[Clinical characteristics of children with SARS-CoV-2 Omicron variant infection in Kunming].

Objective: To investigate the clinical characteristics of hospitalized children infected with the Omicron variant in Kunming after the withdrawal of non-pharmaceutical interventions (NPI) and analyze the risk factors of severe cases. Methods: Clinical data was retrospectively collected from 1 145 children with SARS-CoV-2 Omicron infection who were hospitalized in six tertiary grade A hospitals in Kunming from December 10th, 2022 to January 9th, 2023. According to clinical severity, these patients were divided into the general and severe SARS-CoV-2 groups, and their clinical and laboratory data were compared. Between-group comparison was performed using t-test, chi-square test and Mann-Whitney U test. Spearman correlation test and multivariate Logistic regression analysis were used to determine the risk factors of severe illness. Results: A total of 1 145 hospitalized patients were included, of whom 677 were male and 468 female. The age of these patients at visit was 1.7 (0.5, 4.1) years. Specifically, there were 758 patients (66.2%) aged ≤3 years at visit and 387 patients (33.8%) aged >3 years. Of these children, 89 cases (7.8%) had underline diseases and the remaining 1 056 cases (92.2%) had no combined diseases. Additionally, of all the patients, 319 cases (27.9%) were vaccinated with one or two doses of SARS-CoV-2 vaccine, 748 cases (65.3%) had acute upper respiratory tract infection (AURTI), and six cases died (0.5%). A total of 1 051 cases (91.8%) were grouped into general SARS-CoV-2 group and 94 cases (8.2%) were grouped into severe SARS-CoV-2 group. Compared with the general cases, the severe cases showed a lower rate of SARS-CoV-2 vaccination and younger median age, lower lymphocyte count, as well as proportions of CD8+T lymphocyte (36 cases (38.3%) vs. 283 cases (26.9%), 0.5 (2.6, 8.0) vs. 1.6 (0.5, 3.9) years, 1.3 (1.0, 2.7) ×109 vs. 2.7 (1.3,4.4)×109/L, 0.17 (0.12, 0.24) vs. 0.21 (0.15, 0.16), respectively, χ2=4.88, Z=-2.21,-5.03,-2.53, all P<0.05). On the other hand, the length of hospital stay, proportion of underline diseases, ALT, AST, creatine kinase isoenzyme, and troponin T were higher in the severe group compared to those in the general group ((11.6±5.9) vs. (5.3±1.8) d, 41 cases (43.6%) vs. 48 cases (4.6%), 67 (26,120) vs. 20 (15, 32) U/L, 51 (33, 123) vs. 44 (34, 58) U/L、56.9 (23.0, 219.3) vs. 3.6 (1.9, 17.9) U/L, 12.0 (4.9, 56.5) vs. 3.0 (3.0, 7.0) ×10-3 pg/L,respectively, t=-20.43, χ2=183.52, Z=-9.14,-3.12,-6.38,-3.81, all P<0.05). Multivariate regression analysis indicated that increased leukocyte count (OR=1.88, 95%CI 1.18-2.97, P<0.01), CRP (OR=1.18, 95%CI 1.06-1.31, P<0.01), ferritin (OR=1.01, 95%CI 1.00-1.00, P<0.01), interleukin (IL)-6 (OR=1.05, 95%CI 1.01-1.08, P=0.012), D-dimer (OR=2.56, 95%CI 1.44-4.56, P<0.01) and decreased CD4+T lymphocyte (OR=0.84, 95%CI 0.73-0.98, P=0.030) were independently associated with the risk of severe SARS-CoV-2 in hospitalized children with Omicron infection. Conclusions: After the withdrawal of NPI, the pediatric inpatients with Omicron infection in Kunming were predominantly children younger than 3 years of age, and mainly manifested as AURTI with relatively low rate of severe SARS-CoV-2 infection and mortality. Elevated leukocyte counts, CRP, ferritin, IL-6, D-dimer, and decreased CD4+T lymphocytes are significant risk factors for developing severe SARS-CoV-2 infection.

