Modeling of auditory neuropathy spectrum disorders associated with the variant reveals impaired gap junction function of iPSC-derived glia-like support cells.

Auditory neuropathy spectrum disorder (ANSD) is an auditory dysfunction disorder characterized by impaired speech comprehension. Its etiology is complex and can be broadly categorized into genetic and non-genetic factors. mutation is identified as a causative factor in ANSD.

Inflammatory adhesion mediates myocardial segmental necroptosis induced by mixed lineage kinase domain-like protein in acute myocardial infarction.

Purpose: Cardiomyocyte death is a major cytopathologic response in acute myocardial infarction (AMI) and involves complex inflammatory interactions. Although existing reports indicating that mixed lineage kinase domain-like protein (MLKL) is involved in macrophage necroptosis and inflammasome activation, the downstream mechanism of MLKL in necroptosis remain poorly characterized in AMI.

Methods: MLKL knockout mice (MLKL), RIPK3 knockout mice (RIPK3), and macrophage-specific MLKL conditional knockout mice (MLKL) were established.

cystatin has protective effects against "two-hit" sepsis in mice by regulating the inflammatory microenvironment.

Objectives: To evaluate the protective effect of cystatin (r-Cystatin) in a mouse mode of "two-hit" sepsis.

Methods: Sixty male C57BL/6 mice randomized equally into sham-operated group, protein group, "two-hit" modeling group, and protein intervention group. In the former two groups, the mice received an intraperitoneal injection of 100 μL PBS followed by exposure of the cecum and then by intraperitoneal injection of 100 μL PBS or 25 μg r-Cystatin 30 min later; In the latter two groups, 100 μL PBS containing LPS (5 mg/kg) was injected intraperitoneally 24 h before cecal ligation and puncture (CLP), and 100 μL PBS or 25 μg r-Cystatin were injected 30 min after CLP.

Direct object recovery from the Fraunhofer diffraction integral.

In this Letter, we present a novel, to the best of our knowledge, approach for recovering objects directly from the Fraunhofer diffraction integral, where the diffraction field of an object is approximated by the Fourier transform of this object augmented by an additional phase factor. This phase factor at the observation plane is universal for the diffraction fields generated by objects located at the same plane and illuminated by the same monochromatic plane wave. It can be first extracted from dividing the Fraunhofer diffraction field by the Fourier transform of an object reference.

Bi-targeting of thioredoxin 1 and telomerase by thiotert promotes cell death of myelodysplastic syndromes and lymphoma.

Thioredoxin1 (TRX1) and telomerase are both attractive oncology targets that are tightly implicated in tumor initiation and development. Here, we reported that the 6-dithio-2-deoxyguanosine analog thiotert exhibits an effective cytotoxic effect on myelodysplastic syndromes (MDS) cell SKM-1 and lymphoma cell U-937. Further studies confirmed that thiotert effectively disrupts cellular redox homeostasis, as evidenced by elevated intracellular reactive oxygen species (ROS) levels, increased MnSOD, accelerated DNA impairment, and activated apoptosis signal.