Ultrasound Stimulation Modulates Voltage-Gated Potassium Currents Associated With Action Potential Shape in Hippocampal CA1 Pyramidal Neurons

Potassium channels (K+) play an important role in the regulation of cellular signaling. Dysfunction of potassium channels is associated with several severe ion channels diseases, such as long QT syndrome, episodic ataxia and epilepsy. Ultrasound stimulation has proven to be an effective non-invasive tool for the modulation of ion channels and neural activity. In this study, we demonstrate that ultrasound stimulation enables to modulate the potassium currents and has an impact on the shape modulation of action potentials (AP) in the hippocampal pyramidal neurons using whole-cell patch-clamp recordings in vitro. The results show that outward potassium currents in neurons increase significantly, approximately 13%, in response to 30 s ultrasound stimulation. Simultaneously, the increasing outward potassium currents directly decrease the resting membrane potential (RMP) from −64.67 ± 1.10 mV to −67.51 ± 1.35 mV. Moreover, the threshold current and AP fall rate increase while the reduction of AP half-width and after-hyperpolarization peak time is detected. During ultrasound stimulation, reduction of the membrane input resistance of pyramidal neurons can be found and shorter membrane time constant is achieved. Additionally, we verify that the regulation of potassium currents and shape of action potential is mainly due to the mechanical effects induced by ultrasound. Therefore, ultrasound stimulation may offer an alternative tool to treat some ion channels diseases related to potassium channels

Exploring the key factors affecting the seasonal variation of phytoplankton in the coastal Yellow Sea

Marine phytoplankton play crucial roles in the ocean’s biological pump and have great impacts on global biogeochemical cycles, yet the knowledge of environmental variables controlling their seasonal dynamics needs to be improved further, especially in the coastal ecosystems. In order to explore the determinants affecting the seasonal variation of phytoplankton, here we conducted three surveys during spring, summer and autumn along the coastal Yellow Sea. Among the phytoplankton community, 49 species of diatoms and 9 species of dinoflagellates were observed in spring, 63 species of diatoms and 10 species of dinoflagellates in summer, and 62 species of diatoms and 11 species of dinoflagellates in autumn. These results thus suggested that there were obvious differences in the number of species across the three seasons, of which diatoms were the most diverse group, followed by dinoflagellates. Additionally, diatoms were the most dominant species of the phytoplankton community and varied largely during different seasons. According to the redundancy analysis, the abundance of phytoplankton community was mainly related to water temperature and dissolved inorganic nitrogen (DIN) during the three seasons, indicating that water temperature and DIN could be the key factors controlling the seasonal variability of phytoplankton community along the coastal Yellow Sea. Also, significant correlations were observed between phytoplankton abundance and heavy metals Zn, As, and Hg during the three seasons, suggesting that these metals also had potential influences on the seasonal dynamics of phytoplankton community in the coastal Yellow Sea

Study on a High-Accuracy Real-Time Algorithm to Estimate SOC of Multiple Battery Cells Simultaneously

In traditional battery equalization strategy, open-circuit voltage (OCV) of battery cells was used to judge the difference of SOC between them. However, OCV is not only determined by SOC but also influenced by internal resistance, polarization voltage, capacity, and other nonlinear factors. As a result, OCV is not an ideal indicator of SOC differences, especially in transient conditions. In order to control battery consistency accurately, it is best to use SOC directly as standard for battery consistency judgment and control. To achieve this, an algorithm that can estimate SOC of multiple battery cells simultaneously with low computational complexity and high accuracy is needed. Limited by computing speed of Battery Control Unit (BCU), existing SOC estimation method is hard to estimate SOC of each battery cell simultaneously with high accuracy. In this research, a new SOC estimation strategy was proposed to estimate SOC of multiple battery cells simultaneously for battery equalization control. Battery model is established based on experimental data, and a processor-in-the-loop test system was established to verify the actual performance of the proposed algorithm. Results of simulation and test indicate that the proposed algorithm can estimate SOC of multiple battery cells simultaneously and achieved good real-time performance and high accuracy

Shp2 in uterine stromal cells critically regulates on time embryo implantation and stromal decidualization by multiple pathways during early pregnancy.

