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As a novel X-ray focusing technology, lobster eye micro-pore optics (MPO) feature both a wide observing field of view and true imaging capability, promising sky monitoring with significantly improved sensitivity and spatial resolution in soft X-rays. Since first proposed by Angel (1979), the optics have been extensively studied, developed and trialed over the past decades. In this Letter, we report on the first-light results from a flight experiment of the Lobster Eye Imager for Astronomy ($LEIA$), a pathfinder of the wide-field X-ray telescope of the Einstein Probe mission. The piggyback imager, launched in July 2022, has a mostly un-vignetted field of view of $18.6^\circ \times 18.6^\circ $. Its spatial resolution is in the range of 4$-$7 arcmin in FWHM and the focal spot effective area is 2$-$3 cm$^2$, both showing only mild fluctuations across the field of view. We present images of the Galactic center region, Sco X-1 and the diffuse Cygnus Loop nebular taken in snapshot observations over 0.5$-$4 keV. These are truly wide-field X-ray images of celestial bodies observed, for the first time, by a focusing imaging telescope. Initial analyses of the in-flight data show excellent agreement between the observed images and the on-ground calibration and simulations. The instrument and its characterization are briefly described, as well as the flight experiment. The results provide a solid basis for the development of the present and proposed wide-field X-ray missions using lobster eye MPO., Comment: 11 pages, 4 figures. Accepted for publication in Astrophysical Journal Letter

目的 探讨真性红细胞增多症（PV）患者干扰素和（或）羟基脲治疗后症状负荷改善与血液学疗效之间的关系。 方法 对190例符合WHO（2016）诊断分型标准、接受干扰素和（或）羟基脲连续治疗≥6个月的PV患者，分别应用外周血细胞计数和骨髓增殖性肿瘤总症状评估量表（MPN-10）评价患者血液学疗效和症状负荷。 结果 全部190例PV患者中，男93例（48.9％），女97例（51.1％）。进行MPN-10评分时，患者中位年龄为60（32～82）岁。全部患者中位MPN-10总分为9（0～67）分，干扰素+羟基脲组（27例）为11（0～67）分，显著高于干扰素组［64例，6（0～56）分，P＝0.019］和羟基脲组［99例，9（0～64）分，P＝0.047］，而干扰素组与羟基脲组差异无统计学意义（P＝0.421）。28.9％（55/190）的患者存在重度症状（单项症状评分≥7分或总分≥44分），干扰素组、羟基脲组、干扰素+羟基脲组重度症状患者占比分别为23.4％、29.3％、40.7％，组间比较差异均无统计学意义（P>0.05）。全部190例患者中，进行MPN-10评分时71例（37.4％）获得完全血液学缓解（CHR），仅55例（28.9％）获得疾病充分控制（获得CHR且无重度症状）。未获得疾病充分控制的患者包括：血细胞增高80例（42.1％），获得CHR但伴重度症状16例（8.4％），血细胞增高且伴重度症状39例（20.5％）。PLT>400×109/L患者中存在重度症状患者比例、MPN-10总分中位数均高于PLT≤400×109/L患者［40.8％（20/49）对24.8％（35/141），P＝0.044；14（0～67）分对7（0～56）分，P＝0.038］。PLT>400×109/L是存在重度症状的危险因素（HR＝2.089，95％CI 1.052～4.147，P＝0.035）。 结论 经干扰素和（或）羟基脲治疗后，PV患者症状负荷未获满意控制仍较突出，部分患者虽然获得CHR，仍存在重度症状负荷。PLT>400×109/L是干扰素和羟基脲治疗后患者存在重度症状的危险因素。

Dys-regulated long noncoding RNAs (lncRNAs) are involved in the cell growth of several malignancies and their aggressive phenotypes. LncRNA DBH-AS1 plays an important role in the advancement of various malignant tumors, but its contribution to non-small cell lung cancer (NSCLC) is still unexplored. This study intends to elucidate the role of the regulatory network of lncRNA DBH-AS1 in NSCLC progression.The LncDBH-AS1 expression in 32 paired NSCLC patients' tissue samples and NSCLC cell lines were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The role of LncDBH-AS1 in NSCLC was investigated through cell counting kit-8 (CCK-8) assay and colony formation assay in vitro. Besides, the interaction between LncDBH-AS1 and miR-155 was also analyzed.The DBH-AS1 expression was significantly down-regulated in NSCLC cell lines and tissue samples. Decreased DBH-AS1 levels promoted the in vitro proliferation of the NSCLC cells. The mechanism was that DBH-AS1 regulated AXIN1 expression by sponging miR-155 in NSCLC cell lines. Importantly, LncDBH-AS1 might inhibit WNT/β-CATENIN activation in NSCLC cells.The progression of NSCLC is facilitated by DBH-AS1 via miR-155 interaction and up-regulation of AXIN1 expression.

