Interference-induced generation of a chirp-free short isolated attosecond pulse in the water window region with multicolor laser fields.

Compensating for the intrinsic attosecond chirp (atto-chirp) of wideband high-order harmonics in the water window region is a significant challenge, in order to obtain isolated attosecond pulses (IAPs) with a width of tens of attoseconds (as). Here, we propose to realize the generation of IAP with duration as short as 20 as, central energy of 365 eV, and bandwidth exceeding 150 eV from chirp-free high harmonics generated by a four-color driving laser, without the necessity for atto-chirp compensation with natural materials. Unlike any other gating methods that an IAP arises from only one electron ionization event, we take advantage of the interference between harmonic radiation produced by multiple ionizing events. We further demonstrate that such chirp-free short IAP survives after taking account of macroscopic propagation effects. Given that the synthesized multicolor laser field can also effectively increase the harmonic flux, this work provides a practical way for experiments to generate the broad bandwidth chirp-free IAPs in the water window region.

Loureirin A Promotes Cell Differentiation and Suppresses Migration and Invasion of Melanoma Cells via WNT and AKT/mTOR Signaling Pathways.

Resina Draconis is a traditional Chinese medicine, with the in-depth research, its medicinal value in anti-tumor has been revealed. Loureirin A is extracted from Resina Draconis, however, research on the anti-tumor efficacy of Loureirin A is rare. Herein, we investigated the function of Loureirin A in melanoma. Our research demonstrated that Loureirin A inhibited the proliferation of and caused G0/G1 cell cycle arrest in melanoma cells in a concentration-dependent manner. Further study showed that the melanin content and tyrosinase activity was enhanced after Loureirin A treatment, demonstrated that Loureirin A promoted melanoma cell differentiation, which was accompanied with the reduce of WNT signaling pathway. Meanwhile, we found that Loureirin A suppressed the migration and invasion of melanoma cells through the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Taken together, this study demonstrated for the first time the anti-tumor effects of Loureirin A in melanoma cells, which provided a novel therapeutic strategy against melanoma.

Controllable waveform terahertz generation using rippled plasma driven by an inhomogeneous electrostatic field.

We theoretically present the waveform controls of terahertz (THz) radiations generated from homogeneous and rippled plasma within inhomogeneous external electrostatic field. The Particle-in-cell (PIC) simulations is implemented to demonstrate generation and controllability of three types of THz pulses: single frequency THz pulse in homogeneous plasma, broadband THz pulse and dual frequency THz pulse in rippled plasma. The single frequency THz pulse can be tuned via shifting the knob of electron density of homogeneous plasma. Waveform of broadband THz pulse can be regulated into an envelope-like shape by varying amplitude of electron density of rippled plasma. The two center frequencies' interval of dual frequency THz pulse can be controlled by wave numbers of density distribution of rippled plasma. This work provides a potential means to generate the dual frequency THz pulses with two harmonic frequencies (ω+Ωω, Ω=2) or incommensurate frequencies (ω+Ωω, Ω=1.7,1.8, 2.2…).

Gamabufotalin Induces Apoptosis and Cytoprotective Autophagy through the mTOR Signaling Pathway in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a malignant tumor with a high rate of recurrence and a poor prognosis. Here, we investigated the effect and the potential antitumor mechanism of Gamabufotalin (CS-6) against HCC. Our results show that CS-6 strikingly reduced cell viability, inhibited colony formation, and promoted apoptosis in Hep3B and Huh7 cells. In vivo, CS-6 inhibited HCC xenograft tumor growth with no toxicity to normal tissues. Mechanistically, we found that CS-6 could induce cytoprotective autophagy through the mTOR-ULK1 signaling pathway through downregulation of p62 and upregulation of LC3 II/LC3 I. Meanwhile, CS-6 activated caspase-3 and PARP mediated apoptosis, and the caspase inhibitor Z-VAD-FMK blocked the CS-6-induced cell death in HCC cells. Moreover, autophagy and apoptosis were found to have antagonistic effects in Hep3B and Huh7 cells. Both the autophagy inhibitor chloroquine (CQ) and the mTOR activator MHY1485 blocked autophagy and further enhanced CS-6-induced apoptosis. Taken together, we demonstrated for the first time that CS-6 promotes apoptosis and cytoprotective autophagy through the mTOR signaling pathway in HCC, which proposes a novel strategy for HCC therapy.

