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Mass resolution of Foureir transform mass spectrometer (FTMS) highly depends on the acquisition time of image charge/current signal. In order to achieve higher resolution with a shorter transient time, apart from increasing the field strength of the analyzer, the high order harmonics in the image charge signal may also be exploited. The image charge or current signal obtained from the planar electrostatic ion trap has a non-sinusoidal waveform which contains many high-order harmonic components. However, presence of high harmonics increases the complexity of spectral analysis, such as identification of a peak for its correct harmonic order, and avoiding quantitation error due to the peak overlapping from different harmonic groups. A new quantitative algorithm consists of a scoring-based peak classification and the least square fitting (SC-LSF), which has been developed to convert image charge or current signal to mass spectrum. The scoring process will go through all the peaks identified above the noise background, for assumptions that the peak belongs to a certain harmonic order. The score will go up when a relevant lower harmonic peak is confirmed. The harmonic order which achieves the highest score, is assigned to the peak so its fundamental frequency can be determined. Through the SC tests, the candidates of all fundamental frequencies are found for all possible m/z of ions. The basis signals for all possible m/z are constructed using the identified fundamental frequencies and are brought to the LSF to determine the intensities of each species. The SC-LSF algorithm was tested using simulated signal from a mixture of 48 different m/z ions. Different levels of artificial noise were added to the signal to challenge the algorithm. The results show a wide range of mass and ion numbers in the sample mixture can be accurately returned through the SC-LSF algorithm even if the transient signal is under high noise condition. LSF in frequency domain is more efficient than in time domain because a subset of frequency points may be selected, so the amount of calculation is massively reduced. In addition, the test proves that good quantitation can be achieved only when LSF is carried out using data in complex number, while fitting with magnitude data results in large errors for ions in the closed mass group. This is because those closed mass peaks are overlapping at certain low-order harmonics and the amplitudes of a FFT spectrum are not addable, thus leading to the fitting errors.

Objective Closed reduction combined with external fixation is a frequently utilized approach for treating distal radial fractures in adults. Nonetheless, the potential for re‐displacement following external fixation remains. Analyzing the factors influencing re‐displacement after nonsurgical treatment of distal radial fractures in adults is vital for preventing re‐displacement and making prognostic assessments. Methods A retrospective analysis was performed on 884 patients who underwent nonsurgical treatment for distal radius fractures in the reduction room of the Orthopedics and Traumatology Department of Integrated Traditional Chinese and Western Medicine at Tianjin Hospital, Tianjin, China, between July 2019 and December 2022. Patients were categorized into two groups, namely displaced and nondisplaced, based on radiographic outcomes. Factors affecting fracture re‐displacement were examined, including sex, age, side, AO/OTA type, external fixation, and radiographic outcomes at pre‐reduction and immediate reduction. Logistic regression analysis was employed to identify the risk factors for fracture re‐displacement, and ROC curves were constructed. Results Among the 884 patients, 563 (63.69%) experienced re‐displacement after fracture reduction. There were no statistically significant differences (p > 0.05) between the two groups in terms of gender, external fixation method, and palmar tilt angle at pre‐reduction and immediate reduction, while significant differences (p 3.26 mm at pre‐reduction, and ulnar variance >2.055 mm at immediate reduction were high‐risk factors for fracture re‐displacement. Conclusions Nonsurgical treatment of distal radius fractures exhibits a higher rate of re‐displacement. Age, AO/OTA type, pre‐reduction, and immediate reduction ulnar variance are key factors predicting fracture re‐displacement.

This paper concentrates on analyzing the stability problems of aperiodic sampled-data systems with time delay. Based on Lyapunov theory, a new time-square-dependent two-side looped-functional (TTLF) is proposed, which can take full advantage of the second order terms with respect to time. And by using the intrinsic relationships of state vectors, a new zero equality is obtained. Then, a less conservative stability condition is gained. In addition, the method proposed is applied to an electric power market (EPM) to study the influence of market clearing time (MCT) and communication delay on system stability. Finally, the effectiveness of the proposed stability criterion is verified based on numerical experiments.

There have been efforts dedicating to investigating the effect of high levels of oxytetracycline (OTC) on tetracycline (TC) resistance among zoonotic pathogen Aeromonas hydrophila (AH), an antibiotic-resistant bacterial indicator. However, the dynamic behavior of TC-resistant AH in response to environmentally relevant OTC concentrations at a population-level has not been fully understood. Here we developed a bacterial population dynamic model to quantify TC-resistant AH posed by OTC-dependent resistance selection pressure. The key environmental factors known as water temperature, water activity, and pH were incorporated into model to produce pattern-oriented simulation outcomes. We estimated resistance acquisition number (R0) and showed that R0 was >1 at water temperature

Abstract Background Kounis syndrome is an acute coronary syndrome that appears in the setting of anaphylactic reaction or hypersensitivity. Many drugs and environmental exposures have been identified as potential offenders, and diagnosis and treatment can be challenging. Case presentation A 62-year-old man with recurrent bladder cancer underwent an intra-iliac artery epirubicin injection. After the injection, he developed chest pain and a systemic allergic reaction, with electrocardiographic alterations and elevated troponin-I levels. Emergent coronary angiography showed right coronary artery spasm and no stenosis of the other coronary arteries. This reaction was considered compatible with an allergic coronary vasospasm. A diagnosis of Kounis syndrome was made. Conclusions Kounis syndrome is common, but a prompt diagnosis is often not possible. This case is the first to suggest that an intraarterial epirubicin injection could potentially be one of its triggers. All physicians should be aware of the pathophysiology of this condition to better recognize it and start appropriate treatment; this will prevent aggravation of the vasospastic cardiac attacks and yield a better outcome.

