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Ping’ou hybrid hazelnut is one of the most profitable tree nuts in China, but economically important cultivars must first be genetically validated to meet industrial demand. Traditional approaches used for cultivar identification are mainly trait-based and unreliable. Previous approaches at the DNA level, focusing on the identification of species or/and varieties that originated in China, were not used widely in hybrid hazelnut because there was no proper standard sample. In this research, a multiplexed fingerprinting test was conducted to allow for hazelnut cultivar identification using SSR markers derived from European hazelnut. Twenty-seven SSR markers were used to fingerprint 57 genetically unique Ping’ou hybrid hazelnut and related wild species. All markers showed a high level of polymorphism, as indicated by mean values for observed heterozygosity (Ho = 0.84), expected heterozygosity (He = 0.80), and polymorphism information content (PIC = 0.78). A total of 301 alleles were detected, and the number of effective alleles varied from 6 for KG817 and GB818 to 18 for B654, with an average of 11.2 alleles per locus. Moreover, the Shannon’s information index (I) ranged from 1.293 for BR215 to 2.385 for B654, with an average of 1.908. The neighbor-joining tree, principal coordinate analysis, and Bayesian analysis revealed clear separation between hybrid cultivars and wild forms (Cluster/group I), as well as the differentiation within hybrid genotypes (Clusters/groups II and III). Additionally, the NJ dendrogram demonstrated a further split within Clusters/group III (III a and III b). Altogether, with the comparable SSR information of the European hazelnut cultivar ‘Barcelona’, the newly developed marker sets can assist in the germplasm identification of hazelnut cultivars and reproductive materials. Importantly, these combined SSR loci can be applied to characterize the genetic relationships and population structures among wild genotypes and hybrid cultivars, which will then provide information to guide hazelnut breeding based on their genetic background.

IntroductionRimmed vacuolar myopathies (RVMs) are a group of genetically heterogeneous diseases that share histopathological characteristics on muscle biopsy, including the aberrant accumulation of autophagic vacuoles. However, the presence of non-coding sequences and structural mutations, some of which remain undetectable, confound the identification of pathogenic mutations responsible for RVMs. Therefore, we assessed the clinical profiles and muscle magnetic resonance imaging (MRI) changes in 36 Chinese patients with RVMs, emphasizing the role of muscle MRI in disease identification and differential diagnosis to propose a comprehensive literature-based imaging pattern to facilitate improved diagnostic workup.MethodsAll patients presented with rimmed vacuoles with varying degrees of muscular dystrophic changes and underwent a comprehensive evaluation using clinical, morphological, muscle MRI and molecular genetic analysis. We assessed muscle changes in the Chinese RVMs and provided an overview of the RVMs, focusing on the patterns of muscle involvement on MRI.ResultsA total of 36 patients, including 24 with confirmed distal myopathy and 12 with limb-girdle phenotype, had autophagic vacuoles with RVMs. Hierarchical clustering of patients according to the predominant effect of the distal or proximal lower limbs revealed that most patients with RVMs could be distinguished. GNE myopathy was the most prevalent form of RVMs observed in this study. Moreover, MRI helped identify the causative genes in some diseases (e.g., desminopathy and hereditary myopathy with early respiratory failure) and confirmed the pathogenicity of a novel mutation (e.g., adult-onset proximal rimmed vacuolar titinopathy) detected using next-generation sequencing.DiscussionCollectively, our findings expand our knowledge of the genetic spectrum of RVMs in China and suggest that muscle imaging should be an integral part of assisting genetic testing and avoiding misdiagnosis in the diagnostic workup of RVM.

