Healthcare, as a basic human right, has often become the focus of the development of innovative technologies. Technological progress has significantly contributed to the provision of high-quality, on-time, acceptable, and affordable healthcare. Advancements in nanoscience have led to the emergence of a new generation of nanostructures. Each of them has a unique set of properties that account for their astonishing applications. Since its inception, nanotechnology has continuously affected healthcare and has exerted a tremendous influence on its transformation, contributing to better outcomes. In the last two decades, the world has seen nanotechnology taking steps towards its omnipresence and the process has been accelerated by extensive research in various healthcare sectors. The inclusion of nanotechnology and its allied nanocarriers/nanosystems in medicine is known as nanomedicine, a field that has brought about numerous benefits in disease prevention, diagnosis, and treatment. Various nanosystems have been found to be better candidates for theranostic purposes, in contrast to conventional ones. This review paper will shed light on medically significant nanosystems, as well as their applications and limitations in areas such as gene therapy, targeted drug delivery, and in the treatment of cancer and various genetic diseases. Although nanotechnology holds immense potential, it is yet to be exploited. More efforts need to be directed to overcome these limitations and make full use of its potential in order to revolutionize the healthcare sector in near future.
The cell autonomous balance of immune-inhibitory and -stimulatory signals is a critical yet poorly understood process in cancer immune evasion. Using patient-derived co-culture models and humanized mouse models, we show that an intact CD58:CD2 interaction is necessary for anti-tumor immunity. Defects in this axis lead to multi-faceted immune evasion through impaired CD2-dependent T cell polyfunctionality, T cell exclusion, impaired intra-tumoral proliferation, and concurrent protein stabilization of PD-L1. We performed genome-scale CRISPR-Cas9 and CD58 co-immunoprecipitation mass spectrometry screens identifying CMTM6 as a key stabilizer of CD58, and show that CMTM6 is required for concurrent upregulation of PD-L1 in CD58 loss. Single-cell RNA-seq analysis of patient melanoma samples demonstrates that most TILs lack expression of primary co-stimulatory signals required for response to PD-1 blockade (e.g. CD28), but maintain strong CD2 expression, thus providing an opportunity to mobilize a so far therapeutically untapped pool of TILs for anti-tumor immunity. We identify two potential therapeutic avenues, including rescued activation of human CD2-expressing TILs using recombinant CD58 protein, and targeted disruption of PD-L1/CMTM6 interactions. Our work identifies an underappreciated yet critical axis at the nexus of cancer immunity and evasion, uncovers a fundamental mechanism of co-inhibitory and -stimulatory signal balancing, and provides new approaches to improving cancer immunotherapies.
For any sequence analysis procedure, a single or multiple sequence must be retrieved, stored, organized. One of the most common public databases used for biological sequence retrieval is GenBank which is a comprehensive public database of nucleotide sequences. However, as the length of the sequence to be retrieved increases such as a chromosome, entire genome, scaffold, etc., the elapsed time to download the file gets even elongated due to slower bandwidth to download/retrieve the sequence.[8] In most cases, during sequence analysis, the researcher requires messenger RNA (mRNA), RNA, DNA, protein sequences of the same sequence-of-interest to work with, which consumes a substantial amount of the researcher in finding and retrieving the sequence files. An access to GenBank through JAVA HTTPS protocols is established to request and receive the sequence files associated with the input accessions. SeqDown was shown to be much efficient in terms of retrieval time of the sequences as compared to the other internet browsers and was found to be 15.27% faster than Mozilla Firefox. SeqDown also provides the feature to retrieve coding DNA sequences & protein sequences present in a single chromosome. Sequence retrieval from the most biological databases don’t have proper naming of their files and the user has to deal with the redundantly named sequence files which leads to incorrect and time-consuming analysis and can be solved with SeqDown. SeqDown is available as a free-to-download software at https://bit.ly/3cUwchz
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