Cell Selective Apoptosis Induced by Polymorphic Alteration of Self-Assembled Silica Nanowebs

The biocompatibility of silicon-based nanomaterials makes them suitable for biophysical and biomedical applications. However, the application of silicon-based nanomaterials has been mainly restricted to nanoparticles (NPs) as a potential drug carrier and the extracellular matrix (ECM) as a platform for cell adhesion and proliferation. Here, we introduce silica NPs self-assembled into a 3D nanoweb architecture that was shown to inherit the therapeutic and proliferative attributes of both NPs and ECMs. The self-assembled silica nanoweb (SNW) has, therefore, not only shown targeted druglike behavior in HeLa cells without the use of biomarkers but has also shown ECM characteristics. The ECM characteristics of SNWs enhanced the cellular attraction and proliferation by which fibroblasts exhibited tissuelike behavior, and HeLa cells underwent an intensified induction of apoptosis. These properties are tailored by the alteration of the polymorphic heterogeneities of the SNW as a novel nanobiointerface for exceptional apoptosis induction through the enhancement of cellular attraction, which, to the best of our knowledge, has not been previously reported. These attributes enable selective functionality with which cancerous HeLa and mammalian fibroblast cells were affected differently. Moreover, simultaneous control of the packing index and crystallinity of the SNWs, to which the cells had been attracted, possessed the additional advantage of modulating the selective functionality of this nanobiointerface. These polymorphic characteristics were tailored by the alteration of the crystallinity of the synthesized SNW via precision control of the ionization level of the silicon substrate, whose requisite ionization energy was generated by an ultrashort pulsed laser. Our results showed that the therapeutic functionality of the SNW-plated template can be elucidated via the endocytosis of amorphous SNWs. Because of the efficient cellular attraction and remarkable contrast in the cellular response to the SNW-plated template, we expect that these findings will provide new insights and opportunities for designing and engineering novel cell–material interfaces for advanced biomedical applications in cancer research

Toward Universal SERS Detection of Disease Signaling Bioanalytes Using 3D Self-Assembled Nonplasmonic near-Quantum-Scale Silicon Probe

Currently, the quantum-scale surface-enhanced Raman scattering (SERS) properties of Si materials have yet to be discovered for universal biosensing applications. In this study, a potential universal biosensing probe is generated by activating the SERS functionality of Si nanostructures through near quantum-scale (nQS) engineering. We introduce herein 3D nonplasmonic Si nanomesh structure with nQS defects for SERS biosensing applications. Through ionization of a single-crystal defect-free Si wafer, highly defect-rich Si subnano-orbs (sNOs) are fabricated and self-assemble as connective 3D Si nanomesh structures with enhanced SERS biosensing activity. By amending the laser ionization and ion–ion interactions, we observe the controlled synthesis of engineered nQS defects in the form of nQS-grain boundary disorder or surface nQS voids within the interconnected Si sNOs. To our knowledge, it is shown here for the first time that defect-rich Si nanomesh structures exhibit enhanced Raman activity, with the nQS morphological and crystallographic defects acting as the prime SERS contributors without a plasmonic contribution. The SERS biosensing sensitivity with the synthesized defect-rich Si nanomesh structures without an additional plasmonic material was evaluated using of a tripeptide biomarker l-glutathione (GSH); we observe an enhancement factor value of ∼10² for the GSH biomolecules with 10^–9 M sensitivity, a phenomena to our knowledge that has yet to be reported. Additionally, the SERS detection of multiple disease-signaling biomolecules (cysteine, tryptophan, and methionine) is achieved at very low analyte concentration (10^–9 M). These results indicate a potential new dimension to universal SERS biosensing applications with these unique nonplasmonic defect-rich 3D nQS-Si nanostructures

Data_Sheet_1_Identification of novel SHANK2 variants in two Chinese families via exome and RNA sequencing.docx