Objective: This study compared the long-term outcomes between rotational atherectomy (RA) for specific indications and on-label use of RA for severely calcified coronary lesions. Methods: Data for patients who underwent RA between 2015 and 2020 in a single-center registry were analyzed. The specific indication group included patients with ostial lesions, unprotected left main coronary artery stenosis, chronic total occlusions, stent ablation, angulated lesions, and cardiac dysfunction, whereas patients with none of the above-mentioned characteristics were included in the on-label group. The primary endpoint was compared between groups. Results: A total of 176 patients in the on-label group and 125 patients in the specific indication group were included. Patient clinical characteristics were comparable between groups. The incidence of complications during the procedure was higher in the specific indication group than in the on-label group (20.0% vs. 10.8%, P=0.018). No significant difference was observed in in-hospital MACCE between groups (12.5% vs 9.7%, P=0.392). During 35 (10–57) months of follow-up, MACCE occurred in 46 patients (15.3%). The incidence of MACCE was much higher in the specific indication group than the on-label group (25.6% vs 13.6%, P=0.034). Conclusions: RA for specific indications, compared with on-label use, had a higher incidence of complications during the procedure and poorer long-term clinical outcomes.

In 2018, the Chronic Total Occlusion Club China (CTOCC) presented a new CTO percutaneous coronary intervention (CTO PCI) algorithm. At the end of 2020, an updated CTOCC algorithm was proposed by this group after the adoption of innovative concepts and novel techniques in CTO PCI. The updated CTOCC algorithm summarizes the contemporary CTO PCI practices in China, in which simultaneous contralateral injection and careful angiographic review, along with strategic changes, are emphasized. Additionally, we provide some new recommendations for techniques such as the “move the cap” and “active greeting” techniques and investment procedures.

Background: The National Chest Pain Centers Program (NCPCP) is the largest nationwide, hospital-based, multifaceted, continuous quality improvement initiative, which aims to monitor and improve the quality of care for patients with acute chest pain. The accreditation of the standardized chest pain center is central to the project. The purpose of establishing chest pain centers is to develop a mechanism for “sending acute chest pain patients to a hospital with capabilities for the best treatment in the shortest time possible.” Objectives: This study aims to evaluate the effectiveness and implementation of the chest pain center accreditation and to identify factors that may influence its implementation in local settings. Study Design and Methods: Hospitals that have been accredited between January 2016 and September 2020 will be recruited in this study. We will conduct a self-controlled retrospective cohort study by comparing the care performance before, during, and after the accreditation. Measures for care performance will be selected based on the American College of Cardiology/American Heart Association clinical practice guidelines, which will be divided into prehospital processes, in-hospital processes, and in-hospital outcomes. For the implementation of the chest pain center accreditation, we will use a modified reach, effectiveness, adoption, implementation, maintenance (RE-AIM) framework to investigate the implementation process, and the consolidated framework for implementation research will be used to identify factors that emerge within the local context and influence the implementation fidelity and feasibility. Progress to Date: As of September 2020, there were 4,621 hospitals that registered the NCPCP, of which 1,507 hospitals were accredited. A total of 5,228,973 patients with a primary diagnosis on admission were enrolled from the registered hospitals, among which 34.6% were acute coronary syndromes. Conclusions: In this study, we proposed recommendations for improving the implementation of chest pain center accreditation, which will improve the quality of care for patients with acute chest pain and promote the sustainable development of chest pain center.

Abstract Background To compare outcomes of bailout and planned rotational atherectomy (RA) in the treatment of severe calcified coronary lesions. Methods Data of patients treated with RA from 2017 to 2018 at a single-center registry were retrospectively analyzed. All patients were divided into planned RA and bailout RA groups, data between two groups were compared. Results A total of 190 patients were included in this study, 138 patients received planned RA and 52 patients received bailout RA. Baseline clinical characteristics had no significant differences between groups. The number of implanted stents and total stents length were similar. But the number of balloon (1.6 ± 0.8 vs. 2.7 ± 1.3, P

Novel (Ti33Zr33Hf33)x(Ni50Cu50)100−x with x = 40–80 at.%, high entropy alloys (HEAs) developed by equiatomic substitution, each element is varied with five levels so that their microstructure and mechanical properties could be compared to define the effect of different contents. Above all, the (Ti33Zr33Hf33)60(Ni50Cu50)40 HEA exhibits enhanced the plasticity with maintaining high strength due to the occurrence of the C14-type phase of homogeneity morphology.Consequently, in this series of HEAs with equiatomic substitution selected composition with a relatively simple phase, and proceeded with the addition of other elements with good chemical compatibility factors such as atomic size different, valence electron concentration, and mixing enthalpy to induce phase transformation.

Quantum electrodynamics (QED) is a foundation of modern physics, yet access to the strong-field QED regime in the laboratory remains a formidable challenge. Currently, high-power lasers at the multi-petawatt level and above are generally believed to be an important approach to test QED physics. Here, we present a different approach by use of an electron beam self-pinched to near-solid-density. The beam self-pinching is realized while it transports through a properly designed hollow cone target, where strong azimuthal magnetic fields are generated by the beam-induced plasma return currents at the inner surface of the cone target. In this way, the beam diameter can be reduced by more than an order of magnitude down to submicron and its density is increased by hundreds of times. The produced ultradense electron beams can unlock a new regime of QED-dominated beam–plasma interactions, for example, more than 60% of the beam energy can be converted into GeV gamma-rays with unprecedented brilliance when such a beam passes through a thin solid foil. Moreover, with proper parameter design, this beam-focusing scheme can also be applied to positron beams and thus may find applications in broad areas, such as particle colliders and strong-field physics.

