Generation of attosecond electron bunches of tunable duration and density by relativistic vortex lasers in near-critical density plasma.

Attosecond electron bunches have wide application prospects in free-electron laser injection, attosecond X/γ-ray generation, ultrafast physics, etc. Nowadays, there is one notable challenge in the generation of high-quality attosecond electron bunch, i.e., how to enhance the electron bunch density. Using theoretical analysis and three-dimensional particle-in-cell simulations, we discovered that a relativistic vortex laser pulse interacting with near-critical density plasma can not only effectively concentrate the attosecond electron bunches to over critical density, but also control the duration and density of the electron bunches by tuning the intensity and carrier-envelope phase of the drive laser. It is demonstrated that this method can efficiently produce attosecond electron bunches with a density up to 300 times of the original plasma density, peak divergence angle of less than 0.5 ∘, and duration of less than 67 attoseconds. Furthermore, by using near-critical density plasma instead of solid targets, our scheme is potential for the generation of high-repetition-frequency attosecond electron bunches, thus reducing the requirements for experiments, such as the beam alignment or target supporter.

Effect of metformin on Wnt5a in individuals new-onset type 2 diabetes with different body mass indexes: The evidences from the real word research.

Aim: Metformin is a first-line therapy for the treatment of Type 2 diabetes mellitus (T2DM), due to its inhibition of hepatic gluconeogenesis. Wingless family member 5a (Wnt5a) was significantly decreased in newly diagnosed T2DM patients and regulates secretion of ß cells through the Wnt/calcium signalling cascades. This study aims to investigate how metformin works on glucose-lowering effects in diabetes and whether the mechanism underlying it is associated with Wnt5a. Methods: A total of 144 participants were enrolled in this study. Serum Wnt5a levels were measured by an enzyme-linked immunosorbent assay (ELISA). The demographic and clinical parameters were evaluated in normal weight, overweight and obese new-onset T2DM subjects grouped. Results: Wnt5a was increased in overweight T2DM patients and obese T2DM patients compared with the levels in normal Body Mass Index (BMI) T2DM. The level of Wnt5a gradually increased after 3 and 6 months of metformin treatment. Among the three groups, the most significant improvement in blood glucose was observed in the obese type 2 diabetic patients, and the improvement showed a significant correlation with Wnt5a protein after patients received metformin treatment. Pearson correlation showed that there was a significant relationship between △2hOGTT and Wnt5a. After further adjusting for sex and age, a significant association existed only between Wnt5a and 2-h oral glucose tolerance test(2hOGTT), and this association was negative. Conclusion: Our results indicate that Wnt5a may play a role in the mechanism by which metformin improves blood glucose in patients with type 2 diabetes.

[Cardiac amyloidosis: pathological classification and clinical analysis of 48 cases].

Objective: To investigate the histological features and clinical manifestations in different types of cardiac amyloidosis to improve diagnostic accuracy. Methods: The histopathological features and clinical manifestations of 48 patients diagnosed with cardiac amyloidosis by Congo red stain and electron microscopy through endomyocardial biopsy were collected in West China Hospital of Sichuan University from January 2018 to December 2021. Immunohistochemical stains for immunoglobulin light chains (κ and λ) and transthyretin protein were carried out, and a review of literature was made. Results: The patients age ranged from 42 to 79 years (mean 56 years) and the male to female ratio was 1.1 to 1.0. The positive rate of endomyocardial biopsy was 97.9% (47/48), which was significantly higher than that of the abdominal wall fat (7/17). Congo red staining and electron microscopy were positive in 97.9% (47/48) and 93.5% (43/46), respectively. Immunohistochemical stains showed 32 cases (68.1%) were light chain type (AL-CA), including 31 cases of AL-λ type and 1 case of AL-κ type; 9 cases (19.1%) were transthyretin protein type (ATTR-CA); and 6 cases (12.8%) were not classified. There was no significant difference in the deposition pattern of amyloid between different types (P>0.05). Clinical data showed that ATTR-CA patients had less involvement of 2 or more organs and lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) than the other type patients (P<0.05). The left ventricular stroke volume and right ventricular ejection fraction of ATTR-CA patients were better than the other patients (P<0.05). Follow-up data of 45 patients was obtained, and the overall mean survival time was 15.6±2.0 months. Univariate survival analysis showed that ATTR-CA patients had a better prognosis, while cardiac amyloidosis patients with higher cardiac function grade, NT-proBNP >6 000 ng/L, and troponin T >70 ng/L had a worse prognosis (P<0.05). Multivariate survival analysis showed that NT-proBNP and cardiac function grade were independent prognostic factors for cardiac amyloidosis patients. Conclusions: AL-λ is the most common type of cardiac amyloidosis in this group. Congo red staining combined with electron microscopy can significantly improve the diagnosis of cardiac amyloidosis. The clinical manifestations and prognosis of each type are different and can be classified based on immunostaining profile. However, there are still a few cases that cannot be typed; hence mass spectrometry is recommended if feasible.