Oxymatrine reduces expression of programmed death-ligand 1 by promoting DNA demethylation in colorectal cancer cells

Background Colorectal cancer (CRC) represents an important neoplasm with high mortality. Although PD-L1/PD-1 system-based immunotherapy has benefits for a certain type of CRC, many efforts should be made to enhance the responses to anti-PD-1/PD-L1 drugs. DNA methylation has been critically implicated in the regulation of tumor immunity. Here, we examined the effects of the natural alkaloid oxymatrine on PD-L1 expression in CRC cells and to elucidate the underlying mechanism. Methods Human CRC SW620 and HCT116 cells were treated with interferon γ (IFNγ) and/or oxymatrine. Cell viability was determined using MTT assays. PD-L1 expression was detected by real-time PCR and Western blot analyses. DNA demethylase activity was measured using kits. Results Oxymatrine did not apparently affect the viability of normal human intestinal epithelial cells. IFNγ at 20 ng/ml increased the viability of CRC cells, but oxymatrine concentration-dependently reduced the viability in the absence or presence of IFNγ. IFNγ increased the mRNA and protein expression of PD-L1 in the two cell lines, but oxymatrine significantly abolished IFNγ-elevated PD-L1 levels at both mRNA and protein levels. Furthermore, DNA demethylase activity was remarkably increased in IFNγ-treated CRC cells, which was abolished by oxymatrine concentration-dependently. In addition, DNA methyltransferase inhibitor 5-azacytidine considerably abrogated oxymatrine-induced downregulation of PD-L1 mRNA and protein levels in IFNγ-stimulated CRC cells. Conclusion Oxymatrine suppressed viability and reduced PD-L1 expression in IFNγ-stimulated CRC cells, which was attributed to enhanced DNA demethylation. Our current discoveries suggested oxymatrine as an epigenetic modulatory agent for immunotherapy against CRC via PD-1/PD-L1 blockade (AU)

Oxymatrine reduces expression of programmed death-ligand 1 by promoting DNA demethylation in colorectal cancer cells.

BACKGROUND: Colorectal cancer (CRC) represents an important neoplasm with high mortality. Although PD-L1/PD-1 system-based immunotherapy has benefits for a certain type of CRC, many efforts should be made to enhance the responses to anti-PD-1/PD-L1 drugs. DNA methylation has been critically implicated in the regulation of tumor immunity. Here, we examined the effects of the natural alkaloid oxymatrine on PD-L1 expression in CRC cells and to elucidate the underlying mechanism. METHODS: Human CRC SW620 and HCT116 cells were treated with interferon γ (IFNγ) and/or oxymatrine. Cell viability was determined using MTT assays. PD-L1 expression was detected by real-time PCR and Western blot analyses. DNA demethylase activity was measured using kits. RESULTS: Oxymatrine did not apparently affect the viability of normal human intestinal epithelial cells. IFNγ at 20 ng/ml increased the viability of CRC cells, but oxymatrine concentration-dependently reduced the viability in the absence or presence of IFNγ. IFNγ increased the mRNA and protein expression of PD-L1 in the two cell lines, but oxymatrine significantly abolished IFNγ-elevated PD-L1 levels at both mRNA and protein levels. Furthermore, DNA demethylase activity was remarkably increased in IFNγ-treated CRC cells, which was abolished by oxymatrine concentration-dependently. In addition, DNA methyltransferase inhibitor 5-azacytidine considerably abrogated oxymatrine-induced downregulation of PD-L1 mRNA and protein levels in IFNγ-stimulated CRC cells. CONCLUSION: Oxymatrine suppressed viability and reduced PD-L1 expression in IFNγ-stimulated CRC cells, which was attributed to enhanced DNA demethylation. Our current discoveries suggested oxymatrine as an epigenetic modulatory agent for immunotherapy against CRC via PD-1/PD-L1 blockade.

Highly active single-layer MoS2 catalysts synthesized by swift heavy ion irradiation.

Two-dimensional molybdenum-disulfide (MoS2) catalysts can achieve high catalytic activity for the hydrogen evolution reaction upon appropriate modification of their surface. The intrinsic inertness of the compound's basal planes can be overcome by either increasing the number of catalytically active edge sites or by enhancing the activity of the basal planes via a controlled creation of sulfur vacancies. Here, we report a novel method of activating the MoS2 surface using swift heavy ion irradiation. The creation of nanometer-scale structures by an ion beam, in combination with the partial sulfur depletion of the basal planes, leads to a large increase of the number of low-coordinated Mo atoms, which can form bonds with adsorbing species. This results in a decreased onset potential for hydrogen evolution, as well as in a significant enhancement of the electrochemical current density by over 160% as compared to an identical but non-irradiated MoS2 surface.

