New steady-state quiescent high-confinement plasma in an experimental advanced superconducting tokamak.

A critical challenge facing the basic long-pulse high-confinement operation scenario (H mode) for ITER is to control a magnetohydrodynamic (MHD) instability, known as the edge localized mode (ELM), which leads to cyclical high peak heat and particle fluxes at the plasma facing components. A breakthrough is made in the Experimental Advanced Superconducting Tokamak in achieving a new steady-state H mode without the presence of ELMs for a duration exceeding hundreds of energy confinement times, by using a novel technique of continuous real-time injection of a lithium (Li) aerosol into the edge plasma. The steady-state ELM-free H mode is accompanied by a strong edge coherent MHD mode (ECM) at a frequency of 35-40 kHz with a poloidal wavelength of 10.2 cm in the ion diamagnetic drift direction, providing continuous heat and particle exhaust, thus preventing the transient heat deposition on plasma facing components and impurity accumulation in the confined plasma. It is truly remarkable that Li injection appears to promote the growth of the ECM, owing to the increase in Li concentration and hence collisionality at the edge, as predicted by GYRO simulations. This new steady-state ELM-free H-mode regime, enabled by real-time Li injection, may open a new avenue for next-step fusion development.

New edge coherent mode providing continuous transport in long-pulse H-mode plasmas.

An electrostatic coherent mode near the electron diamagnetic frequency (20-90 kHz) is observed in the steep-gradient pedestal region of long pulse H-mode plasmas in the Experimental Advanced Superconducting Tokamak, using a newly developed dual gas-puff-imaging system and diamond-coated reciprocating probes. The mode propagates in the electron diamagnetic direction in the plasma frame with poloidal wavelength of ∼8 cm. The mode drives a significant outflow of particles and heat as measured directly with the probes, thus greatly facilitating long pulse H-mode sustainment. This mode shows the nature of dissipative trapped electron mode, as evidenced by gyrokinetic turbulence simulations.

Clostridium sporogenes delivers interleukin-12 to hypoxic tumours, producing antitumour activity without significant toxicity.

UNLABELLED: Clostridium sporogenes ATCC 3584 is an obligate anaerobe that has been reported to possess excellent tumour-targeting capacity. Here, we use Cl. sporogenes as a vector to deliver IL-12, a potent antitumour cytokine that bears numerous antitumour properties but that has limited clinical applications due to its strong toxicity when delivered systemically. In this study, Cl. sporogenes was genetically engineered to secrete murine IL-12, and its antitumour efficacy and toxicity were investigated in a murine EMT6 mammary carcinoma model. After intravenous injection, Cl. sporogenes was able to selectively settle and reproduce in the tumours without encroaching on normal tissues, resulting in a clear delay of tumour growth and a 14·3% cure rate. Importantly, the mice showed no obvious toxicity-associated side effects, such as diarrhoea and weight loss, during the treatment process. The significant antitumour efficacy and low toxicity of this treatment may be explained by the selective tumour-targeting properties of Cl. sporogenes and by the sustained release of IL-12 accompanying bacterial proliferation. This moderate local IL-12 concentration would not induce the severe response in the entire body, that is inevitable when IL-12 is administered directly. SIGNIFICANCE AND IMPACT OF THE STUDY: Interleukin-12 (IL-12) is a potent antitumour cytokine, but it is toxic when administrated systemically. This study demonstrates that murine IL-12 can be systemically delivered to hypoxic sites in solid tumours by Clostridium sporogenes, producing a clear delay in tumour growth and a 14·3% cure rate in a mouse tumour model. Importantly, there is no obvious toxicity associated with IL-12 during the treatment process. This result may be accounted for by the excellent tumour-targeting capacity of Cl. sporogenes, targeting IL-12 directly to the tumour site instead of to the entire body.

[Research progress on prevention and local intervention of oral mucositis in patients with hematopoietic stem cell transplantation].