Oxytetracycline (OTC), one of the most important antibiotics in aquaculture industry, has been linked to emergence of antibiotic resistant genes in the aquatic environment. Given rapid growth of the aquaculture industry and unregulated use of antibiotics, it is necessary to implement measures to mitigate the impact of antibiotic resistance risk on environmental and human health. However, there is a lack of quantitative models to properly assess risk of antibiotic resistance associated with environmentally relevant antibiotic residues. To address this issue, here we developed a computational framework to assess antibiotic resistance risk posed by low-concentration OTC in aquaculture ponds and rivers across Taiwan regions. To this end, estimated amount of aquaculture used OTC as a crucial input parameter was incorporated into a multimedia fugacity model to predict environmental concentrations of OTC in surface water/sediment. A pharmacodynamic-based dose–response model was used to characterize the OTC concentration–antibiotic resistance relationships. The risk of antibiotic resistance selection in an aquatic environment could be assessed based on a probabilistic risk model. We also established a control measure model to manage the risks of substantial OTC-induced antibiotic resistance impacts. We found that OTC residues were likely to pose a high risk of tetracycline resistance (tetR) genes selection in aquaculture ponds among all the study basins, whereas risk of tetR genes selection in rivers experienced a variably changing fashion. We also showed that it was extremely difficult to moderate the tetR genes selection rates to less than 10% increase in aquaculture ponds situated at northeastern river basins in that the minimum reductions on OTC emission rates during spring, summer, and autumn were greater than 90%. On the other hand, water concentrations of OTC during spring and summer in southwestern rivers should be prioritized to be severely limited by reducing 67 and 25% of OTC emission rate, respectively. Overall, incorporating a computational fugacity model into a risk assessment framework can identify relative higher risk regions to provide the risk-based control strategies for public health decision-making and development of robust quantitative methods to zero-in on environment with high risk of tetR genes selection in relation to aquaculture-used pharmaceutical residues.

Summary: Urbanization is a pressing challenge for earth’s humans because it is changing not only natural environments but also agricultural lands. Yet, the consequences of cropland loss on pest insect populations that largely depend on these habitats remain largely unclear. We used a 17-year data set to investigate the dynamics of three moth pest species (i.e., striped stem borer, yellow stem borer, and pink stem borer) and their driving forces across the largest mega-urban region of China. Total abundance of three pest species is declined by about 80%, which was strongly associated with cropland loss during rapid urbanization. Our findings indicate that not only the increasing conversion of natural areas to human-dominated landscapes but also that of agricultural lands to urban landscapes can be critical to insect populations. It is therefore essential to monitor and understand the insect dynamics in rapidly urbanizing regions, which are currently found in many developing countries worldwide.

Objective A retrospective analysis of the clinical and pathological features of an anaplastic large cell lymphoma (ALCL) with cavernous sinus syndrome as its first symptom. Methods and Results A 35-year-old woman had head and facial pain for a month, diplopia for 7 d, right eyelid drooped for 4 d. Head MRI showed abnormal signals in right cavernous sinus, and pituitary adenoma or carvernous sinus syndrome were considered. Partial tumor resection was performed after hormone therapy was failed. Histological manifestations revealed that the tumor cells were diffuse and heterogeneous with abundant and pink stained cytoplasm, round, oval, irregular or kidney-shaped nuclei. Immunohistochemical staining showed that CD30 and CD56 were positive on the membrane, and epithelial membrane antigen (EMA) was positive on membrane and cytoplasm, and anaplastic lymphoma kinase (ALK) was negative. Ki-67 labeling index was 80%. Unfortunately, this patient died 3 weeks later after the operation, because of severe illness and intolerance to radiotherapy and chemotherapy. Conclusions The diagnosis of ALCL should be considered when cavernous sinus syndrome as the clinical symptom, and pathological examination should be performed if necessary. It should be differentiated from some tumors, such as undifferentiated non-keratinizing nasopharyngeal carcinoma, germinoma, plasmablastic lymphoma, malignant melanoma and Hodgkin's lymphoma (HL). DOI:10.3969/j.issn.1672-6731.2019.09.014

Laser-driven radiation pressure acceleration (RPA) is one of the most promising candidates to achieve quasi-monoenergetic ion beams. In particular, many petawatt systems are under construction or in the planning phase. Here, a stable radiation pressure acceleration (SRPA) scheme is investigated, in which a circularly-polarized (CP) laser pulse illuminates a CH2 thin foil followed by a large-scale near-critical-density (NCD) plasma. In the laser-foil interaction, a longitudinal charge-separated electric field is excited to accelerate ions together with the heating of electrons. The heating can be alleviated by the continuous replenishment of cold electrons of the NCD plasma as the laser pulse and the pre-accelerated ions enter into the NCD plasma. With the relativistically transparent propagation of the pulse in the NCD plasma, the accelerating field with large amplitude is persistent, and its propagating speed becomes relatively low, which further accelerates the pre-accelerated ions. Our particle-in-cell (PIC) simulation shows that the SRPA scheme works efficiently with the laser intensity ranging from 6.85×1021 W cm−2 to 4.38×1023 W cm−2, e.g., a well-collimated quasi-monoenergetic proton beam with peak energy ∼1.2 GeV can be generated by a 2.74 × 1022 W cm−2 pulse, and the energy conversion efficiency from the laser pulse to the proton beam is about 16%. The QED effects have slight influence on this SRPA scheme.

