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For a linear locally recoverable (LRC) code with length $n$ , dimension $k$ and locality $r$ , its minimum distance $d$ satisfies ${d} \leq {n}-{k}+2-\lceil \frac {{k}}{{r}}\rceil $ . A code attaining this bound is called optimal. Many families of optimal locally recoverable codes have been constructed by using different techniques in finite fields or algebraic curves. However only optimal LRC codes with lengths ${n}>>{q}$ and minimum distances restricted to few constants smaller than 9, have been given in previous constructions. No optimal LRC code over a general finite field ${\mathrm{F}}_{{q}}$ with the length ${n}\sim {q}^{2}$ and the minimum distance ${d}\geq 9$ has been constructed. In this article we present a general construction of optimal LRC codes over arbitrary finite fields. Over any given finite field ${\mathrm{F}}_{{q}}$ , for any given ${r} \in \{1,2,\ldots,{q}-1\}$ and given $d$ satisfying $3 \leq {d} \leq \min \{{r}+1,{q}+1-{r}\}$ , we construct explicitly an optimal LRC code with length ${n}={q}({r}+1)$ , locality $r$ and minimum distance $d$ . We also give an asymptotic bound of $q$ -ary LRC codes with locality $r ({r}\leq {q}-1)$ , which is better than some known previous asymptotic bounds in some parameter range. Moreover many long LRC codes with locality $r ({r} \leq {q}-1)$ and small defect ${s}={n}-{k}+2-\lceil \frac {{k}}{{r}} \rceil -{d}$ are also constructed from algebraic curves with many rational points.

Background. Flow diversion (FD) has become a widely adopted treatment method for intracranial aneurysms in the clinic, but a comprehensive meta-analysis of large-sample studies including anterior and posterior circulation is still lacking. Methods. The PubMed, Embase, Web of Science, and Cochrane databases were searched between January 1, 2008, and December 1, 2019. A random-effect model was used to calculate the efficacy and safety data as well as 95% confidence intervals (CIs). Results. The pooled sample size of all included studies was 6695 patients; the mean age was 55.5 years old, with a total of 7406 aneurysms. For efficacy, the complete occlusion rate in angiographic follow-up (AFU) at 6 months was 78% (95% CI, 0.77, 0.80), and the AFU rate at 6-12 months was 90% (95% CI, 0.88, 0.92). For safety, the hemorrhagic event rate was 2%, the ischemic event rate was 5%, and the mortality rate was 3%. Conclusion. FD is an effective and safe treatment for intracranial aneurysm with high complete occlusion rate and acceptable complication rate.

Background The prevalence of human brucellosis in Qinghai Province of China has been increasing rapidly, with confirmed cases distributed across 31 counties. However, the epidemiology of brucellosis transmission has not been fully elucidated. To characterize the infecting strains isolated from humans, multiple-locus variable-number tandem repeats analysis (MLVA) and whole-genome single-nucleotide polymorphism (SNP)-based approaches were employed. Methods Strains were isolated from two males blood cultures that were confirmed Brucella melitensis positive following biotyping and MLVA. Genomic DNA was extracted from these two strains, and whole-genome sequencing was performed. Next, SNP-based phylogenetic analysis was performed to compare the two strains to 94 B. melitensis strains (complete genome and draft genome) retrieved from online databases. Results The two Brucella isolates were identified as B. melitensis biovar 3 (QH2019001 and QH2019005) following conventional biotyping and were found to have differences in their variable number tandem repeats (VNTRs) using MLVA-16. Phylogenetic examination assigned the 96 strains to five genotype groups, with QH2019001 and QH2019005 assigned to the same group, but different subgroups. Moreover, the QH2019005 strain was assigned to a new subgenotype, IIj, within genotype II. These findings were then combined to determine the geographic origin of the two Brucella strains. Conclusions Utilizing a whole-genome SNP-based approach enabled differences between the two B. melitensis strains to be more clearly resolved, and facilitated the elucidation of their different evolutionary histories. This approach also revealed that QH2019005 is a member of a new subgenotype (IIj) with an ancient origin in the eastern Mediterranean Sea.

A novel electromagnetic probe array (EMPA) diagnostic, which consists of a magnetic probe array and an electrostatic probe array, has recently been developed on EAST. The EMPA is fixed near the first wall at horizontal port P. The magnetic probe array of the EMPA consists of 24 identical magnetic probes, each of them capable of measuring toroidal, poloidal and radial magnetic fluctuations simultaneously, providing additional toroidal magnetic fluctuation measurements compared with the regular magnetic probes on EAST. With a higher sampling rate and self-resonant frequency, the EMPA magnetic probes can provide higher frequency magnetic fluctuation measurements. The magnetic probe array of the EMPA is composed of two parallel layers of magnetic probes with a radial distance of 63 mm, and each layer of magnetic probes is arranged in four poloidal rows and three toroidal columns. The compact arrangement of the EMPA magnetic probe array largely improves the toroidal mode number measurement ability from − 8 ≤ n ≤ 8 to − 112 ≤ n ≤ 112 , and also improves the high poloidal wave number measurement ability of magnetic fluctuations compared with the regular high frequency magnetic probes on EAST. The electrostatic probe array of the EMPA consists of two sets of four-tip probes and a single-tip probe array with three poloidal rows and four toroidal columns. It complements the electrostatic parameter measurements behind the main limiter and near the first wall in EAST. The engineering details of the EMPA diagnostic, including the mechanical system, the electrical system, the acquisition and control system, and the effective area calibration, are presented. The preliminary applications of the EMPA in L-mode and H-mode discharges on EAST have demonstrated that the EMPA works well for providing information on the magnetic and electrostatic fluctuations and can contribute to deeper physical analysis in future EAST experiments.

