Breast cancer is now the most frequently diagnosed malignancy, and metastasis remains the leading cause of death in breast cancer. However, little is known about the dynamic changes during the ...evolvement of dissemination. In this study, 65 968 cells from four patients with breast cancer and paired metastatic axillary lymph nodes are profiled using single‐cell RNA sequencing (scRNA‐seq) and spatial transcriptomics. A disseminated cancer cell cluster with high levels of oxidative phosphorylation (OXPHOS), including the upregulation of cytochrome C oxidase subunit 6C and dehydrogenase/reductase 2, is identified. The transition between glycolysis and OXPHOS when dissemination initiates is noticed. Furthermore, this distinct cell cluster is distributed along the tumor's leading edge. The findings here are verified in three different cohorts of breast cancer patients and an external scRNA‐seq dataset, which includes eight patients with breast cancer and paired metastatic axillary lymph nodes. This work describes the dynamic metabolic evolvement of early disseminated breast cancer and reveals a switch between glycolysis and OXPHOS in breast cancer cells as the early event during lymph node metastasis.
By single‐cell RNA sequencing and spatial transcriptomics, the early early‐disseminated breast cancer cells are found to travel from the border of primary tumor to axillary lymph nodes. During this metastasis, a switch between glycolysis and oxidative phosphorylation occurs in early disseminated breast cancer cells, indicating an interesting dynamic metabolic evolvement.
Continuous‐wave (CW) room‐temperature (RT) laser operation with low energy consumption is an ultimate goal for electrically driven lasers. A monolithically integrated perovskite laser in a chip‐level ...fiber scheme is ideal. However, because of the well‐recognized air and thermal instabilities of perovskites, laser action in a perovskite has mostly been limited to either pulsed or cryogenic‐temperature operations. Most CW laser operations at RT have had poor durability. Here, crystal fibers that have robust and high‐heat‐load nature are shown to be the key to enabling the first demonstration of ultralow‐threshold CW RT laser action in a compact, monolithic, and inexpensive crystal fiber/nanoperovskite hybrid architecture that is directly pumped with a 405 nm diode laser. Purcell‐enhanced light–matter coupling between the atomically smooth fiber microcavity and the perovskite nanocrystallites gain medium enables a high Q (≈1500) and a high β (0.31). This 762 nm laser outperforms previously reported structures with a record‐low threshold of 132 nW and an optical‐to‐optical slope conversion efficiency of 2.93%, and it delivers a stable output for CW and RT operation. These results represent a significant advancement toward monolithic all‐optical integration.
Purcell‐enhanced light–matter coupling between an atomically smooth fiber microcavity and perovskite gain nanocrystallites enables a high Q (≈1500) and a high β (0.31), outperforming previously reported structures with a 132 nW record‐low threshold. This is thought to be the first demonstration of monolithic integration of a perovskite laser into a compact and inexpensive fiber platform.
Another evidence is that CD4+ cells in the late stage of AIDS patients, whose CD4+ cell counts already reach zero or close to zero, can recover after cART treatment. ...the strategy of TCDT is ...applicable. ...although CD4+ cells have reached zero in the late stage of AIDS patients, the patients will die rather than cure, due to a large number of free viruses and immunodeficiency in the absence of cART treatment. ...to remove free viruses, cART is a very important prerequisite for TCDT. ...what will we do if CD4+ cannot reach zero, and there are some residual CD4+ cells after anti-CD4 antibody treatment? Because Nef production requires viral replication, cART can inhibit Nef production. ...in the early stage of TCDT therapy, cART must be applied to inhibit HIV replication and deplete free viruses as much as possible. ...in the HIV-infected cells, around 93% of the pre-viruses are replication-defective, and only the remaining 7% can replicate.
The selection of trajectory and speed is a crucial factor in automobile driving behavior. However, almost all the research objects of existing Driver models are developed for driving on city streets ...and general highways but are not applicable to driving simulations on minor traffic roads with complex shapes, in particular. Therefore, according to the practical automobile driving processes and characteristics in the real world, this paper proposed a trajectory calculation strategy, which we named as "selecting trajectory point on a preview cross section." According to this strategy, objective functions was established to describe the different selection patterns of "trajectory and speed" of drivers. Constraint expressions were then designed on the basis of the roadway geometry and pavement condition, passenger car performance and ride comfort. A rolling-horizon algorithm for simultaneous solving, i.e., "target trajectory-target speed," was proposed. Eventually, validations of the proposed model were conducted using a race circuit and a complex mountain road as a simulation example, and the results indicated that the anticipated computational results could be obtained using the proposed decision-making model and algorithm. The result also showed a fairly good agreement with the trajectory and speed of a car on a practical circuit and mountain road.
