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Background: Recent development in tau‐sensitive tracers has sparkled significant interest in tracking tauopathies using positron emission tomography (PET) biomarkers. However, the ability of 18F‐florzolotau PET imaging to topographically characterize tau pathology in corticobasal syndrome (CBS) remains unclear. Further, the question as to whether disease‐level differences exist with other neurodegenerative tauopathies is still unanswered. Objective: To analyze the topographical patterns of tau pathology in the living brains of patients with CBS using 18F‐florzolotau PET imaging and to examine whether differences with other tauopathies exist. Methods: 18F‐florzolotau PET imaging was performed in 20 consecutive patients with CBS, 20 cognitively healthy controls (HCs), 20 patients with Alzheimer's disease (AD), and 16 patients with progressive supranuclear palsy–Richardson's syndrome (PSP‐RS). Cerebrospinal fluid (CSF) levels of β‐amyloid biomarkers were quantified in all patients with CBS. 18F‐florzolotau uptake was quantitatively assessed using standardized uptake value ratios. Results: Of the 20 patients with CBS, 19 (95%) were negative for CSF biomarkers of amyloid pathology; of them, three had negative 18F‐florzolotau PET findings. Compared with HCs, patients with CBS showed increased 18F‐florzolotau signals in both cortical and subcortical regions. In addition, patients with CBS were characterized by higher tracer retentions in subcortical regions compared with those with AD and showed a trend toward higher signals in cortical areas compared with PSP‐RS. An asymmetric pattern of 18F‐florzolotau uptake was associated with an asymmetry of motor severity in patients with CBS. Conclusions: In vivo 18F‐florzolotau PET imaging holds promise for distinguishing CBS in the spectrum of neurodegenerative tauopathies. © 2023 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

The objective of this work was to develop a simple, selective, and sensitive LC–MS/MS method for the quantitation of the mepivacaine in Chinese biological matrix. The calibration curve of mepivacaine ranged from 0.5 to 2000 ng/mL with the lower limit of quantitation being 0.5 ng/mL. This sensitivity was high enough to describe the profile of blood mepivacaine level versus time. Thereby it was very desirable for the pharmacokinetic study because of its high sensitivity and accuracy. The study used a single-dose two-period crossover design principle. For the pharmacokinetic analysis of plasma, the mean (SD) values obtained were as follows: t1/2, 1.63 (0.43) h;Cmax, 435.3 (67.4) ng/ml;AUC0-t, 1546.9 (339.7) ng/ml·h;AUC0-∞, 1982.3 (421.4) ng/ml·h;Tmax, 0.62 (0.31) h. The validated method has been successfully applied to assess the pharmacokinetic study of mepivacaine after a single administration to Chinese volunteers. [ABSTRACT FROM PUBLISHER]

Macroautophagy/autophagy is a fundamental cellular catabolic process that delivers cytoplasmic components into double-membrane vesicles called autophagosomes, which then fuse with lysosomes and their contents are degraded. Autophagy recycles cytoplasmic components, including misfolded proteins, dysfunctional organelles and even microbial invaders, thereby playing an essential role in development, immunity and cell death. Autophagosome formation is the main step in autophagy, which is governed by a set of ATG (autophagy related) proteins. ATG16L1 interacts with ATG12–ATG5 conjugate to form an ATG12–ATG5-ATG16L1 complex. The complex acts as a ubiquitin-like E3 ligase that catalyzes the lipidation of MAP1LC3/LC3 (microtubule associated protein 1 light chain 3), which is crucial for autophagosome formation. In the present study, we found that ATG16L1 was subject to S-palmitoylation on cysteine 153, which was catalyzed by ZDHHC7 (zinc finger DHHC-type palmitoyltransferase 7). We observed that re-expressing ATG16L1 but not the S-palmitoylation-deficient mutant ATG16L1C153S rescued a defect in the lipidation of LC3 and the formation of autophagosomes in ATG16L1-KO (knockout) HeLa cells. Furthermore, increasing ATG16L1 S-palmitoylation by ZDHHC7 expression promoted the production of LC3-II, whereas reducing ATG16L1 S-palmitoylation by ZDHHC7 deletion inhibited the LC3 lipidation process and autophagosome formation. Mechanistically, the addition of a hydrophobic 16-carbon palmitoyl group on Cys153 residue of ATG16L1 enhances the formation of ATG16L1-WIPI2B complex and ATG16L1-RAB33B complex on phagophore, thereby facilitating the LC3 lipidation process and autophagosome formation. In conclusion, S-palmitoylation of ATG16L1 is essential for the lipidation process of LC3 and the formation of autophagosomes. Our research uncovers a new regulatory mechanism of ATG16L1 function in autophagy.Abbreviation: ABE: acyl-biotin exchange; ATG: autophagy related; Baf-A1: bafilomycin A1; 2-BP: 2-bromopalmitate; CCD: coiled‐coil domain; co-IP: co-immunoprecipitation; CQ: chloroquine; EBSS: Earle’s balanced salt solution; HAM: hydroxylamine; KO: knockout; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NP-40: Nonidet P-40; PBS: phosphate-buffered saline; PE: phosphatidylethanolamine; PtdIns3K-C1: class III phosphatidylinositol 3-kinase complex I; PTM: post-translational modification; RAB33B: RAB33B, member RAS oncogene family; RB1CC1/FIP200: RB1 inducible coiled-coil 1; SDS: sodium dodecyl sulfate; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscope; WD: tryptophan and aspartic acid; WIPI2B: WD repeat domain, phosphoinositide interacting 2B; WT: wild-type; ZDHHC: zinc finger DHHC-type palmitoyltransferase. [ABSTRACT FROM AUTHOR]