The generation of highly polarized high-energy brilliant γ-rays via laser–plasma interaction is investigated in the quantum radiation-reaction regime. We employ a quantum electrodynamics particle-in-cell code to describe spin-resolved electron dynamics semiclassically and photon emission and polarization quantum mechanically in the local constant field approximation. As an ultrastrong linearly polarized (LP) laser pulse irradiates a near-critical-density (NCD) plasma followed by an ultrathin planar aluminum target, the electrons in the NCD plasma are first accelerated by the driving laser to ultrarelativistic energies and then collide head-on with the laser pulse reflected by the aluminum target, emitting brilliant LP γ-rays via nonlinear Compton scattering with an average polarization of about 70% and energy up to hundreds of MeV. Such γ-rays can be produced with currently achievable laser facilities and will find various applications in high-energy physics and laboratory astrophysics.

Cysteine cathepsins are described as lysosomal proteases with housekeeping and highly specialised functions in many organisms. In this study, cysteine cathepsins were identified from the transcriptome profile of blunt snout bream (Megalobrama amblycephala). A total of 41 cysteine cathepsin-like sequences were found and divided into groups of cathepsin (Cts): B, C, F, H, K, L, S, and Z. Twenty-nine of these sequences contained coding sequences, encoding 92-473 amino acids, which exhibited the highest (78%-95%) homology to the counterparts from zebrafish (Danio rerio). Multiple sequence alignment of the amino acids showed highly conserved domains among the cysteine cathepsins of M. amblycephala to its homologs. The putative proteins, including maCtsb1, maCtsc1, maCtsf2, maCtsh1, maCtsk5, maCtsl5, maCtss1, and maCtsz5 were characterised and structured using in silico methods. Additionally, codon usage of full length open reading frame sequences of these cathepsins was analysed. This study provided basic information for further studies on the specific functions of cysteine cathepsins of M. amblycephala in the future.

Abstract Background Weight loss, especially fat mass reduction, helps to improve blood glucose control, insulin sensitivity, and β-cell function. This study aimed to compare the effect of exenatide and glargine on body composition in overweight and obese patients with type 2 diabetes (T2DM) who do not achieve adequate glycemic control with metformin. Methods We performed a prospective, randomized study of 37 overweight or obese patients with T2DM who had inadequate glycemic control with metformin. The patients were treated with either exenatide or glargine for 16 weeks. Dual-energy X-ray absorptiometry was used to assess body composition. Results Post-intervention weight, body mass index (BMI), waist circumference, body mass, and fat mass were lower in patients treated with exenatide, while weight and BMI significantly increased with glargine. Reductions in weight, BMI, body fat mass, and percent fat mass (except for gynoid) were greater with exenatide than with glargine, and percent lean tissue (other than the limbs) increased with exenatide. In all body regions except for the limbs, fat mass decreased with exenatide to a greater extent than lean tissue. Glucose control, insulin resistance, and β-cell function were not different between the treatment groups. Conclusions For overweight and obese patients whose T2DM was inadequately controlled with metformin, exenatide and glargine achieved similar improvements in glycemic control, insulin sensitivity, and β-cell function.However, exenatide produced better weight and fat mass reduction, which were beneficial for blood glucose control. Our findings may guide the selection of appropriate drugs for glycemic and weight control. Trial registration NCT02325960, registered 25 December 2014.

Background/Aims: Fish is a protein-rich food and is increasingly favored by consumers. It has been well recognized that the flesh composition of fish is closely related to its maturation and growth stage, but few studies have explored these differences. Additionally, hormone residues in fish after artificial induction of reproduction also attract consumer concern. In this study, we attempt to address these concerns by using a combination of transcriptomics and metabolomics analyses to identify key regulated pathways, genes, and metabolites that may affect the flesh nutrition of one typical aquaculture species in China, blunt snout bream (Megalobrama amblycephala). Methods: The four groups of fish were used for transcriptomics and metabolomics analyses, including one-year-old immature (group I), two-year-old immature (group II), two-year-old mature (group III) and successfully spawned (group IV) female M. amblycephala after artificial induction of reproduction. Results: We identified a total of 1460 differential compounds and 1107 differentially expressed unigenes in muscle among the different groups. Differential metabolites related to fish age (group II vs group I, group III vs group I) were largely enriched in “Glycerophospholipid metabolism”, “Linoleic acid metabolism”, “α-Linolenic acid metabolism”, and “Biosynthesis of unsaturated fatty acids”. Between these two pairwise comparisons, metabolites that are beneficial to human health, such as docosapentaenoic acid, α-Linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid were found to be significantly decreased in two-year-old (group II, group III) compared with one-year-old (group I) M. amblycephala. Only one differential metabolite related to fish maturation, a triglyceride, was detected between groups III and II. Transcriptomics data showed that differently expressed genes (between group III vs group II, group III vs group I) related to maturation were highly enriched in “Cell adhesion molecules (CAMs)”, “Sphingolipid metabolism” and “Phagosome”. DEGs (between group II vs group I, group III vs group I) relating to fish age were enriched in the “cGMP-PKG signaling pathway”, “FoxO signaling pathway”, and “AMPK signaling pathway”. The gene-metabolite interaction network showed pivotal genes, including fumarate hydratase and GNPAT, which played a major role in the regulation of glycerphospholipid metabolism. The nutritional components were also measured, which verified the metabolomics results. Moreover, the metabolomics results showed that after 24 hours of artificial hormone injection, the drug was completely metabolized. Conclusion: Integrated analysis demonstrated that the nutrition value of fish fillet was much more related to fish age compared with maturation status in M. amblycephala females.