Microspherule protein 1 (Mcrs1) is a component of the nonspecific lethal (NSL) complex and the chromatin remodeling INO80 complex, which participates in transcriptional regulation during mitosis. ...Here, we investigate the roles of Mcrs1 during female meiosis in mice. We demonstrate that Mcrs1 is a novel regulator of the meiotic G2/M transition and spindle assembly in mouse oocytes. Mcrs1 is present in the nucleus and associates with spindle poles and chromosomes of oocytes during meiosis I. Depletion of Mcrs1 alters HDAC2‐mediated H4K16ac, H3K4me2, and H3K9me2 levels in nonsurrounded nucleolus (NSN)‐type oocytes, and reduces CDK1 activity and cyclin B1 accumulation, leading to G2/M transition delay. Furthermore, Mcrs1 depletion results in abnormal spindle assembly due to reduced Aurora kinase (Aurka and Aurkc) and Kif2A activities, suggesting that Mcrs1 also plays a transcription‐independent role in regulation of metaphase I oocytes. Taken together, our results demonstrate that the transcription factor Mcrs1 has important roles in cell cycle regulation and spindle assembly in mouse oocyte meiosis.
Synopsis
Microspherule protein 1 (Mcrs1) is involved in meiotic resumption in female mice by regulating histone modifications and the maturation promotion factor (MPF) in germinal vesicle (GV)‐stage oocytes. It also interacts with Aurora kinases to regulate spindle assembly during metaphase I.
Mcrs1 regulates CDK1 activity and cyclin B1 accumulation in oocyte meiosis.
Mcrs1 regulates histone modifications and transcriptional activity in GV oocytes.
Mcrs1 regulates meiotic spindle assembly via the Aurora kinases in oocytes.
Microspherule protein 1 is involved in meiotic resumption in female mice by regulating histone modifications and the maturation promotion factor (MPF) in germinal vesicle (GV)‐stage oocytes. It also interacts with Aurora kinases to regulate spindle assembly during metaphase I.
The expansion of anatomically modern humans (AMHs) from Africa around 65,000 to 45,000 y ago (ca. 65 to 45 ka) led to the establishment of present-day non-African populations. Some ...paleoanthropologists have argued that fossil discoveries from Huanglong, Zhiren, Luna, and Fuyan caves in southern China indicate one or more prior dispersals, perhaps as early as ca. 120 ka. We investigated the age of the human remains from three of these localities and two additional early AMH sites (Yangjiapo and Sanyou caves, Hubei) by combining ancient DNA (aDNA) analysis with a multimethod geological dating strategy. Although U-Th dating of capping flowstones suggested they lie within the range ca. 168 to 70 ka, analyses of aDNA and direct AMS
C dating on human teeth from Fuyan and Yangjiapo caves showed they derive from the Holocene. OSL dating of sediments and AMS
C analysis of mammal teeth and charcoal also demonstrated major discrepancies from the flowstone ages; the difference between them being an order of magnitude or more at most of these localities. Our work highlights the surprisingly complex depositional history recorded at these subtropical caves which involved one or more episodes of erosion and redeposition or intrusion as recently as the late Holocene. In light of our findings, the first appearance datum for AMHs in southern China should probably lie within the timeframe set by molecular data of ca. 50 to 45 ka.