BackgroundIn the past 5 years, ferroptosis-associated cancer immunity has been attracted significant research interest.ObjectiveThis study was performed to identify and analyze the global output trend for ferroptosis in cancer immunity.MethodsRelevant studies were retrieved from the Web of Science Core Collection on Feb 10th, 2023. The VOSviewer and Histcite softwares were utilized to perform the visual bibliometric and deep mining analyses.ResultsA total of 694 studies (530 articles (76.4%) and 164 (23.6%) review articles) were retrieved from the Web of Science Core Collection for visualization analyses. The top 3 key keywords were ferroptosis, prognosis and immunotherapy. The top 30 local citation score (LCS) authors were all collaborators of Zou Weiping. Deep mining of 51 nanoparticle-related articles showed that BIOMATERIALS was the most popular journal. The primary goal of gene signatures related to ferroptosis and cancer immunity was to establish prognostic predictions.ConclusionThere has been a significant increase in ferroptosis-associated immune publications in the recent 3 years. The key research hotspots include mechanisms, prediction and therapeutic outcomes. The most influential article was from the Zou Weiping’s group, which proposed that system xc-mediated ferroptosis is induced by CD8(+) T cell-secreted IFNγ after PD-L1 blockage for immunotherapy. The frontier of research in the field of ferroptosis-associated immune is the study on nanoparticle and gene signature The limitation of this bibliometric study is that publications on this topic are few.

Late Paleozoic magmatic rock outcrops are common in the Northern Alxa, Southern Central Asian Orogenic Belt (CAOB), which is a key area for understanding tectonic processes and defining the final closure time of the Paleo-Asian Ocean (PAO). We present zircon U‒Pb chronology and whole-rock geochemistry data for late Paleozoic magmatic rocks from the Yagan area of northern Alxa. This paper reveals two periods of magmatism: syenogranite (374.8 Ma) and bimodal intrusive rocks, which consist of gabbro (261.4 Ma), diabase (262.9 Ma) and biotite monzogranite (263.4 Ma). The syenogranite is high-K calc-alkaline and shows enrichments in Th, Zr, Hf and LREEs; depletions in Sr, Nb, Ta, and Ti; and low Mg# values (6.9–13.2); the syenogranite was derived from partial melting of the crust and has volcanic arc characteristics. The gabbro and diabase have similar geochemical characteristics, such as enrichments in Pb, Rb, Sr, Zr, and Hf and depletions in Nb, Ta, and Ti, with positive εHf(t) values (+0.9–+2.7 and +2.6–+3.6, respectively), indicating that they originated from partial melting of depleted mantle and experienced crustal contamination during magma emplacement. The biotite monzogranite shows depletions in Nb, Ta, and Ti and εNd (t) values of -2.6 to −2.4 and resulted from partial melting of the lower crust caused by asthenospheric underplating. The bimodal intrusive rocks formed in a postcollision extensional setting. Combined with previous data, we conclude that northern Alxa was an active continental margin during the late Devonian and that the final closure of the Yagan branch ocean of the PAO occurred prior to the middle Permian.

Very recently, a 3$d$ based honeycomb cobaltate Na$_2$Co$_2$TeO$_6$ has garnered tremendous attention due to the proposed proximity to the Kitaev spin-liquid state as its 4$d$/5$d$ counterparts. Here, we use Zn to substitute Co in a broad range and perform systematic studies on Na$_2$Co$_{2-x}$Zn$_x$TeO$_6$ by structural, magnetic, and thermodynamic measurements, and track the doping evolution of its magnetic ground states. Due to the extremely close radii of Zn$^{2+}$ and high-spin Co$^{2+}$ ions, the substitution can be easily achieved. X-ray diffractions reveal no structural transition but only minor changes on the lattice parameter $c$ over a wide substitution range $0 \leq x \leq 1.5$. Magnetic susceptibility and specific heat measurements both suggest an antiferromagnetic ground state which is gradually suppressed with doping. It can survive with $x$ up to $\sim1.0$. Then it evolves into a spin-glass phase with short-range order that is rapidly supplanted by a magnetically disordered state when $x \geq 1.3$. By summarizing all these data, we construct a magnetic phase diagram of Na$_2$Co$_{2-x}$Zn$_x$TeO$_6$. Our results demonstrate that the Zn doping can effectively suppress the magnetic order and induce a possibe quantum paramagnetic state. These may serve as a platform to investigate the Kitaev physics in this system., Comment: 9 pages, 5 figures