Background CBCSG006 trial reported the superior efficacy of cisplatin plus gemcitabine (GP) regimen than paclitaxel plus gemcitabine (GT) regimen as first-line treatment of metastatic triple-negative breast cancer (mTNBC). This study focused on the updated survival data and the explorations of potential biomarkers for efficacy. Patients and methods Germ-line mutations of homologous recombination (HR) panel, BRCA1/2 included, were evaluated in 55.9% (132/236) patients. PD-L1 expression was evaluated in 48.3% (114/236) patients. A nonparametric sliding-window subpopulation treatment effect pattern plot (STEPP) methodology was used to analyze the absolute survival benefits. All statistical tests were two-sided. Results Median progression-free survival (PFS) was 7.73 [95% confidence interval (CI) 6.46–9.00] months for GP arm and 6.07 (95% CI 5.32–6.83) months for GT arm (P = 0.005). No significant difference in overall survival (OS) was observed. There was significant interaction between HR status and treatment for PFS and status of HR deficient significantly correlated with higher objective response rate (ORR) and longer PFS in GP arm than in GT arm (71.9% versus 38.7%, P = 0.008; 10.37 versus 4.30 months, P = 0.011). There was no significant interaction between germ-line BRCA1/2 (gBRCA1/2) status and treatment for PFS. Patients with gBRCA1/2 mutation had numerically higher ORR and prolonged PFS in GP arm than in GT arm (83.3% versus 37.5%, P = 0.086; 8.90 versus 3.20 months, P = 0.459). There was no significant interaction between PD-L1 status and treatment for PFS, and no significant differences in ORR, PFS or OS between two arms regardless of PD-L1 status. In STEPP analysis, patients with lower composite risks had more absolute benefits in PFS than those with higher composite risks. Conclusions GP regimen has superior efficacy than GT regimen as first-line chemotherapy for mTNBC patients. Germ-line mutations of BRCA1/2 and HR panel are possible biomarkers for better performance of cisplatin-based regimens. A composite risk model was developed to guide patient selection for GP treatment in TNBC patients. Trial registration ClinicalTrials.gov, NCT01287624.

With the continuous attention to the microplastics pollution in the world, since 2014, Chinese scholars have rapidly carried out a large number of microplastics pollution investigation and experimental research. This paper summarizes the research results of microplastics pollution in abiotic environment (ocean, land water, soil, atmosphere) in this stage, in order to provide support for the future research.

To investigate the role of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in the cardioprotective mechanisms of exercise preconditioning (EP).Eighty male Sprague-Dawley (SD) rats were randomized into the Group control, Group EE, Group EP+EE, Group EP+EE+AG, and Group EE+AG. By using 3 days of intermittent treadmill exercise, this study established the EP animal model. Rats were subjected to run to exhaustion on the treadmill at 30 m/min with 0% grade as an exhaustive exercise (EE) protocol. The myocardial injury induced by exhaustive exercise was produced 24 h after EP. JAK2 inhibitor (AG490, 3 mg/kg) was injected before EP. Serum cardiac troponin I (cTnI) levels and hematoxylin basic fuchsine picric acid (HBFP) staining were used to observe the degree of myocardial ischemia. TUNEL, Bcl2, and cleaved caspase-3 levels were used to evaluate the change of myocardial apoptosis. Moreover, the phosphorylations of JAK2 and STAT3 were analyzed as possible mechanisms that might explain the EP-induced cardioprotection.EP significantly attenuated the exhaustive exercise-induced myocardial ischemia injury, associated with lower serum cTnI levels, decreased myocardial infarct area, reduced myocardial apoptosis, increased Bcl2 level, decreased cleaved caspase-3 level, and the increased phosphorylations of JAK2 and STAT3. Treatment with AG490 abolished the cardioprotective effects and the enhanced phosphorylations of JAK2 and STAT3 induced by EP.EP plays its cardioprotective role via activating the JAK2/STAT3 signaling pathway, reducing the apoptosis of myocardial cells and alleviating myocardial ischemia injury.