Hypothesis Previous use of linear elastic fracture mechanics to estimate toughness of wet particulate materials underestimates the toughness because it does not account for plastic deformation as a dissipation mechanism. Plastic deformation is responsible for the majority of energy dissipated during the fracture of wet colloidal particulate materials. Plastic deformation around the crack tip increases with saturation of the particulate body. The toughness of the body increases with increasing saturation. Experiments Elastic plastic fracture mechanics using the J-integral approach was used for the first time to measure the fracture toughness (JIC) of wet micron sized alumina powder bodies as a function of saturation. The samples were prepared by slip casting. The saturation was controlled by treatment in a humidity chamber. The elastic modulus (E) and the energy dissipated by plastic flow (Apl) were measured in uniaxial compression. The critical stress intensity factor (KIC) was measured using a diametral compression sample with a flaw of known size. The fracture toughness (JIC) was calculated from these measured quantities and the geometry of the specimen. Findings Elastic plastic fracture mechanics was used for the first time to quantitively account for plastic deformation of wet particulate materials. The linear elastic fracture mechanics approach previously used accounted for less than 1% of the total energy dissipated in fracture. Toughness (JIC) was found to increase with increasing saturation due to plastic deformation that increased with saturation level. The improved understanding of toughness as a function of saturation will aid in providing quantitative analysis of cracking in drying colloidal films and bodies.

In this paper the authors give an efficient bounded distance decoding (BDD for short) algorithm for NTRU lattices under some conditions about the modulus number q and the public key h. They then use this algorithm to give plain-text recovery attack to NTRU Encrypt and forgery attack on NTRU Sign. In particular the authors figure out a weak domain of public keys such that the recent transcript secure version of NTRU signature scheme NTRUMLS with public keys in this domain can be forged.

The blob properties in I-mode and ELM-free H-mode plasmas compared to L-mode have been investigated on the EAST tokamak, including the blob detection rate N b , size δ b , lifetime τ b and radial velocity v r , b . The blob properties in L-mode and I-mode are similar, and those in ELM-free H-mode are different to them. The blob N b is smaller while τ b is larger in H-mode. The experimental blob size δ b and velocity scalings v r , b − δ b show a good agreement with the theoretical models. The variation in blob properties during the L-I and H-L transitions, and their relations to the scrape-off layer (SOL) density, edge and SOL turbulence, and SOL collisionality are discussed. The suppression of the edge (inside the last closed flux surface) turbulence is not reflected in the blob behavior, while the blob detection rate shows a correlation with the SOL density and its low-frequency (3–50 kHz) fluctuations. In addition, the blob detection rate is found to increase with the divertor collisionality Λ div , indicating a dependence of blob behavior on Λ div . The differences in blob detection rates among the three operating regimes might be due to their different SOL densities and collisionalities. The investigation contributes to understanding the influences of edge and SOL plasma parameters on the blob behavior.

A new long-pulse high electron temperature ( T e ) regime has been achieved on experimental advanced superconducting tokamak by pure radio frequency heating. In this new scenario, there are mainly two confinement states involving two magneto-hydrodynamic (MHD) modes, one of which is identified as m/n = 1/1 kink mode (where m and n are the poloidal and toroidal mode numbers, respectively). The frequency evolution of the kink mode is investigated through the three-dimensional, toroidal, and nonlinear Hall-MHD code CLT. We firstly find that the frequency of the m/n = 1/1 kink mode significantly increases during each sawtooth crash and then confirmed it through the experimental data. The simulation results indicate that the increase of the mode frequency is mainly due to the significant increase of the electron diamagnetic frequency nearby the reconnection region. We have also observed the internal transport barrier (ITB) during the m/n = 1/1 kink mode. To further investigate this m/n = 1/1 kink mode in this new regime, the multi-scale interactions between the m/n = 1/1 kink mode and turbulence are discussed.

In 2021, EAST realized a steady-state long pulse with a duration over 100 s and a core electron temperature over 10 keV. This is an integrated operation that resolves several key issues, including active control of wall conditioning, long-lasting fully noninductive current and divertor heat/particle flux. The fully noninductive current is driven by pure radio frequency (RF) waves with a lower hybrid current drive power of 2.5 MW and electron cyclotron resonance heating of 1.4 MW. This is an excellent experimental platform on the timescale of hundreds of seconds for studying multiscale instabilities, electron-dominant transport and particle recycling (plasma-wall interactions) under weak collisionality.

Toxoplasma gondii is an opportunistic protozoan, which widely infects humans and other warm-blooded animals. The type I interferon (IFN) such as IFN-α/β is involved in cGAS-STING signaling to resist T. gondii infection. We found in RAW264.7 cells, that T. gondii virulence factor TgROP18

Patients of non-small cell lung cancer (NSCLC) with activated EGFR mutations is more apt to develop leptomeningeal metastasis (LM) than the other types of lung cancers [1]. Examination of circulating tumor DNA (ctDNA) in cell-free cerebrospinal fluid (CSF) has been shown to be useful in detecting the genomic mutations of tumors in central nervous system (CNS) and has also been used to monitor tumor progression and evaluate the response to treatments [2]. Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, is considered to be a recent standardized treatment for EGFR Thr790Met-mutant NSCLC because of its good efficacy in both systemic and CNS metastasis [3].

Two pairs of space-resolved extreme ultraviolet (EUV) spectrometers working at 5–138 Å with different vertical observation ranges of −7 ≤ Z ≤ 19 and −18 ≤ Z ≤ 8 cm have been newly developed to observe the radial profile of impurity line emissions and to study the transport of high-Z impurity ions intrinsically existing in EAST tokamak plasmas. Both spectrometers are equipped with a complementary metal-oxide semiconductor (CMOS) detector (Andor Marana-X 4.2B-6, Oxford Instruments) with sensitive area of 13.3 × 13.3 mm2 and number of pixels equal to 2048 × 2048 (6.5 × 6.5 µm2/pixels). Compared to the currently operating space-resolved EUV spectrometers with a charge-coupled detector (CCD: 1024 × 255 pixels, 26 × 26 µm2) working at 30–520 Å, this spectrometer’s performance was substantially improved by using the CMOS detector. First, the spectral resolution measured at full width at half maximum was improved in the whole wavelength range, e.g., Δλ1/2_CMOS = 0.092 Å and Δλ1/2_CCD = 0.124 Å at C VI 33.73 Å and Δλ1/2_CMOS = 0.104 Å and Δλ1/2_CCD = 0.228 Å at Mo XXXI 115.999 Å, thus enabling a more accurate analysis of spectra with complicated structure such as tungsten unresolved transition array in the range 45–65 Å. Second, the temporal resolution was largely improved due to the high-speed data acquisition system of the CMOS detector, e.g., Δt_CMOS = 15 ms/frame and Δt_CCD = 200 ms/frame at routine operation in the radial profile measurement. Third, signal saturation issues that occurred when using the old CCD sensor during impurity accumulation now disappeared entirely using the CMOS detector due to lower exposure time at high readout rates, which largely improved the observation performance in similar impurity burst events. The above-mentioned performance improvements of the space-resolved EUV spectrometer led to a rapid change in the W XXXIII (52.22 Å) radial profile during a single cycle of low-frequency sawtooth oscillation with fst = 5–6 Hz at a sufficient detector count rate.

