Bioengineered miR-124-3p prodrug selectively alters the proteome of human carcinoma cells to control multiple cellular components and lung metastasis in vivo.

With the understanding of microRNA (miRNA or miR) functions in tumor initiation, progression, and metastasis, efforts are underway to develop new miRNA-based therapies. Very recently, we demonstrated effectiveness of a novel humanized bioengineered miR-124-3p prodrug in controlling spontaneous lung metastasis in mouse models. This study was to investigate the molecular and cellular mechanisms by which miR-124-3p controls tumor metastasis. Proteomics study identified a set of proteins selectively and significantly downregulated by bioengineered miR-124-3p in A549 cells, which were assembled into multiple cellular components critical for metastatic potential. Among them, plectin (PLEC) was verified as a new direct target for miR-124-3p that links cytoskeleton components and junctions. In miR-124-3p-treated lung cancer and osteosarcoma cells, protein levels of vimentin, talin 1 (TLN1), integrin beta-1 (ITGB1), IQ motif containing GTPase activating protein 1 (IQGAP1), cadherin 2 or N-cadherin (CDH2), and junctional adhesion molecule A (F11R or JAMA or JAM1) decreased, causing remodeling of cytoskeletons and disruption of cell-cell junctions. Furthermore, miR-124-3p sharply suppressed the formation of focal adhesion plaques, leading to reduced cell adhesion capacity. Additionally, efficacy and safety of biologic miR-124-3p therapy was established in an aggressive experimental metastasis mouse model in vivo. These results connect miR-124-3p-PLEC signaling to other elements in the control of cytoskeleton, cell junctions, and adhesion essential for cancer cell invasion and extravasation towards metastasis, and support the promise of miR-124 therapy

Erratum: Author correction to Bioengineered miR-124-3p prodrug selectively alters the proteome of human carcinoma cells to control multiple cellular components and lung metastasis in vivo [Acta Pharmaceutica Sinica B 11 (2021) 3950-3965].

[This corrects the article DOI: 10.1016/j.apsb.2021.07.027.]

Author correction to ‘Bioengineered miR-124-3p prodrug selectively alters the proteome of human carcinoma cells to control multiple cellular components and lung metastasis in vivo’ [Acta Pharmaceutica Sinica B 11 (2021) 3950–3965]

[This corrects the article DOI: 10.1016/j.apsb.2021.07.027.]

The Optimization of a Carbon Paper/MnO₂ Composite Current Collector for Manufacturing a High-Performance Li–S Battery Cathode

High theoretical energy density endows lithium–sulfur batteries to be a promising candidate of the secondary batteries. Numerous studies have been implemented relying on exploring efficient host materials or separator modifying layers to solve the problematic shuttling and insufficient conversion of soluble polysulfides, whereas few studies have focused on the modification of the cathode collector. Herein, a high-performance sulfur cathode is manufactured with carbon paper/MnO2 as the cathode collector and liquid lithium polysulfides as the electrode material. The interface of carbon paper/MnO2 is proposed to afford fast electronic transport, strong chemical adsorption, and effective electrocatalysis to confine the diffusion of lithium polysulfides and facilitate their conversion during the charge/discharge process. More importantly, with no conductive additives and binders assisting, the gravimetric energy density of the sulfur cathode could be largely improved. Specifically, lithium–sulfur batteries using carbon paper/MnO2 as a cathode collector could stably circulate for 200 cycles at 0.2 C with a capacity of 664 mAh g−1, which is higher than that of carbon paper as a cathode collector (486 mAh g−1). This work may provide a new perspective to enhance the electrochemical performance of lithium–sulfur batteries by optimizing the cathode collector

Special issue on advances and applications of artificial intelligence and machine learning for wireless communications

11Nsciescopuskc

A ~200 ka pollen record from Okinawa Trough: Paleoenvironment reconstruction of glacial-interglacial cycles

International audiencePollen analysis was carried out on the Core MD982194 of 29.78 m retrieved from the Middle Okinawa Trough which was dated as old as ~200 ka BP. The results revealed that pollen assemblages mainly presented an alternation of coniferous and herb pollen. The coniferous saccate pollen, principally Pinus and Tsuga, predominated in most parts of the core, especially highlighted in the interstadial stages including MIS 1,3, 5 and MIS7, whereas the herb pollen significantly increased in the gla- cial periods. Thus the pollen flora and their percentages showed the sensitive changes under the influence of ice volume during the glacial and interglacial periods. Our record from this core has first documented that the percentage of Cyperaceae was ex- tremely high in the glacial stages with a notable increase in Artemisia, Gramineae, Asteraceae, Chenopodiaceae, and freshwa- ter algae, which can be used as a proxy for sea-level change at the study site because of their close negative correlation of the orbital-scale changes in sea level. The distance between the continental coastline and the Okinawa Trough has deeply short- ened due to the sea-level drop in the LGM. As a result, the sediment materials from Yangtze River were extensively deposited on the flat, exposed continental shelf owing to the rapid decline of river flow speed, leading to that pollen grains from Okinawa Trough are derived mainly from the flat coastal vegetation of exposed continental shelf at glacial stages. Changes of pollen as- semblage were consistent with the variation of temperature and humidity, which showed that the percentage of arboreal pollen was highly augmented at MIS 7, 5 and MIS 1, corresponding to the strengthening of the East Asian summer monsoon and in- creasing of rainfall. Moreover, the peak of Pinus percentage in MIS 5.3, 5.1 and MIS 3.3 may be closely linked by orbital and sub-orbital cycles of solar radiation and monsoonal variability. The present study of core MD981294 implied lower tempera- ture and precipitation during the lowest sea-level stage (LGM), and more visibly testified that the vegetation of the flat plain on the exposed continental shelf was dominated by intrazonal communities such as halophyte grasslands and freshwater wetlands instead of zonal steppe or semi-arid desert. All above evidence demonstrated that the fundamental changes of pollen assem- blage and their origins in Okinawa Trough since ~200 ka BP were affected by combine factors including the coastline position and climate fluctuation. Moreover, the substantial shortening of distance between shoreline and the Okinawa Trough driven by orbital insolation cycles was clearly indicated by the pollen spectra, whereas the source-area climate signal of the pollen record was largely weakened

