EMX2 inhibits clear cell renal cell carcinoma progress via modulating Akt/FOXO3a pathway.

Empty spiracles homeobox 2 (EMX2) is initially identified as a key transcription factor that plays an essential role in the regulation of neuronal development and some brain disorders. Recently, several studies emphasized that EMX2 could as a tumor suppressor, but its role in human clear cell renal cell carcinoma (ccRCC) remains unclear. In the present study, we investigated the role and underlying mechanism of EMX2 in the regulation of ccRCC progress. Our results demonstrated that EMX2 expression was markedly decreased in ccRCC tissues and cell lines, and low EMX2 expression predicted the poor prognosis of ccRCC patients. In addition, forced expression of EMX2 significantly inhibited the cell growth, migration, and invasion in vitro, as well as ccRCC tumor growth in nude mice, via, at least in part, regulating Akt/FOXO3a pathway. In detail, EMX2 could attenuate the phosphorylation levels of Akt and FOXO3a, and increase FOXO3a expression without affecting total Akt expression in vivo and in vitro. Meanwhile, shRNA-mediated knockdown of FOXO3a expression could obviously attenuate the effects of EMX2 on cell growth, migration, invasion, and tumor growth. Furthermore, EMX2 could significantly attenuate the interaction between Akt and FOXO3a. Taken together, our results demonstrated that EMX2 could inhibit ccRCC progress through, at least in part, modulating Akt/FOXO3a signaling pathway, thus representing a novel role and underlying mechanism of EMX2 in the regulation of ccRCC progress.

ß-Arrestin2 promotes docetaxel resistance of castration-resistant prostate cancer via promoting hnRNP A1-mediated PKM2 alternative splicing.

PURPOSE: To investigate the influence of ß-arrestin2 on the docetaxel resistance in castration-resistant prostate cancer (CRPC) and elucidate the underlying molecular mechanisms. METHODS: PC3 and DU145 cells with stable ß-arrestin2 overexpression and C4-2 cells with stable ß-arrestin2 knockdown, were constructed via using lentivirus and puromycin selection. MTT and colony formation assays were carried out to investigate the effect of ß-arrestin2 expression on the docetaxel resistance of CRPC cells. Glycolysis analysis was used to assess the glycolytic capacity modulated by ß-arrestin2. GO enrichment analysis, gene set enrichment analysis and Spearman correlation test were carried out to explore the potential biological function and mechanism via using public data from GEO and TCGA. The expressions of PKM2, Phospho-PKM2, Phospho-ERK1/2 and hnRNP A1 were detected by western blot. Functional blocking experiments were carried out to confirm the roles of PKM2 and hnRNP A1 in the regulation of ß-arrestin2's biological functions via silencing PKM2 or hnRNP A1 expression in cells with stable ß-arrestin2 overexpression. Finally, nude mice xenograft models were established to confirm the experimental results of cell experiments. RESULTS: ß-Arrestin2 significantly decreased the sensitivity of CRPC cells to docetaxel stimulation, through enhancing the phosphorylation and expression of PKM2. Additionally, ß-arrestin2 increased PKM2 phosphorylation via the ERK1/2 signaling pathway and induced PKM2 expression in a post-transcriptional manner through an hnRNP A1-dependent PKM alternative splicing mechanism, rather than by inhibiting its ubiquitination degradation. CONCLUSION: Our findings indicate that the ß-arrestin2/hnRNP A1/PKM2 pathway could be a promising target for treating docetaxel-resistant CRPC.

A critical appraisal of urolithiasis clinical practice guidelines using the AGREE II instrument.

Background: The Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument was developed to improve the methodological quality of clinical practice guidelines (CPGs). High-quality guidelines can provide reliable recommendations for different clinical issues. Currently, there is no quality appraisal of CPGs for urolithiasis. This study evaluated the quality of evidence-based CPGs for urolithiasis and provided new insights into improving guideline quality on urolithiasis. Methods: Systematic reviews were conducted to identify urolithiasis CPGs in PubMed, electronic databases, and websites of medical associations from January 2009 to July 2022. The quality of included CPGs was evaluated by four reviewers using the AGREE II instrument. Subsequently, the scores of all domains in the AGREE II instrument were calculated. Results: A total of 19 urolithiasis CPGs were identified for review: seven from Europe, six from USA, three from international union, two from Canada, and one from Asia. The agreement among reviewers was rated good [intraclass correlation coefficient (ICC), 0.806; 95% CI: 0.779-0.831]. The domains with the highest scores were scope and purpose (69.7%, 54.2-86.1%) and clarity of presentation (76.8%, 59.7-90.3%). The domains of stakeholder involvement (44.9%, 19.4-84.7%) and applicability (48.5%, 30.2-72.9%) gained the lowest score. Only five guidelines (26.3%) were considered "strongly recommended". Conclusions: The overall quality of the eligible CPGs was relatively high; however, future work is still needed in the domains of rigor of development, editorial independence, applicability, and stakeholder involvement.