A scheme is proposed for generating a polarized positron beam via multiphoton Breit-Wheeler process during the collision of a 10-GeV-level, 20-pC seeding electron beam with a second 10-GeV, multi-nC driving electron beam. The high-density driving beam with the length and transverse size less than 1 μm provides a strong self-generated field. The field experienced by the seeding beam can be unipolar by incorporating a proper impact parameter, which is crucial to realizing the positron polarization. We employ semiclassical Monte Carlo simulations to calculate the spin- and polarization-resolved photon emission and electron-positron pair production in the locally constant-field approximation. The simulation results show that a highly polarized positron beam with a polarization degree above 40% can be generated in several femtoseconds, which is robust against the beam parameters. The positron polarization degree can be further increased to 60% provided the seeding beam is initially polarized.

Abstract Background Global trend of the introduction of high levels of relatively cheap carbohydrates to reduce the amount of costly protein in the aquatic animal feed production has affected the aquaculture of an economically important cyprinid fish, blunt snout bream (Megalobrama amblycephala). This dietary shift has resulted in increased prevalence of metabolic disorders, often causing economic losses. High dietary intake of carbohydrates, associated with obesity, is one of the major causes of non-alcoholic fatty liver disease (NAFLD) in humans. Results We have conducted an eight-week feeding trial to better understand how a high-carbohydrate diet (HCBD) affects the liver health in this fish. Hepatosomatic index and lipid content were significantly (P

The spin effect of electrons/positrons ( e ^− / e ^+ ) and polarization effect of γ photons are investigated in the interaction of two counter-propagating linearly polarized laser pulses of peak intensity 8.9 × 10 ^23 W cm ^−2 with a thin foil target. The processes of nonlinear Compton scattering and nonlinear Breit–Wheeler pair production based on the spin- and polarization-resolved probabilities are implemented into the particle-in-cell (PIC) algorithm by Monte Carlo methods. It is found from PIC simulations that the average degree of linear polarization of emitted γ photons can exceed 50%. This polarization effect leads to a reduced positron yield by about 10%. At some medium positron energies, the reduction can reach 20%. Furthermore, we also observe that the local spin polarization of e ^− / e ^+ leads to a slight decrease of the positron yield about 2% and some anomalous phenomena about the positron spectrum and photon polarization at the high-energy range, due to spin-dependent photon emissions. Our results indicate that spin and polarization effects should be considered in calculating the pair production and laser-plasma interaction with the laser power of 10 PW to 100 PW classes.

An ever-increasing number of strong-field applications, such as ultrafast coherent control over matter and light, require driver light pulses that are both high power and spectrally tunable. The realization of such a source in the terahertz (THz) band has long been a formidable challenge. Here, we demonstrate, via experiment and theory, efficient production of terawatt (TW)-level THz pulses from high-intensity picosecond laser irradiation on a metal foil. It is shown that the THz spectrum can be manipulated effectively by tuning the laser pulse duration or target size. A general analytical framework for THz generation is developed, involving both the high-current electron emission and a time-varying electron sheath at the target rear, and the spectral tunability is found to stem from the change of the dominant THz generation mechanism. In addition to being an ultrabright source (brightness temperature of about 10^{21} K) for extreme THz science, the THz radiation presented here also enables a unique in situ laser-plasma diagnostic. Employing the THz radiation to quantify the escaping electrons and the transient sheath shows good agreement with experimental measurements.

MyD88 and TRAF6 play an essential role in the innate immune response in most animals. This study reports the full-length MaMyD88 and MaTRAF6 genes identified from the blunt snout bream (Megalobrama amblycephala) transcriptome profile. MaMyD88 is 2501 base pairs (bp) long, encoding a putative protein of 284 amino acids (aa), including the N-terminal DEATH domain of 78 aa and the C-terminal TIR domain of 138 aa. MaTRAF6 is 2252 bp long, encoding a putative protein of 542 aa, including the N-terminal low-complexity region, RING domain (40 aa), a coiled-coil region (64 aa) and C-terminal MATH domain (147 aa). Coding regions of MaMyD88 and MaTRAF6 genomic sequences consisted of five and six exons, respectively. Physicochemical and functional characteristics of the proteins were analysed. Alpha helices were dominant in the secondary structure of the proteins. Homology models of the MaMyD88 and MaTRAF6 domains were constructed applying the comparative modelling method. RT-qPCR was used to analyse the expression of MaMyD88 and MaTRAF6 mRNA transcripts in response to Aeromonas hydrophila challenge. Both genes were highly upregulated in the liver, spleen and kidney during the first 24 h after the challenge. While MyD88 and TRAF6 have been reported in various aquatic species, this is the first report and characterisation of these genes in blunt snout bream. This research also provides evidence of the important roles of these two genes in the blunt snout bream innate immune system.

