The blood-brain barrier (BBB) remains a major obstacle for effective delivery of therapeutics to treat central nervous system (CNS) disorders. Although transferrin receptor (TfR)-mediated transcytosis is widely employed for brain drug delivery, the inefficient release of therapeutic payload hinders their efficacy from crossing the BBB. Here, we developed a pH-responsive anti-polyethylene glycol (PEG) × anti-TfR bispecific antibody (pH-PEG engager) that can complex with PEGylated nanomedicine at physiological pH to trigger TfR-mediated transcytosis in the brain microvascular endothelial cells, while rapidly dissociating from PEGylated nanomedicine at acidic endosomes for efficient release of PEGylated nanomedicine to cross the BBB.
View Article and Find Full Text PDFBalance control, a complex sensorimotor skill, declines with age. Assessing balance is crucial for identifying fall risk and implementing interventions in the older population. This study aimed to measure age-dependent changes in static and dynamic balance using inertial measurement units in a clinical setting.
View Article and Find Full Text PDFBackground: Missing values in datasets present significant challenges for data analysis, particularly in the medical field where data accuracy is crucial for patient diagnosis and treatment. Although MissForest (MF) has demonstrated efficacy in imputation research and recursive feature elimination (RFE) has proven effective in feature selection, the potential for enhancing MF through RFE integration remains unexplored.
Methods: This study introduces a novel imputation method, "recursive feature elimination-MissForest" (RFE-MF), designed to enhance imputation quality by reducing the impact of irrelevant features.
Treatment-resistant depression (TRD) is a condition wherein patients with depression fail to respond to antidepressant trials. A new form of repetitive transcranial magnetic stimulation (rTMS), called theta-burst stimulation (TBS), which includes intermittent theta-burst stimulation (iTBS) and continuous theta-burst stimulation (cTBS), is non-inferior to rTMS in TRD treatment. However, the mechanism of iTBS and cTBS underlying the treatment of TRD in the prefrontal cortex (PFC) remains unclear.
View Article and Find Full Text PDFNanoprobes provide advantages for real-time monitoring of tumor markers and tumorigenesis during cancer progression and development. Epidermal growth factor receptor (EGFR) is a key protein that plays crucial roles for tumorigenesis and cancer therapy of lung cancers. Here, we show a carbon-based nanoprobe, nanodiamond (ND), which can be applied for targeting EGFR and monitoring tumorigenesis of human lung cancer cells in vitro and in vivo.
View Article and Find Full Text PDFIn Taiwan, emergency physicians often perform wrist joint reduction and cast immobilization before orthopedic surgeons arrange for surgical management. Prophylactic antibiotics can decrease the risk of wound infection and have been routinely employed in orthopedic surgery. In Taiwan, emergency physicians also regularly perform blood investigations and administer prophylactic antibiotics to prevent infection if the patient exhibits leukocytosis.
View Article and Find Full Text PDFThis paper reports on the assembly of a compact, low-cost, pulsed-power facility used for plasma studies. The construction uses two modules placed on opposite sides of the test chamber to minimize the system impedance and improve access to test samples. The stored energy is 1 kJ with a peak current of 135 kA and a 1592 ns quarter-period time.
View Article and Find Full Text PDFThe biting midge Culicoides arakawae is the vector for the parasite Leucocytozoon caulleryi. Birds infected with L. caulleryi develop leucocytozoonosis.
View Article and Find Full Text PDFBackground: This work aims to help develop new protein engineering techniques based on a structural rearrangement phenomenon called circular permutation (CP), equivalent to connecting the native termini of a protein followed by creating new termini at another site. Although CP has been applied in many fields, its implementation is still costly because of inevitable trials and errors.
Results: Here we present CirPred, a structure modeling and termini linker design method for circularly permuted proteins.
Protein secondary structure prediction (SSP) has a variety of applications; however, there has been relatively limited improvement in accuracy for years. With a vision of moving forward all related fields, we aimed to make a fundamental advance in SSP. There have been many admirable efforts made to improve the machine learning algorithm for SSP.
View Article and Find Full Text PDFMultiple Rydberg series converging to the O2+c4Σ-u state, accessed by 20-25 eV extreme ultraviolet (XUV) light, serve as important model systems for the competition between nuclear dissociation and electronic autoionization. The dynamics of the lowest member of these series, the 3sσg state around 21 eV, has been challenging to study owing to its ultra-short lifetime (<10 fs). Here, we apply transient wave-mixing spectroscopy with an attosecond XUV pulse to investigate the decay dynamics of this electronic state.
View Article and Find Full Text PDFA rail-gap switch with a multistep triggering system was developed. The rail-gap switch consisted of two rail-like electrodes and a knife-edge electrode parallel to each other. It was assembled from many pieces and filled with unpressurized-flowing dry air.