Effect of glucagon-like peptide-1 receptor agonist on insulin secretion index and serum Wnt5a protein in patients with new-onset type 2 diabetes mellitus.

Objective: Previous studies have found that wnt5a promotes ß-cell insulin secretion and reduced concentrations in patients with type 2 diabetes. GLP-1RA (Glucagon-like peptide-1 receptor agonists) can regulate insulin secretion. However, the evidence that GLP-1RA affect insulin secretion through the Wnt5a is inconclusive. Therefore, this study aimed to evaluate the effect of GLP-1 RA on wnt5a levels in patients with type 2 diabetes. Methods: A total of 56 onset diabetics were selected our study, 29 of them were treated by GLP-1RAs (1.2mg subcutaneous injection once a day, liraglutide, Novo Nordisk), the rest (27 case) treated by Metformin (0.5 g twice a day, Glucophage, Merck). Individuals who were using medications to manage platelet (Aspirin) and cholesterol (Statins) were enrolled and continued treatment throughout the study. Results: Our study found that the waist circumference and insulin secretion index in the GLP-1RA intervention group were significantly increased, and the insulin resistance index was lower than that of the control group. More interestingly, the serum Wnt5a protein level increased dramatically after the GLP-1RA intervention, and the level of Secreted frizzled-related protein 5 (Sfrp5) decreased compared with the control group. Multivariate linear regression analysis showed that the change of HOMA-ß (Homeostasis model assessment- ß) was significantly correlated with the changes of Wnt5a and Sfrp5, and the change of Wnt5a protein was positively correlated with HOMA-ß. Conclusion: Our results confirmed that GLP-1RA may improve HOMA-ß in patients with type 2 diabetes by affecting the level of Wnt5a protein.

Direct acceleration of collimated monoenergetic sub-femtosecond electron bunches driven by a radially polarized laser pulse.

High-quality ultrashort electron beams have diverse applications in a variety of areas, such as 4D electron diffraction and microscopy, relativistic electron mirrors and ultrashort radiation sources. Direct laser acceleration (DLA) mechanism can produce electron beams with a large amount of charge (several to hundreds of nC), but the generated electron beams usually have large divergence and wide energy spread. Here, we propose a novel DLA scheme to generate high-quality ultrashort electron beams by irradiating a radially polarized laser pulse on a nanofiber. Since electrons are continuously squeezed transversely by the inward radial electric field force, the divergence angle gradually decreases as electrons transport stably with the laser pulse. The well-collimated electron bunches are effectively accelerated by the circularly-symmetric longitudinal electric field and the relative energy spread also gradually decreases. It is demonstrated by three-dimensional (3D) simulations that collimated monoenergetic electron bunches with 0.75° center divergence angle and 14% energy spread can be generated. An analytical model of electron acceleration is presented which interprets well by the 3D simulation results.

[Epithelioid glioblastoma with BRAF V600E mutation: a clinicopathological and molecular study].

