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.

Probiotics have shown excellent application prospects in preventing and treating many diseases. However, their sensitivity to the harsh environment in vivo always leads to a massive loss of viability and insufficient therapeutic effect. Fortunately, modified probiotics have emerged and provide multiple possibilities for their use in various diseases. Modification not only endows probiotics with extra capacity to resist severe environments but also gives them exogenous characteristics, such as prolonged retention time and improved therapeutic effects. Modified probiotics could combine with other therapies, which has opened up new avenues to enhance the efficacy of probiotic-based therapy. In this review, we have summarized the current physicochemical and biological modification strategies of probiotics. In addition, the progress of research on probiotic-based combination therapy has also been extensively reviewed, which contributes to the enhanced delivery of probiotics or other active constituents and provides new ideas for disease treatment, bioimaging, and diagnosis.

Objective To explore the application of 3D printing templates for titanium plate contouring (TrPC) in pelvic ring surgery.Methods From May 2016 to June 2018,12 patients with pelvic ring injury were treated by internal fixation with 24 titanium plates at Department of Orthopedics and Trauma,Sanshui People's Hospital.After solid digital models of the damaged pelves of the patients were reconstructed from their CT images via software,the hollowed ones were created with the wall thickness of 1.2 mm.After the models of damaged pelves were restored to be intact,the templates for titanium plate contouring were designed based on the area of fixation and manufactured via a stereo lithography apparatus.The total manufacturing time and material consumption of 3D printing TTPC were recorded and compared with those of 3D printing solid and hollow models.Before operation,the titanium plates were contoured according to the templates.The time for preoperative shaping the plate and the time for intraoperative preparing the plate before installation were recorded.After operation,all patients underwent CT scan again for reconstruction of 3D models of the postoperative pelves which were compared with their corresponding preoperative ones in the software.Matta criteria were used to evaluate the pelvic reduction and Majeed criteria to evaluate the functional recovery 6 months after operation.Results All patients were followed up for 6 to 28 months (average,16.3 months).The total manufacturing time and material consumption of 3D printing a TTPC were significantly less than those of 3D printing a solid or hollow model (P ＜ 0.05).The time for preoperative shaping the plate was 12.8 ± 4.1 minutes and the time for intraoperative preparing the plate was 1.4 ± 1.1 minutes.The average deviation between the preoperative 3D models and the postoperative ones was 1.4 ± 1.1 mm.According to the Matta criteria for pelvic reduction,6 cases were excellent,4 good and 2 satisfactory.According to the Majeed criteria,the pelvic functions were excellent in 7 cases,good in 4,and fair in one.Conclusion Application of 3D printing TTPC in the surgery for pelvic ring injury is advantageous in lowering the costs of 3D printing and reducing the intraoperative time for contouring the titanium plate,leading to satisfactory outcomes.

Objective: To explore clinical characteristics, treatment, and prognosis of a family with childhood-onset rapid-onset dystonia parkinsonism (RDP) caused by ATP1A3 gene mutation and review literatures. Method: The clinical data of a RDP child, his brother and mother had been analyzed retrospectively. This family was admitted to Xiangya Hospital in January 2016. DNA samples were analyzed by the next-generation sequencing and confirmed by Sanger sequencing. Related literature from PubMed, Online Mendelian Inheritance in Man (OMIM), CNKI and Wanfang databases to date (up to October 2016) with"Rapid-onset dystonia-parkinsonism""RDP""DYT12" as key words was reviewed. Result: The proband boy was three years and four months old (April 2015) when he had the first attack of the disease. After a febricity, he suddenly acquired acute aphasia and limb movement disorder. Rehabilitation therapy and supportive treatment made his speech gradually recovered but still slurred. However, his abnormal walking posture still existed. Nine months later (January 2016, 4 years and one months old), symptoms including aphasia, dysphagia, and weakness with rostrocaudal gradient reoccured after fever. The disease progressed to the critical condition within 24 hours. He"seizured" four times with tonic spasms of limbs but without loss of consciousness. Family history showed his grandparents were consanguineous marriage. His mother and brother also developed abnormal gait and dysarthria after an infection before primary school age. Their symptoms improved gradually without relapsing. However, they did not recover entirely with mild intellectual disability. His mother had a healthy brother and sister. This proband had no other siblings but the brother. Heterozygous missense mutation p. R756H in ATP1A3 gene was detected in this proband, his mother and his brother. This mutation had been reported pathogenically related to RDP, and it located in highly conserved gene region. Benzodiazepine was used for the proband and his brother, with the proband being improved better although not completely. Meanwhile, benzodiazepine had no significant effect on his mother because of poor compliance. This is the first case report of RDP in China. The mutations of ATP1A3 have been previously reported in 51 patients including 6 large families and 16 other unrelated patients. A total of 14 different mutations in ATP1A3 gene with RDP have been reported to date, including 12 missense mutations, a 3-bp in-frame deletion, and a 3-bp in-frame insertion. The sporadic cases all had the typical clinical phenotypes of RDP, such as the abrupt onset of dysarthria, dysphagia, limb dystonia with bradykinesia, and postural instability. The symptoms of bulbar and arms were much more obvious. It was hard to diagnose RDP in a family because some patients had typical symptoms of RDP, while the others might experience from mild symptoms to no symptoms, which might be related to incomplete penetrance of RDP. Two cases carrying the same mutation as our patients also presented some overlapping phenotypes. Conclusion The p. R756H heterozygous mutation in ATP1A3 gene is the pathogenic mutation of RDP, analysis of genotype-phenotype correlations of RDP will be very important and meaningful.