Oridonin, an ent-kaurene diterpenoid isolated from the traditional Chinese herb Rabdosia rubescens, has been reported to be a potent cytotoxic agent against a wide array of cancer cells. However, its effect on human nasopharyngeal carcinoma (NPC) cells has not been well investigated. The present study aimed to explore the anti-tumour effect of oridonin in NPC cells and its underlying mechanisms. Cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay and colony formation assay. Apoptosis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and expression of apoptosis-related proteins were analysed by flow cytometry with propidium iodide staining, JC-1 staining, DCFH-DA staining, and Western blot analysis, respectively. The results showed that oridonin concentration-dependently inhibited the cell viability, decreased the colony formation, and enhanced the apoptotic rate in NPC cells. Further, oridonin-induced apoptosis was mediated by the mitochondrial pathway in NPC cells, which was confirmed by the loss of MMP, downregulation of anti-apoptotic Bcl-2 family protein Mcl-1 and Bcl-2, upregulation of pro-apoptotic Bcl-2 family member Bax, and activation of caspase-3 and PARP. Notably, the augmented ROS generation played an essential role in oridonin-induced apoptosis in NPC cells, as the apoptosis-inducing effect was attenuated by ROS scavenger N-acetyl-L-cysteine. These results indicate that oridonin triggers apoptosis through the ROSmediated mitochondrial pathway in NPC cells. This study supports oridonin to be an interesting candidate drug for the treatment of human NPC.

A superconducting 16-pole 2.6T wiggler with period 170mm of The High-Energy Photon Source and the Test Facility Project (HEPS-TF) designed and fabricating in the Institute of High Energy Physics (IHEP) in China is described. This wiggler will be installed in Beijing Electron-Positron Collider II (BEPCII). The main parameters and structure of the wiggler are presented. Besides, some vertical testing results are involved.

Esophageal Squamous Cell Carcinoma (ESCC) is one of the most common human cancers with a particularly high incidence in certain regions of China. Differentially expressed genes (DEG) between the esophageal squamous carcinoma tissues and matched normal esophageal mucosal epithelial tissues can be detected by employing the gene microarray technology. This can aid the analysis of the underlying disease mechanism and can help to identify potentially critical genes as well as related molecular signalling pathways.The potentially critical genes and related signal pathways are examined by bioinformatics analysis including Gene Ontology (GO) analysis, pathway analysis and signal transduction networks. Here, we performed microarray analysis with 8 pairs of ESCC and normal esophageal mucosal epithelial tissues.Compared to the control group, 347 and 203 genes were found to be up-regulated and down-regulated in the experimental group, respectively. Based on pathway analysis, 52 and 51 signal transduction pathways were involved in the up-regulated and the down-regulated genes, respectively. SLC27A6, RAB11A, ABCA8, JAM2, HNMT, GSTM1, and CDKN3, which play critical roles in regulating the expression of ESCC, were identified among the key genes involved in the signal transduction networks.Investigation of the mechanism underlying ESCC can provide a direction for the clinical prevention and treatment of ESCC.

We investigated the effects of genetic down- and up-regulation of sac1 expression on Aβ42 accumulation and the associated neural deficits in flies with direct expression of arctic mutant Aβ42 (Aβarc) in the neurons of GF pathway.We genetically down-regulated and up-regulated the level of sac1, encoding a major phosphoinositide phosphatases in a disease model, in which arctic mutant Aβ42 is directly expressed in the neurons of a neural pathway of adult fruit flies.We conducted a time-course analysis of Aβ42 level in the model and found an age-dependent elevation of Aβ42 accumulation, closely correlated to the age-dependent decline of climbing ability in the model flies. Neither sac1 insufficiency nor sac1 over-expression significantly changed the three phenotypes.We found that the alterations of sac1 expression did not change Aβ42 accumulation and neural deficits in the model.

As a new sweetener, fructooligosaccharide is paid more and more attention for its health improvement property. It includes trisaccharide, tetrasaccharide and pentasaccharide, and can be produced from sucrose by the fermentation of microorganism. In order to analyze the content of fructooligosaccharide in fermented sugar by gas chromatography, fructooligosaccharide was transformed into trimethylsilyl derivatives. Based on the modified gas chromatograph SP2308, and under the chosen chromatographic conditions with 0.53 mm capillary column of OV-101, the contents of fructose, glucose, sucrose and fructooligosaccharide were determined by programmed temperature chromatography. The recovery of fructooligosaccharide was satisfactory.

C9H13AgN3O4.50, monoclinic, C12/c1 (No. 15), a = 8.331(2) Å, b = 11.645(2) Å, c = 23.947(5) Å, β = 94.845(3)°, V = 2314.8 Å3, Z = 8, Rgt(F) = 0.030, wRref(F2) = 0.072, T = 298 K.

