Carbon dots (CDs) are light-emitting nanoparticles that show great promise for applications in biology and medicine due to the ease of fabrication, biocompatibility, and attractive optical ...properties. Optical chirality, on the other hand, is an intrinsic feature inherent in many objects in nature, and it can play an important role in the formation of artificial complexes based on CDs that are implemented for enantiomer recognition, site-specific bonding, etc. We employed a one-step hydrothermal synthesis to produce chiral CDs from the commonly used precursors citric acid and ethylenediamine together with a set of different chiral precursors, namely, L-isomers of cysteine, glutathione, phenylglycine, and tryptophan. The resulting CDs consisted of O,N-doped (and also S-doped, in some cases) carbonized cores with surfaces rich in amide and hydroxyl groups; they exhibited high photoluminescence quantum yields reaching 57%, chiral optical signals in the UV and visible spectral regions, and two-photon absorption. Chiral signals of CDs were rather complex and originated from a combination of the chiral precursors attached to the CD surface, hybridization of lower-energy levels of chiral chromophores formed within CDs, and intrinsic chirality of the CD cores. Using DFT analysis, we showed how incorporation of the chiral precursors at the optical centers induced a strong response in their circular dichroism spectra. The optical characteristics of these CDs, which can easily be dispersed in solvents of different polarities, remained stable during pH changes in the environment and after UV exposure for more than 400 min, which opens a wide range of bio-applications.
DNA repair mechanisms keep genome integrity and limit tumor-associated alterations and heterogeneity, but on the other hand they promote tumor survival after radiation and genotoxic chemotherapies. ...We screened pathway activation levels of 38 DNA repair pathways in nine human cancer types (gliomas, breast, colorectal, lung, thyroid, cervical, kidney, gastric, and pancreatic cancers). We took RNAseq profiles of the experimental 51 normal and 408 tumor samples, and from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium databases - of 500/407 normal and 5752/646 tumor samples, and also 573 normal and 984 tumor proteomic profiles from Proteomic Data Commons portal. For all the samplings we observed a congruent trend that all cancer types showed inhibition of G2/M arrest checkpoint pathway compared to the normal samples, and relatively low activities of p53-mediated pathways. In contrast, other DNA repair pathways were upregulated in most of the cancer types. The G2/M checkpoint pathway was statistically significantly downregulated compared to the other DNA repair pathways, and this inhibition was strongly impacted by antagonistic regulation of (i) promitotic genes CCNB and CDK1, and (ii) GADD45 genes promoting G2/M arrest. At the DNA level, we found that ATM, TP53, and CDKN1A genes accumulated loss of function mutations, and cyclin B complex genes – transforming mutations. These findings suggest importance of activation for most of DNA repair pathways in cancer progression, with remarkable exceptions of G2/M checkpoint and p53-related pathways which are downregulated and neutrally activated, respectively.
•Most of DNA repair pathways are upregulated in cancers.•In contrast, G2/M checkpoint pathway is instead strongly inhibited.•Whereas other p53-related pathways are neutrally activated.•G2/M checkpoint inhibition is mediated by CCNB, CDK1, GADD45 expression.•ATM, TP53, CDKN1A accumulate loss of function, CCNB – transforming mutations.
Remote monitoring of natural afforestation processes on abandoned agricultural lands is crucial for assessments and predictions of forest cover dynamics, biodiversity, ecosystem functions and ...services. In this work, we built on the general approach of combining satellite and field data for forest mapping and developed a simple and robust method for afforestation dynamics assessment. This method is based on Landsat imagery and index-based thresholding and specifically targets suitability for limited field data. We demonstrated method’s details and performance by conducting a case study for two bordering districts of Rudnya (Smolensk region, Russia) and Liozno (Vitebsk region, Belarus). This study area was selected because of the striking differences in the development of the agrarian sectors of these countries during the post-Soviet period (1991-present day). We used Landsat data to generate a consistent time series of five-year cloud-free multispectral composite images for the 1985–2020 period via the Google Earth Engine. Three spectral indices, each specifically designed for either forest, water or bare soil identification, were used for forest cover and arable land mapping. Threshold values for indices classification were both determined and verified based on field data and additional samples obtained by visual interpretation of very high-resolution satellite imagery. The developed approach was applied over the full Landsat time series to quantify 35-year afforestation dynamics over the study area. About 32% of initial arable lands and grasslands in the Russian district were afforested by the end of considered period, while the agricultural lands in Belarus’ district decreased only by around 5%. Obtained results are in the good agreement with the previous studies dedicated to the agricultural lands abandonment in the Eastern Europe region. The proposed method could be further developed into a general universally applicable technique for forest cover mapping in different growing conditions at local and regional spatial levels.