The honeycomb-lattice cobaltate Na$_3$Co$_2$SbO$_6$ has recently been proposed to be a proximate Kitaev quantum spin liquid~(QSL) candidate. However, non-Kitaev terms in the Hamiltonian lead to a zigzag-type antiferromagnetic~(AFM) order at low temperatures. Here, we partially substitute magnetic Co$^{2+}$ with nonmagnetic Zn$^{2+}$ and investigate the chemical doping effect in tuning the magnetic ground states of Na$_3$Co$_{2-x}$Zn$_x$SbO$_6$. X-ray diffraction characterizations reveal no structural transition but quite tiny changes on the lattice parameters over our substitution range $0\leq x\leq0.4$. Magnetic susceptibility and specific heat results both show that AFM transition temperature is continuously suppressed with increasing Zn content $x$ and neither long-range magnetic order nor spin freezing is observed when $x\geq0.2$. More importantly, a linear term of the specific heat representing fermionic excitations is captured below 5~K in the magnetically disordered regime, as opposed to the $C_{\rm m}\propto T^3$ behavior expected for bosonic excitations in the AFM state. Based on the data above, we establish a magnetic phase diagram of Na$_3$Co$_{2-x}$Zn$_x$SbO$_6$. Our results indicate the presence of gapless fractional excitations in the samples with no magnetic order, evidencing a potential QSL state induced by doping in a Kitaev system., Comment: 10 pages, 5 figures

Traumatic temporomandibular joint ankylosis refers to fibrous or bony fusion between the condyle and the glenoid fossa. It can cause problems with mouth-opening limitations, mastication difficulties, obstructive sleep apnea and hypopnea syndrome. When traumatic temporomandibular joint ankylosis occurs during childhood, it can cause facial asymmetry, micrognathia, and malocclusion, which significantly affect the physical and mental health. Once temporomandibular joint ankylosis occurs, it will be refractory and recurrent. The pathogenesis of temporomandibular joint ankylosis has not been completely elucidated and has always been a research hotspot in the oral and maxillofacial fields. In this paper, worldwide research was conducted, and the pathogenesis of traumatic temporomandibular joint ankylosis was clarified, such as “damage of condyle”,“disc displacement or rupture”,“damage to the glenoid fossa” and “lateral pterygoid muscle distraction”. The relative pathogenesis hypotheses were summarized, such as “hematoma organization” and “lateral pterygoid muscle distraction osteogenesis”. The related pathogenesis of traumatic temporomandibular joint ankylosis was discussed based on the latest cytology and molecular biology research.

Light has long been known to have a profound influence on the growth and development of fish. The previous studies showed that different spectra had different effects on the growth of juvenile Takifugu rubripes. Among them, green light can promote the growth of Takifugu rubripes, but the influence mechanism is unknown. In this study, how different LED spectrums affect fish growth from the perspective of GH/IGF-I axis-related genes and apoptosis genes were deeply explored. In the experiment, juvenile Takifugu rubripes with an initial body length of (9.01 ± 0.70) cm and an initial body weight of (18.05 ± 3.17) g were selected as the research objects. 525 Takifugu rubripes juveniles were selected, cultured and monitored in five different LED spectrum treatment groups: white light (WL, λ 400-780nm), red light (RL, λ 625-630nm), yellow light (YL, λ 590-595nm), green light (GL, λ 525-530nm) and blue light (BL, λ 450-455nm). The photoperiod was 12L:12D, and the light intensity was set to 250 mW/m2. The effects of light spectrum on growth, melatonin synthesis, GH/IGF-I axis and relative expressions of apoptosis-related genes in juvenile Takifugu rubripes were studied, including arylalkylamine N-acetyltransferase (AANAT2), growth hormone (GH), growth hormone receptor type 1 (GHR1), growth hormone releasing hormone (GHRH), insulin-like growth factor type I (IGF-I), insulin-like growth factor type II (IGF-II), insulin-like growth factor binding protein (IGFBP), Bcl-2 protein family (Bcl-2), tumor suppressor (p53) and cysteine protease family (caspase 3, caspase 8, caspase 10) genes. The results showed that the final weight was the highest in the GL group (29.36 ± 3.78 g) and the lowest in the YL group (21.28 ± 2.56 g). The GL indeed promote the growth of Takifugu rubripes. The GHR1, IGF-I, IGF-II and IGFBP of juvenile Takifugu rubripes cultured under GL were significantly higher than those of WL (control group), BL and YL groups. The relative expression levels of GH and GHRH genes had no difference from those in the WL control group, and the relative expression levels of apoptosis genes in the GL group were significantly lower than those in the BL and YL groups. Under RL, the relative expression levels of all growth genes on the GH/IGF-I growth axis were relatively high. But at the same time, the relative expression of caspase 10 gene in juvenile Takifugu rubripes was high, and the growth state was inhibited. It is speculated that RL might disturb the endocrine system of the juvenile Takifugu rubripes, thus impeded its growth and development. Therefore, different LED spectra can affect the growth of juvenile Takifugu rubripes by affecting the expressions of GH/IGF-I growth axis and apoptosis-related genes: GL significantly promotes the growth of Takifugu rubripes, which may be due to that GL promoted the expressions of growth factors genes such as GHR1, IGF-I, and IGF-II, and decreased the expression of apoptosis-related genes, while the situation in the YL, BL and WL groups was on the contrary. RL significantly inhibited the growth of juvenile Takifugu Rubripes, which may be due to the fact that juvenile Takifugu Rubripes under RL were in a stressful state and the high expression of growth axis-related genes was not sufficient to offset the negative effects of the stress response, resulting in the inhibition of growth performance.