Background: To investigate the contributions of CYP2C19 polymorphisms to the various clopidogrel responses tested by thrombelastography (TEG) in Chinese patients with the acute coronary syndrome (ACS). Methods: Patients were screened prospectively with ACS diagnose and were treated with clopidogrel and aspirin dual antiplatelet therapy. CYP2C19 loss of function (LOF) and gain of function (GOF) genotype, adenosine 5′-diphosphate (ADP)-channel platelet inhibition rate (PIR) tested by TEG and the occurrence of 3-month major adverse cardiovascular events and ischemic events were assessed in 116 patients. Results: High on-treatment platelet reactivity (HTPR) prevalence defined by PIR

To study Megalobrama amblycephala adaption to water hypoxia, the changes in physiological levels, innate immune responses, redox balance of M.amblycephala during hypoxia were investigated in the present study. When M. amblycephala were exposed to different dissolved oxygen (DO) including control (DO: 5.5 mg/L) and acute hypoxia (DO: 3.5 and 1.0 mg/L, respectively), hemoglobin (Hb), methemoglobin (MetHb), glucose, Na+, succinatedehydrogenase (SDH), lactate, interferon alpha (IFNα), and lysozyme (LYZ), except hepatic glycogen and albumin gradually increased with the decrease of DO level. When M. amblycephala were exposed to different hypoxia time including 0.5 and 6 h (DO: 3.5 mg/L), and then reoxygenation for 24 h after 6 h hypoxia, Hb, MetHb, glucose, lactate, and IFNα, except Na+, SDH, hepatic glycogen, albumin, and LYZ increased with the extension of hypoxia time, while the above investigated indexes (except albumin, IFNα, and LYZ) decreased after reoxygenation. On the other hand, the liver SOD, CAT, hydrogen peroxide (H2O2), and total ROS were all remained at lower levels under hypoxia stress. Finally, Hif-1α protein in the liver, spleen, and gill were increased with the decrease of oxygen concentration and prolongation of hypoxia time. Interestingly, one Hsp70 isoforms mediated by internal ribozyme entry site (IRES) named junior Hsp70 was only detected in liver, spleen and gill. Taken together, these results suggest that hypoxia affects M. amblycephala physiology and reduces liver oxidative stress. Hypoxia-reoxygenation stimulates M. amblycephala immune parameter expressions, while Hsp70 response to hypoxia is tissue-specific.

Phylogenetic relationships among snails (Caenogastropoda) are still unresolved, and many taxonomic categories remain non-monophyletic. Paraphyly has been reported within a large family of freshwater snails, Viviparidae, where the taxonomic status of several species remains questionable. As many endemic Chinese viviparid species have become endangered during the last few decades, this presents a major obstacle for conservation efforts. Mitochondrial genomes (mitogenomes) carry a large amount of data, so they can often provide a much higher resolution for phylogenetic analyses in comparison to the traditionally used molecular markers. To help resolve their phylogenetic relationships, the complete mitogenomes of eight Chinese viviparid snails, Viviparus chui, Cipangopaludina chinensis, C. ussuriensis, C. dianchiensis (endangered), Margarya melanioides (endangered), M. monodi (critically endangered), Bellamya quadrata and B. aeruginosa, were sequenced and compared to almost all of the available caenogastropod mitogenomes. Viviparidae possess the largest mitogenomes (16 392 to 18 544 bp), exhibit the highest A+T bias (72.5% on average), and some exhibit unique gene orders (a rearrangement of the standard MYCWQGE box), among the Caenogastropoda. Apart from the Vermetidae family and Cerithioidea superfamily, which possessed unique gene orders, the remaining studied caenogastropod mitogenomes exhibited highly conserved gene order, with minimal variations. Maximum likelihood and Bayesian inference analyses, used to reconstruct the phylogenetic relationships among 49 almost complete (all 37 genes) caenogastropod mitogenomes, produced almost identical tree topologies. Viviparidae were divided into three clades: a) Margarya and Cipangopaludina (except C. ussuriensis), b) Bellamya and C. ussuriensis, c) Viviparus chui. Our results present evidence that some Cipangopaludina species (dianchiensis and cathayensis) should be renamed into the senior genus Margarya. The phylogenetic resolution obtained in this study is insufficient to fully resolve the relationships within the 'b' clade, but if C. chinensis proves to be a valid representative of the genus, C. ussuriensis may have to be reassigned a different genus (possibly Bellamya, or even a new genus). Non-monophyly also remains pervasive among the higher (above the family-level) Caenogastropod taxonomic classes. Gene order distance matrix produced a different phylogenetic signal from the nucleotide sequences, which indicates a limited usability of this approach for inferring caenogastropod phylogenies. As phenotypic homoplasy appears to be widespread among some viviparid genera, in order to effectively protect the rapidly diminishing endemic Viviparid populations in China, further detailed molecular phylogenetic studies are urgently needed to resolve the taxonomic status of several species.

Intermuscular bones (IBs) specially exist in lower teleost fish and the molecular mechanism for its development remains to be clarified. In this study, different staining methods and comparative proteomics were conducted to investigate the histological structure and proteome of IB development in Megalobrama amblycephala, including four key IB developmental stages (S1—IBs have not emerged in the tail part; S2—several small IBs started to ossify in the tail part; S3—IBs appeared rapidly; S4—all the IBs appeared with mature morphology). Alcian blue and alizarin red S stained results indicated that IBs were gradually formed from S2 to S4, undergoing intramembranous ossification without a cartilaginous phase. A total of 3368 proteins were identified by using the isobaric tags for relative and absolute quantitation (iTRAQ) approach. Functional annotation showed that proteins which were differentially expressed among stages were involved in calcium, MAPK, Wnt, TGF-β, and osteoclast pathways which played a critical role in bone formation and differentiation. Three proteins (collagen9α1, stat1, tnc) associated with chondrocytes did not exhibit significant changes through S2 to S4; however, proteins (entpd5, casq1a, pvalb, anxa2a, anxa5) which associated with osteoblasts and bone formation and differentiation showed significantly a higher expression level from S1 to S2, as well as to S3 and S4. These further demonstrated that development of IBs did not go through a cartilaginous phase. The inhibitors of TGF-β and Wnt pathways were tested on zebrafish (sp7/eGFP) and the results indicated that both inhibitors significantly delayed IB development. This study provides a comprehensive understanding of the IB ossification pattern, which will help further elucidate the molecular mechanisms for IB development in teleosts.