C16H18Ag2N6O14, triclinic, P1̅ (No. 2), a = 6.978(2) Å, b = 12.919(5) Å, c = 15.029(5) Å, α = 84.320(6)°, β = 76.81 (5)°, ϒ = 79.612(6)°, V = 1295.1 Å3, Z = 2, Rgt(F) = 0.065, wRref(F2) = 0.091, T = 298 K.

C16H18Cl2N2O4, monoclinic, C12/c1 (No. 15), a = 21.92(1) Å, b = 9.015(5) Å, c = 8.620(5) Å, β = 96.151(9)°, V = 1693.3 Å3, Z = 4, Rgt(F) = 0.064, wRref(F2) = 0.186, T = 298 K.

C10H18AgN3O6, triclinic, P1 (No. 2), a = 7.139(2) Å, b = 7.509(2) Å, c = 14.007(4) Å, α = 78.505(5)°, β = 78.789(4)°, γ = 82.023(4)°, V = 717.8 Å3, Z = 2, Rgt(F) = 0.036, wRref(F2) = 0.096, T = 298 K.

GRB-2 is a small SH2- and SH3 domain-containing adapter protein that associates with the mammalian SOS homolog to regulate p21ras during growth factor signaling. During insulin stimulation, GRB-2 binds to the phosphorylated Y895VNI motif of IRS-1. Substitution of Tyr-895 with phenylalanine (IRS-1F-895) prevented the IRS-1-GRB-2 association in vivo and in vitro. The myeloid progenitor cell line, 32-D, is insensitive to insulin because it contains few insulin receptors and no IRS-1. Coexpression of IRS-1 or IRS-1F-895 with the insulin receptor was required for insulin-stimulated mitogenesis in 32-D cells, while expression of the insulin receptor alone was sufficient to mediate insulin-stimulated tyrosine phosphorylation of Shc and activation of p21ras and mitogen-activated protein (MAP) kinase. The Shc-GRB-2 complex formed during insulin stimulation is a possible mediator of p21ras and MAP kinase activation in IRS-1-deficient 32-D cells. Interestingly, IRS-1, but not IRS-1F-895, enhanced the stimulation of MAP kinase by insulin in 32-D cells expressing insulin receptors. Thus, IRS-1 contributes to the stimulation of MAP kinase by insulin, probably through formation of the IRS-1-GRB-2 complex at Tyr-895. Our results suggest that the Shc-GRB-2 complex and the activation of p21ras-dependent signaling pathways, including MAP kinase, are insufficient for insulin-stimulated mitogenesis and that the essential function(s) of IRS-1 in proliferative signaling is largely unrelated to IRS-1-GRB-2 complex formation.

Insulin-stimulated autophosphorylation of the cytoplasmic juxtamembrane region of the human insulin receptor was examined by Tricine/SDS-PAGE. Various mutant receptor molecules were used to identify two tryptic phosphopeptides associated with the juxtamembrane region which accounts for 15% of the autophosphorylation of partially purified insulin receptor. These phosphopeptides were immunoprecipitated with an antipeptide antibody against the juxtamembrane sequence and were phosphorylated exclusively on tyrosine. Substitution of both Tyr960 and Tyr953 with alanine eliminated insulin-stimulated phosphorylation of the juxtamembrane region without affecting tyrosine autophosphorylation in the C terminus or regulatory regions. Monosubstitution of Tyr960 with phenylalanine or alanine reduced phosphorylation in the juxtamembrane region by more than 50%, and manual Edman degradation indicated that Tyr960 was phosphorylated in wild-type receptor. In vivo, phosphorylation of the juxtamembrane region accounts for one-third of the insulin receptor phosphorylation and contains both phosphoserine and phosphotyrosine. Deletion of Tyr960 and 11 adjacent amino acids eliminated insulin-stimulated phosphorylation of the juxtamembrane region. Substitution of Tyr960 reduced this phosphorylation by more than 50%. The insulin receptor also undergoes serine phosphorylation outside of the juxtamembrane region which depends on the presence of Tyr1151. Together with our previous studies, this report suggests that phosphorylation of Tyr960 may play an important role in signal transduction by the insulin receptor.