Objective: With the rapid development of proteomics sequencing and RNA sequencing technology, multi-omics analysis has become a current research hotspot. Our previous study indicated that Xinjiang brown cattle have better meat quality than Kazakh cattle. In this study, Xinjiang brown cattle and Kazakh cattle were used as the research objects.Methods: Proteome sequencing and RNA sequencing technology were used to analyze the proteome and transcriptome of the longissimus dorsi muscle of the two breeds of adult steers (n = 3).Results: In this project, 22,677 transcripts and 1,874 proteins were identified through quantitative analysis of the transcriptome and proteome. By comparing the identified transcriptome and proteome, we found that 1,737 genes were identified at both the transcriptome and proteome levels. The results of the study revealed 12 differentially expressed genes and proteins: troponin I1, crystallin alpha B, cysteine, and glycine rich protein 3, phosphotriesterase-related, myosin-binding protein H, glutathione s-transferase mu 3, myosin light chain 3, nidogen 2, dihydropyrimidinase like 2, glutamate-oxaloacetic transaminase 1, receptor accessory protein 5, and aspartoacylase. We performed functional enrichment of these differentially expressed genes and proteins. The Kyoto encyclopedia of genes and genomes results showed that these differentially expressed genes and proteins are enriched in the fatty acid degradation and histidine metabolism signaling pathways. We performed parallel reaction monitoring (PRM) verification of the differentially expressed proteins, and the PRM results were consistent with the sequencing results.Conclusion: Our study provided and identified the differentially expressed genes and proteins. In addition, identifying functional genes and proteins with important breeding value will provide genetic resources and technical support for the breeding and industrialization of new genetically modified beef cattle breeds.

BackgroundTai Chi can show improvement in balance and motor ability of elderly patients with PD. However, there were few reports on differences in outcomes associated with different types of Tai Chi on improving exercise capacity in elderly patients with PD. We compared the improvement of motor function in Parkinson's patients with different types of Tai Chi, for finding an optimal intervention.MethodsThe following databases were searched from the beginning of the establishment of each database to 10 January 2022: PubMed, EMBASE, The Cochrane Library, CNKI, Wanfang Database, and VIP Database. Randomized controlled trials incorporating different types of Tai Chi for PD were included. The outcome measures were UPDRSIII and BBS. NMA was conducted using Stata 15.0 based on a frequentist framework.ResultsA total of twenty trials were eligible, including 996 participants. In conventional meta-analysis, as for the UPDRSIII scale, 24-form simplified Tai Chi (SMD = −1.272, 95% CI [−2.036, −0.508], P < 0.05, I2 > 50%), Tai Chi exercise program (SMD = −0.839, 95% CI [−1.828, 0.151], P > 0.05, I2 > 50%), 8-form simplified Yang style Tai Chi (SMD = −0.325, 95% CI [−1.362, 0.713], P > 0.05, I2 > 50%), and 8-form simplified Chen style Tai Chi (SMD = −0.28, 95% CI [−0.97, 0.42], P > 0.05, I2 > 50%) were statistically more efficient than the control group. For BBS outcome, 24-form simplified Tai Chi (MD = 3.979, 95% CI [3.364, 4.595], P < 0.05, I2 P > 0.05, I2 > 50%), and 8-form simplified Chen style Tai Chi (MD = 1.25, 95% CI [0.52, 1.98], P < 0.05, I2 > 50%) were better than the control group. In the network meta-analysis, the results of UPDRSIII were as follows: 24-form > TCEP > 8-form YS > 8-form CS > control. The ranking probability of BBS was as follows: TCEP > 24-form > 8-form CS > control.ConclusionAmong the four treatments studied, 24-form Tai Chi and Tai Chi exercise programs have shown better efficacy than other types. Our study provides new insights into exercise therapy for PD and may contribute to the formulation of a clinical exercise prescription.Systematic review registrationIdentifier: CRD42021285005.

