We investigate electrostatic waves in a magnetopause reconnection event around a secondary electron diffusion region. Near the current sheet mid‐plane, parallel electron beam‐mode waves are modulated ...by whistler waves. We conclude that the anisotropy of energized electrons in the reconnection exhaust excites whistler waves, which produce spatially modulated electron beams through nonlinear Landau resonance, and these beams excite beam‐mode electrostatic waves. In the separatrix region, parallel propagating electrostatic waves associated with field‐aligned electron beams and perpendicular propagating electron cyclotron harmonic waves with loss cone distributions exhibit modulation frequencies in the lower‐hybrid wave (LHW) frequency range. We infer that LHWs scatter electrons to produce beams and alter loss cones to modulate electrostatic waves. The results advance our understanding about the regimes and mechanisms of electrostatic waves in reconnection, with an emphasis on their coupling with lower‐frequency electromagnetic waves.
Plain Language Summary
Magnetic reconnection is an important energy dissipation process at the Earth's dayside magnetopause. In its central region, plasmas deviate from the thermal equilibrium and form structured distribution functions, which excite plasma waves. We investigate high‐frequency electrostatic waves in an event, where the waves are associated with electron beam—plasma interaction or anisotropy of distribution functions. We find that electrostatic waves are driven and modulated by lower‐frequency waves, as the latter alters the particle distribution functions. The results help us understand how various processes couple with each other to achieve the energy dissipation.
Key Points
Parallel electron beam‐mode waves are modulated by whistler near the current sheet mid‐plane, by driving beams through Landau resonance
Electron beam‐mode and cyclotron waves are modulated by lower‐hybrid waves near separatrices, with beam and loss cone distributions
Multidimensional and large‐scale parallel manipulation of light, especially on‐demand tailoring of the working frequency and spatial phase front, is highly pursued in modern optics. Here, broadband ...tunable planar optics is demonstrated by electrically driving the nanohelix of photopatterned heliconical cholesterics. By preprogramming the initial orientation of the helixes using a dynamic‐mask photoalignment technique, spatial geometric phases can be arbitrarily encoded to the reflected light in a reconfigurable way. Due to the reversible electrically variant pitch of the heliconical superstructures, the reflective Bragg band can be precisely selected in the range from 380 to 1550 nm. In addition to wavelength selection and geometric phase modulation, spatial amplitude modulation and spin reversion can be further expected. This may offer a platform for full‐dimensional manipulation of light, including wavelength/frequency, phase, amplitude, time, and spin, thus upgrading optical information processing techniques.
A strategy for a spatial phase modulator with an electrically customizable working band is proposed via heliconical cholesterics. The photoalignment technique is adopted to realize arbitrary geometric phases. Electrically controllable heliconical superstructures enable working band selectivity over a broad range from near‐UV to near‐IR. This work enriches chiral superstructure manipulation and will upgrade present optical systems.
A novel Ebola virus (EBOV) first identified in March 2014 has infected more than 25,000 people in West Africa, resulting in more than 10,000 deaths. Preliminary analyses of genome sequences of 81 ...EBOV collected from March to June 2014 from Guinea and Sierra Leone suggest that the 2014 EBOV originated from an independent transmission event from its natural reservoir followed by sustained human-to-human infections. It has been reported that the EBOV genome variation might have an effect on the efficacy of sequence-based virus detection and candidate therapeutics. However, only limited viral information has been available since July 2014, when the outbreak entered a rapid growth phase. Here we describe 175 full-length EBOV genome sequences from five severely stricken districts in Sierra Leone from 28 September to 11 November 2014. We found that the 2014 EBOV has become more phylogenetically and genetically diverse from July to November 2014, characterized by the emergence of multiple novel lineages. The substitution rate for the 2014 EBOV was estimated to be 1.23 × 10(-3) substitutions per site per year (95% highest posterior density interval, 1.04 × 10(-3) to 1.41 × 10(-3) substitutions per site per year), approximating to that observed between previous EBOV outbreaks. The sharp increase in genetic diversity of the 2014 EBOV warrants extensive EBOV surveillance in Sierra Leone, Guinea and Liberia to better understand the viral evolution and transmission dynamics of the ongoing outbreak. These data will facilitate the international efforts to develop vaccines and therapeutics.