Background: Recent development in tau-sensitive tracers has sparkled significant interest in tracking tauopathies using positron emission tomography (PET) biomarkers. However, the ability of 18 F-florzolotau PET imaging to topographically characterize tau pathology in corticobasal syndrome (CBS) remains unclear. Further, the question as to whether disease-level differences exist with other neurodegenerative tauopathies is still unanswered., Objective: To analyze the topographical patterns of tau pathology in the living brains of patients with CBS using 18 F-florzolotau PET imaging and to examine whether differences with other tauopathies exist., Methods: 18 F-florzolotau PET imaging was performed in 20 consecutive patients with CBS, 20 cognitively healthy controls (HCs), 20 patients with Alzheimer's disease (AD), and 16 patients with progressive supranuclear palsy-Richardson's syndrome (PSP-RS). Cerebrospinal fluid (CSF) levels of β-amyloid biomarkers were quantified in all patients with CBS. 18 F-florzolotau uptake was quantitatively assessed using standardized uptake value ratios., Results: Of the 20 patients with CBS, 19 (95%) were negative for CSF biomarkers of amyloid pathology; of them, three had negative 18 F-florzolotau PET findings. Compared with HCs, patients with CBS showed increased 18 F-florzolotau signals in both cortical and subcortical regions. In addition, patients with CBS were characterized by higher tracer retentions in subcortical regions compared with those with AD and showed a trend toward higher signals in cortical areas compared with PSP-RS. An asymmetric pattern of 18 F-florzolotau uptake was associated with an asymmetry of motor severity in patients with CBS., Conclusions: In vivo 18 F-florzolotau PET imaging holds promise for distinguishing CBS in the spectrum of neurodegenerative tauopathies. © 2023 International Parkinson and Movement Disorder Society., (© 2023 International Parkinson and Movement Disorder Society.)

Objective: To observe the curative effect of different duration of mild moxibustion in superficial gastritis patients with deficiency cold pattern of spleen and stomach., Methods: A total of 84 superficial gastritis patients were randomly divided into moxibustion-20 min group, moxibustion-40 min group and medication (Ranitidine) group, with 28 cases in each group. Mild moxibustion was applied to bilateral Zusanli (ST 36) and Zhongwan (CV 12, odd days), Pishu (BL 20) and Weishu (BL 21, even-numbered days) for 20 min and 40 min respectively, once daily for 20 days. The symptom integrative score of superficial gastritis patients and the therapeutic effects were assessed according to "The Scoring Table for Symptoms and Signs of Gastrointestinal Disorders of Chinese Medicine", etc., Results: Following 20 days' treatment, of the three 28 gastrititis patients in the medication, moxibustion-20 min and moxibustion-40 min groups, 0, 1, and 0 cases were cured, 5, 7 and 12 experienced marked improvement in their symptoms, 15, 16 and 12 had an improvement, and 8, 4 and 4 were invalid, with the effective rates being 71.4%, 85.7% and 85.7%, respectively. After one month's follow up, of the three 28 cases in the medication, moxibustion-20 min and moxibustion-40 min groups, 0, 4 and 0 cases were cured, 4, 8, and 13 experienced marked improvement, 15, 16 and 13 had an improvement, 9, 0 and 2 were ineffective, with the effective rates being 67.9%, 100% and 92.9%, respectively. Self-comparison of each group showed that the integrative scores of symptoms were all decreased significantly after the treatment and one-month's follow up in the three groups (P < 0.01). The effective rates of both moxibustion-20 min and -40 min were significantly higher than that of the medication group after one month's follow up (P < 0.01, P < 0.05). The therapeutic effect of moxibustion-20 min group was significantly superior to that of the medication group in lowering the integrative score of symptoms after one month's follow up (P < 0.01). No significant differences were found among the three groups in the therapeutic effects and in reducing integrative scores of symptoms after 20 days' treatment (P > 0.05)., Conclusion: Mild moxibustion is significantly superior to medication in long-term therapeutic effects in the treatment of superficial gastritis patients with spleen-stomach deficiency-cold pattern.