Analysis of low-frequency THz emission from monolayer graphene irradiated by a long two-color laser pulse.

Terahertz (THz) radiations from graphene are expected to provide a powerful light source for their wide applications. However, their conversion efficiencies are limited with either long-duration or few-cycle single-color laser pulses. Here, we theoretically demonstrate that THz waves can be efficiently generated from monolayer graphene by using a long-duration two-color laser pulse at normal incidence. Our simulated results show that low-frequency THz emissions are sensitive to the phase difference between two colors, the laser intensity, and the fundamental wavelength. Their dependence on these parameters can be very well reproduced by asymmetry parameters accounting for electron populations of conduction and valence bands. On the contrary, a newly defined σ parameter including the Landau-Zener tunneling probability cannot precisely predict such dependence. Furthermore, the waveform of THz electric field driven by two-color laser pulses exhibits the typical feature of a half-cycle pulse.

Intensity-surged and bandwidth-extended terahertz radiation in two-foci cascading plasmas.

The two-color strong-field mixing in gas medium is a widely used approach to generate bright broadband terahertz (THz) radiation. Here, we present a new, to the best of our knowledge, and counterintuitive method to promote THz performance in the two-color scheme. Beyond our knowledge that the maximum THz generation occurs with two-color foci overlapped, we found that, when the foci of two-color beams are noticeably separated along the propagation axis resulting in cascading plasmas, the THz conversion efficiency is surged by one order of magnitude and the bandwidth is stretched by more than two times, achieving 10-3 conversion efficiency and >100 THz bandwidth under the condition of 800/400 nm, ∼35 fs driving lasers. With the help of the pulse propagation equation and photocurrent model, the observations can be partially understood by the compromise between THz generation and absorption due to the spatial redistribution of laser energy in cascading plasmas. The present method can be extended to a mid-infrared driving laser, and new records of THz peak power and conversion efficiency are expected.

Sanggenon C Suppresses Tumorigenesis of Gastric Cancer by Blocking ERK-Drp1-Mediated Mitochondrial Fission.

Sanggenon C is a flavonoid extracted from the root bark of white mulberry, which is a traditional Chinese medicine with anti-inflammatory, antioxidative, and antitumor pharmacological effects. In this study, sanggenon C was found to inhibit human gastric cancer (GC) cell proliferation and colony formation, induce GC cell cycle arrest in the G0-G1 phase, and promote GC cell apoptosis. Moreover, sanggenon C was found to decrease the level of mitochondrial membrane potential in GC cells and inhibit mitochondrial fission. Mechanistically, RNA sequencing, bioinformatics analysis, and a series of functional analyses confirmed that sanggenon C inhibited mitochondrial fission to induce apoptosis by blocking the extracellular regulated protein kinases (ERK) signaling pathway, and constitutive activation of ERK significantly abrogated these effects. Finally, sanggenon C was found to suppress the growth of tumor xenografts in nude mice without obvious side effects to the vital organs of animals. This study reveals that sanggenon C could be a novel therapeutic strategy for GC treatment.

Controlling the atomic-orbital-resolved photoionization for neon atoms by counter-rotating circularly polarized attosecond pulses.

We theoretically investigate the atomic-orbital-resolved vortex-shaped photoelectron momentum distributions (PMDs) and ionization probabilities by solving the two-dimensional time-dependent Schrödinger equation (2D-TDSE) of neon in a pair of delayed counter-rotating circularly polarized attosecond pulses. We found that the number of spiral arms in vortex patterns is twice the number of absorbed photons when the initial state is the ψm=±1 state, which satisfy a change from c2n+2 to c2n (n is the number of absorbed photons) rotational symmetry of the vortices if the 2p state is replaced by 2p+ or 2p- states. For two- and three-photon ionization, the magnetic quantum number dependence of ionization probabilities is quite weak. Interestingly, single-photon ionization is preferred when the electron and laser field corotate and ionization probabilities of 2p- is much larger than that of 2p+ if the proper time delay and wavelength are used. The relative ratio of ionization probabilities between 2p- and 2p+ is insensitive to laser peak intensity, which can be controlled by changing the wavelength, time delay, relative phase and amplitude ratio of two attosecond pulses.

