Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer's disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and A...Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer's disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and Alzheimer's disease model mice. However, the effects of magnesium-L-threonate on the gut microbiota in Alzheimer's disease remain unknown. Previously, we reported that magnesium-L-threonate treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of Alzheimer's disease model mice expressing the amyloid-β precursor protein and mutant human presenilin 1(APP/PS1). Here, we performed 16S r RNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-Lthreonate exposure in a similar mouse model. Magnesium-L-threonate modulated the abundance of three genera in the gut microbiota, decreasing Allobaculum and increasing Bifidobacterium and Turicibacter. We also found that differential metabolites in the magnesiumL-threonate-regulated serum were enriched in various pathways associated with neurodegenerative diseases. The western blotting detection on intestinal tight junction proteins(zona occludens 1, occludin, and claudin-5) showed that magnesium-L-threonate repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that magnesium-L-threonate may reduce the clinical manifestations of Alzheimer's disease through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of Alzheimer's disease.展开更多
番茄褐色皱纹果病毒(tomato brown rugose fruit virus,ToBRFV)严重威胁番茄等茄科园艺作物的生产安全。本研究根据其外壳蛋白(coat protein,CP)基因及其同属病毒的差异序列,设计了特异性重组酶介导等温核酸扩增技术(recombinase-aided ...番茄褐色皱纹果病毒(tomato brown rugose fruit virus,ToBRFV)严重威胁番茄等茄科园艺作物的生产安全。本研究根据其外壳蛋白(coat protein,CP)基因及其同属病毒的差异序列,设计了特异性重组酶介导等温核酸扩增技术(recombinase-aided amplification,RAA)引物,并基于CRISPR/Cas12a的设计原则,设计了靶向RT-RAA扩增产物的CRISPR RNA(crRNA)。通过优化获得了检测信号最强的反应体系,其中报告基因FQ终浓度为600nmol/L、Cas12a和crRNA终浓度分别为200nmol/L和1000nmol/L,最终总反应时间仅为30 min。该方法可特异性检测ToBRFV,对携带ToBRFV的番茄样品RNA检测灵敏度为RT-PCR和RT-qPCR的10000和100倍,检测限为3.46fg/μL。阳性样品验证结果显示,本研究建立的RT-RAA-CRISPR/Cas12a检测技术可以在不同来源的辣椒、番茄侵染的植物叶片、果实及种子中检测到ToBRFV,表明该技术可用于番茄褐色皱纹果病毒的快速、灵敏的可视化检测。展开更多
BACKGROUND Syphilis is an infectious disease caused by Treponema pallidum that can invade the central nervous system,causing encephalitis.Few cases of anti-N-methyl-Daspartate receptor autoimmune encephalitis(AE)secon...BACKGROUND Syphilis is an infectious disease caused by Treponema pallidum that can invade the central nervous system,causing encephalitis.Few cases of anti-N-methyl-Daspartate receptor autoimmune encephalitis(AE)secondary to neurosyphilis have been reported.We report a neurosyphilis patient with anti-γ-aminobutyric acid-B receptor(GABABR)AE.CASE SUMMARY A young man in his 30s who presented with acute epileptic status was admitted to a local hospital.He was diagnosed with neurosyphilis,according to serum and cerebrospinal fluid(CSF)tests for syphilis.After 14 d of antiepileptic treatment and anti-Treponema pallidum therapy with penicillin,epilepsy was controlled but serious cognitive impairment,behavioral,and serious psychiatric symptoms were observed.He was then transferred to our hospital.The Mini-Mental State Examination(MMSE)crude test results showed only 2 points.Cranial magnetic resonance imaging revealed significant cerebral atrophy and multiple fluidattenuated inversion recovery high signals in the white matter surrounding both lateral ventricles,left amygdala and bilateral thalami.Anti-GABABR antibodies were discovered in CSF(1:3.2)and serum(1:100).The patient was diagnosed with neurosyphilis complicated by anti-GABABR AE,and received methylprednisolone and penicillin.Following treatment,his mental symptoms were alleviated.Cognitive impairment was significantly improved,with a MMSE of 8 points.Serum anti-GABABR antibody titer decreased to 1:32.The patient received methylprednisolone and penicillin after discharge.Three months later,the patient’s condition was stable,but the serum anti-GABABR antibody titer was 1:100.CONCLUSION This patient with neurosyphilis combined with anti-GABABR encephalitis benefited from immunotherapy.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82101271 (to WL),82171178 (to JL)Basic and Applied Basic Research Foundation of Guangdong Province,Nos.2020A1515110317 (to WL),2021A1515010705 (to WL)+1 种基金Young Talent Support Project of Guangzhou Association for Science and Technology (to WL)Technology Key Project of Shenzhen,No.JCYJ202001091 14612308 (to ZS)。