Heterogeneous ribonucleoprotein (hnRNP) A1 is a member of the A/B subfamily of ubiquitously expressed hnRNPs, which have a wide variety of functions in gene expression and signal transduction. To ...investigate the biological function and clinical significance of hnRNP A1 in hepatocellular carcinoma (HCC), we measured hnRNP A1 expression in four HCC cell lines and two independent cohorts of HCC patients. We found that hnRNP A1 was overexpressed in the highly metastatic HCC cell lines and in tumor tissues of patients with recurrent HCC. Knockdown of hnRNP A1 in highly metastatic HCC cells caused a significant decrease in cell invasion, while upregulation of hnRNP A1 in poorly metastatic HCC cells led to a significant increase in their invasive capacity. We found that this effect may occur through the regulation of CD44v6 expression by hnRNP A1 in HCC cells. Both quantitative reverse transcription‐polymerase chain reaction (qRT‐RCR) and immunohistochemistry revealed that hnRNP A1 was upregulated in HCC tissues and coincided with overexpression of CD44v6. HCC patients with high hnRNP A1 tended to have higher levels of CD44v6, shorter overall survival (OS) and higher rates of tumor recurrence. Multivariate analyses revealed that hnRNP A1 alone or in combination with CD44v6 were independent prognostic indicators for OS and time to recurrence and have potential as therapeutic targets. In conclusion, overexpression of hnRNP A1 promotes HCC invasion by regulating the level of CD44v6 and indicates a poor prognosis for HCC patients after curative resection.
What's new?
This study indicates that hnRNP A1 is positively related to the metastatic potential of hepatocellular carcinoma (HCC) cells and that overexpression of hnRNP A1 promotes HCC cells invasion through the regulation of CD44v6 expression. Overexpression of hnRNP A1 predicts lower overall survivor and higher recurrence rates for HCC patients after curative resection. The expression levels of hnRNP A1 alone or in combination with CD44v6 in HCC patients are important because they may provide not only a predictor for HCC prognosis but also a therapeutic target for future studies.
GW190425 is the second neutron star merger event detected by the Advanced LIGO/Virgo detectors. If interpreted as a double neutron star merger, the total gravitational mass is substantially larger ...than that of the binary systems identified in the Galaxy. In this work we analyze the gravitational-wave data within the neutron star-black hole merger scenario. For the black hole, we yield a mass of and an aligned spin of . As for the neutron star we find a mass of and the dimensionless tidal deformability of . These parameter ranges are for 90% credibility. The inferred masses of the neutron star and the black hole are not in tension with current observations and we suggest that GW190425 is a viable candidate of a neutron star-black hole merger event. Benefitting from the continual enhancement of the sensitivities of the advanced gravitational detectors and the increase of the number of the observatories, similar events are anticipated to be much more precisely measured in the future and the presence of black holes below the so-called mass gap will be unambiguously clarified. If confirmed, the mergers of neutron stars with (quickly rotating) low-mass black holes are likely important production sites of the heaviest r-process elements.
Purpose
The trajectory of a vehicle is comprehensively affected by the interactions between the vehicle, the driving behavior, and the road environment. High-risk driving behaviors and accident-prone ...road sections can be identified based on the relationship between the trajectory and road geometry. Previous related studies mostly focused on the trajectory deviation at a few points on the road, which cannot capture the continuous variation of the trajectory in an entire curve, and seldom considered the trajectory characteristics along curves with large deflection angles. The aim of this study is to investigate the trajectories passenger cars take on two-lane mountain roads and thus to determine the track patterns and its relevant risks.
Methods
Field driving experiments were performed on four two-lane mountain highways, and vehicle trajectories under natural driving conditions were acquired. The continuous change in the lateral deviation rate of the trajectory was also determined by putting the measured trajectories into the coordinate frame together with the edge line of roadway. Further, the morphological features of the vehicle trajectory and how it is affected by the highway geometry were analyzed.
Results and conclusions
The following were observed: i) Typical track patterns were determined according to features of LDRT profiles, four patterns for left-hand bends and five patterns for right-hand bends, which can be used to identify crash prone position and reveal the mechanism of crash. ii) Inertia may cause the vehicle to move too close to the outer side of the curve after a cut, for which reason the driver has to correct the trajectory, although overcorrection may move the vehicle into the oncoming lane. iii) A higher speed at curve entry adopt by the driver could result in a larger encroachment into opposite lane or shoulder. iv) The smaller the radius of the horizontal curve, the more frequently the trajectory entered the oncoming lane. These findings could provide a better understanding of the track behavior of passenger cars, judge the safety implications of driver behavior, and thus identify crash prone positioning and the potential mechanisms of head-on crashes, run-off-road and guardrail collisions.
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