Experiments on pellet fueling have been carried out in edge localized mode (ELM)-free high-confinement mode (H-mode) plasmas with q 95 ∼ 6 in the EAST tokamak. Cryogenic deuterium pellets were injected into the ELM-free plasmas at a frequency of 10 or 5 Hz from ∼45 cm above the mid-plane on the low-field side. It is found that the ELM-free H-mode plasmas are still sustained even if both the edge and core plasma are impacted by the pellet injections (PIs). Several small ELMs would appear and the edge coherent mode accompanying the ELM-free phase fades or even disappears just after the pellet events, but the plasma would rapidly recover to the ELM-free state. Although the ELMing phase is very short, it may be an issue that still needs to be resolved in the future. Meanwhile, the 3/2 tearing mode often appearing in ELM-free discharges would be stabilized by the PIs, and the high-Z impurity concentration would be reduced during the PIs. All these results will be meaningful to International Thermonuclear Experimental Reactor and future fusion reactors.

A significant reduction in neutron yield in the plasma core has been observed in EAST neutral beam injection into plasmas with a low-edge safe factor of [Formula: see text] and a n = 2 resonant magnetic perturbation (RMP) during a sawtooth crash. Harmonics of the m/ n = 1/1 mode ( m and n being the poloidal and toroidal mode numbers) develop simultaneously. A sawtooth crash is triggered when the current of the RMP exceeds a critical value; saturated fishbone phase occurs with small RMP currents. Soft x-ray (SXR) tomographic patterns obtained during sawtooth crashes have annular hot-ring shapes outside the q = 1 surface that are similar to those of double tearing modes triggered by off-axis sawtooth crashes in TFTR reversed magnetic shear plasma. M3D nonlinear simulations confirmed the initial penetration of the n = 2 RMP in the plasma core and further demonstrated a complete sawtooth crash with the appearance of a right annular hot ring near the q = 1 surface. Reconstruction of the trajectory of SXR signals before the crash shows chaotic behavior. Moreover, a high-frequency mode was seen to appear just before the sawtooth crash, accompanied by an edge geodesic acoustic mode. This edge mode is free in the saturated fishbone phase. The role of high-frequency mode in the sawtooth crash remains unclear.

Mode structures and excitation conditions for the low-frequency modes (LFMs) have been investigated in experimental advanced superconducting tokamak (EAST) plasmas with q min ⩽ 2. Two different stages/categories of the LFM instabilities are observed during the oscillation of annular/central collapse events: (I) the upward sweeping frequency of LFMs; (II) the upward frequency jumpsof LFMs. The annular/central events are triggered by the m/n = 2/1 double tearing modes with different q-profiles, while the LFMs are characterized by higher mode numbers m/n = 4/2, 6/3, …, where m and n are the poloidal and toroidal mode numbers, respectively. The maximum radial coverage of the LFMs is located in the annular region of 1.97 ⩽ R ⩽ 2.07 m with the normalized minor radius 0.2 ⩽ ρ ⩽ 0.4, while the higher-frequency (or upward sweeping frequency) branch is more localized to the radial position of 2 ⩽ R ⩽ 2.02 m (q min). The frequency characteristics of upward sweeps or upward jumps of the LFMs are mainly attributed to the change in the q-profile, e.g. the upward sweeping frequency in stage I is caused by q min decreasing. Accordingly, the linear wave properties of LFMs in EAST with weak/reversed magnetic shear are studied numerically and analytically based on a general fishbone-like dispersion relation. Without considering the contribution of energetic ions, it is shown that the LFM with Alfvénic polarization is an MHD-unstable kinetic ballooning mode with frequency of the order of the ion diamagnetic drift frequency. Several important factors for the excitation of LFM instability are analyzed: (1) the role of energetic ions is unimportant, and the LFMs can be excited under the two conditions of with/without energetic ions; (2) the higher τ = T e/T i with larger η i = L ni /L Ti are required, namely the normalized pressure gradient α ∝ (1 + τ)(1 + η i) should be large enough to overcome the stability effect of finite field line bending; (3) the weak/reversed shear q-profile with q min ⩽ 2 and suitable S ≡ (r/q)(q″)1/2 are required.

Soft x-ray (SXR) cameras in a tokamak are limited spatially by ports of the vacuum vessel, and SXR tomography (SXT) technology is developed for reconstructing a two-dimensional SXR profile. However, traditional SXT is time-consuming and has difficulty achieving abundant and quick reconstructions for a tokamak. Based on experimental SXR data and Fourier–Bessel SXT codes at the EAST tokamak, three typical neural networks are built and trained. All the trained neural networks complete reconstruction within several milliseconds on a personal computer and succeed in constraining the SXR profile to match most of the data. In particular, the best-performing fully convolutional neural network provides SXR reconstruction images on the 2D evolution of a sawtooth, and shows its generalization. In the future, it is possible to provide an outstanding deep learning substitute to give abundant and quick SXT images instead of traditional SXT, after training for a few days.