Since chirality is one of the phenomena often occurring in nature, optically active chiral compounds are important for applications in the fields of biology, pharmacology, and medicine. With this in ...mind, chiral carbon dots (CDs), which are eco-friendly and easy-to-obtain light-emissive nanoparticles, offer great potential for sensing, bioimaging, enantioselective synthesis, and development of emitters of circularly polarized light. Herein, chiral CDs have been produced via two synthetic approaches using a chiral amino acid precursor l/d-cysteine: (i) surface modification treatment of achiral CDs at room temperature and (ii) one-pot carbonization in the presence of chiral precursor. The chiral signal in the absorption spectra of synthesized CDs originates not only from the chiral precursor but from the optical transitions attributed to the core and surface states of CDs. The use of chiral amino acid molecules in the CD synthesis through carbonization results in a substantial (up to 8 times) increase in their emission quantum yield. Moreover, the synthesized CDs show two-photon absorption which is an attractive feature for their potential bioimaging and sensing applications.
Biofouling is among the key factors slowing down healing of acute and chronic wounds. Here we report both anti-biofilm and wound-healing properties of the chitosan-immobilized Ficin. The proposed ...chitosan-adsorption approach allowed preserving ~90% of the initial total activity of the enzyme (when using azocasein as a substrate) with stabilization factor of 4.9, and ~70% of its specific enzymatic activity. In vitro, the chitosan-immobilized Ficin degraded staphylococcal biofilms, this way increasing the efficacy of antimicrobials against biofilm-embedded bacteria. In vivo, in the presence of Ficin (either soluble or immobilized), the S.aureus-infected skin wound areas in rats reduced twofold after 4 instead of 6 days treatment. Moreover, topical application of the immobilized enzyme resulted in a 3-log reduction of S. aureus cell count on the wound surfaces in 6 days, compared to more than 10 days required to achieve the same effect in control. Additional advantages include smoother reepithelisation, and new tissue formation exhibiting collagen structure characteristics closely reminiscent of those observed in the native tissue. Taken together, our data suggest that both soluble and immobilized Ficin appear beneficial for the treatment of biofilm-associated infections, as well as speeding up wound healing and microbial decontamination.
•Adsorption-based immobilization of Ficin on the chitosan matrix preserves up to 86% of its initial enzymatic activity.•The immobilized Ficin increases the efficiency of antimicrobials against biofilm-embedded Staphylococci in vitro.•Ficin treatment leads to 2-day reduction of the wound half-closure time and 4-day speed up of its microbial decontamination.•The treatment of wounds by immobilized Ficin improves the recovery of tissues structure.
Although chirality plays an important role in the natural world, it has also attracted much scientific attention in nanotechnology, in particular, spintronics and bioapplications. Chiral carbon dots ...(CDs) are promising nanoparticles for sensing and bioimaging since they are biocompatible, ecofriendly, and free from toxic elements. Herein, green and red emissive chiral CDs are fabricated via surface modification treatment of achiral CDs at room temperature. After modification with l-cysteine molecules, the treated CDs demonstrate an intense chiral signal in the region of 200–300 nm with a dissymmetry factor up to 2.3 × 10–4 and high photoluminescence quantum yields of 19% and 15% for green and red emission bands, respectively. These CDs preserve their chiral signal in different ion systems, such as those with pH changes or in the presence of metal ions, along with remarkably low cytotoxicity, making them potential candidates for use as photoluminescent labels for biological objects.