Insulin stimulates the formation of binary and ternary signaling complexes between the phosphatidylinositol (PtdIns) 3'-kinase, IRS-1, and the insulin receptor in vivo. Binary complex formation between IRS-1 and the PtdIns 3'-kinase occurs in intact cells and requires the tyrosyl phosphorylation IRS-1, as mutant insulin receptors which weakly phosphorylate IRS-1 in vivo do not mediate formation of IRS-1/PtdIns 3'-kinase complexes in transfected CHO cells. Association with IRS-1 involves as much as 70% of total cellular PtdIns 3'-kinase activity. Insulin also stimulates the formation of ternary signaling complexes, as both IRS-1 and the PtdIns 3'-kinase are present in anti-insulin receptor immunoprecipitates from insulin-stimulated cells. Overexpression of IRS-1 in CHO cells increases the amount of PtdIns 3'-kinase activity in alpha IR immunoprecipitates, and IRS-1 markedly increases the in vitro binding of p85 alpha and PtdIns 3-kinase activity to anti-receptor immunoprecipitates. The mechanism for this association is unknown, but appears to involve the binding of IRS-1/PtdIns 3'-kinase complexes to the insulin receptor. The formation of binary and ternary complexes between the insulin receptor, IRS-1 and the PtdIns 3'-kinase may play a critical role in transmission of the insulin signal.

IRS-1 is a major insulin receptor substrate which may play an important role in insulin signal transmission. The mRNA for IRS-1 in rat cells and tissues is about 9.5 kilobases (kb). Rat liver IRS-1 was stably expressed in Chinese hamster ovary (CHO) cells (CHO/IRS-1). Although its calculated molecular mass is 131 kDa, IRS-1 from quiescent cells migrated between 165 and 170 kDa during sodium dodecyl sulfate-polyacrylamide gel electrophoresis. IRS-1 was phosphorylated strongly on serine residues and weakly on threonine residues before insulin stimulation. Insulin immediately stimulated tyrosine phosphorylation of IRS-1, and after 10-30 min with insulin its apparent molecular mass increased to 175-180 kDa. Expression of the human insulin receptor and rat IRS-1 together in CHO/IR/IRS-1 cells increased the basal serine phosphorylation of IRS-1 and strongly increased tyrosine phosphorylation during insulin stimulation. Purified insulin receptors directly phosphorylated baculovirus-produced IRS-1 exclusively on tyrosine residues. By immunofluorescence, IRS-1 was absent from the nucleus, but otherwise distributed uniformly before and after insulin stimulation. Some IRS-1 associated with the insulin receptor during insulin stimulation. In addition, a phosphatidylinositol 3'-kinase associated with IRS-1 during insulin stimulation, and this association was more sensitive to insulin in CHO cells overexpressing the insulin receptor (CHO/IR cells), more responsive to insulin to CHO/IRS-1 cells, and both sensitive and responsive in CHO/IR/IRS-1 cells. Similarly, insulin-stimulated DNA synthesis was more sensitive to insulin in CHO/IR cells, and more responsive in CHO/IRS-1 cells; however, insulin-stimulated DNA synthesis was sensitive but poorly responsive to insulin in CHO/IR/IRS-1 cells. Together, these results suggest that IRS-1 is a direct physiologic substrate of the insulin receptor and may play an important role in insulin signal transmission.

For the multisensor multichannel autoregressive moving average (ARMA) signals with time-delayed measurements, a measurement transformation approach is presented, which transforms the equivalent state space model with measurement delays into the state space model without measurement delays, and then using the Kalman filtering method, under the linear minimum variance optimal weighted fusion rules, three distributed optimal fusion Wiener filters weighted by matrices, diagonal matrices and scalars are presented, respectively, which can handle the fused filtering, prediction and smoothing problems. They are locally optimal and globally suboptimal. The accuracy of the fuser is higher than that of each local signal estimator. In order to compute the optimal weights, the formulae of computing the cross-covariances among local signal estimation errors are given. A Monte Carlo simulation example for the three-sensor target tracking system with time-delayed measurements shows their effectiveness.

Human antithrombin III (AT-III) was partially reduced under mild conditions in the absence or presence of low molecular weight heparin. Quantitation of reduced disulfide bonds was facilitated by the application of a water-soluble color reagent, 4-N,N-dimethylaminoazobenzene-4'-iodoacetamido-2'-sulfonic acid (S-DABIA). The study shows that the three disulfide linkages of AT-III can be sequentially reduced, with Cys8-Cys128 being the most sensitive, followed by Cys21-Cys95, while Cys247-Cys430 is the most resistant to the mild reduction conditions. The rate of reduction of Cys8-Cys128 and Cys21-Cys95 was significantly decreased in the presence of heparin. The reduction of Cys8-Cys128 was also found to correlate quantitatively with the loss of heparin-accelerated antithrombin activity, heparin binding affinity, and heparin-induced fluorescence enhancement. These results suggest that Cys8-Cys128 is required for the integrity of the heparin binding domain of AT-III and support previous findings that lysyl residues surrounding Cys128 (Lys107, Lys114, Lys125, and Lys136) constitute an important part of the heparin binding site in AT-III.