Background Proanthocyanidins (PAs) are important plant secondary metabolites that confer flavor, nutritional value, and resistance to pathogens. Persimmon is one of the PA richest crops. Mature fruits can be inedible because of the astringency caused by high PA levels and need to go through a de-astringency treatment before consumption. The molecular basis for PA accumulation is poorly known, particularly transcriptional regulators. We characterised three genotypes (‘Luotiantianshi’ (LT), ‘Mopanshi’ (MP), and ‘Youhou’ (YH)) with different PA accumulation patterns using an approach that combined PacBio full-length sequencing and Illumina-based RNA sequencing to build high-quality full-length transcriptomes. Additionally, we analysed transcriptome dynamics of the three genotypes (LT, MP, and YH) at four key fruit developmental stages. Results A total of 96,463 transcripts were obtained. We identified 80,075 protein-coding sequences (CDSs), 71,137 simple sequence repeats (SSRs), and 27,845 long noncoding RNAs (lncRNAs). Pearson correlation coefficient (PCC), principal component analysis (PCA), and differentially expressed transcripts (DETs) analyses indicated that the four different developmental stages within a genotype exhibited similar transcriptome activities. A total of 2,164 transcripts specific to each fruit developmental stage were detected. The transcripts specific to early stages were attributed to phenylpropanoid and flavonoid biosynthesis. Co-expression network analyses revealed MEbrown and MEblue modules were strongly associated to PA accumulation. From these two modules, 20 hub TFs are potential regulators for PA accumulation. Among them, Cluster_78388 (SBP protein), Cluster_63454 (bZIP protein), and Cluster_66595 (MYB protein) appear to involve in the PA biosynthesis in Chinese genotypes. Conclusions This is the first high-quality reference transcriptome for commercial persimmon. Our work provides insights into the molecular pathways underlying PA accumulation and enhances our global understanding of transcriptome dynamics throughout fruit development.

An Agrobacterium-mediated transient transformation system was established for gene functional analysis in persimmon (Diospyros kaki Thunb.) utilizing sonication followed by vacuum infiltration of seedlings in vitro. The optimal vacuum conditions for agroinfiltration of persimmon were evaluated by monitoring expression of GUS reporter gene. The technique was further applied to evaluate five different genotypes. Among the genotypes examined in vitro, ‘Xiaoguo-tianshi’ (Chinese PCNA type) produced the highest expression levels of both GUS and GFP, and was the most ideal genotype. Furthermore, the developed system was successfully utilized for DkLAR (leucoanthocyanidin reductase) gene transient silencing. DMACA (4- dimethylaminocinnamaldehyde) staining and the Folin-Ciocalteau assay revealed that the proanthocyanidins (PAs) levels was markedly decrease in ‘Xiaoguo-tianshi’ and ‘Mopanshi’ (Chinese PCA type) leaves. These results confirmed that DkLAR plays an important role in the accumulation of PAs in persimmon. In conclusion, based on the Agrobacterium-mediated vacuum infiltration, we developed a reliable and highly efficient transient transformation system that can be used for gene functional analysis through the seedlings in vitro.

In order to study the radial transport of tungsten ions in long-pulse H-mode discharges, a space-resolved spectrometer working at 30–520 A has been newly developed to measure a radial profile of the tungsten line emission. The spectrometer is installed behind a long extension vacuum tube connected to a horizontal midplane diagnostic port of EAST tokamak. The long distance between the plasma and spectrometer, 8835.5 mm, enables observation of the radial profile of impurity line emissions in a wide vertical range of − 8 . 5 ≤ Z ≤ 40 cm ( − 0 . 1 ≤ ρ ≤ 0 . 6 ) . A good spectral resolution of Δ λ 0 = 4 − 5 pixels at the foot position of spectral line profiles and a high spatial resolution of Δ Z = 2 . 5 cm are obtained in addition to a sufficient temporal resolution, e.g. 50 ms/frame. As a result, accurate radial profiles have been successfully obtained in EAST Ohmic and H-mode discharges for several impurity species such as carbon, oxygen, argon, iron and tungsten. The radial profiles of tungsten line emissions from W 42 + – W 45 + ions with 4p–4s transitions measured at two wavelength ranges of 45–70 A and 120–140 A are analyzed for the ion density evaluation based on the photon emissivity coefficient from ADAS database. The result shows that the density of W 43 + – W 45 + ions ranges at 2–6 × 108 cm−3 in steady H-mode discharges with T e ( 0 ) = 3 keV and n e ( 0 ) = 4 × 1013 cm−3.

This paper uses the implicit Monte–Carlo full-orbit-following parallel program ISSDE to calculate the prompt loss and slowing down process of neutral beam injection (NBI)-generated fast ions due to Coulomb collisions in the equilibrium configuration of Experimental Advanced Superconducting Tokamak (EAST). This program is based on the weak equivalence of the Fokker–Planck equation under Rosenbluth MacDonald Judd (RMJ) potential and Stratonovich stochastic differential equation (SDE). The prompt loss with the LCFS boundary and the first wall (FW) boundary of the two co-current neutral injection beams are studied. Simulation results indicate that the loss behavior of fast ions using the FW boundary is very different from that of the LCFS boundary, especially for fast ions with a large gyration radius. According to our calculations, about 5.11% of fast ions generated by perpendicular injection drift out of the LCFS and then return inside the LCFS to be captured by the magnetic field. The prompt loss ratio of fast ions and the ratio of orbital types depend on the initial distribution of fast ions in the Pζ –Λ space. Under the effect of Coulomb collisions, the pitch-angle scattering and stochastic diffusion happens, which will cause more fast ion loss. For short time scales, among the particles lost due to collisions, the fraction of banana ions reaches 92.31% in the perpendicular beam and 58.65% in the tangential beam when the fraction of banana ions in the tangential beam is 3.4% of the total ions, which means that the effect of Coulomb collisions on banana fast ions is more significant. For long time scales, the additional fast ion loss caused by Coulomb collisions of tangential and perpendicular beams accounted for 16.21% and 25.05% of the total particles, respectively. We have also investigated the slowing down process of NBI fast ions.

Toxoplasma gondii is an intracellular pathogen that exerts its virulence through inhibiting host’s innate immune responses, which is mainly related to the type II interferon (IFN-γ) response. IFN-γ inducible tripartite motif 21 (TRIM21), an E3 ligase, plays an important role in anti-infection responses against the intracellular pathogens including bacteria, virus, and parasite. We found that T. gondii virulence factor ROP18 of the type I RH strain (TgROP18I) interacted with human TRIM21, and promoted the latter’s phosphorylation, which subsequently accelerated TRIM21 degradation through lysosomal pathway. Furthermore, TRIM21 protein level was found to be upregulated during RH and CEP strains of T. gondii infection. TRIM21 knocking down reduced the ubiquitin labeling on the parasitophorous vacuole membrane (PVM) [which led to parasitophorous vacuole (PV) acidification and death of CEP tachyzoites], and relieved the inhibition of CEP proliferation induced by IFN-γ in human foreskin fibroblast (HFF) cells which was consistent with the result of TRIM21 overexpression. On the other hand, TRIM21 overexpression enhanced the inhibition of CEP proliferation, and inhibited the binding of IκB-α with p65 to activate the IFN-γ-inducible NF-κB pathway, which might be resulted by TRIM21-IκB-α interaction. In brief, our research identified that in human cells, IFN-γ-inducible TRIM21 functioned in the innate immune responses against type III T. gondii infection; however, TgROP18I promoted TRIM21 phosphorylation, leading to TRIM21 degradation for immune escape in type I strain infection.

