Opinion statement
Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is associated with poor long-term outcomes compared to other breast cancer subtypes. Currently, ...chemotherapy remains the main modality of treatment for early-stage TNBC, as there is no approved targeted therapy for this subtype. The biologic heterogeneity of TNBC has hindered the development and evaluation of novel agents, but recent advancements in subclassifying TNBC have paved the way for further investigation of more effective systemic therapies, including cytotoxic and targeted agents. TNBC is enriched for germline
BRCA
mutation and for somatic deficiencies in homologous recombination DNA repair, the so-called “BRCAness” phenotype. Together, germline
BRCA
mutations and BRCAness are promising biomarkers of susceptibility to DNA-damaging therapy. Various investigational approaches are consequently being investigated in early-stage TNBC, including immune checkpoint inhibitors, platinum compounds, PI3K pathway inhibitors, and androgen receptor inhibitors. Due to the biological diversity found within TNBC, patient selection based on molecular biomarkers could aid the design of early-phase clinical trials, ultimately accelerating the clinical application of effective new agents. TNBC is an aggressive breast cancer subtype, for which multiple targeted approaches will likely be required for patient outcomes to be substantially improved.
As the primary cellular location for respiration and energy production, mitochondria serve in a critical capacity to the cell. Yet, by virtue of this very function of respiration, mitochondria are ...subject to constant oxidative stress that can damage one of the unique features of this organelle, its distinct genome. Damage to mitochondrial DNA (mtDNA) and loss of mitochondrial genome integrity is increasingly understood to play a role in the development of both severe early-onset maladies and chronic age-related diseases. In this article, we review the processes by which mtDNA integrity is maintained, with an emphasis on the repair of oxidative DNA lesions, and the cellular consequences of diminished mitochondrial genome stability.
Protein arginine deimination leading to the non-coded amino acid citrulline remains a key question in the field of post-translational modifications ever since its discovery by Rogers and Simmonds in ...1958. Citrullination is catalyzed by a family of enzymes called peptidyl arginine deiminases (PADIs). Initially, increased citrullination was associated with autoimmune diseases, including rheumatoid arthritis and multiple sclerosis, as well as other neurological disorders and multiple types of cancer. During the last decade, research efforts have focused on how citrullination contributes to disease pathogenesis by modulating epigenetic events, pluripotency, immunity and transcriptional regulation. However, our knowledge regarding the functional implications of citrullination remains quite limited, so we still do not completely understand its role in physiological and pathological conditions. Here, we review the recently discovered functions of
-mediated citrullination of the C-terminal domain of RNA polymerase II in transcriptional regulation in breast cancer cells and the proposed mechanisms to reshape the transcription regulatory network that promotes cancer progression.
A simple approach was developed to prepare carboxycellulose nanofibers directly from untreated biomass using nitric acid or nitric acid-sodium nitrite mixtures. Experiments indicated that this ...approach greatly reduced the need for multichemicals, and offered significant benefits in lowering the consumption of water and electric energy, when compared with conventional multiple-step processes at bench scale (e.g., TEMPO oxidation). Additionally, the effluent produced by this approach could be efficaciously neutralized using base to produce nitrogen-rich salts as fertilizers. TEM measurements of resulting nanofibers from different biomasses, possessed dimensions in the range of 190–370 and 4–5 nm, having PDI = 0.29–0.38. These nanofibers exhibited lower crystallinity than untreated jute fibers as determined by TEM diffraction, WAXD and 13C CPMAS NMR (e.g., WAXD crystallinity index was ∼35% for nanofibers vs 62% for jute). Nanofibers with low crystallinity were found to be effective for removal of heavy metal ions for drinking water purification.
Nanocelluloses (NC) are nature-based sustainable biomaterials, which not only possess cellulosic properties but also have the important hallmarks of nanomaterials, such as large surface area, ...versatile reactive sites or functionalities, and scaffolding stability to host inorganic nanoparticles. This class of nanomaterials offers new opportunities for a broad spectrum of applications for clean water production that were once thought impractical. This Review covers substantial discussions based on evaluative judgments of the recent literature and technical advancements in the fields of coagulation/flocculation, adsorption, photocatalysis, and membrane filtration for water decontamination through proper understanding of fundamental knowledge of NC, such as purity, crystallinity, surface chemistry and charge, suspension rheology, morphology, mechanical properties, and film stability. To supplement these, discussions on low-cost and scalable NC extraction, new characterizations including solution small-angle X-ray scattering evaluation, and structure–property relationships of NC are also reviewed. Identifying knowledge gaps and drawing perspectives could generate guidance to overcome uncertainties associated with the adaptation of NC-enabled water purification technologies. Furthermore, the topics of simultaneous removal of multipollutants disposal and proper handling of post/spent NC are discussed. We believe NC-enabled remediation nanomaterials can be integrated into a broad range of water treatments, greatly improving the cost-effectiveness and sustainability of water purification.
