Microglial lipid droplet accumulation in tauopathy brain is regulated by neuronal AMPK.

The accumulation of lipid droplets (LDs) in aging and Alzheimer's disease brains is considered a pathological phenomenon with unresolved cellular and molecular mechanisms. Utilizing stimulated Raman scattering (SRS) microscopy, we observed significant in situ LD accumulation in microglia of tauopathy mouse brains. SRS imaging, combined with deuterium oxide (D2O) labeling, revealed heightened lipogenesis and impaired lipid turnover within LDs in tauopathy fly brains and human neurons derived from induced pluripotent stem cells (iPSCs). Transfer of unsaturated lipids from tauopathy iPSC neurons to microglia induced LD accumulation, oxidative stress, inflammation, and impaired phagocytosis. Neuronal AMP-activated protein kinase (AMPK) inhibits lipogenesis and promotes lipophagy in neurons, thereby reducing lipid flux to microglia. AMPK depletion in prodromal tauopathy mice increased LD accumulation, exacerbated pro-inflammatory microgliosis, and promoted neuropathology. Our findings provide direct evidence of native, aberrant LD accumulation in tauopathy brains and underscore the critical role of AMPK in regulating brain lipid homeostasis.

Multiscale Interface Engineering of Sulfur-Doped TiO2 Anode for Ultrafast and Robust Sodium Storage.

Sodium-ion batteries (SIBs) are a promising electrochemical energy storage system; however, their practical application is hindered by the sluggish kinetics and interfacial instability of anode-active materials. Here, to circumvent these issues, we proposed the multiscale interface engineering of S-doped TiO2 electrodes with minor sulfur/carbon inlaying (S/C@sTiO2), where the electrode-electrolyte interface (SEI) and electrode-current collector interface (ECI) are tuned to improve the Na-storage performance. It is found that the S dopant greatly promotes the Na+ diffusion kinetics. Moreover, the ether electrolyte generates much less NaF in the cycled electrode, but relatively richer NaF in the SEI in comparison to fluoroethylene carbonate-contained ester electrolyte, leading to a thin (9 nm), stable, and kinetically favorable SEI film. More importantly, the minor sodium polysulfide intermediates chemically interact with the Cu current collector to form a Cu2S interface between the electrode and the Cu foil. The conductive tree root-like Cu2S ECI serves not only as active sites to boost the specific capacity but also as a 3D "second current collector" to reinforce the electrode and improve the Na+ reaction kinetics. The synergy of S-doping and optimized SEI and ECI realizes large specific capacity (464.4 mAh g-1 at 0.1 A g-1), ultrahigh rate capability (305.8 mAh g-1 at 50 A g-1), and ultrastable cycling performance (91.5% capacity retention after 3000 cycles at 5 A g-1). To the best of our knowledge, the overall SIB performances of S/C@sTiO2 are the best among all of the TiO2-based electrodes.

[Expression of CK19 mRNA and EGFR mRNA in the peripheral blood and its relationship with lymphatic metastasis in laryngeal carcinoma model].

OBJECTIVE: To explore clinical evaluate of CK19 mRNA and EGFR mRNA for diagnosis of laryngeal carcinoma micrometastasis, correlation between circulation tumor cell and lymph node metastasis. METHOD: Of 30 nude mice, 25 were randomly divided into 5 experimental groups (5 mice in each group), 5 were acted as control group. The mice were killed 2,4,6,8 and 10 weeks after injection. The expression of CK19 and EGFR mRNA in the peripheral blood and tumor tissue were detected by RT-PCR assay. The expression of EGFR in tumor tissue were detected by immunohistochemistry and lymph node transfer were confirmed using continuous pathological dying. RESULT: None of CK19 and EGFR mRNA were detected in peripheral blood of control group, CK19 mRNA-positive rate was 48% and 80% in peripheral blood and tumor tissue from the experimental group, respectively, and EGFR mRNA-positive rate was 36% and 76%, respectively. Lymph node metastasis happened in the exponential growth phase and transfer rate was 60%(15/25). The expression of CK19 mRNA and EGFR mRNA in lymphatic metastasis groups was higher than that of control, with a positive correlation between lymphatic metastasis and CTC (r = 0.655 , P < 0.01). The protein positive expression rate of EGFR were 88%(22/25) in tumor tissue. All peripheral blood expressed EGFR concomitant EGFR expressing in tumor tissues, and a high expression of EGFR in tumor tissue displayed high expression of EGFR in peripheral blood as well. CONCLUSION: The expression of CK19 and EGFR mRNA in the peripheral blood can provide predictive information of lymphatic metastasis, EGFR mRNA might be a new target of treatment and diagnosis for malignant tumour.

