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Purpose: To investigate the clinical features and cytochrome P450 family 4 subfamily V polypeptide 2 (CYP4V2) gene mutations in 14 Chinese families with Bietti crystalline dystrophy (BCD). Methods: Seventeen patients from 14 unrelated Chinese families with BCD were recruited for complete clinical ophthalmic examination and genetic study. The 11 exons of CYP4V2 were amplified from genomic DNA of all patients and their family members by polymerase chain reaction (PCR) and then sequenced. Exons of TIMP3 were also sequenced in BCD patient associated with choroidal neovascularization (CNV). One hundred and seventy unrelated healthy Chinese subjects were screened for mutations in CYP4V2. Results: All 17 patients with BCD had mutations in CYP4V2; one of these mutations was novel (c.219T>A, p.F73L) and four other mutations had been reported. The p.F73L mutation was a commonly detected mutation in our study (seven out of 34 alleles), either in the homozygous state or in the heterozygous state. Among the patients, considerable phenotypic variability was detected, both within and between families. Screening of TIMP3 did not find any mutation in the BCD patient associated with CNV. Conclusion: The novel CYP4V2 c.219T>A (p.F73L) mutation may be another recurrent mutation in Chinese patients with BCD. Our study expands the mutation spectrum of CYP4V2 and characterizes novel genotype–phenotype associations in Chinese patients with BCD. [ABSTRACT FROM AUTHOR]

This paper presents a filterless Class-D amplifier with pseudorandomized carrier frequency modulation (PRCFM) to mitigate electromagnetic interference (EMI) issue associated with the removal of an off-chip LC filter. The designed filterless Class-D amplifier occupies a total area of 1 mm^2 and is fabricated in 0.18-μm CMOS process technology. The proposed PRCFM circuit occupies only less than 1% of the IC area. Measurement results have demonstrated the effectiveness of the PRCFM scheme for EMI reduction. The PRCFM scheme consumes very little additional power and therefore does not affect the power efficiency of the amplifier. In addition, the proposed scheme also maintains very good total harmonic distortion over the audio band of interest (100 Hz to 6 kHz) and modulation index range. [ABSTRACT FROM AUTHOR]

Ferroptosis is an iron-dependent mode of cell death associated with the occurrence and development of age-related neurodegenerative diseases. Currently, there are no effective drugs available to prevent or treat these aging-related neurodegenerative diseases. Vitamin D (VD) is an antioxidant and immunomodulator, but its relationship with ferroptosis in aging-related neurodegenerative diseases has not been extensively studied. In this study, we aimed to investigate the role of VD in learning and memory in aging mice. To examine whether VD protects aging hippocampal neurons, we used physiologically active 1,25(OH)2D3. We established aging models in vivo (C57BL/6 mice) and in vitro (HT22 cells) using D-galactose (D-gal). The results demonstrated that VD could improve learning and memory in mice aged via the use of D-gal, and it reduced damage to hippocampal neurons. VD could regulate ferroptosis-related proteins (increasing GPX4 expression and decreasing ACSL4 and ALOX15 protein expression levels), increasing GSH levels, reducing MDA and intracellular and mitochondrial ROS levels, as well as total iron and Fe2+ levels, and improving mitochondrial morphology, thereby alleviating ferroptosis in aging hippocampal neurons. Additionally, VD activated the VDR/Nrf2/HO-1 signaling pathway, thereby inhibiting ferroptosis. Notably, when the VDR was knocked down, VD lost its ability to activate Nrf2. Consequently, inhibiting Nrf2 decreased the protective effect of VD against ferroptosis in aged hippocampal neurons. In summary, VD activates the Nrf2/HO-1 signaling pathway through the VDR, effectively preventing ferroptosis induced by aging in hippocampal neurons. [ABSTRACT FROM AUTHOR]