The integration of metal nanoparticles and solid carriers can achieve ideal stability, high load and good conductivity. In this work, copper nanoparticles (Cu NPs) were sequentially deposited on a cobalt metal-organic framework (Co-MOF) by bonding with exposed imino groups, followed by a reduction reaction to prepare a new Cu@Co-MOF composite. Cu@Co-MOF acts as a non-enzymatic electrochemical sensor to detect glucose (Glu) in an alkaline medium. The composite working electrode of Cu@Co-MOF/GCE (GCE = glassy carbon electrode) improves the electrocatalytic activity for Glu oxidation. Cu@Co-MOF/GCE shows excellent electrocatalytic performances in Glu concentration ranging 0.005~1.8 mmol∙L−1 (mM): the sensitivities are 282.89 μA∙mM−1∙cm−2 in 0.005-0.4 mM Glu and 113.15 μA∙mM−1∙cm−2 in 0.4-1.8 mM Glu respectively with low detection limit of 1.6 μM (S/N = 3) and high selectivity and stability.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has a high recurrence rate. Accurate prediction of recurrence risk is urgently required for tailoring personalized treatment programs for individual HCC patients in advance. In this study, we analyzed a gene expression dataset from an HCC cohort with 247 samples and identified five genes including ENY2, GPAA1, NDUFA4L2, NEDD9, and NRP1 as the variables for the prediction of HCC recurrence, especially the early recurrence. The Cox model and risks score were validated in two public HCC cohorts (GSE76427 and The Cancer Genome Atlas (TCGA)) and one cohort from Huashan Hospital, which included a total of 641 samples. Moreover, the multivariate Cox regression analysis revealed that the risk score could serve as an independent prognostic factor in the prediction of HCC recurrence. In addition, we found that ENY2, GPAA1, and NDUFA4L2 were significantly upregulated in HCC of the two validation cohorts, and ENY2 had significantly higher expression levels than another four genes in malignant cells, suggesting that ENY2 might play key roles in malignant cells. The cell line analysis revealed that ENY2 could promote cell cycle progression, cell proliferation, migration, and invasion. The functional analysis of the genes correlated with ENY2 revealed that ENY2 might be involved in telomere maintenance, one of the fundamental hallmarks of cancer. In conclusion, our data indicate that ENY2 may regulate the malignant phenotypes of HCC via activating telomere maintenance.

n this paper, we try to give a security evaluation of LIZARD stream cipher in regard to fault attacks, which, to the best of our knowledge, is the first fault analysis on LIZARD. We design a differential engine of LIZARD to track the differential trail of the keystreams. It is shown that the distributions of the keystream differences are heavily biased. Utilizing this characteristic, we propose an improved method to identify the fault location for LIZARD whose success probability approaches 1. Then we use the fault-free keystream and faulty keystreams to generate system of equations in internal state variables and solve it by SAT solver. The result shows that with 100 keystream bits, only 6 different faults are needed to recover the internal state. Finally, the comparison between LIZARD and Grain v1 shows that LIZARD is more resistable than Grain v1 in regard to fault attacks.