In urban set up, increasing combustion and processing activities have contaminated the air with toxic heavy metals which are generally enriched on atmospheric particulate matter. Vegetation around ...urban area act as a sink where such metal enriched particles generally deposit on the foliar surfaces, however, role of vegetation in uptake of metals adhered on the atmospheric particulate matter is yet not explored properly and is important to study to evaluate their role as bio-remediator. The undertaken work examines the foliar surface of Morus alba for its potential to deposit and accumulate atmospheric heavy metals. Further, to understand foliar uptake mechanism and translocation of atmospheric metal enriched on particulate matter a simulated experiment was conducted by labeling the known particle size (45 μm and 120 μm) with radio labeled 65Zn, applied on the tagged leaf with two particle loads, 25 mg and 50 mg. The study showed that owing to its rough foliar surface with trichomes and grooves, Morus alba efficiently trap heavy metal enriched particles and was capable of accumulating metals from particulate matter into different plant parts. It was recorded that 65Zn adhered on different size particles was taken up by tagged leaf of mulberry and majorly translocated to the lower stem and roots. It was also inferred from the study that both particle size and particle load significantly affect the foliar uptake and translocation of atmospheric heavy metal. The study focuses on the fact that urban avenue trees are capable of taking up atmospheric heavy metals and can play a crucial role in improving air quality.
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•The atmospheric particulate matter (PM) are rich carriers of heavy metals such as , Zn, Fe, Pb, Ni etc. as evident from the present study.•Whether roadside plants can act as efficient sink for the PM associated metal species and mechanism thereof is poorly understood.•Morphological feature like trichomes and grooves on the foliage may enhance PM-metal capture and absorption by the tree species.•Radiotracer studies using 65Zn enriched PM in Morus alba clearly evidence that foliar uptake and translocation of PM-metal depends on the PM size and foliar load.•Study supports that avenue trees like Morus alba not only efficiently trap atmospheric PM but also exhibit foliar uptake and in plant translocation and accumulation of PM-metals.
Membrane technology remains the most energy‐efficient process for removing contaminants (micrometer‐size particles to angstrom‐size hydrated ions) from water. However, the current membrane ...technology, involving relatively expensive synthetic materials, is often nonsustainable for the poorest communities in the society. In this article, perspectives are provided on the emerging nanocellulose‐enabled membrane technology based on nanoscale cellulose fibers that can be extracted from almost any biomass. It is conceivable that nanocellulose membranes developed from inexpensive, abundant, and sustainable resources (such as agriculture residues and underutilized biomass waste) can lower the cost of membrane separation, as these membranes offer the ability to remove a range of pollutants in one step, via size exclusion and/or adsorption. The nanocellulose‐enabled membrane technology not only may be suitable for tackling global drinking water challenges, but it can also provide a new low‐cost platform for various pressure‐driven filtration techniques, such as microfiltration, ultrafiltration, nanofiltration, and reverse osmosis. Some relevant parameters that can control the filtration performance of nanocellulose‐enabled membranes are comprehensively discussed. A short review of the current state of development for nanocellulose membranes is also provided.
Membrane technology remains the most energy‐efficient process for removing contaminants from water. However, the current membrane technology, involving relatively expensive synthetic materials, is often nonsustainable for the poorest communities in the society. In this article, perspectives are provided on the emerging nanocellulose‐enabled membrane technology based on nanoscale cellulose fibers that can be extracted from almost any biomass.
•This is the first thermal study comparing mono-, di- and tri-functional carboxy and aldehyde derivatives of cellulose.•Even minor substitution of C6-COOH caused extensive degradation of ...cellulose.•Extensive 2,3-dialdehyde functionalization of cellulose did not significantly affect thermal stability of cellulose.•Comparison of C6-COOH and C6-CH2OCH2COOH indicates the former causes is less thermally stable as compared to the latter.•Thermal stability trend DAC>DCC>nanoparticles>dextrose>glucuronic acid due to more reducing ends and COOH groups.