Oral mucositis (OM) is a common complication during hematopoietic stem cell transplantation. When OM occurs, with the destruction of oral mucosal barrier function, the formation of oral bacterial environment is accelerated, which has a negative impact on the life quality and clinical outcomes of patients. OM can be prevented by keeping the oral cavity clean, using the mouthwash properly, and limiting the delivery of cytotoxic drugs to oral tissues. This review describes the research progress on the prevention and local intervention of OM in patients with hematopoietic stem cell transplantation, in order to provide ideas for the selection of clinical intervention and management strategies on OM, and to provide references for exploring effective management methods for OM.

[A cohort study on the correlation between alanine aminotransferase trajectories and new-onset metabolic fatty liver disease].

Objective: To explore the correlation between alanine aminotransferase (ALT) trajectories and new-onset metabolic fatty liver disease (MAFLD) to provide a scientific basis for the prevention and treatment of MAFLD. Methods: The study cohort was composed of 3 553 subjects who met the inclusion criteria in the cohort study of the Henan physical examination population. According to the ALT levels of the subjects' physical examination from 2017-2019, three different ALT trajectory groups were determined by R LCTMtools, namely low-stable group, medium-stable group, and high-stable group. The incidence of MAFLD during physical examination in 2020 was followed up, the cumulative incidence rate in each group was calculated by product-limit method, and Cox proportional hazards regression model analyzed the correlation between different ALT trajectories and new-onset MAFLD. Results: The incidence rate of MAFLD parallelly increased with the increase of ALT locus, which was 6.93%, 15.42%, and 19.05%, respectively, and the difference was statistically significant (P<0.001). After adjusting for multiple confounding factors, such as gender, waist circumference, blood pressure, BMI, fasting blood sugar, and blood lipid by Cox proportional hazards regression model, the risks of MAFLD in ALT medium-stable and the high-stable group were still 1.422 times (95%CI:1.115-1.813) and 1.483 times (95%CI:1.040-2.114) of low-stable ALT group (P<0.05). Conclusions: The risk of MAFLD parallelly increases with the increase of ALT level in the normal long-term range. it is necessary to carry out the intervention for MAFLD with long-term average high value to avoid the progress of MAFLD disease to achieve the early prevention on MAFLD.

First evidence of the role of zonal flows for the L-H transition at marginal input power in the EAST tokamak.

A quasiperiodic Er oscillation at a frequency of <4 kHz, much lower than the geodesic-acoustic-mode frequency, with a modulation in edge turbulence preceding and following the low-to-high (L-H) confinement mode transition, has been observed for the first time in the EAST tokamak, using two toroidally separated reciprocating probes. Just prior to the L-H transition, the Er oscillation often evolves into intermittent negative Er spikes. The low-frequency Er oscillation, as well as the Er spikes, is strongly correlated with the turbulence-driven Reynolds stress, thus providing first evidence of the role of the zonal flows in the L-H transition at marginal input power. These new findings not only shed light on the underlying physics mechanism for the L-H transition, but also have significant implications for ITER operations close to the L-H transition threshold power.