BACKGROUNDSuperficial siderosis of the central nervous system (SSCNS) is a rare condition that results from hemosiderin deposition in the brain, brainstem, cerebellum, and spinal cord as a result of chronic, repeated, and recurrent subarachnoid hemorrhage. SSCNS that originates in the spinal cord is rarely reported, and epilepsy as a manifestation of such a case has not been reported before.OBSERVATIONSThe authors reported a rare case of SSCNS with epilepsy originating from traumatic cervical injury and presented a literature review of all reported SSCNS cases that originated in the spine. The patient was a 29-year-old man with a 16-year history of progressive headache accompanied by seizures, ataxia, and sensorineural hearing loss. He had experienced a traumatic cervical injury at age 7. Magnetic resonance imaging revealed a characteristic hypointense rim around the pons and cervical spinal cord on susceptibility-weighted imaging scans. Cerebrospinal fluid examination during a headache episode confirmed subarachnoid hemorrhage and increased intracranial pressure. Surgical exploration revealed a C6 dural defect with bone spurs inserted into the dura mater. After the patient underwent dura mater repair and shunt implantation, his symptoms disappeared completely except for hearing loss.LESSONSThis rare case indicated that symptomatic epilepsy followed by SSCNS can be eliminated by complete repair of the cervical dura mater.

Background: Toxoplasma gondii is a zoonotic intracellular protozoon that is estimated to infect about 30% of the world’s population, resulting in toxoplasmosis in immuno-compromised patients and adverse outcomes in the primary infection during pregnancy. Exosomes are tubular vesicles secreted by cells, and they function in intercellular communication. It has been reported that the exosomes secreted by T. gondii-infected immune cells transmit infection signals to the uninfected cells. However, the mechanism and effect of the exosome transmission are still vague. We therefore investigated the function of the exosomes transmitted from DC2.4 cells infected with T. gondii RH strain (Tg-DC-Exo) to the uninfected cells, as well as their roles in anti-infection. Methods: We conducted exosome isolation and identification with ultracentrifugation, transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and Western blotting. Recipient cells taken up exosomes by PKH67 assay. The signal transmission and the abundance of mir155-5p were determined using transwell assay and qRT-PCR. For the immune responses, cytokines was evaluated. T. gondii B1 gene was determined to evaluate tachyzoites proliferation.Results: We observed that Toxoplasma infection up-regulated mir155-5p expression in DC2.4 cells secreted exosomes, and those exosomes can be ingested by murine macrophage RAW264.7 cells. Tg-DC-Exo and mir155-5p stimulating host proinflammatory immune responses such as proinflammatory cytokine (IL6,iNOS and TNF-α) production increased and NF-κB signal pathway activation by down regulating SOCS1, leading to inhibit T. gondii tachyzoite proliferation in RAW264.7 cells. Conclusion: Our findings provide a novel mechanism for how infected cells transmit infection signals to the uninfected cells through exosome secretion after T. gondii infection, followed by inflammatory responses and anti-infection reactions, which may help us develop a new intervention strategy for toxoplasmosis prevention, especially in immuno-compromised patients.

Background Breast cancer is the most common cause of cancer-related death among women, and prognosis is especially poor for patients with triple-negative breast cancer (TNBC); therefore, there is an urgent need for new effective therapies. Recent studies have demonstrated that the uracil auxotroph Toxoplasma gondii vaccine displays anti-tumor effects. Here, we examined the immunotherapy effects of an attenuated uracil auxotroph strain of T. gondii against 4T1 murine breast cancer. Methods We constructed a uracil auxotroph T. gondii RH strain via orotidine 5′-monophosphate decarboxylase gene deletion (RH-Δompdc) with CRISPR/Cas9 technology. The strain’s virulence in the T. gondii-infected mice was determined in vitro and in vivo by parasite replication assay, plaque assay, parasite burden detection in mice peritoneal fluids and survival analysis. The immunomodulation ability of the strain was evaluated by cytokine detection. Its anti-tumor effect was evaluated after its in situ inoculation into 4T1 tumors in a mouse model; the tumor volume was measured, and the 4T1 lung metastasis was detected by hematoxylin and eosin and Ki67 antibody staining, and the cytokine levels were measured by an enzyme-linked immunosorbent assay. Results The RH-Δompdc strain proliferated normally when supplemented with uracil, but it was unable to propagate without the addition of uracil and in vivo, which suggested that it was avirulent to the hosts. This mutant showed vaccine characteristics that could induce intense immune responses both in vitro and in vivo by significantly boosting the expression of inflammatory cytokines. Inoculation of RH-Δompdc in situ into the 4T1 tumor inhibited tumor growth, reduced lung metastasis, promoted the survival of the tumor-bearing mice and increased the secretion of Th1 cytokines, including interleukin-12 (IL-12) and interferon-γ (INF-δ), in both the serum and tumor microenvironment (TME). Conclusion Inoculation of the uracil auxotroph RH-Δompdc directly into the 4T1 tumor stimulated anti-infection and anti-tumor immunity in mice, and resulted in inhibition of tumor growth and metastasis, promotion of the survival of the tumor-bearing mice and increased secretion of IL-12 and IFN-γ in both the serum and TME. Our findings suggest that the immunomodulation caused by RH-Δompdc could be a potential anti-tumor strategy. Graphical abstract

Using data collected with the BESIII detector operating at the Beijing Electron Positron Collider, we search for the process $e^+e^-\rightarrow \eta_c\eta \pi^+\pi^-$. The search is performed using five large data sets recorded at center-of-mass energies of 4.23, 4.26, 4.36, 4.42, and 4.60 GeV. The $\eta_c$ meson is reconstructed in 16 exclusive decay modes. No signal is observed in the $\eta_c$ mass region at any center-of-mass energy. The upper limits on the reaction cross sections are determined to be 6.2, 10.8, 27.6, 22.6 and 23.7 pb at the 90% confidence level at the center-of-mass energies listed above.