BACKGROUND:The effects of advanced glycation end products (AGEs) on osteoclast-induced bone resorption is controversial and the underlying mechanisms remain unclear. Most of the studies indicate that AGEs can enhance bone resorption, while some othersshowthe opposite effects.
OBJECTIVE:To investigate the effects of AGEs on osteoclast-induced inorganicmatrixdissolution and organic componentdegradation and the underlying mechanisms.
METHODS:RAW 264.7 cels were induced to generate osteoclasts,and AGEs (50-400 μg/mL) or control-bovine serum albumin (100 μg/mL) was added since the beginning of the induction. The effect of AGEs on bone resorption was evaluated by analyzing the area of resorption pits on the Osteo Assay Surface plates and the expression of cathepsin K. Furthermore, the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cels, nuclei per osteoclasts and the expression of integrinανβ3were detected.
RESULTS AND CONCLUSION:The area of resorption pits and expression of cathepsin K in AGEs groups were significantly decreased compared withthecontrol group, and this inhibiting effect became more obvious with the increase of AGEs concentration. TRAP staining also showed that number of TRAP-positivemultinucleated celsand nuclei per osteoclast were significantly reduced in an AGE dose-dependent manner. Quantitative PCR revealed that the expression of integrin ανβ3decreased significantly with the extension of AGEs incubation time. These data indicate that AGEs can exert inhibitory effects on organic and inorganicmatrixdegradation induced by osteoclasts. The underlying mechanism may be involved in the inhibitory effects of AGEs on directed differentiation and cel fusion of osteoclast precursor cels, and migration and adhension of osteoclasts.

Urinary tract infection complicated with urinary tract calculi( lithangiuria)is one of the most common diseases causing serious urinary sepsis and septic shock. Recent studies show that the accurate diagnosis,rational use of antibiotics and timely treatment of complications are the key to treatment success. In this article,the latest progress and the treatment strategies for urinary tract infections complicated with lithangiuria are explored.

OBJECTIVETo study on the feasibility of cutting process of fresh Angelica sinensis.

METHODQualitative and quantitative chemical analysis methods were used to evaluate the quality of different cutting processed A. sinensis.

RESULTThe contents of ligustilide and ferulic acid in the fresh cutting processed were both lower than the traditional cutting process, and the similarity of fingerprints of two different cutting processed A. sinensis were basically above 90%.

CONCLUSIONThe method of cutting process of fresh A. sinensis was not suitable apparently, and the effect on clinical application of these two different cutting processed A. sinensis need more study.

4-Butyrolactone ; analogs & derivatives ; analysis ; Angelica sinensis ; chemistry ; Chromatography, High Pressure Liquid ; Coumaric Acids ; analysis ; Drugs, Chinese Herbal ; analysis ; Plant Roots ; chemistry ; Technology, Pharmaceutical ; methods