LncRNA SNHG20 enhances the progression of oral squamous cell carcinoma by regulating the miR-29a/DIXDC1/Wnt regulatory axis.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) comprises approximately ~90% of all oral malignancies and exhibits a significant mortality rate worldwide. Although the dysregulation of small nucleolar RNA host gene 20 (SNHG20) participates in the development of multiple malignancies, the molecular mechanisms underlying its regulation of OSCC progression remain to be fully elucidated. PATIENTS AND METHODS: The expression levels of SNHG20, microRNA-29a (miR-29a), and Disheveled-Axin Domain Containing 1 (DIXDC1) were detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). The protein expression levels of DIXDC1 and ß-catenin were measured by Western blotting. In addition, MTT assay was performed to measure the cell proliferation ability in SCC9 and SCC15 cells. Cell migration and invasion abilities were measured by wound healing assay and transwell assay, respectively. The cell apoptosis was assessed by flow cytometry assay. Besides, Luciferase reporter assay was employed to examine the interrelation between miR-29a and SNHG20 or DIXDC1. RESULTS: It was demonstrated that SNHG20 and DIXDC1 were significantly upregulated in OSCC tissues and cell lines, while miR-29a was markedly downregulated. Moreover, the high expression of SNHG20 was found to predict a lower survival rate in OSCC patients. In addition, loss-of-function experiments demonstrated that SNHG20 knockdown inhibited the development and progression of OSCC, whereas the miR-29a inhibitor significantly abolished the effect of SNHG20 depletion on OSCC progression by directly binding to SNHG20. DIXDC1 was shown to enhance si-SNHG20 and miR-29a mimic-attenuated cell viability, migration, and invasion by directly binding to miR-29a. Furthermore, it was also found that DIXDC1 activated Wnt signaling in OSCC cells. CONCLUSIONS: Our study demonstrated that SNHG20 promoted OSCC progression via the miR-29a/DIXDC1/Wnt signaling pathway, which might provide a novel theoretical basis for the treatment of OSCC.

Streamflow calculation for medium-to-small rivers in data scarce inland areas.

Inland streamflow estimation is essential in global water supply and environment protection. In data-scarce areas a highly efficient way of estimating streamflow is through remote sensing methods. However, high requirement of most previous methods on ground-measured data hinder their wide use in data-scarce areas. Therefore, this paper presented a new framework for estimation of streamflow in medium-to-small rivers with few ground measurements by using high-resolution unmanned aerial vehicle (UAV) imagery. A new Virtual Hydraulic Radius (VHR) method was proposed to complement AMHG (at-many-stations hydraulic geometry), a method not requiring any ground measurements when global parameters are used (global-AMHG) in large-scaled rivers but yielding great uncertainties in smaller scaled rivers, thus creating a VHR-AMHG method for medium-to-small rivers. The accuracy verification of the proposed method was performed by comparing it to field measurement data and the global parameters of the original AMHG (global-AMHG). Results showed that the root mean square error calculated from VHR-AMHG was 32.15 m3/s, while that from global-AMHG was 305.65 m3/s, indicating that the VHR-AHRG method yields a significantly higher accuracy for streamflow estimation for medium-to-small rivers. We found that regardless of the size of the river, AMHG is not applicable for rivers having excessively small b values in the equation w = aQb (low-b rivers). For medium-to-small rivers with b < 0.25, AMHG is not recommended. The accuracy of the original AMHG method is limited by the initial value of the model parameters and the condition that the congruent discharge (Qc) has to be within the range of observational discharge. The initial value setting of the model parameters significantly impacts the calculation accuracy. The VHR-AMHG method is able to overcome the deficiencies of the original AMHG, i.e. being overly dependent on the initial value setting with long-series known discharge data. It also eliminates the limitation of the Qc condition, as it achieves a higher accuracy for rivers in which Qc does not satisfy the condition compared to using global-AMHG on rivers that actually meet the condition, thus greatly expanding its usage scope. Thus VHR-AMHG method can provide detailed data on the spatial and temporal distribution of regional and national streamflow for governments and stakeholders, and offer scientific data support for wisely making water supply polices and sustainably protecting eco-environment.

Validation of fast-ion D-alpha spectrum measurements during EAST neutral-beam heated plasmas.

To investigate the fast ion behavior, a fast ion D-alpha (FIDA) diagnostic system has been installed on EAST. Fast ion features can be inferred from the Doppler shifted spectrum of Balmer-alpha light from energetic hydrogenic atoms. This paper will focus on the validation of FIDA measurements performed using MHD-quiescent discharges in 2015 campaign. Two codes have been applied to calculate the Dα spectrum: one is a Monte Carlo code, Fortran 90 version FIDASIM, and the other is an analytical code, Simulation of Spectra (SOS). The predicted SOS fast-ion spectrum agrees well with the measurement; however, the level of fast-ion part from FIDASIM is lower. The discrepancy is possibly due to the difference between FIDASIM and SOS velocity distribution function. The details will be presented in the paper to primarily address comparisons of predicted and observed spectrum shapes/amplitudes.