[The impact of PDTC on circulating tumor cells of laryngocarcinoma in nude mice model].

OBJECTIVE: To investigate the correlation of the nuclear factor (NF-kappaB) and laryngocarcinoma circulating tumor cells (CTC), observe nuclear factor inhibitor PDTC on laryngeal cancer CTC and its possible mechanism. METHOD: In order to establish of laryngocarcinoma nude mice model ,The nude mice inoculated with laryngo carcinoma Hep-2 cells. To 50 nude mice were randomly divided into experimental group (PDTC pretreatment group), the control group (saline group), and Sham group (not inoculated carcinoma cells), tumor inoculated mice were labeled with CK-19 CTC markers, and sacrificed after 8 weeks, then RT-PCR detect CK-19mRNA expression in peripheral blood as to understand the expression of laryngocarcinoma CTC; removed tumor to determine its size, immunohistochemical expression of NF-kappaB in laryngocarcinoma, real-time fluorescence Quantitative PCR detection of laryngocarcinoma VEGF and MMP-9mRNA expression. RESULT: CTC occurrence and the expression of NF-kappaB was not obviously associated, expression in the CTC-positive laryngeal carcinoma, NF-kappaB-positive rate was 90%, while the expression of negative CTC laryngocarcinoma, NF-kappaB-positive rate was 56.7% (P>0.05), but connected with the activity of NF-kappaB; PDTC can inhibit NF-kappaB activation, reduce the incidence of CTC in laryngocarcinoma nude mice model, PDTC group CTC positive rate of 5%, significantly lower than the control group CTC positive rate of 45% (P<0.01). CONCLUSION: PDTC can reduce the incidence of CTC in the laryngocarcinoma nude mouse model, its role may benefit from PDTC reduced the ability of laryngocarcinoma metastasis, which may be as PDTC inhibit NF-kappaB activity, thus make VEGF-C and the expression of MMP-9 down, reducing angiogenesis and reduce tumor invasion of the larynx.

[Expression of glucose transporter 1 in human laryngeal squamous cell carcinoma and its clinical significance].

OBJECTIVE: To investigate the expression of glucose transporter 1 (GLUT1) in human laryngeal squamous cell carcinoma and its relationship to clinical pathologic factors. METHOD: Tumor tissues and the peritumoral and normal laryngeal tissue were collected from 57 patients with laryngeal squamous cell carcinoma. The expression of GLUT1 was evaluated at protein and mRNA level by immunohistochemistry and reverse transcription polymerase chain reaction(RT-PCR) in relation to clinical pathologic characteristics. RESULT: GLUT1 protein and mRNA expression were significantly higher in tumoral tissues than in peritumoral and normal tissues (P < 0.01, respectively). Poorly differentiated tumor expressed higher levels of GLUT1 protein and mRNA compared to well differentiated ones (P < 0.05, respectively). Stronger GLUT1 protein and mRNA were detected in larger tumors compared with that in smaller ones (P < 0.05, respectively). There were significant differences in GLUT1 protein and mRNA expression in relation to TNM stage (P < 0.05, respectively). The expression levels of GLUT1 protein and mRNA were positively correlated with lymphatic metastasis (P < 0.05, respectively). CONCLUSION: GLUT1 may play an important role in tumorigenesis, development, differentiation, lymphatic metastasis and prognosis of human laryngeal squamous cell carcinoma, and may be a useful marker of diagnosis and prognosis.