The catalytic activity of 3-mercaptopyruvate (3MP) sulfurtransferase (MPST) converts 3MP to hydrogen sulfide (H₂S). However, the regulatory mechanisms governing MPST and its impact on the brain remain largely unexplored. Our study reveals the neuroprotective role of endothelial MPST-generated H₂S, regulated by protein phosphatase 2A (PP2A). Bioinformatics analysis and RNA sequencing demonstrated that endothelial PP2A is associated with neurodegenerative disease pathways. Cerebral ischemic mice exhibited significant inactivation of endothelial PP2A, evidenced by the reduction of PP2Acα in the brain endothelium. Mice with endothelium-specific null PP2A (PP2A^EC-cKO) exhibited neuronal loss, cognitive dysfunction, and long-term potentiation deficits. Postnatal inactivation of endothelial PP2A also contributes to cognitive dysfunction and neuronal loss. However, regaining endothelial PP2A activity by overexpressing Ppp2ca rescued neuronal dysfunction. Mechanistically, PP2A deficiency is intricately linked to the MPST-H₂S signaling pathway. A robust reduction in endothelial MPST-dependent H₂S production followed PP2A deficiency. Exogenous H₂S treatment and AAV-mediated overexpression of MPST in brain endothelial cells significantly mitigated neuronal dysfunction in PP2A^EC-cKO mice. Furthermore, PP2A deficiency promotes an increase in calcium influx and calpain2 phosphorylation, subsequently leading to MPST degradation. The PP2A activator (FTY720) and MPST activator (3MP sodium) both remarkably restored endothelial MPST-dependent H₂S production, subsequently rescuing ischemia-induced neurological deficits. In conclusion, our study demonstrates that endothelial PP2A deficiency leads to MPST degradation by activating calpain2, thus damaging neuronal function.

OBJECTIVE: Explore the model of universal NICU newborns' hearing screening in high-risk neonates, preliminary understanding factor of hearing damage. METHOD: Transient evoked otoacoustic emissions (TEOAE) and automatic auditory brainstem response (AABR) were used to detect newborns' hearing in 13 315 objects, that is newborns' hearing screening in NICU with TEOAE test who not pass, 42 days after will use AABR rescreening. Children's Hearing Center of Guangxi Child Health Hospital will diagnose the newborns that did not pass in 3 months. RESULT: In these 13 315 newborns, 5 151 subjects who did not pass the initial screening, 1910 subjects who also did not pass after 42 days, 1167 subjects cannot pass the rescreening after 3 months, 642 subjects were diagnosed congenital hearing impairment by Brainstem Auditory Evoked Potential Test, the rate is 4.82%. CONCLUSION TEOAE and AABR are the suitable model of universal newborns' hearing screening in high-risk neonates.
Evoked Potentials, Auditory, Brain Stem ; Female ; Follow-Up Studies ; Hearing Tests ; Humans ; Infant, Newborn ; Intensive Care Units, Neonatal ; Male ; Neonatal Screening

OBJECTIVETo investigate the effect of betulinic acid (BA) on the proliferation, migration, apoptosis and cell cycle of pancreatic cancer cells (BxPC-3) in vitro and elucidate the underlying.

METHODThe effect of BA on the proliferation of BxPC-3 was measured by using sulforhodamine B (SRB) assay. Migratory ability of BxPC3 cells were detected by wound healing assay, and the morphological change was observed with light microscope. The influence of BA on cell cycle of BxPC-3 cells was tested by flow cytometry (FCM). Apoptosis was analyzed by using Hochest33342-PI double staining. Western blot technologies were applied to detect the expression of Bcl-2 and Bax.

RESULTBA exhibited significant cell proliferation and migration inhibition, as well as its potency of inducing apoptosis in BxPC-3 cells in vitro in a dose-dependent manner. The IC50 value for 72 h was 16.54 mg x L(-1). Cell migration was significantly inhibited at 5 mg x L(-1) of BA. Cells treated with BA showed increased cell population in G0 phase, with decreased G2/M phase population. The expression of Bax and Bcl-2 was up and down-regulated respectively in BA-treated BxPC-3 cells in a dose-dependent manner.

CONCLUSIONBA exerted potent effect on growth inhibition, G0 cell cycle arrest and induction of apoptosis in BxPC-3 cells in vitro, possibly associated with the down-regulation of Bcl-2 and up-regulation of Bax expression. The potent antitumor capacity of BA suggested that it could be a promising new anticancer agent in human pancreatic cancer treatment.

Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Pancreatic Neoplasms ; drug therapy ; genetics ; metabolism ; physiopathology ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Triterpenes ; pharmacology ; bcl-2-Associated X Protein ; genetics ; metabolism