Full-Privacy Secured Search Engine Empowered by Efficient Genome-Mapping Algorithms.

Since the 90s, keyword-based search engines have been the only option for people to locate relevant web content through a simple query comprising one to a few keywords. These engines, whether free or paid, retained users' search queries and preferences, often to deliver targeted ads. Additionally, user-uploaded articles for plagiarism detection can further be stored as part of service providers' expanding databases for profit. Essentially, users could not search without exposing their queries to these providers. We present a new solution here: a method for searching the internet using a full article as a query without disclosing the content. Our Sapiens Aperio Veritas Engine (S.A.V.E.) uses an encoding scheme and an FM-index search, borrowed from next-generation human genome sequencing. Each word in a user's query is transformed into one of 12 "amino acids" to create a pseudo-biological sequence (PBS) on the user's device. Plagiarism checks are done by users submitting their locally created PBSs to our cloud service. This detects identical content in our database, which includes all English and Chinese Wikipedia articles and Open Access journals up to April 2021. PBSs, longer than 12 "amino acids", show accurate results with less than 0.8% false positives. Performance-wise, S.A.V.E. runs at a similar genome-mapping speed as Bowtie and is >5 orders faster than BLAST. With both standard and private modes, S.A.V.E. offers a revolutionary, privacy-first search and plagiarism check system. We believe this sets an exciting precedent for future search engines prioritizing user confidentiality. S.A.V.E. can be accessed at https://dyn.life.nthu.edu.tw/SAVE/.

MiR34 contributes to spinal muscular atrophy and AAV9-mediated delivery of MiR34a ameliorates the motor deficits in SMA mice.

Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by the selective loss of spinal motor neurons (MNs) and concomitant muscle weakness. Mutation of SMN1 is known to cause SMA, and restoring SMN protein levels via antisense oligonucleotide treatment is effective for ameliorating symptoms. However, this approach is hindered by exorbitant costs, invasive procedures, and poor treatment responses of some patients. Here, we seek to circumvent these hurdles by identifying reliable biomarkers that could predict treatment efficacy. We uncovered that MiR34 exhibits consistent downregulation during SMA progression in both human and rodent contexts. Importantly, Mir34 family-knockout mice display axon swelling and reduced neuromuscular junction (NMJ) endplates, recapitulating SMA pathology. Introducing MiR34a via scAAV9 improved the motor ability of SMNΔ7 mice, possibly by restoring NMJ endplate size. Finally, we observed a consistent decreasing trend in MiR34 family expression in the cerebrospinal fluid (CSF) of type I SMA patients during the loading phase of nusinersen treatment. Baseline CSF MiR34 levels before nusinersen injection proved predictive of patient motor skills 1 year later. Thus, we propose that MiR34 may serve as a biomarker of SMA since it is associated with the pathology and can help evaluate the therapeutic effects of nusinersen.