In halophytic plants, the high-affinity potassium transporter HKT gene family can selectively uptake K＋ in the presence of toxic concentrations of Na＋. This has so far not been well examined in ...glycophytic crops. Here, we report the characterization of SbHKTI;4, a member of the HKT gene family from Sorghum bicolor. Upon Na＋ stress, SbHKT1;4 expression was more strongly upregulated in salt-tolerant sorghum accession, correlating with a better balanced Na＋/ K＋ ratio and enhanced plant growth. Heterogeneous expression analyses in mutants of Saccharomyces cerevisiae and Arabidopsis thaliana indicated that overexpressing SbHKT1;4 resulted in hypersensitivity to Na＋ stress, and such hypersensitivity could be alleviated with the supply of elevated levels of K＋, implicating that SbHKT1;4 may mediate K＋ uptake in the presence of excessive Na＋. Further electrophysiological evidence demonstrated that SbHKT1;4 could transport Na＋ and K＋ when expressed in Xenopus laevis oocytes. The relevance of the finding that SbHKTI;4 functions to maintain optimal Na＋/K＋ balance under Na＋ stress to the breeding of salt-tolerant glycophytic crops is discussed.
The present study was performed to investigate the therapeutic performance of polymer‐lipid hybrid nanoparticles towards the delivery of lapatinib (LPT) in breast cancers. We have successfully ...developed the lapatinib‐loaded polymer‐lipid hybrid nanosystem and showed its therapeutic potential in in vitro and in vivo models of breast cancer. The nanoformulations consisted of a polymeric core (polylactide‐co‐glycolide‐D‐a‐tocopheryl polyethylene glycol 1000 succinate PLGA–TPGS), which was then enveloped by a PEGylated lipid layer (DSPE‐PEG) (PLPT) to maintain the structural integrity. The PLPT formulation controlled the drug release in pH 7.4 conditions and accelerated the release at pH 5.5 conditions. The PLPT showed a remarkable cellular internalization and efficiently killed the MCF‐7 cancer cells in a time‐ and concentration‐dependent manner. Moreover, LPT‐loaded nanoparticles effectively induced apoptosis of cancer cells than compared to free LPT. Pharmacokinetic data suggested that nanoparticles could significantly enhance the blood circulation time of LPT by reducing the uptake by a reticuloendothelial system (RES). The prolonged blood circulation of PLPT could allow the preferential accumulation of drug in the tumor tissues. Importantly, PLPT significantly reduced the tumor burden of cancerous mice and effectively controlled the tumor cell proliferation. TUNEL assay further showed a greater apoptosis of tumor tissues in the PLPT treated mice group. Our results suggest that the use of a hybrid system may allow a decrease in the dosage regimen without the loss of therapeutic effect. Overall, lapatinib‐loaded hybrid nanoparticles hold great potential for achieving an optimal therapeutic effect in breast cancer treatment. The present anticancer drug delivery system could be potentially applied for the treatment of other cancers.
The present study was performed to investigate the therapeutic performance of polymer‐lipid hybrid nanoparticles towards the delivery of lapatinib (LPT) in breast cancers. We have successfully developed the lapatinib‐loaded polymer‐lipid hybrid nanosystem and showed its therapeutic potential in in vitro and in vivo models of breast cancer.
Although inhibitors targeting tumor angiogenic pathway have provided improvement for clinical treatment in patients with various solid tumors, the still very limited anti‐cancer efficacy and acquired ...drug resistance demand new agents that may offer better clinical benefits. In the effort to find a small molecule potentially targeting several key pathways for tumor development, we designed, discovered and evaluated a novel multi‐kinase inhibitor, CS2164. CS2164 inhibited the angiogenesis‐related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα and c‐Kit), mitosis‐related kinase Aurora B and chronic inflammation‐related kinase CSF‐1R in a high potency manner with the IC50 at a single‐digit nanomolar range. Consequently, CS2164 displayed anti‐angiogenic activities through suppression of VEGFR/PDGFR phosphorylation, inhibition of ligand‐dependent cell proliferation and capillary tube formation, and prevention of vasculature formation in tumor tissues. CS2164 also showed induction of G2/M cell cycle arrest and suppression of cell proliferation in tumor tissues through the inhibition of Aurora B‐mediated H3 phosphorylation. Furthermore, CS2164 demonstrated the inhibitory effect on CSF‐1R phosphorylation that led to the suppression of ligand‐stimulated monocyte‐to‐macrophage differentiation and reduced CSF‐1R+ cells in tumor tissues. The in vivo animal efficacy studies revealed that CS2164 induced remarkable regression or complete inhibition of tumor growth at well‐tolerated oral doses in several human tumor xenograft models. Collectively, these results indicate that CS2164 is a highly selective multi‐kinase inhibitor with potent anti‐tumor activities against tumor angiogenesis, mitosis and chronic inflammation, which may provide the rationale for further clinical assessment of CS2164 as a therapeutic agent in the treatment of cancer.