BackgroundSHANK2 encodes a postsynaptic scaffolding protein involved in synapse formation, stabilization and homeostasis. Variations or microdeletions in the SHANK2 gene have been linked to a variety of neurodevelopmental disorders, including autism spectrum disorders (ASD) and mild to moderate intellectual disability (ID) in human. However, the number of reported cases with SHANK2 defects remains limited, with only 14 unrelated patients documented worldwide.MethodsIn this study, we investigated four patients from three families with ID. Whole-exome sequencing (WES) was performed to explore the genetic causes, while Sanger sequencing was used to confirm the identified variants. Furthermore, RNA sequencing and functional enrichment analysis were performed on patients with likely pathogenic variants to gain further insights into the molecular landscape associated with these variants.ResultsTwo novel variants in the SHANK2 gene: a heterozygous splicing substitution (NM_012309.5:c.2198-1G>A p.Pro734Glyfs*22) in Family 1, and a heterozygous nonsense variant [NM_012309.5:c.2310dupT p.(Lys771*)] in Family 2 were identified by WES and confirmed by Sanger sequencing. RNA sequencing and cohort analysis identified a total of 1,196 genes exhibiting aberrant expression in three patients. Functional enrichment analysis revealed the involvement of these genes in protein binding and synaptic functions.ConclusionWe identified two novel loss of function variants that broadens the spectrum of SHANK2 variants. Furthermore, this study enhances our understanding of the molecular mechanisms underlying SHANK2-related disorders.</p

Table_1_Identification of novel SHANK2 variants in two Chinese families via exome and RNA sequencing.xlsx

BackgroundSHANK2 encodes a postsynaptic scaffolding protein involved in synapse formation, stabilization and homeostasis. Variations or microdeletions in the SHANK2 gene have been linked to a variety of neurodevelopmental disorders, including autism spectrum disorders (ASD) and mild to moderate intellectual disability (ID) in human. However, the number of reported cases with SHANK2 defects remains limited, with only 14 unrelated patients documented worldwide.MethodsIn this study, we investigated four patients from three families with ID. Whole-exome sequencing (WES) was performed to explore the genetic causes, while Sanger sequencing was used to confirm the identified variants. Furthermore, RNA sequencing and functional enrichment analysis were performed on patients with likely pathogenic variants to gain further insights into the molecular landscape associated with these variants.ResultsTwo novel variants in the SHANK2 gene: a heterozygous splicing substitution (NM_012309.5:c.2198-1G>A p.Pro734Glyfs*22) in Family 1, and a heterozygous nonsense variant [NM_012309.5:c.2310dupT p.(Lys771*)] in Family 2 were identified by WES and confirmed by Sanger sequencing. RNA sequencing and cohort analysis identified a total of 1,196 genes exhibiting aberrant expression in three patients. Functional enrichment analysis revealed the involvement of these genes in protein binding and synaptic functions.ConclusionWe identified two novel loss of function variants that broadens the spectrum of SHANK2 variants. Furthermore, this study enhances our understanding of the molecular mechanisms underlying SHANK2-related disorders.</p

DEEP Surveillance of Brain Cancer Using Self-Functionalized 3D Nanoprobes for Noninvasive Liquid Biopsy

Brain cancers, one of the most fatal malignancies, require accurate diagnosis for guided therapeutic intervention. However, conventional methods for brain cancer prognosis (imaging and tissue biopsy) face challenges due to the complex nature and inaccessible anatomy of the brain. Therefore, deep analysis of brain cancer is necessary to (i) detect the presence of a malignant tumor, (ii) identify primary or secondary origin, and (iii) find where the tumor is housed. In order to provide a diagnostic technique with such exhaustive information here, we attempted a liquid biopsy-based deep surveillance of brain cancer using a very minimal amount of blood serum (5 μL) in real time. We hypothesize that holistic analysis of serum can act as a reliable source for deep brain cancer surveillance. To identify minute amounts of tumor-derived material in circulation, we synthesized an ultrasensitive 3D nanosensor, adopted SERS as a diagnostic methodology, and undertook a DEEP neural network-based brain cancer surveillance. Detection of primary and secondary tumor achieved 100% accuracy. Prediction of intracranial tumor location achieved 96% accuracy. This modality of using patient sera for deep surveillance is a promising noninvasive liquid biopsy tool with the potential to complement current brain cancer diagnostic methodologies

Forest plot meta-analyses of studies evaluating the sensitivity of live stiffness measured by TE to predict the overall postoperative complications.

<p>Forest plot meta-analyses of studies evaluating the sensitivity of live stiffness measured by TE to predict the overall postoperative complications.</p

The fundamental features of the included studies.

<p>The fundamental features of the included studies.</p

Diagnostic data of each studies evaluating the performance of TE for postoperative complications.

<p>Diagnostic data of each studies evaluating the performance of TE for postoperative complications.</p

SROC curves for 6 studies of live stiffness measured by TE to predict the overall postoperative complications.

<p>SROC curves for 6 studies of live stiffness measured by TE to predict the overall postoperative complications.</p

Flow diagram of the study selection process.

<p>Flow diagram of the study selection process.</p