Oxidized cellulose containing carboxyl and aldehyde functional groups represent an important class of cellulose derivatives. In this study effect of incrementally increasing COOH and CHO groups at C2, C3, and C6 positions of cellulose and nanocellulose has been investigated, with a view to understanding their effect on thermal treatment of cellulose. The results show that 2,3-dialdehyde cellulose (DAC) is the most thermally stable oxidized product of cellulose while the most unstable derivatives contain carboxyl group at the C6 position (6CC). Carboxymethylcellulose (CMC), with carboxymethyl group on C6 position, is more stable than 6CC. Multi-functionalized celluloses 2,3,6-tricarboxycellulose and 6-carboxy-2,3-dialdehyde, have the same level of thermal stability as 6CC, showing that the presence of carboxyl at the C6 is a key destabilizing factor in the thermal stability of oxidized cellulose products. More the number of reducing end groups on the polymer chain, lower the thermal stability of the cellulose, as proved by comparing the TGA/DTG of monomeric analogs dextrose, cellobiose and glucuronic acid with the oxidized celluloses. The thermal stability trend observed for oxidized celluloses was DAC>DCC>nanoparticles>dextrose>glucuronic acid, caused by extent of reducing ends and COOH groups.
Regenerated microfibrillated cellulose (R-MFC) fibers were prepared successfully by a combined dissolution and regeneration approach using phosphoric acid/ethanol treatment on jute cellulose. The ...prepared R-MFC fibers possessed high surface area (10.74 m2/g), good aspect ratio (L/D = 30), and excellent thermal stability (T max = 352 °C). In addition, the fibers exhibited 3.84 wt % of phosphate groups (PO4 2–) with a ζ-potential of −8.4 mV and low crystallinity index (CI) of 47.5%. These R-MFC fibers were in the cellulose II polymorph, confirmed by 13C CPMAS NMR and WAXD measurements, and they were effective to anchor the growth of ZnO nanocrystals. WAXD and TEM examinations on the imbedded ZnO nanocrystals indicated that they possessed the hexagonal wurtzite crystal structure and could assemble into a flower-like morphology in the R-MFC scaffold. A R-MFC composite containing 41 wt % of ZnO nanocrystals was found to be very efficient to remove arsenic (As(V)) ions from water with the maximum capacity of 4,421 mg/g at neutral pH (7), based on the Langmuir isotherm analysis. The binding stability study between ZnO nanocrystals and R-MFC confirmed that the composite scaffold only had negligible release of ZnO at neutral pH, indicating the viability of this system for practical water purification applications. This is the first study on preparation of R-MFC from nonwood cellulose (jute), while most of the earlier studies were on microcrystalline wood-based cellulose.
Melanoma patients' plasma contains exosomes produced by malignant and normal cells. Plasma exosomes were isolated and separated by immunocapture into two fractions: melanoma cell-derived exosomes ...(MTEX) and normal cell-derived exosomes (non-MTEX). Immunosuppressive effects of MTEX on primary human immune cells were evaluated. Exosomes were isolated from plasma of 12 melanoma patients and six healthy donors (HDs). Expression levels of 19 immunoregulatory proteins in MTEX, non-MTEX and HDs exosomes were evaluated by on-bead flow cytometry. Functional/phenotypic changes induced in CD8
T or natural killer (NK) cells by MTEX or non-MTEX were compared. Plasma protein levels were higher in patients than HDs (P < 0.0009). In patients, MTEX accounted for 23-66% of total exosomes. MTEX were enriched in immunosuppressive proteins (P = 0.03). MTEX, but not HDs exosomes, inhibited CD69 expression (P ≤ 0.0008), induced apoptosis (P ≤ 0.0009) and suppressed proliferation (P ≤ 0.002) in CD8
T cells and downregulated NKG2D expression in NK cells (P = 0.001). Non-MTEX were enriched in immunostimulatory proteins (P = 0.002) and were only weakly immunosuppressive. Elevated MTEX/total exosome ratios and, surprisingly, non-MTEX ability to induce apoptosis of CD8
T cells emerged as positive correlates of disease stage. MTEX emerge as the major mechanism of tumor-induced immune suppression and as an underestimated barrier to successful melanoma immunotherapy.
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