Today, the development of nanomaterials with sensing properties attracts much scientific interest because of the demand for low-cost nontoxic colloidal nanoprobes with high sensitivity and ...selectivity for various biomedical and environment-related applications. Carbon dots (CDs) are promising candidates for these applications as they demonstrate unique optical properties with intense emissions, biocompatibility, and ease of fabrication. Herein, we developed synthesis protocols to obtain CDs based on o-phenylenediamine with a variety of optical responses depending on additional precursors and changes in the reaction media. The obtained CDs are N-doped (N,S-doped in case of thiourea addition) less than 10 nm spherical particles with emissions observed in the 300−600 nm spectral region depending on their chemical composition. These CDs may act simultaneously as absorptive/fluorescent sensing probes for solvent polarity with ∆S/∆ENT up to 85, for ∆ENT from 0.099 to 1.0 and for pH values in the range of 3.0−8.0, thus opening an opportunity to check the pH in non-pure water or a mixture of solvents. Moreover, CDs preserve their optical properties when embedded in cellulose strips that can be used as sensing probes for fast and easy pH checks. We believe that the resulting dual-purpose sensing nano probes based on CDs will have high demand in various sensing applications.
Carbon dots can be used for the fabrication of colloidal multi-purpose complexes for sensing and bio-visualization due to their easy and scalable synthesis, control of their spectral responses over a ...wide spectral range, and possibility of surface functionalization to meet the application task. Here, we developed a chemical protocol of colloidal complex formation via covalent bonding between carbon dots and plasmonic metal nanoparticles in order to influence and improve their fluorescence. We demonstrate how interactions between carbon dots and metal nanoparticles in the formed complexes, and thus their optical responses, depend on the type of bonds between particles, the architecture of the complexes, and the degree of overlapping of absorption and emission of carbon dots with the plasmon resonance of metals. For the most optimized architecture, emission enhancement reaching up to 5.4- and 4.9-fold for complexes with silver and gold nanoparticles has been achieved, respectively. Our study expands the toolkit of functional materials based on carbon dots for applications in photonics and biomedicine to photonics.
Normal tissues are essential for studying disease-specific differential gene expression. However, healthy human controls are typically available only in postmortal/autopsy settings. In cancer ...research, fragments of pathologically normal tissue adjacent to tumor site are frequently used as the controls. However, it is largely underexplored how cancers can systematically influence gene expression of the neighboring tissues. Here we performed a comprehensive pan-cancer comparison of molecular profiles of solid tumor-adjacent and autopsy-derived “healthy” normal tissues. We found a number of systemic molecular differences related to activation of the immune cells, intracellular transport and autophagy, cellular respiration, telomerase activation, p38 signaling, cytoskeleton remodeling, and reorganization of the extracellular matrix. The tumor-adjacent tissues were deficient in apoptotic signaling and negative regulation of cell growth including G2/M cell cycle transition checkpoint. We also detected an extensive rearrangement of the chemical perception network. Molecular targets of 32 and 37 cancer drugs were over- or underexpressed, respectively, in the tumor-adjacent norms. These processes may be driven by molecular events that are correlated between the paired cancer and adjacent normal tissues, that mostly relate to inflammation and regulation of intracellular molecular pathways such as the p38, MAPK, Notch, and IGF1 signaling. However, using a model of macaque postmortal tissues we showed that for the 30 min – 24-hour time frame at 4ºC, an RNA degradation pattern in lung biosamples resulted in an artifact “differential” expression profile for 1140 genes, although no differences could be detected in liver. Thus, such concerns should be addressed in practice.
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Despite significant progress made over the past two decades in the treatment of chronic myeloid leukemia (CML), there is still an unmet need for effective and safe agents to treat patients with ...resistance and intolerance to the drugs used in clinic. In this work, we designed 2-arylaminopyrimidine amides of isoxazole-3-carboxylic acid, assessed
in silico
their inhibitory potential against Bcr-Abl tyrosine kinase, and determined their antitumor activity in K562 (CML), HL-60 (acute promyelocytic leukemia), and HeLa (cervical cancer) cells. Based on the analysis of computational and experimental data, three compounds with the antitumor activity against K562 and HL-60 cells were identified. The lead compound efficiently suppressed the growth of these cells, as evidenced by the low IC
50
values of 2.8 ± 0.8 μM (K562) and 3.5 ± 0.2 μM (HL-60). The obtained compounds represent promising basic structures for the design of novel, effective, and safe anticancer drugs able to inhibit the catalytic activity of Bcr-Abl kinase by blocking the ATP-binding site of the enzyme.
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