Controllable photonic and phononic topological state transfers in a small optomechanical lattice.

We propose a scheme to achieve the photonic and the phononic state transfers via the topological protected edge channel based on a one-dimensional small optomechanical lattice. We find that the optomechanical lattice can be mapped into a Su-Schrieffer-Heeger model after eliminating the counter rotating wave terms. By dint of the edge channel of the Su-Schrieffer-Heeger model, we show that the quantum state transfer between the photonic left and the right edge states can be achieved with a high fidelity. Especially, our scheme can also achieve another phononic state transfer based on the same channel via controlling the next-nearest-neighboring interactions between the cavity fields; this is different from the previous investigations achieving only one kind of quantum state transfer. Our scheme provides a novel, to the best of our knowledge, path to switch two different kinds of quantum state transfers in a controllable way.

Improved molecular diagnosis by the detection of exonic deletions with target gene capture and deep sequencing.

PURPOSE: We aimed to demonstrate the detection of exonic deletions using target capture and deep sequencing data. METHODS: Sequence data from target gene capture followed by massively parallel sequencing were analyzed for the detection of exonic deletions using the normalized mean coverage of individual exons. We compared the results with those obtained from high-density exon-targeted array comparative genomic hybridization and applied similar analysis to examine samples from patients with pathogenic exonic deletions. RESULTS: Thirty-eight samples, each containing 2,134, 2,833, or 4,688 coding exons from different panels, with a total of 103,863 exons, were analyzed by capture-massively parallel sequencing and array comparative genomic hybridization. Ten deletions detected by array comparative genomic hybridization were all detected by massively parallel sequencing, whereas only two of three duplications were detected. We were able to detect all pathogenic exonic deletions in 11 positive cases. Thirty-one exonic copy number changes from nine perspective clinical samples were also identified. CONCLUSION: Our results demonstrated the feasibility of using the same set of sequence data to detect both point mutations and exonic deletions, thus improving the diagnostic power of massively parallel sequencing-based assays.

[Chemical constituents from supercritical CO2 extraction of Schisandra chinensis].

OBJECTIVE: To study the chemical constituents from the supercritical CO2 extraction of Schisandra chinensis. METHODS: The compounds were separated and purified by conventional column chromatography and their structures were identified by spectroscopic methods. RESULTS: Nine compounds were isolated from the supercritical CO2 extraction of Schisandra chinensis, and their structures were identified as chrysophanol(1),schisandrin B(2), ß-sitosterol(3), schisandrin C(4),schisandrol A(5), angeloylgomisin H(6), daucosterol(7) 1, 5-dimethyl citrate (8), and shikimic acid (9). CONCLUSION: Compounds 1, 8 and 9 are isolated from Schisandra chinensis for the first time,and compound 1 as an anthraquinone is isolated from this genus for the first time.

[Clinical and electrophysiological characteristics, and prognosis of acute motor axonal neuropathy in children].

OBJECTIVE: To investigate the clinical and electrophysiological characteristics and prognosis of acute motor axonal neuropathy (AMAN) in children in South China. METHODS: The clinical and electrophysiological data of 6 children with AMAN was analyzed, and they were followed up. RESULTS: The mean age of onset was 4.4 years. Most patients came from rural areas and 5 cases had a history of prodromal infection. There were no seasonal differences in clinical onset among the patients. The most common first symptom was muscle weakness, and the mean time from onset to the most severe disease status was 4.2 days. Nerve conduction test results revealed that all patients showed significantly lower amplitude of motor nerve action potential, only 22.3%-73.4% of the lower limit of normal. Injury to the nerves of distal extremities was more serious than injury to the nerves of proximal extremities (P<0.05), while there was no significant difference in the injury to the nerves of upper and lower extremities (P>0.05). Motor nerve conduction velocity and sensory nerve conduction velocity were normal. All patients received intravenous immunoglobulin (IVIG). Of the 6 AMAN patients, 4 could walk independently after a follow-up of 3 months to 1 year. CONCLUSIONS: AMAN in children occurs mostly in rural areas. There is no seasonal difference in the clinical onset of the disease. Muscle weakness is the most common first symptom and the worst status of AMAN appears in the early stage of the disease. Electrophysiological examination provides important information for the diagnosis of AMAN. Some children with AMAN regain the ability to walk independently 1 year after onset. Early application of IVIG treatment may help recovery of neural function.