The transport mechanism of organic materials is still far away from being well understood and controlled although conducting polymers have been discovered since 1977. It is rare to see conducting polyers possessing high bipolar (p- and n-type) electrical conductivities within a single bulk doped organic polymer without the assistant of gate voltage. Here, we report a novel approach to provide high performance n-type materials by p-type doping. More importantly, the bipolar electrical conductivities of the donor-acceptor conducting polymer are high, resulting high bipolar power factors among the solution-processable ambipolar D-A copolymers. A fully organic p-n junction is created in a planar film, exhibiting a high rectification ratio of 2 x 102 at +5 V with a high current density of 3 A/cm2. Structural and spectroscopic tests have been performed to provide a fundamental understanding of the polarity switching mechanism. The results open the opportunity of making p- and n-type modules with a single conducting polymer for future modern organic electronics.

Background/aims The morbidity of deep venous thrombosis (DVT) is increasing rapidly and the current therapeutic strategies for DVT are unsatisfactory. Accumulating evidence suggest that venous thrombi resolve (VTR) may provide new insights into DVT therapeutic strategies. The aim of this study was to investigate the role of curcumin in VTR process and try to reveal the potential mechanism. Methods Immunofluorescence and HE staining were performed to investigate the therapeutic angiogenesis effect of curcumin in VTR process. Microarray analysis and RT-PCR were performed to examine the expression level of miR-499 in thrombosis after curcumin administration. Cell proliferation, migration and angiogenesis capacity were tested by CCK8 assay, Transwell assay and Tube formation assay, respectively. Dual-luciferase reporter assay (DLR) was used to confirm the connection between miR-499 and paired phosphate and tension homology deleted on chromosome ten (PTEN). Results We found that curcumin could effectively promote VTR process by activating angiogenesis in thrombus in vivo. The expression of miR-499 exhibited notably downregulated after curcumin administration. The proangiogenic effect of curcumin in HUVECs could be blocked by miR-499 overexpression. In addition, we confirmed that miR-499 directly target to the 3′UTR region of PTEN. Conclusion Curcumin promotes VTR process in DVT through activating therapeutic angiogenesis. Mechanically, curcumin promotes therapeutic angiogenesis by regulating miR-499 mediated PTEN/VEGF/Ang-1 signaling pathway.

The dependence of fishbone cycle on energetic particle intensity has been investigated in EAST low-magnetic-shear plasmas. It is observed that the fishbone mode growth rate, saturation amplitude as well as fishbone cycle frequency clearly increase with increasing neutral beam injection (NBI) power. Moreover, enhanced electron density and temperature perturbations as well as energetic particle loss were observed with greater injected NBI power. Simulation results using M3D-K code show that as the NBI power increases, the resonant frequency and the energy of the resonant particles become higher, and the saturation amplitude of the mode also changes, due to the non-perturbative energetic particle contribution. The relationship between the calculated energetic particle pressure ratio and fishbone cycle frequency is obtained as ${f_{\textrm{FC}}} = 2.2{(1000{\beta _{\textrm{ep,calc}}} - 0.1)^{5.9 \pm 0.5}}$ . Results consistent with the experimental observations have been achieved based on a predator–prey model.

The multifaceted asymmetric radiation from the edge (MARFE), which is generally considered to be the result of a radiation thermal instability in the edge and usually occurs in high density operation, has been first observed to move up and down along the poloidal cross-section due to edge cooling after cryogenic deuterium pellet injections in EAST tokamak with tungsten divertor. A maximum electron density of 0.84 × n GW has been obtained using continuous cryogenic pellet fueling. In the meantime, MARFEs, initially located near the divertors of EAST, moves to the inner wall on high field side after each pellet injection. This movement should be attributed to the asymmetry of the power flow to the two sides of the MARFE after pellet injections. Accompanied with MARFE movement, two kinds of strong density fluctuations have been observed. The ones with continuous and regular frequency spectrum, which does not cause a reduction of main plasma density, are confirmed to be induced by MARFE. The others, appearing with magnetic fluctuations, have been determined to be induced by the m/n = 2/1 magnetohydrodynamic activities after pellet injections. All the investigations in this paper will be meaningful for the steady high density operation of future fusion reactors, such as ITER.

The impact of the low-Z impurity concentration on mode stabilization has been investigated in the EAST tokamak. A series of tearing modes (TMs) with multiple helicities are excited by the low-Z (carbon) impurity concentration, and the dominant mode structure features m/n = 2/1 magnetic islands that propagate in the electron diamagnetic drift direction (m and n are poloidal and toroidal mode numbers, respectively). The m/n = 2/1 locked modes (LMs) can be formed by the redistribution of low-Z impurity concentration, and are unlocked spontaneously due to the decrease in the impurity concentration, where the width of the magnetic islands can reach w ≈ 5 cm (w/a ≈ 0.1, a is the minor radius). The increase in the electromagnetic brake torque is the primary reason for the mode locking, and the ‘O’-point of the m/n = 2/1 magnetic islands is locked by the tungsten protector limiter (toroidal position: −0.4π ⩽ ϕ ⩽ −0.3π) with separation of Δϕ ≈ 0. The 3D asymmetric structure of the m/n = 2/1 magnetic islands is formed for the interaction with the tungsten protector limiter, and the electromagnetic interaction decreases dramatically for the separation of Δϕ ⩾ 0.2π. The mode excitation and locking mechanisms can be illustrated by the ‘hysteresis effect’ between the low-Z impurity concentration and the width of the m/n = 2/1 magnetic islands; namely, the growth of magnetic islands is modulated by the low-Z impurity concentration, and the rotation velocity is decelerated accordingly. However, the intrinsic mechanism for the unlocking of m/n = 2/1 LMs is complicated by considering the concentration of the low-Z impurity, and the possible unlocking mechanism is discussed. Therefore, understanding the relationship between the impurities and magnetic islands is more important for optimization of the control techniques (resonant magnetic perturbations → LMs, electron cyclotron resonant heating (ECRH) → neoclassical tearing mode (NTM), impurity seeding → major collapse, etc).

