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The misfolding of amyloid-β (Aβ) peptides from the natural unfolded state to β-sheet structure is a critical step, leading to abnormal fibrillation and formation of endogenous Aβ plaques in Alzheimer's disease (AD). Previous studies have reported inhibition of Aβ fibrillation or disassembly of exogenous Aβ fibrils in vitro. However, soluble Aβ oligomers have been reported with increased cytotoxicity; this might partly explain why current clinical trials targeting disassembly of Aβ fibrils by anti-Aβ antibodies have failed so far. Here we show that Au23(CR)14 (a new Au nanocluster modified by Cys-Arg (CR) dipeptide) is able to completely dissolve exogenous mature Aβ fibrils into monomers and restore the natural unfolded state of Aβ peptides from misfolded β-sheets. Furthermore, the cytotoxicity of Aβ40 fibrils when dissolved by Au23(CR)14 is fully abolished. More importantly, Au23(CR)14 is able to completely dissolve endogenous Aβ plaques in brain slices from transgenic AD model mice. In addition, Au23(CR)14 has good biocompatibility and infiltration ability across the blood–brain barrier. Taken together, this work presents a promising therapeutics candidate for AD treatment, and manifests the potential of nanotechnological approaches in the development of nanomedicines. [ABSTRACT FROM AUTHOR]

Heavy metal Cr3+ has been regarded as a threat to the environment and human health. So it is crucial to find a rapid method for detecting Cr3+, especially for the trace amounts. Here, HgS/ZnS core/shell quantum dots (HgS/ZnS QDs) with a quantum yield of 22.6% were synthesized as a fluorescent nanoprobe for detection of Cr3+ with a detection limit of 0.19 nM. With captopril as stabilizer, the formation of the core/shell structure of HgS/ZnS QDs was demonstrated by high-resolution high-angle annular dark-field scanning transmission electron microscopy (HR-HAADF-STEM). The substantial fluorescence (580 nm) quenching of HgS/ZnS QDs which could be seen immediately by the naked eyes was induced selectively and sensitively by Cr3+, even in the case of Cr3+ mixed with other interfering ion. The HgS/ZnS QDs exhibited a stable visual response to Cr3+ from 1 μM, which just conformed to World Health Organization (WHO) standards for drinking water. Moreover, further experiments indicated that the mechanism of fluorescence quenching lied on the aggregation of the HgS/ZnS QDs. These results provide a novel insight for in situ rapid visual detection of heavy metal ions. Graphical abstract A rapid visual method was developed for in-situ detection of Cr3+ from 1 μM (WHO standards for the drinking water) through the orange fluorescence quenching (seen by naked eyes) which resulted from the Cr3+ induced the aggregation of captopril coated HgS/ZnS core/shell QDs [ABSTRACT FROM AUTHOR]

Heavy metal Cr3+ has been regarded as a threat to the environment and human health. So it is crucial to find a rapid method for detecting Cr3+, especially for the trace amounts. Here, HgS/ZnS core/shell quantum dots (HgS/ZnS QDs) with a quantum yield of 22.6% were synthesized as a fluorescent nanoprobe for detection of Cr3+ with a detection limit of 0.19 nM. With captopril as stabilizer, the formation of the core/shell structure of HgS/ZnS QDs was demonstrated by high-resolution high-angle annular dark-field scanning transmission electron microscopy (HR-HAADF-STEM). The substantial fluorescence (580 nm) quenching of HgS/ZnS QDs which could be seen immediately by the naked eyes was induced selectively and sensitively by Cr3+, even in the case of Cr3+ mixed with other interfering ion. The HgS/ZnS QDs exhibited a stable visual response to Cr3+ from 1 μM, which just conformed to World Health Organization (WHO) standards for drinking water. Moreover, further experiments indicated that the mechanism of fluorescence quenching lied on the aggregation of the HgS/ZnS QDs. These results provide a novel insight for in situ rapid visual detection of heavy metal ions. Graphical abstract A rapid visual method was developed for in-situ detection of Cr3+ from 1 μM (WHO standards for the drinking water) through the orange fluorescence quenching (seen by naked eyes) which resulted from the Cr3+ induced the aggregation of captopril coated HgS/ZnS core/shell QDs [ABSTRACT FROM AUTHOR]

Hepatic metachronous oligometastatic nasopharyngeal carcinoma (hmoNPC) exhibits distinct clinical characteristics compared to other types of metastatic NPC. We investigated the optimal therapy for hmoNPC. 160 patients with hmoNPC treated in Sun Yat-sen University Cancer Center between 2010 and 2021 were retrospectively recruited. A total of 56 patients were classified into the local therapy (LT) cohort, 23 into the systemic therapy (ST) cohort and 81 into the combination therapy (LT + ST) cohort. The median PFS was 7.9 months (95% confidence interval [CI]: 4.1-11.9 months) in the LT cohort, 15.5 months (95% CI: 10.5-32.3 months) in the ST cohort, and 31.3 months (95% CI: 20.3 to NA months) in the LT + ST cohort. The median OS was 41.1 months (95% CI: 30.0-54.0 months) in the LT cohort, 50.4 months (95% CI: 41.5 to NA months) in the ST cohort and not reached (NR) (95% CI: 77.3 to NA months) in the LT + ST cohort. Cox analysis was used to construct nomograms to predict patient outcomes. Among patients with no evidence of disease status after LT, the prognosis was significantly better in the LT + ST cohort than LT cohort (median PFS: NR [95% CI: 29.0 to NA months] vs. 20.0 months [95% CI: 10.4 to NA months]). More survival benefits were achieved with platinum-based chemotherapy than oral monotherapy (median PFS: NR [95% CI: 21.7 to NA months] vs. 17.2 months [95% CI: 10.2 to NA months]). Fewer postoperative early progression events were observed in neoadjuvant chemotherapy cohort than in adjuvant chemotherapy cohort (2.78% vs. 18.81%, P = .013). In conclusion, combining neoadjuvant platinum-based chemotherapy and local therapy was the best strategy for patients with hmoNPC., (© 2024 UICC.)

The misfolding of amyloid-β (Aβ) peptides from the natural unfolded state to β-sheet structure is a critical step, leading to abnormal fibrillation and formation of endogenous Aβ plaques in Alzheimer's disease (AD). Previous studies have reported inhibition of Aβ fibrillation or disassembly of exogenous Aβ fibrils in vitro . However, soluble Aβ oligomers have been reported with increased cytotoxicity; this might partly explain why current clinical trials targeting disassembly of Aβ fibrils by anti-Aβ antibodies have failed so far. Here we show that Au 23 (CR) 14 (a new Au nanocluster modified by Cys-Arg (CR) dipeptide) is able to completely dissolve exogenous mature Aβ fibrils into monomers and restore the natural unfolded state of Aβ peptides from misfolded β-sheets. Furthermore, the cytotoxicity of Aβ 40 fibrils when dissolved by Au 23 (CR) 14 is fully abolished. More importantly, Au 23 (CR) 14 is able to completely dissolve endogenous Aβ plaques in brain slices from transgenic AD model mice. In addition, Au 23 (CR) 14 has good biocompatibility and infiltration ability across the blood-brain barrier. Taken together, this work presents a promising therapeutics candidate for AD treatment, and manifests the potential of nanotechnological approaches in the development of nanomedicines., (© The Author(s) 2019. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)