文摘Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer's disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and Alzheimer's disease model mice. However, the effects of magnesium-L-threonate on the gut microbiota in Alzheimer's disease remain unknown. Previously, we reported that magnesium-L-threonate treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of Alzheimer's disease model mice expressing the amyloid-β precursor protein and mutant human presenilin 1(APP/PS1). Here, we performed 16S r RNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-Lthreonate exposure in a similar mouse model. Magnesium-L-threonate modulated the abundance of three genera in the gut microbiota, decreasing Allobaculum and increasing Bifidobacterium and Turicibacter. We also found that differential metabolites in the magnesiumL-threonate-regulated serum were enriched in various pathways associated with neurodegenerative diseases. The western blotting detection on intestinal tight junction proteins(zona occludens 1, occludin, and claudin-5) showed that magnesium-L-threonate repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that magnesium-L-threonate may reduce the clinical manifestations of Alzheimer's disease through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of Alzheimer's disease.
文摘番茄褐色皱纹果病毒(tomato brown rugose fruit virus,ToBRFV)严重威胁番茄等茄科园艺作物的生产安全。本研究根据其外壳蛋白(coat protein,CP)基因及其同属病毒的差异序列,设计了特异性重组酶介导等温核酸扩增技术(recombinase-aided amplification,RAA)引物,并基于CRISPR/Cas12a的设计原则,设计了靶向RT-RAA扩增产物的CRISPR RNA(crRNA)。通过优化获得了检测信号最强的反应体系,其中报告基因FQ终浓度为600nmol/L、Cas12a和crRNA终浓度分别为200nmol/L和1000nmol/L,最终总反应时间仅为30 min。该方法可特异性检测ToBRFV,对携带ToBRFV的番茄样品RNA检测灵敏度为RT-PCR和RT-qPCR的10000和100倍,检测限为3.46fg/μL。阳性样品验证结果显示,本研究建立的RT-RAA-CRISPR/Cas12a检测技术可以在不同来源的辣椒、番茄侵染的植物叶片、果实及种子中检测到ToBRFV,表明该技术可用于番茄褐色皱纹果病毒的快速、灵敏的可视化检测。
文摘BACKGROUND Syphilis is an infectious disease caused by Treponema pallidum that can invade the central nervous system,causing encephalitis.Few cases of anti-N-methyl-Daspartate receptor autoimmune encephalitis(AE)secondary to neurosyphilis have been reported.We report a neurosyphilis patient with anti-γ-aminobutyric acid-B receptor(GABABR)AE.CASE SUMMARY A young man in his 30s who presented with acute epileptic status was admitted to a local hospital.He was diagnosed with neurosyphilis,according to serum and cerebrospinal fluid(CSF)tests for syphilis.After 14 d of antiepileptic treatment and anti-Treponema pallidum therapy with penicillin,epilepsy was controlled but serious cognitive impairment,behavioral,and serious psychiatric symptoms were observed.He was then transferred to our hospital.The Mini-Mental State Examination(MMSE)crude test results showed only 2 points.Cranial magnetic resonance imaging revealed significant cerebral atrophy and multiple fluidattenuated inversion recovery high signals in the white matter surrounding both lateral ventricles,left amygdala and bilateral thalami.Anti-GABABR antibodies were discovered in CSF(1:3.2)and serum(1:100).The patient was diagnosed with neurosyphilis complicated by anti-GABABR AE,and received methylprednisolone and penicillin.Following treatment,his mental symptoms were alleviated.Cognitive impairment was significantly improved,with a MMSE of 8 points.Serum anti-GABABR antibody titer decreased to 1:32.The patient received methylprednisolone and penicillin after discharge.Three months later,the patient’s condition was stable,but the serum anti-GABABR antibody titer was 1:100.CONCLUSION This patient with neurosyphilis combined with anti-GABABR encephalitis benefited from immunotherapy.