View Article and Find Full Text PDFNAFLD (non-alcoholic fatty liver disease) is a multifactorial liver disease related to multiple causes or unhealthy conditions, including obesity and chronic inflammation. The accumulation of excess triglycerides, called steatosis, is known as a hallmark of an imbalance between the rates of hepatic fatty acid uptake/synthesis and oxidation/export. Furthermore, occurrence of NAFLD may lead to a cocktail of disease consequences caused by the altered metabolism of glucose, lipids, and lipoproteins, for instance, insulin resistance, type II diabetes, nonalcoholic steatohepatitis (NASH), liver fibrosis, and even hepatocarcinogenesis.
View Article and Find Full Text PDFPhototriggered drug delivery systems (PTDDSs) facilitate controlled delivery of drugs loaded on photoactive platform to the target region under light stimulation. The present study investigated the synthesis and efficacy of carbazole-coumarin (CC)-fused heterocycles as a PTDDS platform for the photocontrolled release of a chemotherapeutic agent, chlorambucil, in an in vitro model of human breast and leukemia cancer cells. CC-fused heterocycles were constructed using 4-hydroxycarbazole as the starting material, and further modification of these heterocycles yielded two CC derivatives.
View Article and Find Full Text PDFThe evolution of flight in feathered dinosaurs and early birds over millions of years required flight feathers whose architecture features hierarchical branches. While barb-based feather forms were investigated, feather shafts and vanes are understudied. Here, we take a multi-disciplinary approach to study their molecular control and bio-architectural organizations.
View Article and Find Full Text PDFUV-excited aromatic molecules with N-H/O-H moieties often possess an important nonradiative relaxation pathway, from an optically bright ππ state to a dark dissociative πσ state. We apply a new time-selected photofragment translational spectroscopy method to disclose a previously unknown triplet-mediated N-H dissociation of aniline prevented by the multiphoton dissociative ionization in conventional methods. We further determined the branching fractions of aniline dissociated in the πσ, triplet, and ground states at 248 nm.
View Article and Find Full Text PDFWe investigate resonance energy transfer (RET) between a donor-acceptor pair above a gold surface (including bulk and thin-film systems) and explore the distance/frequency dependence of RET enhancements using the theory we developed previously. The mechanism of RET above a gold surface can be attributed to the effects of mirror dipoles, surface plasmon polaritons (SPPs), and retardation. To clarify these effects on RET, we analyze the enhancements of RET by the mirror method, the decomposition of s- and p-polarization, and the SPP dispersion of charge-symmetric and charge-antisymmetric modes.
View Article and Find Full Text PDFPhenol is an important model molecule for the theoretical and experimental investigation of dissociation in the multistate potential energy surfaces. Recent theoretical calculations [X. Xu et al.
View Article and Find Full Text PDFCholestasis and hepatitis can cause continuous liver damage that may ultimately result in liver fibrosis. In a previous study, we demonstrated that microRNA-29a (miR-29a) protects against liver fibrosis. Toll-like receptor 2 (TLR2) and TLR4 are pattern recognition receptors of bacterial lipoprotein and lipopolysaccharide, both of which participate in activating hepatic stellate cells and liver fibrosis.
View Article and Find Full Text PDFMultivalent carbohydrate-protein interactions are essential for many biological processes. Convenient characterization for multivalent binding property of proteins will aid the development of molecules to manipulate these processes. We exploited the polyproline helix II (PPII) structure as molecular scaffolds to adjust the distances between glycan ligand attachment sites at 9, 18, and 27 Å on a peptide scaffold.
View Article and Find Full Text PDFHepatic fibrosis was caused by a number of signaling pathways that damage liver integrity. We have previously shown that microRNA-29a (miR-29a) protects against liver fibrosis. Aberrant endoplasmic reticulum (ER) and autophagy function reportedly exaggerate hepatic disorders.
View Article and Find Full Text PDFThe original ion imaging technique has low velocity resolution, and currently, photodissociation is mostly investigated using velocity map ion imaging. However, separating signals from the background (resulting from undissociated excited parent molecules) is difficult when velocity map ion imaging is used for the photodissociation of large molecules (number of atoms ≥ 10). In this study, we used the photodissociation of phenol at the S band origin as an example to demonstrate how our multimass ion imaging technique, based on modified spatial map ion imaging, can overcome this difficulty.
View Article and Find Full Text PDFHyaluronan is a linear glycosaminoglycan that has received special attention in the last few decades due to its extraordinary physiological functions. This highly viscous polysaccharide is not only a lubricator, but also a significant regulator of cellular behaviors during embryogenesis, morphogenesis, migration, proliferation, and drug resistance in many cell types, including stem cells. Most hyaluronan functions require binding to its cellular receptors CD44, LYVE-1, HARE, layilin, and RHAMM.
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