Alteration of resting brain function by genetic variation in angiotensin converting enzyme in amnestic-type mild cognitive impairment of Chinese Han

Using a cross-sectional case–control study of amnestic-mild cognitive impairment (aMCI), we characterised the relationships among cognitive function, serum levels of angiotensin converting enzyme (ACE), brain activity, and ACE insertion or deletion (I/D) polymorphism. Forty-eight patients with aMCI and 36 well-matched normal controls were assessed by a comprehensive battery of standardized neuropsychological tests. In addition, regional homogeneity (ReHo) approaches were used to analyze blood oxygen level-dependent functional magnetic resonance imaging data on the resting state in all subjects, and genotyping of the serum ACE was measured in aMCI patients. The D carriers with aMCI patients were found to have markedly higher serum ACE levels than I homozygote carriers. Importantly, compared with the carried I homozygote group of patients with aMCI, the D carriers of aMCI patients were significantly impaired in the AVLT-delayed recall and had decreased ReHo over the bilateral precuneus, left middle occipital gyrus, right inferior parietal lobe, and right angular gyrus, whilst increased ReHo was found mainly in the left medial frontal gyrus, right paracentral lobe, and right anterior cingulate cortex. The findings indicated that ACE genotype was associated with episodic memory, serum levels of ACE, and resting-state brain activity in aMCI patients, and the findings of cognitive function and brain activity further suggests that the ACE D allele may have a specific role in semantic memory dysfunction and brain activity in aMCI

Dental scaling and lower risk of spontaneous intracranial hemorrhage

Background: —Spontaneous intracranial hemorrhage (ICH) has high fatality while has few proven treatments. We aim at investigating the association between dental scaling (DS) and the risk of ICH. Methods: —In this cohort study, two cohorts were matched by propensity score based on potential confounders. Data from ICH between January 2008 and December 2014 in Taiwan were analyzed. The subjects underwent DS at least 6 times between January 1, 2002, and December 31, 2007, while the matched controls did not undergo any DS during the same period. Cumulative incidences and hazard ratios (HRs) were calculated after adjusting for competing confounders. Results: —Each cohort consisted of 681,126 subjects. Compared with the non-DS cohort, the regular-DS cohort had a significantly lower incidence of ICH (0.8% vs 1.2%; P < 0.0001), and the adjusted hazards ratio (aHR) of 7-year ICH was 0.61 (95% confidence interval, CI, 0.59–0.63; P < 0.0001). The 30–39-year age group of the regular-DS cohort had the lowest HR (0.57; 95% CI, 0.52–0.61; P < 0.0001) of 7-year ICH when compared with similar controls. Compared with the controls, the regular-DS cohort also had significantly lower HR (0.82; 95% CI, 0.81–0.82; P < 0.0001) of 7-year hypertension. Compared with those without DS, the lowest risk of intracerebral hemorrhage was observed in the male participants with regular DS (0.43; 95% CI, 0.40–0.47; P < 0.0001). Conclusions: —Regular DS was consistently associated with lower ICH risk in subjects aged 30–59 years, which may benefit from the decreased HBP risk. DS had a potential role in the prophylaxis for ICH, a condition with a high disability or mortality

PLK1 maintains DNA methylation and cell viability by regulating phosphorylation-dependent UHRF1 protein stability

Abstract PLK1 is a key serine/threonine kinase as well as a master mitotic regulator, but it has never been reported that PLK1 regulates DNA methylation. In the present study, we for the first time found that PLK1 inhibition disrupted global DNA methylation and elevated the expression level of tumor suppressor genes. Mechanistically, we found that PLK1 interacts UHRF1 protein to induce its phosphorylation at serine 265. Phosphorylation is required for the maintenance of UHRF1 protein stability by recruiting a deubiquitinase USP7. Conversely, PLK1 inhibition decreases UHRF1 protein interaction with USP7 and activates the ubiquitin-proteasome pathway, thereby accelerating UHRF1 protein degradation. UHRF1 degradation decreases the recruitment of DNMT1 to chromatin, and decreases the level of genome-wide DNA methylation, thereby elevating the expression of tumor suppressor genes and decreasing cell viability. We here presented the first report on the novel role of PLK1 in DNA methylation maintenance through UHRF1-DNMT1 pathway, and revealed a novel anticancer mechanism of PLK1 inhibitors