Objective: To investigate the clinicopathological and molecular characteristics of the epithelioid glioblastoma (eGBM) with BRAF V600E mutation. Methods: Sixteen cases of eGBM with BRAF V600E mutation diagnosed at the West China Hospital of Sichuan University, China from 2012 to 2019 were collected. Their clinicopathological and molecular characteristics were analyzed. Results: The range of patients' age was from 7 to 61 years (median 31.5 years). There were 4 males and 12 females, with a male to female ratio of 1∶3. Eleven cases were newly diagnosed eGBM and five cases had a previous history of astrocytomas. Most of the tumors were located in the cerebral hemisphere, often in the frontal lobe, with an average diameter of 4.6 cm (2.0-8.0 cm). The tumors were composed of relatively uniform, closely packed epithelioid cells, some showing discohesion, with distinct cell membrane, eosinophilic cytoplasm, eccentric nuclei, distinct nucleoli and mitotic activity. Palisaded/coagulative necrosis was seen in all cases. Glomerular microvascular proliferation was seen in most of the cases, while mono-or multi-nucleated tumor giant cells were seen in some cases. Focal sarcomatoid area was seen in 2 cases, and focal pleomorphic xanthoastrocytoma (PXA)-like area was seen in 3 cases. Immunohistochemistry showed variable positivity for GFAP, Olig2 and p53. The median Ki-67 index was 30% (10%-50%). Only one case lost ATRX protein expression. Sanger sequencing identified the BRAF V600E mutation in all sixteen patients. Five cases also had mutations in the TERT gene promoter. No IDH1 (R132) or IDH2 (R172) mutation was detected. Surgical resection of the tumors was performed for all patients, and 3 patients also received adjuvant radiotherapy and chemotherapy. Follow-up data were available for 15 patients, with a follow-up time of 1-89 months (median 10 months). Among the 15 patients, 7 patients died of disease and another 5 patients had recurrences. The overall survival time of the patients under 35 years of age was significantly longer than that of the patients aged 35 years or older (P=0.014), but their progression-free survival was not statistically different (P=0.232). Conclusions: eGBM with BRAF V600E mutation is more commonly detected in young women than other the populations (i.e. elderly or male). The epithelioid morphology should include rhabdoid meningioma, anaplastic PXA, atypical teratoid/rhabdoid tumor, metastatic tumors, and melanoma in its differential diagnosis. PXA-like area is observed in some eGBM cases, suggesting a relationship of these two types of tumor. eGBM is a high-grade malignant tumor and most of the cases show recurrences or deaths in a short-period time. The younger patients have a relatively better prognosis than the older ones.

Coexistence of hyper-uricaemia and low urinary uric acid excretion further increases risk of chronic kidney disease in type 2 diabetes.

AIM: To investigate whether hyper-uricaemia and decreased urinary uric acid excretion (UUAE) are associated with increased risk of chronic kidney disease (CKD), and whether the coexistence of hyper-uricaemia and low UUAE further increases CKD risk in type 2 diabetes mellitus (T2DM). METHODS: In this cross-sectional study based on serum uric acid (SUA) and UUAE levels, 2846 T2DM inpatients were divided into those with normal SUA and UUAE (group 1), normal SUA and low UUAE (group 2), hyper-uricaemia and normal UUAE (group 3), and hyper-uricaemia and low UUAE (group 4). Hyper-uricaemia was defined as SUA levels ≥ 420 µmol/L in men and ≥ 360 µmol/L in women. Low UUAE was defined as levels below the first UUAE quintiles (< 2161 µmol/24 h in men, 1977 µmol/24 h in women). RESULTS: There were trends for significantly increased prevalences of CKD (4.3%, 12.6%, 18.3%, 47.8%; P < 0.001), albuminuria (20.2%, 26.4%, 36.9%, 54.9%; P < 0.001) and macroalbuminuria (3.3%, 10.1%, 10.7%, 31.9%; P < 0.001) from groups 1 to 4, respectively. After controlling for multiple confounding factors, prevalences of CKD (P < 0.001) and urinary albumin levels (P = 0.013) showed significantly increasing trends, whereas eGFR levels were markedly decreased from groups 1 to 4 (P < 0.001). CONCLUSION: Hyper-uricaemia and low UUAE levels are closely associated with presence of CKD, and the concomitant presence of hyper-uricaemia and decreased UUAE levels further increased CKD risk in T2DM. Thus, the combined consideration of SUA and UUAE levels may help to identify those T2DM patients at higher CKD risk.