New dual gas puff imaging system with up-down symmetry on experimental advanced superconducting tokamak.

Gas puff imaging (GPI) offers a direct and effective diagnostic to measure the edge turbulence structure and velocity in the edge plasma, which closely relates to edge transport and instability in tokamaks. A dual GPI diagnostic system has been installed on the low field side on experimental advanced superconducting tokamak (EAST). The two views are up-down symmetric about the midplane and separated by a toroidal angle of 66.6°. A linear manifold with 16 holes apart by 10 mm is used to form helium gas cloud at the 130×130 mm (radial versus poloidal) objective plane. A fast camera is used to capture the light emission from the image plane with a speed up to 390,804 frames/s with 64×64 pixels and an exposure time of 2.156 µs. The spatial resolution of the system is 2 mm at the objective plane. A total amount of 200 Pa.L helium gas is puffed into the plasma edge for each GPI viewing region for about 250 ms. The new GPI diagnostic has been applied on EAST for the first time during the recent experimental campaign under various plasma conditions, including ohmic, L-mode, and type-I, and type-III ELMy H-modes. Some of these initial experimental results are also presented.

Peak effect in the critical current of type II superconductors with strong magnetic vortex pinning.

We perform 2D Langevin simulations studying the peak effect (PE) of the critical current taking into account the temperature dependence of the competing forces. We observe and report that the PE results from the competition of vortex-vortex interactions and vortex-pin interactions which have different temperature dependencies. The simulations reveal that the PE can take place only for certain pinning strengths, densities of pinning centers, and driving forces, which is in good agreement with experiments. No apparent vortex order-disorder transition is observed across the PE regime. In addition, the PE is a dynamical phenomenon, and thermal fluctuations can speed up the process for the formation of the PE.

[Treatment of chronic osteomyelitis of leg with free latissimus dorsi musculocutaneous flap anastomosed to contralateral leg vessels].

A free latissimus dorsi musculocutaneous flap was first anastomosed to dorsal vessels of the contralateral leg. It was then used to cover a large defect of the leg as a result of chronic osteomyelitis. The use of such a cross-leg flap was not affected by the poor circulatory condition of the diseased leg. It was done in 20 patients with satisfactory results. All of them could take part in the physical work.

A scaffoldin of the Bacteroides cellulosolvens cellulosome that contains 11 type II cohesins.

A cellulosomal scaffoldin gene, termed cipBc, was identified and sequenced from the mesophilic cellulolytic anaerobe Bacteroides cellulosolvens. The gene encodes a 2,292-residue polypeptide (excluding the signal sequence) with a calculated molecular weight of 242,437. CipBc contains an N-terminal signal peptide, 11 type II cohesin domains, an internal family III cellulose-binding domain (CBD), and a C-terminal dockerin domain. Its CBD belongs to family IIIb, like that of CipV from Acetivibrio cellulolyticus but unlike the family IIIa CBDs of other clostridial scaffoldins. In contrast to all other scaffoldins thus far described, CipBc lacks a hydrophilic domain or domain X of unknown function. The singularity of CipBc, however, lies in its numerous type II cohesin domains, all of which are very similar in sequence. One of the latter cohesin domains was expressed, and the expressed protein interacted selectively with cellulosomal enzymes, one of which was identified as a family 48 glycosyl hydrolase on the basis of partial sequence alignment. By definition, the dockerins, carried by the cellulosomal enzymes of this species, would be considered to be type II. This is the first example of authentic type II cohesins that are confirmed components of a cellulosomal scaffoldin subunit rather than a cell surface anchoring component. The results attest to the emerging diversity of cellulosomes and their component sequences in nature.