High resolution AFM studies of irradiated mica-following the traces of swift heavy ions under grazing incidence.

High resolution AFM imaging of swift heavy ion irradiated muscovite mica under grazing incidence provides detailed insight into the created nanostructure features. Swift heavy ions under grazing incidence form a complex track structure along the surface, which consists of a double track of nanohillocks at the impact site accompanied by a single, several 100 nm long protrusion. Detailed track studies by varying the irradiation parameters, i.e. the angle of incidence (0.2°-2°) and the kinetic energy of the impinging ions (23, 55, 75, 95 MeV) are presented. Moreover, the track formation in dependence of the sample temperature (between room temperature and 600 °C) and of the chemical composition (muscovite mica and fluorphlogopite mica) is studied.

The Neutrons for Science Facility at SPIRAL-2.

The neutrons for science (NFS) facility is a component of SPIRAL-2, the new superconducting linear accelerator built at GANIL in Caen (France). The proton and deuteron beams delivered by the accelerator will allow producing intense neutron fields in the 100 keV-40 MeV energy range. Continuous and quasi-mono-kinetic energy spectra, respectively, will be available at NFS, produced by the interaction of a deuteron beam on a thick Be converter and by the 7Li(p,n) reaction on thin converter. The pulsed neutron beam, with a flux up to two orders of magnitude higher than those of other existing time-of-flight facilities, will open new opportunities of experiments in fundamental research as well as in nuclear data measurements. In addition to the neutron beam, irradiation stations for neutron-, proton- and deuteron-induced reactions will be available for cross-sections measurements and for the irradiation of electronic devices or biological cells. NFS, whose first experiment is foreseen in 2018, will be a very powerful tool for physics, fundamental research as well as applications like the transmutation of nuclear waste, design of future fission and fusion reactors, nuclear medicine or test and development of new detectors.

Fabrication of nanoporous graphene/polymer composite membranes.

Graphene is currently investigated as a promising membrane material in which selective pores can be created depending on the requirements of the application. However, to handle large-area nanoporous graphene a stable support material is needed. Here, we report on composite membranes consisting of large-area single layer nanoporous graphene supported by a porous polymer. The fabrication is based on ion-track nanotechnology with swift heavy ions directly creating atomic pores in the graphene lattice and damaged tracks in the polymer support. Subsequent chemical etching converts the latent ion tracks in the supporting polymer foil, here polyethylene terephthalate (PET), into open microchannels while the perfectly aligned pores in the graphene top layer remain unaffected. To avoid unintentional damage creation and delamination of the graphene layer from the substrate, the graphene is encapsulated by a protecting poly(methyl methacrylate) (PMMA) layer. By this procedure a stable composite membrane is obtained consisting of nanoporous graphene (coverage close to 100%) suspended across selfaligned track-etched microchannels in a polymer support film. Our method presents a facile way to create high quality suspended graphene of tunable pore size supported on a flexible porous polymeric support, thus enabling the development of membranes for fast and selective ultrafiltration separation processes.

NaYbF4 nanoparticles as near infrared light excited inorganic photosensitizers for deep penetration in photodynamic therapy.

Photodynamic therapy (PDT) is a non-invasive therapy with many advantages over other therapeutic methods, but it is restricted to treat superficial cancers due to the shallow tissue penetration of visible light. The biological window in the near infrared region (NIR) offers hope to extend the penetration depth, but there is no natural NIR excited photosensitizer. Here, we report a novel photosensitizer: NaYbF4 nanoparticles (NPs). By using a 1,3-diphenylisobenzofuran (DPBF) sensor, we show that the Yb3+ ions can absorb the NIR light and transfer energy directly to oxygen to generate reactive oxygen species (ROS). The efficiency of transferring energy to oxygen by NaYbF4 NPs is comparable to that of traditional photosensitizers. We have carried out PDT both in vitro and in vivo based on NaYbF4 NPs; the results demonstrate that NaYbF4 NPs are indeed an effective NIR photosensitizer, which can help extend the application of PDT to solid tumors owing to the much deeper penetration depth of NIR light.