[Prognostic significance of combined TERT and IDH gene mutation analysis in diffusely infiltrating gliomas].

Objective: To investigate the status and prognostic significance of TERT and IDH1/2 genes mutations in diffusely infiltrating gliomas. Methods: Hot spot mutations of TERT and IDH1/2 genes were detected by DNA sequencing in 236 cases of gliomas at West China Hospital from 2012 to 2016, including pilocytic astrocytoma (WHO grade Ⅰ, 16 cases), diffuse astrocytoma and oligodendroglioma (WHO grade Ⅱ, 89 cases), anaplastic astrocytoma and oligodendroglioma (WHO grade Ⅲ, 72 cases) and glioblastoma (WHO grade Ⅳ, 59 cases). The prognostic significance of TERT and IDH1/2 hot spot mutations was evaluated. Results: No IDH or TERT mutations were detected in pilocytic gliomas. TERT promoter mutation frequency was higher in patients aged ≥40 years(60.8%, 93/153) than in patients aged <40 years (32.8%, 22/67; P<0.01). TERT promoter mutation rate was also significantly higher in oligodendroglioma (87.5% , 56/64) than that in astrocytoma(37.8%, 59/156; P<0.01). Young age (<40 years), oligodendroglioma and IDH1 mutation were favorable prognostic factors for diffusely infiltrating astrocytic and oligodendroglial tumors. TERT mutation alone was not of prognostic significance. Diffusely infiltrating astrocytic and oligodendroglial tumors were divided into four molecular subtypes according to TERT and IDH1 mutation status: IDH(+ )/TERT(+ ), IDH(+ )/TERT(-), IDH(-)/TERT(-) and IDH(-)/TERT(+ ). There was significant prognostic difference among the 4 subtypes. Conclusions: Combined IDH and TERT gene mutation analysis may be useful for prognostic subgrouping. Notably, IDH1 wild-type cases can be further subdivided into TERT(+ ) or (-) subgroups with significant prognostic difference.

[The relationship between non-alcoholic fatty liver disease and metabolic syndrome in patients with latent autoimmune diabetes in adults].

Objective: To investigate the relationship between non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) in patients with latent autoimmune diabetes in adults (LADA). Methods: A total of 223 hospitalized patients were recruited between January 2007 and June 2009 in Department of Endocrinology and Metabolism of the Sixth People's Hospital Affiliated to Shanghai Jiaotong University. Finally, 142 patients with complete clinical data and without history of drinking were included in this study. According to the Chinese Medical Association's Guidelines of NAFLD, based on the result of ultrasound, all subjects were divided into two groups including patients with LADA and NAFLD (n=37) and patients with LADA but without NAFLD (n=105). Clinical data including diabetes duration, history of smoking and medications, height, weight, blood pressure, blood lipids, blood glucose, C-peptide, and liver and kidney function were collected. The prevalence and components of MetS were compared between two groups. The association between MetS and NAFLD was also explored. Results: After adjusting for age and sex, compared with the subjects without NAFLD, the subjects with NAFLD were older and had higher percentage of hypertension, and had higher body mass index[(26.5±3.7) kg/m(2) vs (21.9±3.1) kg/m(2)], waist-hip ratio(0.92±0.06 vs 0.86±0.07), low density lipoprotein cholesterol[(3.26±0.72) mmol/L vs (2.70±0.87) mmol/L], C-reactive protein, fasting C-peptide, 2 h postprandial C-peptide, systolic blood pressure, diastolic blood pressure, alanine aminotransferase and triglyceride (all P<0.05). But they had lower high-density lipoprotein cholesterol[(1.17±0.43) mmol/L vs (1.35±0.40) mmol/L]and HbA1c[(8.83±2.14) % vs (10.02±2.79)%](both P<0.05). In addition, after adjusting for age and sex, compared with the patients with LADA but without NAFLD, the prevalence of MetS in the patients with LADA and NAFLD was obviously higher (97.3% vs 47.6%, P<0.001), and the proportion of the patients with four (32.4% vs 16.2%, P<0.001) and five (43.2% vs 5.7%, P<0.001) components of MetS in the patients with LADA and NAFLD was also significantly increased than that in the patients with LADA but without NAFLD. Binary regression analysis showed that NAFLD was an independent factor associated with MetS in the patients with LADA after correcting other confounding factors (P<0.001). Conclusions: Compared with the patients with LADA but without NAFLD, the prevalence of MetS was obviously higher, and had more serious metabolic disorder in the patients with LADA and NAFLD. The presence of NAFLD was an independent factor associated with MetS in the patients with LADA.

