Enhancing assistive technology design: Biomechanical finite element modeling for grasping strategy optimization in exoskeleton data gloves.

This paper endeavors to enhance the control mechanisms governing the grasping strategy of exoskeleton data gloves. A comprehensive approach was devised, integrating finite element numerical simulation techniques with the computerized control system of exoskeleton data gloves, establishing a novel, precise, and three-dimensional biomechanical finite element model of the hand. By amalgamating finite element modeling technology, biomechanical understanding, and hand kinematics, a straightforward yet efficient virtual grasping methodology was introduced to replicate three typical grasping actions dynamically.

HLTF resolves G4s and promotes G4-induced replication fork slowing to maintain genome stability.

G-quadruplexes (G4s) form throughout the genome and influence important cellular processes. Their deregulation can challenge DNA replication fork progression and threaten genome stability. Here, we demonstrate an unexpected role for the double-stranded DNA (dsDNA) translocase helicase-like transcription factor (HLTF) in responding to G4s.

Nanofiber-reinforced self-healing polysaccharide-based hydrogel dressings for pH discoloration monitoring and treatment of infected wounds.

The escalating global health concern arises from chronic wounds induced by bacterial infections, posing a significant threat to individuals. Consequently, an imperative exist for the development of hydrogel dressings to facilitate prompt wound monitoring and efficacious wound management. To this end, pH-sensitive bromothymol blue (BTB) and pH-responsive drug tetracycline hydrochloride (TH) were introduced into the polysaccharide-based hydrogel to realize the integration of wound monitoring and controlled treatment.

A ZIF-8-encapsulated interpenetrated hydrogel/nanofiber composite patch for chronic wound treatment.

Designing wound dressings necessitates the crucial considerations of maintaining a moist environment and implementing effective bacterial control. Furthermore, developing a three-dimensional framework emulating the extracellular matrix (ECM) confers advantages in fostering cellular migration and proliferation. Inspired by this, hydrogel/nanofiber composites have been demonstrated as promising materials for wound dressings.

Negative DNA supercoiling induces genome-wide Cas9 off-target activity.

CRISPR-Cas9 is a powerful gene-editing technology; however, off-target activity remains an important consideration for therapeutic applications. We have previously shown that force-stretching DNA induces off-target activity and hypothesized that distortions of the DNA topology in vivo, such as negative DNA supercoiling, could reduce Cas9 specificity. Using single-molecule optical-tweezers, we demonstrate that negative supercoiling λ-DNA induces sequence-specific Cas9 off-target binding at multiple sites, even at low forces.

Progress of Hydrogel Dressings with Wound Monitoring and Treatment Functions.

Hydrogels are widely used in wound dressings due to their moisturizing properties and biocompatibility. However, traditional hydrogel dressings cannot monitor wounds and provide accurate treatment. Recent advancements focus on hydrogel dressings with integrated monitoring and treatment functions, using sensors or intelligent materials to detect changes in the wound microenvironment.

Early patellofemoral cartilage and bone pathology in a rat model of noninvasive anterior cruciate ligament rupture.

Objective: Anterior cruciate ligament rupture (ACLR) is a risk factor for the development of post-traumatic osteoarthritis (PTOA). While PTOA in the tibiofemoral joint compartment is well-characterized, very little is known about pathology in the patellofemoral compartment after ACL injury. Here, we evaluated the extent to which ACLR induces early patellofemoral joint damage in a rat model.

Search and processing of Holliday junctions within long DNA by junction-resolving enzymes.

Resolution of Holliday junctions is a critical intermediate step of homologous recombination in which junctions are processed by junction-resolving endonucleases. Although binding and cleavage are well understood, the question remains how the enzymes locate their substrate within long duplex DNA. Here we track fluorescent dimers of endonuclease I on DNA, presenting the complete single-molecule reaction trajectory for a junction-resolving enzyme finding and cleaving a Holliday junction.

CRISPR/Cas9 On- and Off-Target Activity Using Correlative Force and Fluorescence Single-Molecule Microscopy.

The discovery of CRISPR/Cas9 as an easily programmable endonuclease heralds a new era of genetic manipulation. With this comes the prospect of novel gene therapy approaches, and the potential to cure previously untreatable genetic diseases. However, reports of spurious off-target editing by CRISPR/Cas9 pose a significant hurdle to realizing this potential.

Reorganization Energy of Electron Transfer in Ionic Liquids.

Bandshape analysis of charge-transfer optical bands in room-temperature ionic liquids (ILs) was performed to extract the reorganization energy of electron transfer. Remarkably, the reorganization energies in ILs are close to those in cyclohexane. This result runs against common wisdom in the field since conducting ILs, which are characterized by an infinite static dielectric constant, and nonpolar cyclohexane fall to the opposite ends of the polarity scale based on their dielectric constants.

Electron-Induced Proton Transfer.

The pathway of activationless proton transfer induced by an electron-transfer reaction is studied theoretically. Long-range electron transfer produces highly nonequilibrium medium polarization that can drive proton transfer through an activationless transition during the process of thermalization, dynamically altering the screening of the electron-proton Coulomb interaction by the medium. The cross electron-proton reorganization energy is the main energy parameter of the theory, which exceeds in magnitude the proton-transfer reorganization energy roughly by the ratio of the electron-transfer to proton-transfer distance.

Cas12a target search and cleavage on force-stretched DNA.