Background: The pathogenesis of breast milk jaundice (BMJ) remains unrevealed. While UGT1A1 gene has been extensively investigated in neonatal BMJ cases, the reason for down-regulation of UGT1A1 gene in neonatal BMJ has not been completely elucidated. In this research, the authors attempt to speculate whether there was some gene regulatory substance exist in human milk and result in BMJ, such as miRNA. This research aims to demonstrate the association between the profile of exosomal miRNA in human milk and the occurrence of neonate breast milk jaundice.Methods: A previous study conducted by Shanghai Children’s Medical Center of the Shanghai Jiao Tong University School of Medicine and the UIB International Maternity Care Center regarding 12 mother-infant dyads were recruited from September 2016 to December 2016. The subjects were divided into two groups (BMJ and control) for exosomal miRNA screening. Four methods of transmission electron microscopy (TEM), a nanoparticle tracking analyzer (NTA), flow cytometry (FCM), and Western blotting were used to identify the exosome in human milk. Based on the previous study, this research determines the expression profile of miRNA in human milk exosomes by small RNA sequencing. Based on the biological information analysis, the authors not only screen the differentially expressed miRNA but also predict the target genes. Then, another 20 mother-infant dyads were recruited for realtime PCR assay to verify the difference of predicted microRNAs expression in breast milk exosomes and to explore the correlation between differentially expressed microRNAs in breast milk and neonatal breast milk jaundice. Results: Human milk exosomes are rich in various types of microRNA, especially let-7g-5p, let-7b-5p, has-miR-21-5p, has-miR-375, has-miR-99a-5p, et al. The predicted target genes of miR-127-3p are statistically significantly overexpressed in BMJ group, including the gene of UGT1A1 which expresses key enzyme in process of bilirubin metabolism. Conclusions: Exosomal miRNA-127-3p plays a potential effect on neonatal breast milk jaundice.

Musculoskeletal changes are the most common clinical manifestation of brucellosis. The main objective of this study was to provide a better understanding of this disease, while also attempting to identify potential markers that can identify the early stage musculoskeletal changes associated with human brucellosis. In this case–control study, 41 male early-stage brucellosis patients (within 6 months of diagnosis) who had not received drug therapy and 44 matched controls were examined. Venous blood samples were collected and serum pyridinoline (PYD), type II collagen cleavage neoepitope (C2C) and osteocalcin (OC) levels were quantified using an enzyme-linked immunosorbent assay (ELISA). In the brucellosis group, the median serum levels of PYD (278.53 µg/L), C2C (82.23 µg/L) and OC (8.41 µg/L) were significantly elevated relative to the control group (Z = 5.686, 3.997, 3.579; P = 0.000). Serum PYD, C2C, and OC levels were increased in early-stage male brucellosis patients, and these factors appear to have promise as potential indicator biomarkers that can reflect the osteoarticular changes that occur in the early stage of human brucellosis.

Background Brucellosis, which is cause by Brucella, is one of the most important zoonoses and is considered a “forgotten, neglected zoonosis” by the WHO. Methods Blood samples were isolated from two brucellosis males that were confirmed B. melitensis positive following multiple loci variable-number tandem repeat analysis (MLVA) and strains QH2019001 and QH2019005 were identified. Genomic DNA was extracted from these samples and whole genome sequencing (WGS) was performed. Next, SNP-based phylogenetic analysis was performed to compare the two strains to 94 B. melitensis strains (complete genome and draft genome) retrieved from online databases. Results The QH2019001 and QH2019005 strains were found to have differences in their variable-number tandem repeats. Phylogenetic examination of the 96 strains assigned them to 5 genotype groups, with QH2019001 and QH2019005 assigned to the same group, but to different subgroups; with the QH2019005 strain assigned to a new subgenotype, IIj. These findings were then combined to determine strain origin. Conclusions Utilizing a whole genome SNP-based approach highlights the diversity between B. melitensis strains, and it can facilitate the elucidation of different evolutionary histories. This approach also revealed that the QH2019005 is part of a new subgenotype with an ancient origin in the eastern Mediterranean Sea.

We report the most precise measurements to date of the strong-phase parameters between D^{0} and D[over ¯]^{0} decays to K_{S,L}^{0}π^{+}π^{-} using a sample of 2.93 fb^{-1} of e^{+}e^{-} annihilation data collected at a center-of-mass energy of 3.773 GeV with the BESIII detector at the BEPCII collider. Our results provide the key inputs for a binned model-independent determination of the Cabibbo-Kobayashi-Maskawa angle γ/ϕ_{3} with B decays. Using our results, the decay model sensitivity to the γ/ϕ_{3} measurement is expected to be between 0.7° and 1.2°, approximately a factor of three smaller than that achievable with previous measurements, based on the studies of the simulated data. The improved precision of this work ensures that measurements of γ/ϕ_{3} will not be limited by knowledge of strong phases for the next decade. Furthermore, our results provide critical input for other flavor-physics investigations, including charm mixing, other measurements of CP violation, and the measurement of strong-phase parameters for other D-decay modes.

Objective Musculoskeletal changes are the most common clinic manifestation of brucellosis,and these musculoskeletal changes are irreversible, so, it is very important to prevention musculoskeletal changes at early stage of human brucellosis . Method This was a case-control study. According to diagnostic criteria of human brucellosis in China(WS269-2007),41 male patients were diagnosed as brucellosis patients at early period (within 6 months) and they were not therapied with drug, 44 \ persons were divided into control group with randomly matching. Venous blood samples were collected from all study subjects, and serum PYD ༌C2C and OC were quantitative measured with method of ELISA. Data were analyzed using SPSS 17.0 software. A p value P = 0.000). Conclusion Serum levels of PYD, C2C and OC were increased among male brucellosis patients at early period, which might be the indicator biomarkers for osteoarticular changes of human brucellosis at early stage..