Diagnostic approaches to apparent homozygosity.

PURPOSE: Sanger sequencing is a mainstay for the identification of gene mutations used in molecular diagnostic laboratories. However, in autosomal recessive disorders, failure of allele amplification can occur for a variety of reasons, leading heterozygous mutations to appear homozygous. We sought to investigate the frequency at which apparently homozygous mutations detected by Sanger sequencing in our laboratory appeared homozygous due to other molecular etiologies. METHODS: A review of 12,406 cases from 40 different genetic tests that were submitted to the Medical Genetics Laboratories at Baylor College of Medicine for Sanger sequence analysis was performed. The molecular status of apparently homozygous cases was further investigated by testing parents using various methods. RESULTS: A total of 291 cases of apparent homozygosity were identified, ranging from 0 to 37% of the total per gene. One-third of the apparently homozygous cases were followed up by parental testing. Parental carrier status was confirmed in 88% of the cases. Of the cases in which parental carrier status could not be confirmed, deletions encompassing point mutations, allele dropout due to single-nucleotide polymorphisms at primer sites, and uniparental isodisomy were observed. CONCLUSION: For individuals with autosomal recessive disorders and apparently homozygous mutations, confirmation by parental testing can rule out other causes of apparent homozygosity, including allele dropout, copy number variations, and uniparental isodisomy.

Mechanisms of tumor necrosis factor-alpha-induced leaks in intestine epithelial barrier.

PURPOSE: The aim of this study was to investigate the signaling mechanisms surrounding changes in tight junction (TJ) and the permeability of human intestinal epithelial cell induced by tumor necrosis factor-alpha (TNF-α). METHODS: To confirm that TNF-α induces epithelial barrier hyperpermeability by disrupting tight junction, Caco-2 cells were exposed to TNF-α, and changes in epithelial permeability (via TER assay), F-actin dynamics (via Rhodamine-phalloidin staining) and tight junction protein expression (via western blot) were monitored. Moreover, to ensure that NF-κB participated in the regulatory mechanisms, Caco-2 cells were transfected with DNMu-IκBα or control plasmids, the above experiments were repeated and the activation effect of TNF-α on NF-κB was detected by luciferase reporter assays. Lastly, we took dominant negative plasmid and knockdown approaches to investigate the potential importance of the NF-κB/myosin light chain kinase (MLCK)/myosin light chain phosphorylation (pMLC) pathways in TNF-a-mediated damage. RESULT: TNF-α could cause NF-κB activation, F-actin rearrangement, tight junction disruption and barrier dysfunction. These effects were alleviated by inhibiting NF-κB. TNF-α induced increase of MLCK transcription and MLC phosphorylation act later than NF-κB activation, which could be suppressed both by inactivating and deleting NF-κB. CONCLUSIONS: TNF-α induces intestinal epithelial cell hyperpermeability by disrupting TJs, in part through MLCK upregulation, in which NF-κB is the positive upstream regulator for MLCK.

Aberrant SERCA3 expression is closely linked to pathogenesis, invasion, metastasis, and prognosis of gastric carcinomas.