Using optical tweezers, we investigate target search and cleavage by CRISPR-Cas12a on force-stretched λ-DNA. Cas12a uses fast, one-dimensional hopping to locate its target. Binding and cleavage occur rapidly and specifically at low forces (≤5 pN), with a 1.

A Minimal Load-and-Lock Ru Luminescent DNA Probe.

Threading intercalators bind DNA with high affinities. Here, we describe single-molecule studies on a cell-permeant luminescent dinuclear ruthenium(II) complex that has been previously shown to thread only into short, unstable duplex structures. Using optical tweezers and confocal microscopy, we show that this complex threads and locks into force-extended duplex DNA in a two-step mechanism.

Generation of versatile ss-dsDNA hybrid substrates for single-molecule analysis.

Here, we describe a rapid and versatile protocol to generate gapped DNA substrates for single-molecule (SM) analysis using optical tweezers via site-specific Cas9 nicking and force-induced melting. We provide examples of single-stranded (ss) DNA gaps of different length and position. We outline protocols to visualize these substrates by replication protein A-enhanced Green Fluorescent Protein (RPA-eGFP) and SYTOX Orange staining using commercially available optical tweezers (C-TRAP).

Single-molecule analysis reveals cooperative stimulation of Rad51 filament nucleation and growth by mediator proteins.

Homologous recombination (HR) is an essential DNA double-strand break (DSB) repair mechanism, which is frequently inactivated in cancer. During HR, RAD51 forms nucleoprotein filaments on RPA-coated, resected DNA and catalyzes strand invasion into homologous duplex DNA. How RAD51 displaces RPA and assembles into long HR-proficient filaments remains uncertain.

Traumatic joint injury induces acute catabolic bone turnover concurrent with articular cartilage damage in a rat model of posttraumatic osteoarthritis.

Assess acute alterations in bone turnover, microstructure, and histomorphometry following noninvasive anterior cruciate ligament rupture (ACLR). Twelve female Lewis rats were randomized to receive noninvasive ACLR or Sham loading (n = 6/group). In vivo μCT was performed at 3, 7, 10, and 14 days postinjury to quantify compartment-dependent subchondral (SCB) and epiphyseal trabecular bone remodeling.

Direct-from-sputum rapid phenotypic drug susceptibility test for mycobacteria.

Background: The spread of multi-drug resistant tuberculosis (MDR-TB) is a leading global public-health challenge. Because not all biological mechanisms of resistance are known, culture-based (phenotypic) drug-susceptibility testing (DST) provides important information that influences clinical decision-making. Current phenotypic tests typically require pre-culture to ensure bacterial loads are at a testable level (taking 2-4 weeks) followed by 10-14 days to confirm growth or lack thereof.

Automated MicroCT-based bone and articular cartilage analysis using iterative shape averaging and atlas-based registration.

Micro-computed tomography (μCT) and contrast-enhanced μCT are important tools for preclinical analysis of bone and articular cartilage (AC). Quantitative data from these modalities is highly dependent on the accuracy of tissue segmentations, which are often obtained via time-consuming manual contouring and are prone to inter- and intra-observer variability. Automated segmentation strategies could mitigate these issues, but few such approaches have been described in the context of μCT.

Pharmacological tools to mobilise mesenchymal stromal cells into the blood promote bone formation after surgery.

Therapeutic approaches requiring the intravenous injection of autologous or allogeneic mesenchymal stromal cells (MSCs) are currently being evaluated for treatment of a range of diseases, including orthopaedic injuries. An alternative approach would be to mobilise endogenous MSCs into the blood, thereby reducing costs and obviating regulatory and technical hurdles associated with development of cell therapies. However, pharmacological tools for MSC mobilisation are currently lacking.

A conserved ATP- and Scc2/4-dependent activity for cohesin in tethering DNA molecules.

Sister chromatid cohesion requires cohesin to act as a protein linker to hold chromatids together. How cohesin tethers chromatids remains poorly understood. We have used optical tweezers to visualize cohesin as it holds DNA molecules.

Optical Absorption by Charge-Transfer Molecules.

An analytical formalism is developed for the calculation of absorption of radiation by charge-transfer molecules with electronic density delocalized between the donor and acceptor parts. The theory consistently incorporates both the vibronic coupling to quantum intramolecular vibrations and electrostatic interactions with a classical polarizable medium. The formulation operates in terms of basis-invariant parameters and can be used for calculations based on both the localized diabatic states and delocalized adiabatic wave function produced by standard quantum-chemistry algorithms.

Longitudinal characterization of intervertebral disc remodeling following acute annular injury in a rat model of degenerative disc disease.

: Characterize 3D remodeling of the rat intervertebral disc (IVD) following acute annular injury via micro-computed tomography (µCT), contrast-enhanced (CE)-µCT, and histology. : Female Lewis rats ( = 4/group) underwent either sham surgery or anterior annular puncture to L3-L4 and L5-L6 ( = 8 IVDs/group) to induce IVD degeneration. Rats were allowed cage activity before and after surgery and underwent µCT scanning at baseline and every 2 weeks post-op for 12 weeks to characterize longitudinal changes in IVD height.

Comparative genomics of 10 new species.

The nematode has been central to the understanding of metazoan biology. However, is but one species among millions and the significance of this important model organism will only be fully revealed if it is placed in a rich evolutionary context. Global sampling efforts have led to the discovery of over 50 putative species from the genus , many of which await formal species description.