Using a sample of (448.1±2.9)×106 ψ(3686) events collected with the BESIII detector, we perform the first partial wave analysis of ψ(3686)→K+K-η. In addition to the well established states, ϕ(1020), ϕ(1680), and K3*(1780), contributions from X(1750), ρ(2150), ρ3(2250), and K2*(1980) are also observed. The X(1750) state is determined to be a 1-- resonance. The simultaneous observation of the ϕ(1680) and X(1750) indicates that the X(1750), with previous observations in photoproduction, is distinct from the ϕ(1680). The masses, widths, branching fractions of ψ(3686)→K+K-η, and the intermediate resonances are also measured.

The cross section of the process e+e-→η′J/ψ is measured at center-of-mass (c.m.) energies from s=4.178 to 4.600 GeV using data samples corresponding to a total integrated luminosity of 11 fb-1 collected with the BESIII detector operating at the BEPCII storage ring. The dependence of the cross section on s shows an enhancement around 4.2 GeV. While the shape of the cross section cannot be fully explained with a single ψ(4160) or ψ(4260) state, a coherent sum of the two states does provide a reasonable description of the data.

An internal transport barrier (ITB) can be formed on EAST in exploring high-parameter operation. Previous studies show that safety factor (q) profiles, Shafranov shift and magnetohydrodynamic behaviors could be helpful in ITB formation by suppressing anomalous transport. Recently, electron density evolution with high resolution demonstrates that fishbone could be dominant in electron density ITB formation and sustainment. The power threshold is low in the fishbone condition and the electron density profile is determined by traits of fishbone. Simulation shows that the low-k ion mode is suppressed by fishbone. Direct measurement of turbulence in the inner region shows that the internal kink mode could sustain an electron temperature ITB by suppressing the trapped electron mode. The multi-scale interaction between the kink mode and turbulence by current could be key in sustaining high-electron-temperature long-pulse operation.

To conveniently prepare the immobilized enzyme for green synthesis of vitamin A palmitate, thermomyces lanuginosus lipase (TLL) was assembled with apatite derived from calcium phosphate in solution to form TLL@apatite hybrid nanoflowers (hNFs) by mimetic biomineralization. The obtained hNFs was characterized by SEM and applied in the enzymatic synthesis of vitamin A palmitate. Under optimal condition, when palmitic acid and vitamin A acetate were used as substrates, the yield of the target product was up to 90.4%, about 1.5 folds of that using free TLL. In addition, when each cycle for catalytic synthesis was carried out in petroleum ether with 20% water content as solvent for 12 h, the hNFs still retains 65.8% of initial catalytic synthetic ability after 10 cycles. These results demonstrated the hNFs was a kind of green biocatalyst with high catalytic activity and high stability with great potential in the green pharmaceuticals industry.

The main problem of constant-dimension subspace coding is to determine the maximal possible size ${\mathbf{A}}_{q}(n,d,k)$ of a set of $k$ -dimensional subspaces in ${\mathbf{F}}_{q}^{n}$ such that the subspace distance satisfies $d(U,V) \geq d$ for any two different subspaces $U$ and $V$ in this set. In this paper, we give a direct construction of constant-dimension subspace codes from two parallel versions of maximum rank-distance codes. The problem about the sizes of our constructed constant-dimension subspace codes is transformed into finding a suitable sufficient condition to restrict number of the roots of $L_{1}(L_{2}(x))-x$ where $L_{1}$ and $L_{2}$ are $q$ -polynomials over the extension field ${\mathbf{F}}_{q^{n}}$ . New lower bounds for ${\mathbf{A}}_{q}(4k,2k,2k)$ , ${\mathbf{A}}_{q}(4k+2,2k,2k+1)$ , and ${\mathbf{A}}_{q}(4k+2,2(k-1),2k+1)$ are presented. Many new constant-dimension subspace codes better than previously best known codes with small parameters are constructed.

Background: Breast milk jaundice (BMJ) is the first cause of neonatal jaundice; however, its underlying mechanism is yet to be deciphered. We conducted a study to investigate intestinal flora in neonates with BMJ and used metabolomics to decipher the possible mechanisms by which intestinal flora induces jaundice. Methods: Microbiota collected from the feces of BMJ patients and jaundice-free breastfeeding newborns was used for 16S rRNA sequencing. In addition, differences in fecal metabolites were analyzed using gas chromatography mass spectrometry (GC/MS). The relationship between intestinal microbiota and the differences in fecal metabolites was then analyzed. Results: There was no significant difference in the richness and diversity of intestinal flora between BMJ and the control group; however, there were differences in the structure. At the phylum level, the relative abundance of Firmicutes was higher in the control group compared to the BMJ group, whereas Proteobacteria was higher in the infants with BMJ. Additionally, at the genus level, the relative abundance of Haemophilus was higher in the control group, whereas the relative abundances of Escherichia, Morganella, and Rothia were lower. More remarkably, the major differences in metabolites between the two groups were glyceric acid, succinic acid, and phenylalanine. Additionally, the abundance of Escherichia was positively correlated with succinic acid and cadaverine levels. Conclusions: The intestinal flora colonization status in BMJ patients is immature. This study reports for the first time that the study of intestinal flora, especially Escherichia, plays an important role in BMJ, and found that it may be associated with the regulation of succinic acid metabolic pathways.

By analyzing a 2.93 fb(-1) data sample of e(+)e(-) collisions, recorded at a center-of-mass energy of 3.773 GeV with the BESIII detector operated at the BEPCII collider, we report the first observa ...

A fishbone oscillation was observed in the neutral beam injection plasma at Experimental Advanced Superconductivity Tokamak (EAST). This m = 1/n = 1 (m, n: poloidal, toroidal mode numbers, respectively) typical internal kink mode travels in the ion-diamagnetism direction in the poloidal section with a rotation speed close to the ion diamagnetic drift frequency. A high thermal plasma beta and high amounts of energetic ions are necessary for the mode to develop. Fishbone oscillations can expel heavy impurities in the core, which favors sustaining a high-performance plasma. The born frequency of the fishbone oscillation is the ion diamagnetic drift frequency and the chirping down of the frequency during the initial growth phase is the result of a drop in iondiamagnetic drift frequency. The excitation energy is thought to be due to the thermal plasma pressure gradient; however, the development of a fishbone oscillation is related to energetic ions.