Approximately 75% of failed pregnancies are considered to be due to embryo implantation failure or defects. Nevertheless, the explicit signaling mechanisms governing this process have not yet been elucidated. Here, we found that conditional deletion of the Shp2 gene in mouse uterine stromal cells deferred embryo implantation and inhibited the decidualization of stromal cells, which led to embryonic developmental delay and to the death of numerous embryos mid-gestation, ultimately reducing female fertility. The absence of Shp2 in stromal cells increased the proliferation of endometrial epithelial cells, thereby disturbing endometrial epithelial remodeling. However, Shp2 deletion impaired the proliferation and polyploidization of stromal cells, which are distinct characteristics of decidualization. In human endometrial stromal cells (hESCs), Shp2 expression gradually increased during the decidualization process. Knockout of Shp2 blocked the decidual differentiation of hESCs, while Shp2 overexpression had the opposite effect. Shp2 knockout inhibited the proliferation of hESCs during decidualization. Whole gene expression profiling analysis of hESCs during the decidualization process showed that Shp2 deficiency disrupted many signaling transduction pathways and gene expression. Analyses of hESCs and mouse uterine tissues confirmed that the signaling pathways extracellular regulated protein kinases (ERK), protein kinase B (AKT), signal transducer and activator of transcription 3 (STAT3) and their downstream transcription factors CCAAT/enhancer binding protein β (C/EBPβ) and Forkhead box transcription factor O1 (FOXO-1) were involved in the Shp2 regulation of decidualization. In summary, these results demonstrate that Shp2 plays a crucial role in stromal decidualization by mediating and coordinating multiple signaling pathways in uterine stromal cells. Our discovery possibly provides a novel key regulator of embryo implantation and novel therapeutic target for pregnancy failure

Deciphering a critical role of uterine epithelial SHP2 in parturition initiation at single cell resolution.

The timely onset of female parturition is a critical determinant for pregnancy success. The highly heterogenous maternal decidua has been increasingly recognized as a vital factor in setting the timing of labor. Despite the cell type specific roles in parturition, the role of the uterine epithelium in the decidua remains poorly understood. This study uncovers the critical role of epithelial SHP2 in parturition initiation via COX1 and COX2 derived PGF2α leveraging epithelial specific Shp2 knockout mice, whose disruption contributes to delayed parturition initiation, dystocia and fetal deaths. Additionally, we also show that there are distinct types of epithelium in the decidua approaching parturition at single cell resolution accompanied with profound epithelium reformation via proliferation. Meanwhile, the epithelium maintains the microenvironment by communicating with stromal cells and macrophages. The epithelial microenvironment is maintained by a close interaction among epithelial, stromal and macrophage cells of uterine stromal cells. In brief, this study provides a previously unappreciated role of the epithelium in parturition preparation and sheds lights on the prevention of preterm birth

Progress and perspectives of perioperative immunotherapy in non-small cell lung cancer

Lung cancer is one of the leading causes of cancer-related death. Lung cancer mortality has decreased over the past decade, which is partly attributed to improved treatments. Curative surgery for patients with early-stage lung cancer is the standard of care, but not all surgical treatments have a good prognosis. Adjuvant and neoadjuvant chemotherapy are used to improve the prognosis of patients with resectable lung cancer. Immunotherapy, an epoch-defining treatment, has improved curative effects, prognosis, and tolerability compared with traditional and ordinary cytotoxic chemotherapy, providing new hope for patients with non-small cell lung cancer (NSCLC). Immunotherapy-related clinical trials have reported encouraging clinical outcomes in their exploration of different types of perioperative immunotherapy, from neoadjuvant immune checkpoint inhibitor (ICI) monotherapy, neoadjuvant immune-combination therapy (chemoimmunotherapy, immunotherapy plus antiangiogenic therapy, immunotherapy plus radiotherapy, or concurrent chemoradiotherapy), adjuvant immunotherapy, and neoadjuvant combined adjuvant immunotherapy. Phase 3 studies such as IMpower 010 and CheckMate 816 reported survival benefits of perioperative immunotherapy for operable patients. This review summarizes up-to-date clinical studies and analyzes the efficiency and feasibility of different neoadjuvant therapies and biomarkers to identify optimal types of perioperative immunotherapy for NSCLC

Superconductivity above 70 K observed in lutetium polyhydrides

The binary polyhydrides of heavy rare earth lutetium that shares a similar valence electron configuration to lanthanum have been experimentally discovered to be superconductive. The lutetium polyhydrides were successfully synthesized at high pressure and high temperature conditions using a diamond anvil cell in combinations with the in-situ high pressure laser heating technique. The resistance measurements as a function of temperature were performed at the same pressure of synthesis in order to study the transitions of superconductivity (SC). The superconducting transition with a maximum onset temperature (Tc) 71 K was observed at pressure of 218 GPa in the experiments. The Tc decreased to 65 K when pressure was at 181 GPa. From the evolution of SC at applied magnetic fields, the upper critical field at zero temperature {\mu}0Hc2(0) was obtained to be ~36 Tesla. The in-situ high pressure X-ray diffraction experiments imply that the high Tc SC should arise from the Lu4H23 phase with Pm-3n symmetry that forms a new type of hydrogen cage framework different from those reported for previous light rare earth polyhydride superconductors