In this paper, we designed, discovered, and evaluated a novel orally active multi‐kinase inhibitor, CS2164, which simultaneously inhibits the angiogenesis‐related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFR‐alpha, and c‐Kit), mitosis‐related kinase Aurora B, and chronic inflammatory‐related kinase CSF‐1R in a high potency manner with the IC50 at a single digital nanomolar range. Through both in vitro cell based studies and in vivo animal xenograft models, we provide solid preclinical evidence for the potent anti‐tumor efficacy of CS2164.
Background
Arrhythmia is not uncommon among pulmonary hypertension (PH) population, and may be associated with disease severity.
Hypothesis
To investigate different spectrums and prevalence of ...arrhythmias in different clinical PH groups in Chinese population.
Methods
Patients diagnosed with PH between April 15, 2019, and August 2, 2021, were enrolled prospectively. The prevalence of different types of arrhythmias in PH patients were calculated. Logistic regression analyses were conducted to determine independent predictors for arrhythmia.
Results
One thousand patients were enrolled. The prevalence of any arrhythmia, sinus node dysfunction, sinus tachycardia, atrial fibrillation, atrial flutter, other types of atrial tachycardia, atrioventricular block, and ventricular tachycardia is 44.4%, 12.2%, 15.2%, 8.1%, 4.1%, 10.2%, 7.1%, and 2.5%. Logistic regression analyses revealed that older age and larger right ventricle (odds ratio: 1.111 and 1.095, p < .05) were independently related with higher probability of supraventricular arrhythmia; Complicating with coronary artery disease, larger right ventricle, and increased left ventricular end‐diastolic diameter (odds ratio: 19.540, 1.106, and 1.085, p < .05) were independently correlated with sinus node dysfunction/atrioventricular block in patients with pulmonary arterial hypertension.
Conclusions
Nearly half of PH patients experienced at least one type of arrhythmia. The most common seen arrhythmias were supraventricular arrhythmia, sinus tachycardia, and sinus node dysfunction. Older age and larger right ventricle were independently related with higher probability of supraventricular arrhythmia; Complicating with coronary artery disease, larger right ventricle and increased left ventricular end‐diastolic diameter were independently correlated with higher probability of sinus node dysfunction/atrioventricular block in patients with pulmonary arterial hypertension.
Ubiquitin-conjugating enzyme E2S (UBE2S), a family of E2 protein in the ubiquitination process, is involved in development of various cancers. However, its role in lung adenocarcinoma, has not been ...well elucidated. In this report, we attempted to investigate expression and function of UBE2S in lung adenocarcinoma. Up-regulation of UBE2S at mRNA, and protein level, was observed in human cancer tissues and lung adenocarcinoma cells. Higher UBE2S expression correlated with poorer prognosis of lung adenocarcinoma patients. UBE2S expression was efficiently suppressed by lentivirus-mediated shRNA strategy in A549 cells, and UBE2S silencing led to reduced cell proliferation, colony formation, and enhanced apoptosis. Inverse results were observed, in UBE2S over-expressed H1299 cells. Microarray analysis indicated that a large number of genes were regulated by UBE2S, and p53 signaling pathway may be critical, to the role of UBE2S in cancer development. Together, UBE2S could be a potential target for lung adenocarcinoma. BMB Reports 2018; 51(12): 642-647
Analyzing the genetic diversity and selection characteristics of sheep (Ovis aries) holds significant value in understanding their environmental adaptability, enhancing breeding efficiency, and ...achieving effective conservation and rational utilization of genetic resources. In this study, we utilized Illumina Ovine SNP 50 K BeadChip data from four indigenous sheep breeds from the southern margin of the Taklamakan Desert (Duolang sheep: n = 36, Hetian sheep: n = 74, Kunlun sheep: n = 27, Qira black sheep: n = 178) and three foreign meat sheep breeds (Poll Dorset sheep: n = 105, Suffolk sheep: n = 153, Texel sheep: n = 150) to investigate the population structure, genetic diversity, and genomic signals of positive selection within the indigenous sheep. According to the Principal component analysis (PCA), the Neighbor-Joining tree (NJ tree), and Admixture, we revealed distinct clustering patterns of these seven sheep breeds based on their geographical distribution. Then used Cross Population Extended Haplotype Homozygosity (XP-EHH), Fixation Index (F.sub.ST), and Integrated Haplotype Score (iHS), we identified a collective set of 32 overlapping genes under positive selection across four indigenous sheep breeds. These genes are associated with wool follicle development and wool traits, desert environmental adaptability, disease resistance, reproduction, and high-altitude adaptability. This study reveals the population structure and genomic selection characteristics in the extreme desert environments of native sheep breeds from the southern edge of the Taklimakan Desert, providing new insights into the conservation and sustainable use of indigenous sheep genetic resources in extreme environments. Additionally, these findings offer valuable genetic resources for sheep and other mammals to adapt to global climate change.
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