Very recently, unconventional superconductivity has been observed in the double twisted trilayer graphene (TLG), where three monolayer graphene (MLG) are stacked on top of each other with two twist angles [J. M. Park, et al., Nature 590, 249 (2021); Z. Hao, et al., Science 371, 1133 (2021); X. Zhang, et al., Phys. Rev. Lett.127, 166802 (2021)]. When some of MLGs in the double twisted TLG are replaced by bilayer graphene (BLG), we get a new family of double twisted moire heterostructure, namely double twisted few layer graphene (DTFLG). In this work, we theoretically investigate the moire band structures of the DTFLGs with diverse arrangements of MLG and BLG. We find that, depending on the relative rotation direction of the two twist angles (alternate or chiral twist) and the middle van der Waals (vdW) layer (MLG or BLG), a general (X+Y+Z)-DTFLG can be classified into four categories, i.e. (X+1+Z)-ATFLG, (X+2+Z)-ATFLG, (X+1+Z)-CTFLG and (X+2+Z)-CTFLG, each of which has its own unique band structure. Here, X, Y, Z denote the three vdW layers, i.e. MLG or BLG. Interestingly, the (X+1+Z)-ATFLGs have a pair of perfect flat bands at the magic angle about $1.54^\circ$ coexisting with a pair of linear or parabolic bands, which is quite like the double twisted TLG. Meanwhile, when the twist angle is smaller than a "magic angle" $1.70^\circ$, the (X+2+Z)-CTFLGs can have two isolated narrow bands at $E_f$ with band width less than 5 meV. The influence of electric field and the topological features of the moire bands have been studied as well. Our work indicates that the DTFLGs, especially the (X+1+Z)-ATFLG and (X+2+Z)-CTFLG, are promising platforms to study the moire flat band induced novel correlation and topological effects., 13 pages, 10 figures

Dimerized magnets forming alternating Heisenberg chains exhibit quantum coherence and entanglement and thus can find potential applications in quantum information and computation. However, magnetic systems typically undergo thermal decoherence at finite temperatures. Here, we show inelastic neutron scattering results on an alternating antiferromagnetic-ferromagnetic chain compound Na$_2$Cu$_2$TeO$_6$ that the excited quasiparticles can counter thermal decoherence and maintain strong correlations at elevated temperatures. At low temperatures, we observe clear dispersive singlet-triplet excitations arising from the dimers formed along the crystalline $b$-axis. The excitation gap is of $\sim$18 meV and the bandwidth is about half of the gap. The band top energy has a weak modulation along the [100] direction, indicative of a small interchain coupling. The gap increases while the bandwidth decreases with increasing temperature, leading to a strong reduction in the available phase space for the triplons. As a result, the Lorentzian-type energy broadening becomes highly asymmetric as the temperature is raised. These results are associated with a strongly correlated state resulting from hard-core constraint and quasiparticle interactions. We consider these results to be not only evidence for strong correlations at finite temperatures in Na$_2$Cu$_2$TeO$_6$, but also for the universality of the strongly correlated state in a broad range of quantum magnetic systems., Published in PRB, 8 pages, 6 figures

Additional file 1: Fig. S1. C3a is present in the tumor tissue of MB patients and C3aR is present on both astrocytes and microglia. a, IHC staining of C3a on human MB sections derived from 4 patients, respectively (P#2–P#5). b, Representative immunostaining of C3aR (in red) and GFAP (in green) or Iba-1(in green) on human MB sections. Fig. S2. C3aR antagonist SB290157 inhibits GFAP expression by C3a-administrated astrocytes. Primary astrocytes were stimulated with C3a (100 nM) with or without SB290157 (2 μΜ) for 48 h in vitro. Immunostaining of GFAP (green) was performed (a), and the percentage of GFAP + cells was quantified (b). Fig. S3. C3a does not activate the Erk pathway in astrocytes. Primary astrocytes were stimulated with 100 nM C3a for 2, 5, 10 and 20 min. Then, the cells were harvested and lysed for total Erk and phosphorylated Erk (p-Erk) detection by western blotting. β-Tubulin served as a protein sample loading control. Fig. S4. Phosphorylation of p38 in C3a-administrated astrocytes is inhibited by C3aR antagonist SB290157. a, Primary astrocytes were stimulated with C3a (100 nM) with or without addition of SB290157 (2 μΜ) for 4 h in vitro. Then, the cells were harvested and lysed for total p38 and phosphorylated p38 (p–p38) detection by western blotting. Fig. S5. GFAP and TNF-α expression and the phosphorylation of p38 in C3a-administrated astrocytes is inhibited by C3aR antagonist SB290157. Primary astrocytes were stimulated with C3a (100 nM, from R&D) in the presence or absence of SB290157 (2 μΜ) for 48 h (a and b), 4 h (c) and 12 h (d), respectively, in vitro. a, Immunostaining of GFAP (in green) was performed, and b, the percentage of GFAP + cells was quantified. c, the cells were harvested and lysed for total p38 and phosphorylated p38 (p–p38) detection by western blotting. d, the cells were harvested to perform qPCR for evaluating TNF-α mRNA levels. ***p < 0.001 vs. C3a (−) & SB290157 (−) group, ##p < 0.01 and ###p < 0.001 vs. C3a ( +) & SB2901570 (−) group. Fig. S6. C3aR antagonist treatment inhibits the p38 MAPK pathway activation in tumor tissue of subcutaneous MB mice. Tumor tissue of C3aR antagonist (SB290157)- and vehicle (MCT)-treated subcutaneous MB mice was harvested at the termination of treatment, and tumor tissue was homogenized to evaluate phosphorylated p38 (p–p38) and total p38 levels by western blotting. β-Tubulin served as a protein sample loading control. Fig. S7. TNF-α receptor is expressed on MB cells. Primary MB cells (pMB), TAAs and BV2 cells were harvested and lysed for RT–PCR assays to detect TNF-α receptor (TNFSF1A) expression. GAPDH served as an internal control.