It is found that there is an upper-limit critical power for self-guided propagation of intense lasers in plasma in addition to the well-known lower-limit critical power set by the relativistic effect. Above this upper-limit critical power, the laser pulse experiences defocusing due to expulsion of local plasma electrons by the transverse ponderomotive force. Associated with the upper-limit power, a lower-limit critical plasma density is also found for a given laser spot size, below which self-focusing does not occur for any laser power. Both the upper-limit power and the lower-limit density are derived theoretically and verified by two-dimensional particle-in-cell simulations. The present study provides new guidance for experimental designs, where self-guided propagation of lasers is essential.

Objective To report our experiences of direct cortical stimulation in surgery of gliomas located in eloquent areas. Methods Clinical data of 157 patients with gliomas underwent awake craniotomy with the direct electrical stimulation for functional mapping of the eloquent areas were analysed retrospectively. Results Negative cortical stimulation was found in 4 patients, and positive cortical stimulation was achieved in 153 patients (97.45% ). Four hundred and ninty ⁃ six cortical sites in 139 patients were detected for motor response by direct electrical stimulation, 70 sites in 21 patients for sensory, 112 sites in 91 patients for language (such as counting and naming). The positive areas of counting disturbance were mainly seen at the lower part of left precentral gyri operculum of left inferior frontal gyri, triangular part of left inferior frontal gyri, posterior part of left middle frontal gyri, and posterior part of left superior frontal gyri. Postoperative MRI showed 92 patients (58.60%) achieved total resection, 55 cases (35.03%) subtotal and 10 cases (6.37%) partial. One hundred and ten patients (70.06%) were diagnosed as having low grade glimas, including 71 cases of astrocytoma, 26 cases of oligodendroglioma, and 13 cases of mixed astro ⁃ oligodendroglioma, 47 patients (29.94% ) were high grade gliomas, including 19 cases of glioblastoma, 15 cases of anaplastic astrocytoma, and 13 cases of anaplastic oligodendroglioma. After operation 53 patients (33.76% ) occurred transient postoperative paralysis, 39 patients (24.84% ) transient language disturbance and 4 patients (2.55%) permanent neurological deficits. Conclusion Intraoperative direct electrical stimulation is a reliable, precise and safety method for functional mapping of the eloquent areas. This technique allows us to achieve 'maximal safety resection' in glioma surgery． DOI：10.3969/j.issn.1672⁃6731.2012.06.011

Hybridization plays an important role in fish breeding. Bream fishes contribute a lot to aquaculture in China due to their economically valuable characteristics and the present study included five bream species, Megalobrama amblycephala, Megalobrama skolkovii, Megalobrama pellegrini, Megalobrama terminalis and Parabramis pekinensis. As maternal inheritance of mitochondrial genome (mitogenome) involves species specific regulation, we aimed to investigate in which way the inheritance of mitogenome is affected by hybridization in these fish species. With complete mitogenomes of 7 hybrid groups of bream species being firstly reported in the present study, a comparative analysis of 17 mitogenomes was conducted, including representatives of these 5 bream species, 6 first generation hybrids and 6 second generation hybrids. The results showed that these 17 mitogenomes shared the same gene arrangement, and had similar gene size and base composition. According to the phylogenetic analyses, all mitogenomes of the hybrids were consistent with a maternal inheritance. However, a certain number of variable sites were detected in all F1 hybrid groups compared to their female parents, especially in the group of M. terminalis (♀) × M. amblycephala (♂) (MT×MA), with a total of 86 variable sites between MT×MA and its female parent. Among the mitogenomes genes, the protein-coding gene nd5 displayed the highest variability. The number of variation sites was found to be related to phylogenetic relationship of the parents: the closer they are, the lower amount of variation sites their hybrids have. The second generation hybrids showed less mitogenome variation than that of first generation hybrids. The non-synonymous and synonymous substitution rates (dN/dS) were calculated between all the hybrids with their own female parents and the results indicated that most PCGs were under negative selection.

The blunt snout bream (Megalobrama amblycephala) is an important freshwater aquaculture fish throughout China. Because of widespread introductions of this species to many regions, the genetic diversity of wild and natural populations is now threatened. In the present study, SRAP (sequence-related amplified polymorphism) markers were used to assess genetic diversity of blunt snout bream. Three natural populations (Liangzi Lake, Poyang Lake and Yuni Lake, one cultured population (Nanxian) and one genetic strain ('Pujiang No. 1') of blunt snout bream were screened with 88 SRAP primer combinations, of which 13 primer pairs produced stable and reproducible amplification patterns. In total, 172 bands were produced, of which 132 bands were polymorphic. Nei's gene diversity (h) and Shannon's information index (I) values provided evidence of differences in genetic diversity among the five populations (Poyang Lake>Liangzi Lake>Nanxian>'Pujiang No. 1'>Yuni Lake). Based on cluster analysis conducted on genetic distance values, the five blunt snout bream populations were divided into three groups, Poyang Lake and Liangzi Lake (natural populations), Nanxian and 'Pujiang No. 1' (cultured population and genetically selected strain), and Yuni Lake (natural population). Significant genetic differentiation was found among the five populations using analysis of molecular variance (AMOVA), with more genetic divergence existing among populations (55.49%), than within populations (44.51%). This molecular marker technique is a simple and efficient method to quantify genetic diversity within and among fish populations, and is employed here to help manage and conserve germplasm variability of blunt snout bream and to support the ongoing selective breeding programme for this fish.