A Flexible Tribotronic Artificial Synapse with Bioinspired Neurosensory Behavior.

As key components of artificial afferent nervous systems, synaptic devices can mimic the physiological synaptic behaviors, which have attracted extensive attentions. Here, a flexible tribotronic artificial synapse (TAS) with bioinspired neurosensory behavior is developed. The triboelectric potential generated by the external contact electrification is used as the ion-gel-gate voltage of the organic thin film transistor, which can tune the carriers transport through the migration/accumulation of ions. The TAS successfully demonstrates a series of synaptic behaviors by external stimuli, such as excitatory postsynaptic current, paired-pulse facilitation, and the hierarchical memory process from sensory memory to short-term memory and long-term memory. Moreover, the synaptic behaviors remained stable under the strain condition with a bending radius of 20 mm, and the TAS still exhibits excellent durability after 1000 bending cycles. Finally, Pavlovian conditioning has been successfully mimicked by applying force and vibration as food and bell, respectively. This work demonstrates a bioinspired flexible artificial synapse that will help to facilitate the development of artificial afferent nervous systems, which is great significance to the practical application of artificial limbs, robotics, and bionics in future.

Friction-Dominated Carrier Excitation and Transport Mechanism for GaN-Based Direct-Current Triboelectric Nanogenerators.

The semiconductor triboelectric nanogenerator (TENG) based on the tribovoltaic effect has the characteristics of direct current and high current density, but the energy transfer and conversion mechanism is not completely clear. Here, a series of gallium nitride (GaN)-based semiconductor direct-current TENGs (SDC-TENGs) are investigated for clarifying the carrier excitation and transport mechanism. During the friction process, the external output current always flows from GaN to silicon or aluminum, regardless of the direction of the built-in electric field, because of the semiconductor types. These results reveal that the carrier transport direction is dominated by the interfacial electric field formed by triboelectrification, which is also verified under different bias voltages. Moreover, the characteristics dependent on the frictional force have been systematically investigated under different normal forces and frictional modes. The open-circuit voltage and short-circuit current of SDC-TENG are both increased with a larger frictional force, which shows that the more severe friction results in both a larger interface electric field and more excited carriers. The maximum voltage can reach 25 V for lighting up a series of LEDs, which is enhanced by four times compared to the cutting-edge reported SDC-TENGs. This work has clarified the friction-dominated carrier excitation and transport mechanism for the tribovoltaic effect, which demonstrates the great potential of semiconductor materials for frictional energy recovery and utilization.

Semiconductor Contact-Electrification-Dominated Tribovoltaic Effect for Ultrahigh Power Generation.

The semiconductor direct-current triboelectric nanogenerator (SDC-TENG) based on the tribovoltaic effect is promising for developing a new semiconductor energy technology with high power density. Here, the first SDC-TENG built using gallium nitride (GaN) and bismuth telluride (Bi2 Te3 ) for ultrahigh-power generation is reported. During the friction process, an additional interfacial electric field is formed by continuous contact electrification (CE), and abundant electron-hole pairs are excited and move directionally to form a junction current that is always internally from Bi2 Te3 to GaN, regardless of the semiconductor type. The peak open-circuit voltage can reach up to 40 V and the power density is 11.85 W m-2 (average value is 9.23 W m-2 ), which is approximately 200 times higher than that of previous centimeter-level SDC-TENGs. Moreover, compared to traditional polymer TENGs under the same conditions, the average power density is remarkably improved by over 40 times. This study provides the first evidence of CE on the tribovoltaic effect and sets the normalized power density record for TENGs, which demonstrates a great potential of the tribovoltaic effect for energy harvesting and sensing.