Laser-Driven Ion Acceleration from Plasma Micro-Channel Targets.

Efficient energy boost of the laser-accelerated ions is critical for their applications in biomedical and hadron research. Achiev-able energies continue to rise, with currently highest energies, allowing access to medical therapy energy windows. Here, a new regime of simultaneous acceleration of ~100 MeV protons and multi-100 MeV carbon-ions from plasma micro-channel targets is proposed by using a ~1020 W/cm2 modest intensity laser pulse. It is found that two trains of overdense electron bunches are dragged out from the micro-channel and effectively accelerated by the longitudinal electric-field excited in the plasma channel. With the optimized channel size, these "superponderomotive" energetic electrons can be focused on the front surface of the attached plastic substrate. The much intense sheath electric-field is formed on the rear side, leading to up to ~10-fold ionic energy increase compared to the simple planar geometry. The analytical prediction of the optimal channel size and ion maximum energies is derived, which shows good agreement with the particle-in-cell simulations.

Generation of bright attosecond x-ray pulse trains via Thomson scattering from laser-plasma accelerators: errata.

We report and correct a couple of calculation errors in the x-ray flux and maximum peak brightness in our paper [Opt. Express 22, 32098 (2014)].

Numerical investigation of the transverse instability on the radiation-pressure-driven foil.

The development of transverse instability in the radiation-pressure-acceleration dominant laser-foil interaction is numerically examined by two-dimensional particle-in-cell simulations. When a plane laser impinges on a foil with modulated surface, the transverse instability is incited, and periodic perturbations of the proton density develop. The growth rate of the transverse instability is numerically diagnosed. It is found that the linear growth of the transverse instability lasts only a few laser periods, then the instability gets saturated. In order to optimize the modulation wavelength of the target, a method of information entropy is put forward to describe the chaos degree of the transverse instability. With appropriate modulation, the transverse instability shows a low chaos degree, and a quasi-monoenergetic proton beam is produced.

Electron density compression and oscillating effects on laser energy absorption in overdense plasma targets.

An analytical model for energy absorption during the interaction of an ultrashort, ultraintense laser with an overdense plasma is proposed. Both the compression effect of the electron density profile and the oscillation of the electron plasma surface are self-consistently included, which exhibit significant influences on the laser energy absorption. Based on our model, the general scaling law of the compression effect depending on laser strength and initial density is derived, and the temporal variation of the laser absorption due to the boundary oscillating effect is presented. It is found that due to the oscillation of the electron plasma surface, the laser absorption rate will vibrate periodically at ω or 2ω frequency for the p-polarized and s-polarized laser, respectively. The effect of plasma collision on the laser absorption has also been investigated, which shows a considerable rise in absorption with increasing electron-ion collision frequency for both polarizations.

Generation of bright attosecond x-ray pulse trains via Thomson scattering from laser-plasma accelerators.