The preparation of rat's acellular spinal cord scaffold and co-culture with rat's spinal cord neuron in vitro.

STUDY DESIGN: The rat's acellular spinal cord scaffold (ASCS) and spinal cord neurons were prepared in vitro to explore their biocompatibility. OBJECTIVES: The preparation of ASCS and co-culture with neuron may lay a foundation for clinical treatment of spinal cord injury (SCI). SETTING: Tianjin Medical University General Hospital, ChinaMethods:ASCS was prepared by chemical extraction method. Hematoxylin and eosin (H&E), myelin staining and scanning electron microscope were used to observe the surface structure of ASCS. Spinal cord neurons of rat were separated in vitro, and then co-cultured with prepared ASCS in virto. RESULTS: The prepared ASCS showed mesh structure with small holes of different sizes. H&E staining showed that cell components were all removed. The ASCS possessed fine three-dimensional network porous structure. DNA components were not found in the ASCS by DNA agarose gel electrophoresis. The cultured cells express neuron-specific enolase (NSE) antigen with long axons. H&E staining showed that the neurons adhered to the pore structures of ASCS, and the cell growth was fine. The survival rate of co-cultured cells was (97.53±1.52%) by MTT detection. Immunohistochemical staining showed that neurons on the scaffold expressed NSE and NeuN antigen. Cells were arranged closely, and the channel structures of ASCS were fully filled with neurons. The cells accumulated in the channel and grew well in good state. CONCLUSION: The structure of ASCS remained intact, and the neurons were closely arranged in the scaffolds. These results may lay a solid foundation for clinical treatment of SCI when considering glial scar replacement by biomaterials.

A new setup for localized implantation and live-characterization of keV energy multiply charged ions at the nanoscale.

An innovative experimental setup, PELIICAEN, allowing the modification of materials and the study of the effects induced by multiply charged ion beams at the nanoscale is presented. This ultra-high vacuum (below 5 × 10-10 mbar) apparatus is equipped with a focused ion beam column using multiply charged ions and a scanning electron microscope developed by Orsay Physics, as well as a scanning probe microscope. The dual beam approach coupled to the scanning probe microscope achieves nanometer scale in situ topological analysis of the surface modifications induced by the ion beams. Preliminary results using the different on-line characterization techniques to study the formation of nano-hillocks on silicon and mica substrates are presented to illustrate the performances of the setup.

Swift heavy ion irradiation of CaF2 - from grooves to hillocks in a single ion track.

A novel form of ion-tracks, namely nanogrooves and hillocks, are observed on CaF2 after irradiation with xenon and lead ions of about 100 MeV kinetic energy. The irradiation is performed under grazing incidence (0.3°-3°) which forces the track to a region in close vicinity to the surface. Atomic force microscopy imaging of the impact sites with high spatial resolution reveals that the surface track consists in fact of three distinct parts: each swift heavy ion impacting on the CaF2 surface first opens a several 100 nm long groove bordered by a series of nanohillocks on both sides. The end of the groove is marked by a huge single hillock and the further penetration of the swift projectile into deeper layers of the target is accompanied by a single protrusion of several 100 nm in length slowly fading until the track vanishes. By comparing experimental data for various impact angles with results of a simulation, based on a three-dimensional version of the two-temperature-model (TTM), we are able to link the crater and hillock formation to sublimation and melting processes of CaF2 due to the local energy deposition by swift heavy ions.

Nanoscopic voltage distribution of operating cascade laser devices in cryogenic temperature.

A nanoscopic exploratory measurement technique to measure voltage distribution across an operating semiconductor device in cryogenic temperature has been developed and established. The cross-section surface of the terahertz (THz) quantum cascade laser (QCL) has been measured that resolves the voltage distribution at nanometer scales. The electric field dissemination across the active region of the device has been attained under the device's lasing conditions at cryogenic temperature of 77 K.

Nanostructuring graphene by dense electronic excitation.