Usher syndrome type 1B is a combined deaf-blindness condition caused by mutations in the MYO7A gene. Loss of functional myosin VIIa in the retinal pigment epithelia (RPE) and/or photoreceptors leads to blindness. We evaluated the impact of subretinally delivered UshStat, a recombinant EIAV-based lentiviral vector expressing human MYO7A, on photoreceptor function in the shaker1 mouse model for Usher type 1B that lacks a functional Myo7A gene. Subretinal injections of EIAV-CMV-GFP, EIAV-RK-GFP (photoreceptor specific), EIAV-CMV-MYO7A (UshStat) or EIAV-CMV-Null (control) vectors were performed in shaker1 mice. GFP and myosin VIIa expression was evaluated histologically. Photoreceptor function in EIAV-CMV-MYO7A treated eyes was determined by evaluating α-transducin translocation in photoreceptors in response to low light intensity levels, and protection from light induced photoreceptor degeneration was measured. The safety and tolerability of subretinally delivered UshStat was evaluated in macaques. Expression of GFP and myosin VIIa was confirmed in the RPE and photoreceptors in shaker1 mice following subretinal delivery of the EIAV-CMV-GFP/MYO7A vectors. The EIAV-CMV-MYO7A vector protected the shaker1 mouse photoreceptors from acute and chronic intensity light damage, indicated by a significant reduction in photoreceptor cell loss, and restoration of the α-transducin translocation threshold in the photoreceptors. Safety studies in the macaques demonstrated that subretinal delivery of UshStat is safe and well-tolerated. Subretinal delivery of EIAV-CMV-MYO7A (UshStat) rescues photoreceptor phenotypes in the shaker1 mouse. In addition, subretinally delivered UshStat is safe and well-tolerated in macaque safety studies These data support the clinical development of UshStat to treat Usher type 1B syndrome.

In the title compound, C14H4Cl4FNO2, the benzene ring and the phthalimide plane are nearly planar, the maximum deviations being 0.005 (2) and 0.010 (2) Å, respectively, but the molecule as a whole is not planar: the dihedral angle between the two planar ring systems is 68.06 (10)°. A short Cl...O contact of 2.914 (2) Å exists in the crystal structure.

In the title compound, C10H2Cl4F3NO2, the isoindoline ring system is almostplanar, the maximum atomic deviation being 0.064 (2) Å. The C—C bond of the ethylene group is twisted with respect to the isoindoline plane by a dihedral angle of 59.58 (12)°. In the crystal, weak intermolecular C—H...F hydrogen bonding links the molecules into supramolecular chains running along the a axis. A short intermolecular Cl...O contact of 2.950 (3) Å is also observed.

In the title compound, C10H6F3NO2, the isoindole ring system is planar, the maximum atomic deviation being 0.012 (2) Å. The C—C bond of the trifluoroethyl group is twisted with respect to the isoindole ring by a dihedral angle of 62.58 (17)°. Weak intermolecular C—H...O and C—H...F hydrogen bonding is present in the crystal structure.

In the title compound, C14H6F3NO2, the benzene ring and the phthalimide ring system make a dihedral angle of 60.12 (7)°. Weak intermolecular C—H...O and C—H...F hydrogen bonds are present in the crystal structure.

The title compound, C14H4Cl4FNO2, has crystallographic twofold symmetry with the N and F atoms and two C atoms of the benzene ring located on a twofold rotation axis. The isoindoledione ring system is almost planar [maximum atomic deviation = 0.036 (3) Å], and is twisted with respect to the florobenzene ring, making a dihedral angle of 58.56 (16)°. Weak intermolecular C—H...Cl hydrogen bonding is present in the crystal structure.

In the title compound, C14H7F2NO2, the phthalimide ring system is nearly planar [maximum atomic deviation = 0.028 (1) Å] and it is twisted with respect to the attached benzene ring, making a dihedral angle of 55.70 (6)°. Weak intermolecular C—H...F hydrogen bonds are present in the crystal structure.

The title compound, C23H31O2P, has three fully extended substituents around the P-atom chiral centre, forming an SP configuration. The phenyl rings are inclined at a dihedral angle of 3.2 (3)°.

Future ultrashort 10^{22}–10^{25} W cm^{-2} laser pulses offer the possibility of producing ultrashort monoenergetic electron beams in the GeV–TeV level by direct laser ponderomotive force acceleration (LPFA) in distances of millimeters to about 1 m. A scheme is proposed that a thin solid foil and a thick solid foil are placed on the laser axis, where the thin foil supplies the electron source for LPFA and the thick foil reflects the laser away, however allows the accelerated electrons to go through. By optimizing the distance between the foils, one can obtain the maximum electron beam energy. This scheme is demonstrated by particle-in-cell simulations.