes in Arabidopsis thaliana.

Agrobacterium tumefaciens-mediated gene transformation caused highly sterile phenotype in T1 transgenic populations of Arabidopsis thaliana. The phenomenon occurred independent of the genes and construct types used for transformation. The occurring frequency is less than 10% and the phenotype is inheritable.