Dysbiotic oral microbiota has been associated with multiple sclerosis. However, the role and mechanism of oral microbiota in the development of multiple sclerosis are still elusive. Here, we ...demonstrated that ligature-induced periodontitis (LIP) aggravated experimental autoimmune encephalomyelitis (EAE) in mice, and this was likely dependent on the expansion of T helper 17 (Th17) cells. LIP increased the splenic richness of Enterobacter sp., which was able to induce the expansion of splenic Th17 cells and aggravate EAE in mice. LIP also led to enrichment of Erysipelotrichaceae sp. in the gut and increased Th17 cells in the large intestinal lamina propria of EAE mice. Fecal microbiota transplantation from EAE mice with LIP also promoted EAE symptoms. In conclusion, periodontitis exacerbates EAE, likely through ectopic colonization of oral pathobionts and expansion of Th17 cells.
Although significant advances have recently been made in the diagnosis and treatment of cervical carcinoma, the long-term survival rate for advanced cervical cancer remains low. Therefore, an urgent ...need exists to both uncover the molecular mechanisms and identify potential therapeutic targets for the treatment of cervical cancer. MicroRNAs (miRNAs) have important roles in cancer progression and could be used as either potential therapeutic agents or targets. miR-506 is a component of an X chromosome-linked miRNA cluster. The biological functions of miR-506 have not been well established. In this study, we found that miR-506 expression was downregulated in approximately 80% of the cervical cancer samples examined and inversely correlated with the expression of Ki-67, a marker of cell proliferation. Gain-of-function and loss-of-function studies in human cervical cancer, Caski and SiHa cells, demonstrated that miR-506 acts as a tumor suppressor by inhibiting cervical cancer growth in vitro and in vivo. Further studies showed that miR-506 induced cell cycle arrest at the G1/S transition, and enhanced apoptosis and chemosensitivity of cervical cancer cell. We subsequently identified Gli3, a hedgehog pathway transcription factor, as a direct target of miR-506 in cervical cancer. Furthermore, Gli3 silencing recapitulated the effects of miR-506, and reintroduction of Gli3 abrogated miR-506-induced cell growth arrest and apoptosis. Taken together, we conclude that miR-506 exerts its anti-proliferative function by directly targeting Gli3. This newly identified miR-506/Gli3 axis provides further insight into the pathogenesis of cervical cancer and indicates a potential novel therapeutic agent for the treatment of cervical cancer.
Elucidating the cellular organization of the cerebral cortex is critical for understanding brain structure and function. Using large-scale single-nucleus RNA sequencing and spatial transcriptomic ...analysis of 143 macaque cortical regions, we obtained a comprehensive atlas of 264 transcriptome-defined cortical cell types and mapped their spatial distribution across the entire cortex. We characterized the cortical layer and region preferences of glutamatergic, GABAergic, and non-neuronal cell types, as well as regional differences in cell-type composition and neighborhood complexity. Notably, we discovered a relationship between the regional distribution of various cell types and the region’s hierarchical level in the visual and somatosensory systems. Cross-species comparison of transcriptomic data from human, macaque, and mouse cortices further revealed primate-specific cell types that are enriched in layer 4, with their marker genes expressed in a region-dependent manner. Our data provide a cellular and molecular basis for understanding the evolution, development, aging, and pathogenesis of the primate brain.
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•A comprehensive cell-type taxonomy is constructed for the entire macaque cortex•Stereo-seq reveals the global distribution of 264 cell types and their marker genes•Regional density and composition of cell types are coupled with cortical hierarchy•Cross-species analysis revealed primate-specific cell types enriched in layer 4
A spatially resolved single-cell transcriptome atlas of macaque cortex is generated that reveals the organization and evolution of primate cortical regions.
A guard-gate based flip-flop circuit temporally hardened against single-event effects is presented in this paper. Compared to several existed techniques, the organization of components inside the ...proposed design allows the improved performance- only one \tau (the maximum width of a single-event transient (SET) to tolerate) is added into the setup time. A previously reported low-power delay element is applied, which helps make the proposed design power-efficient. The proposed design was implemented in a 65 nm CMOS bulk technology. Alpha and heavy-ions radiation experiments were performed to characterize its soft-error rates. Experimental results show that the proposed design presents no error with LETs up to 37.3 MeV-cm 2 /mg. Simulation results from the TFIT further validate the experimental results.