The ability to manufacture tailored graphene nanostructures is a key factor to fully exploit its enormous technological potential. We have investigated nanostructures created in graphene by swift heavy ion induced folding. For our experiments, single layers of graphene exfoliated on various substrates and freestanding graphene have been irradiated and analyzed by atomic force and high resolution transmission electron microscopy as well as Raman spectroscopy. We show that the dense electronic excitation in the wake of the traversing ion yields characteristic nanostructures each of which may be fabricated by choosing the proper irradiation conditions. These nanostructures include unique morphologies such as closed bilayer edges with a given chirality or nanopores within supported as well as freestanding graphene. The length and orientation of the nanopore, and thus of the associated closed bilayer edge, may be simply controlled by the direction of the incoming ion beam. In freestanding graphene, swift heavy ion irradiation induces extremely small openings, offering the possibility to perforate graphene membranes in a controlled way.

Differential gene expression of epigenetic modifying enzymes between Tibet pig and Yorkshire in high and low altitudes.

Epigenetic modifying enzymes play important roles in the adaptation to hypoxia, although no studies have examined their expression levels in Tibet pigs. The lung is an important functional organ in hypoxia adaptation. In this study, we examined the mRNA expression level of 5 enzymes in the lung of Tibet pigs using real-time polymerase chain reaction to determine the epigenetic performance of hypoxia adaptation. We selected four groups of pig as the study object, which were Tibet pig in highland (TH), Yorkshire in highland (YH), Tibet pig in lowland (TL), Yorkshire in lowland (YL). Expression of Dnmt1 in Tibet pig was higher than that in Yorkshire (P < 0.01), although there was no significant difference between different altitudes within each breed. Expression of Dnmt3a was higher in Tibet pig than that in Yorkshire (P < 0.01), and higher in pigs from highland than that in lowland areas (P < 0.05). Expression of Hdac1 was higher in group TH than in Yorkshire (P < 0.01). Expression of Kdm3a was higher in group TH than in the rest of the groups (P < 0.01). Expression of Uhrf1 was higher in Tibet pig than in Yorkshire (P < 0.01). In conclusion, the expression levels of the 5 epigenetic modifying genes were higher in group TH than in group YH. Under conditions of oxygen deficiency, breed was the most important factor affecting DNA methylation and gene expression.

Graphitic nanostripes in silicon carbide surfaces created by swift heavy ion irradiation.

The controlled creation of defects in silicon carbide represents a major challenge. A well-known and efficient tool for defect creation in dielectric materials is the irradiation with swift (E(kin) ≥ 500 keV/amu) heavy ions, which deposit a significant amount of their kinetic energy into the electronic system. However, in the case of silicon carbide, a significant defect creation by individual ions could hitherto not be achieved. Here we present experimental evidence that silicon carbide surfaces can be modified by individual swift heavy ions with an energy well below the proposed threshold if the irradiation takes place under oblique angles. Depending on the angle of incidence, these grooves can span several hundreds of nanometres. We show that our experimental data are fully compatible with the assumption that each ion induces the sublimation of silicon atoms along its trajectory, resulting in narrow graphitic grooves in the silicon carbide matrix.

An innovative experimental setup for the measurement of sputtering yield induced by keV energy ions.

An innovative experimental equipment allowing to study the sputtering induced by ion beam irradiation is presented. The sputtered particles are collected on a catcher which is analyzed in situ by Auger electron spectroscopy without breaking the ultra high vacuum (less than 10(-9) mbar), avoiding thus any problem linked to possible contamination. This method allows to measure the angular distribution of sputtering yield. It is now possible to study the sputtering of many elements such as carbon based materials. Preliminary results are presented in the case of highly oriented pyrolytic graphite and tungsten irradiated by an Ar(+) beam at 2.8 keV and 7 keV, respectively.

Two-dimensional profiling of carriers in terahertz quantum cascade lasers using calibrated scanning spreading resistance microscopy and scanning capacitance microscopy.

