Site-specific tethering nanobodies on recombinant adeno-associated virus vectors for retargeted gene therapy.

Recombinant adeno-associated viruses (rAAVs) have been extensively studied for decades as carriers for delivering therapeutic genes. However, designing rAAV vectors with selective tropism for specific cell types and tissues has remained challenging. Here, we introduce a strategy for redirecting rAAV by attaching nanobodies with desired tropism at specific sites, effectively replacing the original tropism.

Physiologically Based Pharmacokinetic Modeling of Lacosamide in Patients With Hepatic and Renal Impairment and Pediatric Populations to Support Pediatric Dosing Optimization.

Purpose: Lacosamide (LCM) is a new-generation anti-seizure medication that is efficacious in patients with focal seizures with or without secondary generalization. Until now, the efficacy, safety, and tolerability of LCM are still lacking in Chinese epilepsy patients, particularly for pediatric populations and patients with renal or hepatic impairment.

Methods: This study was conducted to develop a physiologically based pharmacokinetic (PBPK) model to characterize the pharmacokinetics of LCM in Chinese populations and predict the pharmacokinetics of LCM in Chinese pediatric populations and patients with renal or hepatic impairment.

Physiologically based pharmacokinetic modeling of candesartan to predict the exposure in hepatic and renal impairment and elderly populations.

Background: Candesartan cilexetil is a widely used angiotensin II receptor blocker with minimal adverse effects and high tolerability for the treatment of hypertension. Candesartan is administered orally as the prodrug candesartan cilexetil, which is wholly and swiftly converted to the active metabolite candesartan by carboxylesterase during absorption in the intestinal tract. In populations with renal or hepatic impairment, candesartan's pharmacokinetic (PK) behavior may be altered, necessitating dosage adjustments.

Purely positive or discriminatorily positive? The development of two-factor attitudes toward lesbians and gay men scales.

Unidimensional bipolar scales based on prejudice against homosexuality neglect the effect of preference for heterosexuality on attitudes toward homosexuality. Additionally, the term "homosexuality" used in these scales may compromise their validity. The current study uses person-centered and variable-centered approaches to examine the structure and classes of attitudes toward lesbians and gay men.

Regulators of epigenetic change in ferroptosis‑associated cancer (Review).

The occurrence of tumors is associated with the upregulation or downregulation of certain genes. The identification of novel tumor therapies has revealed that regulation of tumor cell death can either promote or suppress the occurrence and development of tumors. Iron‑dependent lipid free oxygen radical accumulation causes tumor cells to die by ferroptosis, a form of regulated cell death.

Comprehensive Sexuality Education Improves Primary Students' Explicit and Implicit Attitudes Toward Homosexuality.

Comprehensive sexuality education (CSE) is a curriculum-based process that is inclusive to gender and sexual orientation. We used the attitude toward homosexuality scale and the single category implicit association test (SC-IAT) to measure differences between explicit and implicit attitudes toward homosexuality between migrant children with 6 years CSE learning experience (experimental group,  = 70) and those without (control group,  = 80). We found that the experimental group had more positive explicit and implicit attitudes toward homosexuality than the control group.

Eggs Polysaccharide Enhances Macrophage Phagocytosis Against Infection by TLR4/STAT3 Axis.

Antibiotics resistance is one of the most significant public health threats globally. Strategies that strengthen host defenses to control pathogen infection has become a hot research field. Macrophages are part of early host defense mechanisms, and are activated host pattern recognition receptors (PRRs), such as Toll-like receptor 4 (TLR4), which then facilitates phagocytosis and elimination of invading pathogens.

Esculetin protects against early sepsis via attenuating inflammation by inhibiting NF-κB and STAT1/STAT3 signaling.

Esculetin, a natural derivative from the traditional and widely-used Chinese medicinal herb Cortex Fraxini, has a variety of pharmacological effects, especially in anti-inflammation. However, it is not clear whether esculetin has a therapeutic effect on sepsis. This study aimed to investigate the anti-inflammatory and protective effects of esculetin on early sepsis.

Ferroelectric behavior of orthogonal smectic phase made of bent-core molecules.

Ferroelectric behavior in the recently reported orthogonal ferroelectric Sm-A(d)P(F) phase in an unsymmetric bent-core molecule with a carbosilane terminal group was studied. The ferroelectricity of the Sm-A(d)P(F) phase was unambiguously confirmed by optical second-harmonic generation activity in the absence of an electric field, ferroelectric response, and high dielectric strength. The long-range polar order is a consequence of weakened interlayer coupling due to the formation of carbosilane sublayers, which allows for the parallel order of dipole moments of bent-core molecules in the neighboring layers.

Polar switching in the smectic- A(d)P(A) phase composed of asymmetric bent-core molecules.

We have studied mesogenic properties in the smectic- A(d)P(A) phase of an asymmetric bent-core liquid crystal by means of polarizing optical microscopy, second-harmonic generation (SHG), electro-optical (EO), and dielectric measurements. In homeotropically aligned cells, EO switching is clearly observed from a schlieren texture with both four- and two-brush defects to a uniform bright domain under the application of very low in-plane electric field below 1 V/microm. The phase is SHG active under an electric field, i.

First symmetrical banana compounds exhibiting SmAP(R) mesophase and unique transition between two orthogonal polar phases.

Novel banana-shaped liquid crystals with stilbene bridges were synthesized. All presented materials exhibit the polarization-randomized non-tilted smectic phase (SmAP(R)) in a broad temperature range and the antiferroelectric non-tilted smectic phase (SmAP(A)) at room temperature.