A DNA vaccine against the hepatitis B virus (HBV), enhanced by IL‐2/IFN‐γ fusion protein expression from a plasmid construct and mediated by in vivo electroporation, was evaluated in a total of 39 ...HBeAg‐positive patients with chronic hepatitis B (CHB). The six of 39 patients with a serum alanine aminotransferase (ALT) value of 1–2 times upper limit of normal (ULN) were assigned to the open‐label arm (Group01) receiving vaccine monotherapy; the remaining 33 patients with an ALT of more than two times ULN were enroled to the randomized and controlled arm (Group02) receiving lamivudine (LAM) monotherapy (LAM+placebo) or combined therapy (LAM+DNA vaccine) in 1:2 ratio. In Group01, a significant elevation of HBV‐specific IFN‐γ‐secreting T‐cell counts in comparison with baseline was observed. In Group02, the proportion of patients with HBV DNA suppression was higher with LAM+DNA vaccine than with LAM monotherapy at each visit time point after the final injection of DNA vaccine at week 36, revealing a significant difference between the two groups (P = 0.03) at week 60. The incidence of dual‐site mutations of rtM204/I/S+rtL180M was significantly lower (P = 0.03) with an identified lower virological breakthrough (VBT) rate (P = 0.03) in patients receiving LAM+DNA vaccine than LAM monotherapy, accompanied with a significant higher positive T‐cell response rate in patients receiving LAM+DNA vaccine (P = 0.03). In conclusion, this study provides evidence that HBV DNA vaccination is safe and immunologically effective, and that the HBV‐specific T‐cell responses induced by DNA vaccination under LAM chemotherapy showed a correlation with the suppression of viral replication in patients with CHB.
The cardinal features of Parkinson's disease (PD) are bradykinesia, rigidity and rest tremor. Abnormal activity in the basal ganglia is predicted to underlie the mechanism of motor symptoms. This ...study aims to characterize properties of oscillatory activity in the basal ganglia and motor thalamus in patients with PD.
Twenty-nine patients with PD who underwent bilateral or unilateral electrode implantation for subthalamic nucleus (STN) DBS (
= 11), unilateral pallidotomy (
= 9) and unilateral thalamotomy (n = 9) were studied. Microelectrode recordings in the STN, globus pallidus internus (GPi) and ventral oral posterior/ventral intermediate of thalamus (Vop/Vim) were performed. Electromyography of the contralateral limbs was recorded. Single unit characteristics including interspike intervals were analyzed. Spectral and coherence analyses were assessed. Mean spontaneous firing rate (MSFR) of neurons was calculated. Analysis of variance and X
test were performed.
Of 76 STN neurons, 39.5% were 4-6 Hz band oscillatory neurons and 28.9% were β frequency band (βFB) oscillatory neurons. The MSFR was 44.2 ± 7.6 Hz. Of 62 GPi neurons, 37.1% were 4-6 Hz band oscillatory neurons and 27.4% were βFB neurons. The MSFR was 80.9 ± 9.6 Hz. Of 44 Vop neurons, 65.9% were 4-6 Hz band oscillatory neurons and 9% were βFB neurons. The MSFR was 24.4 ± 4.2 Hz. Of 30 Vim oscillatory neurons, 70% were 4-6 Hz band oscillatory neurons and 13.3% were βFB neurons. The MSFR was 30.3 ± 3.6 Hz. Further analysis indicated that proportion of βFB oscillatory neurons in STN and GPi was higher than that of similar neurons in the Vop and Vim (
< 0.05). Conversely, the proportion of 4-6 Hz band oscillatory neurons and tremor related neurons in the Vim and Vop was higher than that of STN and GPi (
< 0.05). The highest MSFR was for GPi oscillatory neurons whereas the lowest MSFR was for Vop oscillatory neurons (
< 0.005).
The alterations in neuronal activity in basal ganglia play a critical role in generation of parkinsonism. β oscillatory activity is more prominent in basal ganglia than in thalamus suggesting that the activity likely results from dopaminergic depletion. While both basal ganglia and thalamus have tremor activity, the thalamus appears to play a more important role in tremor production, and basal ganglia β oscillatory activity might be the trigger.
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