Refinement of nanoporous copper by dealloying the Al-Cu alloy in NaOH solution containing sodium dodecyl sulfate.

This work reports the refinement of nanoporous copper (NPC) ligaments by introducing the sodium dodecyl sulfate (SDS) surfactant in the dealloying process. The Al80Cu20 (at%) alloy precursor is chemically dealloyed in a mixed solution of NaOH and SDS surfactant, producing NPC with a hierarchical microstructure. Micron-scaled skeletons that build up higher level networks consist of geometrically similar nano-scaled bi-continuous ligament-pore networks at the lower level. It has been found that the size of the ligaments in the lower level networks reduces from ∼32 nm to ∼24 nm with increasing SDS concentration to 1 mM. Further increasing the SDS concentration to 5 mM only leads to a slight ligament size decrease to ∼21 nm. Remarkably, nano-sized cones are formed on the lower level network surface in the dealloying solution containing 1 mM SDS, and the cone number greatly rises when the SDS concentration increases to 5 mM. The surface diffusivity of Cu adatoms is evaluated based on the experimental data, and the refinement of the ligament as well as the formation of cones are associated with the decreased surface diffusivity and the retarded Cu adatom motions with the addition of SDS. Quantum chemical calculations and molecular dynamics simulations are performed to model the adsorption behavior of SDS. It has been found that the SDS-substrate interaction increases with the number of SDS molecules before SDS reaches saturation.

Targeting vulnerable microcircuits in the ventral hippocampus of male transgenic mice to rescue Alzheimer-like social memory loss.

BACKGROUND: Episodic memory loss is a prominent clinical manifestation of Alzheimer's disease (AD), which is closely related to tau pathology and hippocampal impairment. Due to the heterogeneity of brain neurons, the specific roles of different brain neurons in terms of their sensitivity to tau accumulation and their contribution to AD-like social memory loss remain unclear. Therefore, further investigation is necessary. METHODS: We investigated the effects of AD-like tau pathology by Tandem mass tag proteomic and phosphoproteomic analysis, social behavioural tests, hippocampal electrophysiology, immunofluorescence staining and in vivo optical fibre recording of GCaMP6f and iGABASnFR. Additionally, we utilized optogenetics and administered ursolic acid (UA) via oral gavage to examine the effects of these agents on social memory in mice. RESULTS: The results of proteomic and phosphoproteomic analyses revealed the characteristics of ventral hippocampal CA1 (vCA1) under both physiological conditions and AD-like tau pathology. As tau progressively accumulated, vCA1, especially its excitatory and parvalbumin (PV) neurons, were fully filled with mislocated and phosphorylated tau (p-Tau). This finding was not observed for dorsal hippocampal CA1 (dCA1). The overexpression of human tau (hTau) in excitatory and PV neurons mimicked AD-like tau accumulation, significantly inhibited neuronal excitability and suppressed distinct discrimination-associated firings of these neurons within vCA1. Photoactivating excitatory and PV neurons in vCA1 at specific rhythms and time windows efficiently ameliorated tau-impaired social memory. Notably, 1 month of UA administration efficiently decreased tau accumulation via autophagy in a transcription factor EB (TFEB)-dependent manner and restored the vCA1 microcircuit to ameliorate tau-impaired social memory. CONCLUSION: This study elucidated distinct protein and phosphoprotein networks between dCA1 and vCA1 and highlighted the susceptibility of the vCA1 microcircuit to AD-like tau accumulation. Notably, our novel findings regarding the efficacy of UA in reducing tau load and targeting the vCA1 microcircuit may provide a promising strategy for treating AD in the future.

Low-Dose Sirolimus Immunoregulation Therapy in Patients with Active Rheumatoid Arthritis: A 24-Week Follow-Up of the Randomized, Open-Label, Parallel-Controlled Trial.

BACKGROUND: We have reported previously the insufficient absolute number or functional defects of regulatory T cells (Tregs) in patients with rheumatoid arthritis (RA), challenging conventional unspecific immunosuppressive therapy. Sirolimus, a mTOR inhibitor, is reported to allow growth of functional Tregs; here, we investigated the efficacy of low-dose sirolimus combined with conventional immunosuppressants (sirolimus immunoregulation therapy) for RA treatment with lower side effects and better tolerance. METHODS: In this nonblinded and parallel-group trial, we randomly assigned 62 patients to receive conventional glucocorticoids and immunosuppressants with or without sirolimus at a dosage of 0.5 mg on alternate days for 24 weeks in a 2 : 1 ratio. The demographic features, clinical manifestations, and laboratory indicators including peripheral blood lymphocyte subgroups and CD4+T subsets were compared before and after the treatment. RESULTS: Finally, 37 patients in the sirolimus group and 18 in the conventional treated group completed the 6-month study. By 24 weeks, the patients with sirolimus experienced significant reduction in disease activity indicators including DAS28, ESR, and the number of tender joints and swollen joints (p < 0.001). Notably, they had a higher level of Tregs as compared with those with conventional therapy alone (p < 0.05), indicating that sirolimus could partly restore the reduced Tregs. Concomitantly, their usage of immunosuppressants for controlling disease activity was decreased as compared with the conventional group with no difference in blood routine, and liver and renal functions both before and after the treatment of sirolimus and between the two groups (p > 0.05). CONCLUSIONS: Low-dose sirolimus immunoregulatory therapy selectively upregulated Tregs and partly replaced the usage of immunosuppressants to control disease activity without overtreatment and evaluable side effect. Further study is required using a large sample of RA patients treated with sirolimus for a longer period. This trial is registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj=17245).

A preliminary study of apparent diffusion coefficient in chemotherapy-induced liver damage.

OBJECTIVES: To investigate changes in the hepatic apparent diffusion coefficient (ADC) in patients undergoing chemotherapy. METHODS: We enrolled 54 patients (25 women; mean age 57.0±13.1 years, range 29-89 years) undergoing chemotherapy for tumor and 10 controls (7 women; mean age 55.1±17.5 years, range 23-81 years). The patients were tested for serum alanine aminotransferase (ALT) activity (abnormal, normal) and fatty liver. Hepatic ADC values were compared among controls, patients and subgroups. Pearson correlation coefficient was used to assess the correlation between ADC and ALT activity. RESULTS: Hepatic ADC0,850 (×10(-3) mm2/s) was lower for patients than controls (1.14±0.18 vs. 1.28±0.12, P=0.02) and was lower for patients with than without fatty liver and controls (1.01±0.06 vs. 1.18±0.18 and 1.28±0.12, respectively, all P<0.01), with no significant difference between patients without fatty liver and controls (P=0.07). ADC0,850 was lower for patients with abnormal ALT than normal ALT activity and controls (0.99±0.06 vs. 1.17±0.18 and 1.28±0.12, respectively, all P<0.05), with a significant difference also being seen between patients with normal ALT activity and controls (P=0.04). Hepatic ADC0,850 was not correlated with ALT activity in patients (r=-0.24, P=0.08). CONCLUSIONS: Although ADC did not correlate with ALT values, it did distinguish patient likely to have chemotherapy-induced liver damage as indicated by abnormal ALT values or fatty liver. These mechanisms need to be disentangled.