A novel cellulosomal scaffoldin from Acetivibrio cellulolyticus that contains a family 9 glycosyl hydrolase.

A novel cellulosomal scaffoldin gene, termed cipV, was identified and sequenced from the mesophilic cellulolytic anaerobe Acetivibrio cellulolyticus. Initial identification of the protein was based on a combination of properties, including its high molecular weight, cellulose-binding activity, glycoprotein nature, and immuno-cross-reactivity with the cellulosomal scaffoldin of Clostridium thermocellum. The cipV gene is 5,748 bp in length and encodes a 1,915-residue polypeptide with a calculated molecular weight of 199,496. CipV contains an N-terminal signal peptide, seven type I cohesin domains, an internal family III cellulose-binding domain (CBD), and an X2 module of unknown function in tandem with a type II dockerin domain at the C terminus. Surprisingly, CipV also possesses at its N terminus a catalytic module that belongs to the family 9 glycosyl hydrolases. Sequence analysis indicated the following. (i) The repeating cohesin domains are very similar to each other, ranging between 70 and 90% identity, and they also have about 30 to 40% homology with each of the other known type I scaffoldin cohesins. (ii) The internal CBD belongs to family III but differs from other known scaffoldin CBDs by the omission of a 9-residue stretch that constitutes a characteristic loop previously associated with the scaffoldins. (iii) The C-terminal type II dockerin domain is only the second such domain to have been discovered; its predicted "recognition codes" differ from those proposed for the other known dockerins. The putative calcium-binding loop includes an unusual insert, lacking in all the known type I and type II dockerins. (iv) The X2 module has about 60% sequence homology with that of C. thermocellum and appears at the same position in the scaffoldin. (v) Unlike the other known family 9 catalytic modules of bacterial origin, the CipV catalytic module is not accompanied by a flanking helper module, e.g., an adjacent family IIIc CBD or an immunoglobulin-like domain. Comparative sequence analysis of the CipV functional modules with those of the previously sequenced scaffoldins provides new insight into the structural arrangement and phylogeny of this intriguing family of microbial proteins. The modular organization of CipV is reminiscent of that of the CipA scaffoldin from C. thermocellum as opposed to the known scaffoldins from the mesophilic clostridia. The phylogenetic relationship of the different functional modules appears to indicate that the evolution of the scaffoldins reflects a collection of independent events and mechanisms whereby individual modules and other constituents are incorporated into the scaffoldin gene from different microbial sources.

Cellulosomal scaffoldin-like proteins from Ruminococcus flavefaciens.

Two tandem cellulosome-associated genes were identified in the cellulolytic rumen bacterium, Ruminococcus flavefaciens. The deduced gene products represent multimodular scaffoldin-related proteins (termed ScaA and ScaB), both of which include several copies of explicit cellulosome signature sequences. The scaB gene was completely sequenced, and its upstream neighbor scaA was partially sequenced. The sequenced portion of scaA contains repeating cohesin modules and a C-terminal dockerin domain. ScaB contains seven relatively divergent cohesin modules, two extremely long T-rich linkers, and a C-terminal domain of unknown function. Collectively, the cohesins of ScaA and ScaB are phylogenetically distinct from the previously described type I and type II cohesins, and we propose that they define a new group, which we designated here type III cohesins. Selected modules from both genes were overexpressed in Escherichia coli, and the recombinant proteins were used as probes in affinity-blotting experiments. The results strongly indicate that ScaA serves as a cellulosomal scaffoldin-like protein for several R. flavefaciens enzymes. The data are supported by the direct interaction of a recombinant ScaA cohesin with an expressed dockerin-containing enzyme construct from the same bacterium. The evidence also demonstrates that the ScaA dockerin binds to a specialized cohesin(s) on ScaB, suggesting that ScaB may act as an anchoring protein, linked either directly or indirectly to the bacterial cell surface. This study is the first direct demonstration in a cellulolytic rumen bacterium of a cellulosome system, mediated by distinctive cohesin-dockerin interactions.