Additional file 3: Figure S1. The number of proteins identified at various molecular weight ranges.

$��$-RuCl$_3$ has been studied extensively because of its proximity to the Kitaev quantum-spin-liquid (QSL) phase and the possibility of approaching it by tuning the competing interactions. Here we present the first polarized inelastic neutron scattering study on $��$-RuCl$_3$ single crystals to explore the scattering continuum around the $��$ point at the Brillouin zone center, which was hypothesized to be resulting from the Kitaev QSL state but without concrete evidence. With polarization analyses, we find that while the spin-wave excitations around the M point vanish above the transition temperature $T_{\rm N}$, the pure magnetic continuous excitations around the $��$ point are robust against temperature. Furthermore, by calculating the dynamical spin-spin correlation function using the cluster perturbation theory, we derive magnetic dispersion spectra based on the $K$-$��$ model, which involves with a ferromagnetic Kitaev interaction of -7.2 meV and an off-diagonal interaction of 5.6 meV. We find this model can reproduce not only the spin-wave excitation spectra around the M point, but also the non-spin-wave continuous magnetic excitations around the $��$ point. These results provide evidence for the existence of fractional excitations around the $��$ point originating from the Kitaev QSL state, and further support the validity of the $K$-$��$ model as the effective minimal spin model to describe $��$-RuCl$_3$., Published in Chinese Physics Letters as Express Letter, 8 pages, 4 figures

Hysteretic switching of domain states is a salient character of all ferroic materials and the foundation for their multifunctional applications. Ferro-rotational order is emerging as a new type of ferroic order featuring structural rotations, but its controlled switching remains elusive due to its invariance under both time reversal and spatial inversion. Here, we demonstrate electrical switching of ferro-rotational domain states in nanometer-thick 1T-TaS$_2$ crystals in its charge-density-wave phases. Cooling from the high-symmetry phase to the ferro-rotational phase under an external electric field induces domain state switching and domain wall formation, realized in a simple two-terminal configuration using a volt-scale voltage. Although the electric field does not couple with the order due to symmetry mismatch, it drives domain wall propagation to give rise to reversible, durable, and nonvolatile isothermal state switching at room temperature. These results pave the path for manipulation of the ferro-rotational order and its nanoelectronic applications.

Additional file 8: Figure S6. Venn plot indicated the overlapped annotated proteins of GO, KEGG, and KOG database.

Additional file 5: Figure S3. The number of peptide fragments for protein identification.

Additional file 7: Figure S5. The KEGG annotation of all expressed proteins.

Additional file 4: Figure S2. The distribution of protein���s sequence coverage.