The distribution of charge carriers inside the active region of a terahertz (THz) quantum cascade laser (QCL) has been measured with scanning spreading resistance microscopy (SSRM) and scanning capacitance microscopy (SCM). Individual quantum well-barrier modules with a 35.7-nm single module thickness in the active region of the device have been resolved for the first time using high-resolution SSRM and SCM techniques at room temperature. SSRM and SCM measurements on the quantum well-barrier structure were calibrated utilizing known GaAs dopant staircase samples. Doping concentrations derived from SSRM and SCM measurements were found to be in quantitative agreement with the designed average doping values of the n-type active region in the terahertz quantum cascade laser. The secondary ion mass spectroscopy provides a partial picture of internal device parameters, and we have demonstrated with our results the efficacy of uniting calibrated SSRM and SCM to delineate quantitatively the transverse cross-sectional structure of complex two-dimensional terahertz quantum cascade laser devices.

Terahertz quantum cascade lasers operating up to ∼ 200 K with optimized oscillator strength and improved injection tunneling.

A new temperature performance record of 199.5 K for terahertz quantum cascade lasers is achieved by optimizing the lasing transition oscillator strength of the resonant phonon based three-well design. The optimum oscillator strength of 0.58 was found to be larger than that of the previous record (0.41) by Kumar et al. [Appl. Phys. Lett. 94, 131105 (2009)]. The choice of tunneling barrier thicknesses was determined with a simplified density matrix model, which converged towards higher tunneling coupling strengths than previously explored and nearly perfect alignment of the states across the injection and extraction barriers at the design electric field. At 8 K, the device showed a threshold current density of 1 kA/cm2, with a peak output power of ∼ 38 mW, and lasing frequency blue-shifting from 2.6 THz to 2.85 THz with increasing bias. The wavelength blue-shifted to 3.22 THz closer to the maximum operating temperature of 199.5 K, which corresponds to ∼ 1.28hω/κB. The voltage dependence of laser frequency is related to the Stark effect of two intersubband transitions and is compared with the simulated gain spectra obtained by a Monte Carlo approach.

Epidemiology of traumatic spinal cord injury in Tianjin, China.

STUDY DESIGN: A retrospective epidemiological study. OBJECTIVES: To provide recent epidemiological characteristics of traumatic spinal cord injuries (TSCIs) in adults living in Tianjin. SETTING: Tianjin, China. METHODS: This study included all TSCI patients aged 15 years or older who were admitted to tertiary hospitals in Tianjin from 2004 to 2008. Epidemiological characteristics, such as age, sex, date of admission, causes of injury, level of injury, America Spinal Injury Association impairment scale and date of discharge were included. RESULTS: A total of 869 patients were included, with an estimated annual incidence was 23.7 per million populations. The male/female ratio was 5.63:1. Mean age of TSCI was 46.0±14.2 years (men 45.8±14.2 years, women 47.5±14.5 years), with a range of 16-90 years. Falls were regarded as the leading causes of injury, followed by motor vehicle collisions. The lesion level was cervical in 71.5%, thoracic in 13.3% and lumbar/sacral in 15.1%. The frequency of tetraplegia (71.5%) was higher than paraplegia (28.5%), and roughly four-fifth of tetraplegia cases were incomplete injury. CONCLUSION: To our knowledge, national or local epidemiological study of spinal cord injury (SCI) has not been carried out previously in China. The number of SCI patients in this country is large and would increase gradually. Similar to other developing countries, falls were the main causes of TSCI. Low falls were more common in those over 60 years old. As the ageing society coming, the number of low falls-induced TSCI would increase gradually, which poses a challenge to the society health system.

Electrically switching transverse modes in high power THz quantum cascade lasers.

The design and fabrication of a high power THz quantum cascade laser (QCL), with electrically controllable transverse mode is presented. The switching of the beam pattern results in dynamic beam switching using a symmetric side current injection scheme. The angular-resolved L-I curves measurements, near-field and far-field patterns and angular-resolved lasing spectra are presented. The measurement results confirm that the quasi-TM(01) transverse mode lases first and dominates the lasing operation at lower current injection, while the quasi-TM(00) mode lases at a higher threshold current density and becomes dominant at high current injection. The near-field and far-field measurements confirm that the lasing THz beam is maneuvered by 25 degrees in emission angle, when the current density changes from 1.9 kA/cm(2) to 2.3 kA/cm(2). A two-dimension (2D) current and mode calculation provides a simple model to explain the behavior of each mode under different bias conditions.