Generation of attosecond x-ray pulse attracts more and more attention within the advanced light source user community due to its potentially wide applications. Here we propose an all-optical scheme to generate bright, attosecond hard x-ray pulse trains by Thomson backscattering of similarly structured electron beams produced in a vacuum channel by a tightly focused laser pulse. Design parameters for a proof-of-concept experiment are presented and demonstrated by using a particle-in-cell code and a four-dimensional laser-Compton scattering simulation code to model both the laser-based electron acceleration and Thomson scattering processes. Trains of 200 attosecond duration hard x-ray pulses holding stable longitudinal spacing with photon energies approaching 50 keV and maximum achievable peak brightness up to 1020 photons/s/mm2/mrad2/0.1%BW for each micro-bunch are observed. The suggested physical scheme for attosecond x-ray pulse trains generation may directly access the fastest time scales relevant to electron dynamics in atoms, molecules and materials.

Simultaneous generation of monoenergetic tunable protons and carbon ions from laser-driven nanofoils.

Simultaneous generation of monoenergetic tunable protons and carbon ions from intense laser multi-component nanofoil interaction is demonstrated by using particle-in-cell simulations. It is shown that, the protons with the largest charge-to-mass ratio are instantly separated from other ion species and are efficiently accelerated in the "phase stable" way. The carbon ions always ride on the heavier oxygen ion front with an electron-filling gap between the protons and carbon ions. At the cost of widely spread oxygen ions, monoenergetic collimated protons and carbon ions are obtained simultaneously. By modulating the heavier ion densities in the foil, it is capable to control the final beam quality, which is well interpreted by a simple analytical model.

Electron bow-wave injection of electrons in laser-driven bubble acceleration.

An electron injection regime in laser wake-field acceleration, namely electron bow-wave injection, is investigated by two- and three-dimensional particle-in-cell simulation as well as analytical model. In this regime electrons in the intense electron bow wave behind the first bubble catch up with the bubble tail and are trapped by the bubble finally, resulting in considerable enhancement of the total trapped electron number. For example, with the increase of the laser intensity from 2 × 10(19) to 1 × 10(20) W/cm(2), the electron trapping changes from normal self-injection to bow-wave injection and the trapped electron number is enhanced by two orders of magnitude. An analytical model is proposed to explain the numerical observation.

Enhanced collimated GeV monoenergetic ion acceleration from a shaped foil target irradiated by a circularly polarized laser pulse.

Using multidimensional particle-in-cell simulations we study ion acceleration from a foil irradiated by a circularly polarized laser pulse at 10;{22} W/cm;{2} intensity. When the foil is shaped initially in the transverse direction to match the laser intensity profile, three different regions (acceleration, transparency, and deformation region) are observed. In the acceleration region, the foil can be uniformly accelerated for a longer time compared to a usual flat target. Undesirable plasma heating is effectively suppressed. The final energy spectrum of the accelerated ion beam in the acceleration region is improved dramatically. Collimated GeV quasi-monoenergetic ion beams carrying as much as 19% of the laser energy are observed in multidimensional simulations.

Genetic complementation to identify DNA elements that influence complement resistance in Leishmania chagasi.

Past studies showed that Leishmania spp. promastigotes exhibit differential sensitivity to complement mediated lysis (CML) during development in vitro and in vivo. Leishmania chagasi promastigotes in cultures during logarithmic and stationary growth phases are CML-sensitive or CML-resistant when exposed to human serum, respectively, but only in cultures recently initiated with parasites from infected animals; serially passaged cultures become constitutively CML-sensitive regardless of growth phase. Building on these observations, a genetic screen was conducted to identify novel complement resistance factors of L. chagasi. A cosmid library containing genomic DNA was transfected into a promastigote line previously subjected to >50 serial passages. Selection with human serum for CML resistance yielded 12 transfectant clones. Cosmids isolated from 7 of these clones conferred CML resistance when transfected into an independent, high-passage promastigote culture; at 12% human serum, the mean survival of transfectants was 37% (+/- 11.6%), and that of control transfectants was about 1%. Inserts within the 7 cosmids were unique. Determination of the complete DNA sequence for 1 cosmid indicated that its 32-kilobase insert was 89% identical (overall) to a 31-kilobase region of Leishmania major chromosome 36, which is predicted to encode 6 genes, all of which encode hypothetical proteins.