Sarco (endo)plasmic reticulum Ca(2+)-ATPase (SERCAs) 3 is involved in calcium mobilization from endoplasmic reticulum into cytosol and closely links to metabolism, neuronal plasticity, gene transcription, cell growth, differentiation, apoptosis, protein folding, and carcinogenesis. To clarify the role of SERCA3 in gastric carcinogenesis and subsequent progression, its expression was examined by immunohistochemistry and in situ hybridization (ISH) on tissue microarrays containing gastric carcinomas, adjacent non-neoplastic mucosa (NNM), and metastatic lymph node. SERCA3 expression was studied in gastric carcinoma tissue and cell lines by Western blot, reverse transcriptase-polymerase chain reaction, or immunofluorescence. The results demonstrated that SERCA3 was distinctively expressed in GES-1, AGS, BGC-823, GT-3TKB, HGC-27, KATO-III, MGC-803, MKN28, MKN45, SCH, SGC-7901, and STKM-2 at both mRNA and protein levels. The carcinomas showed higher SERCA3 mRNA expression than the matched NNM by real-time PCR and ISH (P > 0.05). Immunohistochemically, SERCA3 expression was decreased from gastric NNM, primary to metastatic carcinoma (P > 0.05). SERCA3 expression was negatively related to depth of invasion, distant metastasis, and tumor node metastasis (TNM) staging (P > 0.05), but not to age, sex, lymphatic or venous invasion, or lymph node metastasis (P > 0.05). Kaplan-Meier analysis indicated that SERCA3 expression was positively associated with favorable prognosis of the patients with gastric carcinoma (P > 0.05). Cox's proportional hazard model indicated that venous invasion, distant metastasis and TNM staging (P > 0.05) were independent prognostic factors for gastric carcinomas. It was suggested that downregulated SERCA3 expression is closely linked to pathogenesis, invasion, metastasis, and prognosis of gastric carcinomas. It might be employed to indicate the pathobiological behaviors and prognosis of gastric carcinomas.

[Effect of extracts from Panax ginseng, Panax notoginseng, and Ligusticum chuanxiong on vascular smooth muscle cells of aging and hypertension rats].

OBJECTIVE: To observe and compare the effects of aging and hypertension on rats' aortic vascular smooth muscle cells (VSMCs) and the effects of the extracts from Panax ginseng, Panax notoginseng and Ligusticum chuanxiong. METHODS: The rat aortic VSMCs model was established using the method of primary cell culture. Of them, the rats of the aging experiment were divided into 5 groups, i.e., the young control group (as Yon), the old group (as Old), the old + probucol group (as Old+Pro), the old +low dose extracts group (as Old+Pro), and the old+high dose extracts group (as Old+High). The rats of the hypertension experiment were divided into 5 groups, i.e., the Wistar-Kyoto control group (as WKY), the spontaneously hypertensive rat group (as SHR), the SHR +Valsartan group (as SHR+Val), the SHR+low dose extracts group (as SHR+Low), and the SHR+high dose extracts group (SHR+High). The proliferation of VSMCs was detected using MTT. The expression of MMP-9 was detected by immunocytochemical assay. The mRNA and protein expressions of peroxisome proliferator activated receptor-gamma (PPAR-gamma) were detected using RT-PCR and Western blot respectively. RESULTS: Compared with the Yon group, the proliferation of VSMCs and the MMP-9 expression increased, the mRNA and protein expressions of PPAR-gamma decreased in the Old group, all showing statistical difference (P < 0.05). Compared with the Old group, the proliferation of VSMCs and the MMP-9 expression obviously decreased, the mRNA expression of PPAR-gamma obviously increased in the Old+Pro group, the Old+High group, and the Old+Low group (all P < 0.05). The PPAR-y protein expression obviously increased in the Old+Pro group and the Old+Low group (P < 0.05). Compared with the WKY group, the proliferation of VSMCs and the expression of MMP-9 obviously increased, the mRNA and protein expressions of PPAR-gamma obviously decreased in the SHR group (all P < 0.05). Compared with the SHR group, the proliferation of VSMCs and the expression of MMP-9 obviously decreased, the mRNA and protein expressions of PPAR-gamma obviously increased in the SHR+Val group, the SHR+High group, and the SHR + Low group (all P < 0.05). CONCLUSIONS: Both aging and hypertension could result in excessive proliferation of rat aortic VSMCs and the expression changes of correlated cytoactive factors. The extracts from Panax ginseng, Panax notoginseng (Burk.) and Ligusticum chuanxiong can lower their proliferation levels and reduce the expressions of negative cytokines, thus reducing aging and hypertension induced injury of VSMCs and delaying angiocellular aging.

Acute pulmonary embolism originating from upper limb venous thrombosis following breast cancer surgery: Two case reports.

BACKGROUND: Upper limb venous thrombosis (ULVT) is rarer than lower-extremity deep venous thrombosis, and is related to Paget-Schroetter syndrome, central venous catheterization, and malignancy. There are few reports of pulmonary embolism (PE) from upper-extremity vein thrombosis due to surgery. Herein, we report two cases of PE that originated from upper limb venous thrombosis on the surgical side in two patients undergoing modified radical mastectomy for breast cancer. These cases challenge the traditional theory that PE originate only from the lower extremities. CASE SUMMARY: We describe two female patients, aged 68 and 65 years, respectively, who had undergone modified radical mastectomy for breast cancer. They did not have a central venous catheter and did not undergo preoperative neoadjuvant chemotherapy. They were transferred to the intensive care unit due to symptomatic PE on the first day after surgery. Colour Doppler ultrasound identified fresh thrombosis in their upper limb veins, which was the presumed source of the PE. They all received anticoagulation therapy, and one of them experienced bleeding that required discontinuation of the drug. Ultimately, they were discharged in stable condition. CONCLUSION: ULVT as a source of PE after breast cancer surgery cannot be ignored.

Expanded molecular features of carnitine acyl-carnitine translocase (CACT) deficiency by comprehensive molecular analysis.

Carnitine-acylcarnitine translocase (CACT) deficiency is a rare autosomal recessive disease of fatty acid oxidation, mainly affecting long chain fatty acid utilization. The disease usually presents at neonatal period with severe hypoketotic hypoglycemia, hyperammonemia, cardiomyopathy and/or arrhythmia, hepatic dysfunction, skeletal muscle weakness, and encephalopathy. Definitive diagnosis of CACT deficiency by molecular analysis of the SLC25A20 gene has recently become clinically available. In contrast to biochemical analysis, sequence analysis is a more rapid and reliable method for diagnosis of CACT deficiency. In this study, we used Sanger sequencing and target array CGH to identify molecular defects in the SLC25A20 gene of patients with clinical features and an acylcarnitine profile consistent with CACT deficiency. Eight novel mutations, including a large 25.9 kb deletion encompassing exons 5 to 9 of SLC25A20 were found. Review of the published cases revealed that CACT deficiency is a pan-ethnic disorder with a broad mutation spectrum. Mutations are distributed along the entire gene without a hot spot. Two thirds of them are nonsense, frame-shift, or splice site mutations resulting in premature stop codons. This study underscores the importance of comprehensive molecular analysis, including sequencing and targeted array CGH of the SLC25A20 gene when CACT deficiency is suspected.

Expansion of CUG RNA repeats causes stress and inhibition of translation in myotonic dystrophy 1 (DM1) cells.

The purpose of this study was to investigate the role of the mutant CUGn RNA in the induction of stress in type 1 myotonic dystrophy (DM1) cells and in the stress-mediated inhibition of protein translation in DM1. To achieve our goals, we performed HPLC-based purification of stress granules (SGs), immunoanalysis of SGs with stress markers TIA-1, CUGBP1, and ph-eIF2, site-specific mutagenesis, and examinations of RNA-protein and protein-protein interactions in myoblasts from control and DM1 patients. The cause-and-effect relationships were addressed in stable cells expressing mutant CUG repeats. We found that the mutant CUGn RNA induces formation of SGs through the increase of the double-stranded RNA-dependent protein kinase (PKR) and following inactivation of eIF2α, one of the substrates of PKR. We show that SGs trap mRNA coding for the DNA repair and remodeling factor MRG15 (MORF4L1), translation of which is regulated by CUGBP1. As the result of the trapping, the levels of MRG15 are reduced in DM1 cells and in CUG-expressing cells. These data show that CUG repeats cause stress in DM1 through the PKR-ph-eIF2α pathway inhibiting translation of certain mRNAs, such as MRG15 mRNA. The repression of protein translation by stress might contribute to the progressive muscle loss in DM1.