We have performed inelastic neutron scattering measurements on optimally-doped Fe$_{0.98}$Te$_{0.5}$Se$_{0.5}$ and 10% Cu-doped Fe$_{0.88}$Cu$_{0.1}$Te$_{0.5}$Se$_{0.5}$ to investigate the substitution effects on the spin excitations in the whole energy range up to 300 meV. It is found that substitution of Cu for Fe enhances the low-energy spin excitations ($\le$ 100 meV), especially around the (0.5, 0.5) point, and leaves the high-energy magnetic excitations intact. In contrast to the expectation that Cu with spin 1/2 will dilute the magnetic moments contributed by Fe with a larger spin, we find that the 10% Cu doping enlarges the effective fluctuating moment from 2.85 to 3.13 $\mu_{\rm B}$/Fe, although there is no long- or short-range magnetic order around (0.5, 0.5) and (0.5, 0). The presence of enhanced magnetic excitations in the 10% Cu doped sample which is in the insulating state indicates that the magnetic excitations must have some contributions from the local moments, reflecting the dual nature of the magnetism in iron-based superconductors. We attribute the substitution effects to the localization of the itinerant electrons induced by Cu dopants. These results also indicate that the Cu doping does not act as electron donor as in a rigid-band shift model, but more as scattering centers that localize the system., Comment: Published in PRB, 8 pages, 3 figures

Additional file 10: Figure S7. The top 10 TF families detected in all expressed proteins.

Due to the observed superconductivity, the alternating twisted trilayer graphene (ATTLG) has drawn great research interest very recently, in which three monolayer graphene (MLG) are stacked in alternating twist way. If one or several of the MLG in ATTLG are replaced by a multilayer graphene, we get a double twisted multilayer graphene (DTMLG). In this work, we theoretically illustrate that, if the DTMLG has a mirror symmetry along z direction like the ATTLG, there exists a mirror symmetry decomposition (MSD), by which the DTMLG can be exactly decoupled into two subsystems with opposite parity. The two subsystems are either a twisted multilayer graphene (single twist) or a multilayer graphene, depending on the stacking configuration. Such MSD can give a clear interpretation about all the novel features of the moir\'{e} band structures of DTMLG, e.g. the fourfold degenerate flat bands and the enlarged magic angle. Meanwhile, in such DTMLG, the parity becomes a new degree of freedom of the electrons, so that we can define a parity resolved Chern number for the moir\'{e} flat bands. More importantly, the MSD implies that all the novel correlated phases in the twisted multilayer graphene should also exist in the corresponding DTMLGs, since they have the exact same Hamiltonian in form. Specifically, according to the MSD, we predict that the superconductivity should exist in the (1+3+1)-DTMLG., Comment: 12 pages, 6 figures

In the local or itinerant extreme, magnetic excitations can be described by the Heisenberg model which treats electron spins as localized moments, or by the itinerant-electron model where the exchange interaction between electrons leads to unequal numbers of electrons with up and down spins. However, it has been elusive when both local moments and itinerant electrons are present in the intermediate range. Using inelastic neutron scattering, we provide direct spectroscopic evidence on the coexistence of and interplay between local moments and itinerant electrons in a van der Waals metallic ferromagnet Fe$_{2.72}$GeTe$_{2}$, which can sustain tunable room-temperature ferromagnetism down to the monolayer limit. We find that there exist ferromagnetic spin-wave excitations dispersing from the zone center at low energies resulting from local moments, and a column-like broad continuum at the zone boundary at high energies up to over 100 meV resulting from itinerant electrons. Unlike the two-dimensional crystal structure, the low-energy mode exhibits a three-dimensional nature, and the high-energy mode also has an out-of-plane dependence. Both modes persist well above the Curie temperature of 160 K. Our neutron spectroscopic data reveal that the low-energy spin waves at 100 K are more coherent than those at 4 K, which is evidence of the weakening of the Kondo screening at high temperatures. These results unambiguously demonstrate the coexistence of local moments and itinerant electrons, and the Kondo effect between these two components in Fe$_{2.72}$GeTe$_{2}$. Such behaviors are generally expected in heavy-fermion systems with heavy $f$ electrons but rarely clearly observed in materials with light $d$ electrons. These findings shed light on the understanding of magnetism in transition-metal compounds., Comment: Main text 15 pages, 5 figures. Supplementary Materials available on PRX

Additional file 13: Figure S9. The results of SDS-PAGE showed that the separated bands were clear, abundant and non-degraded, and the bands were consistent among all samples. The F1, F2 and F3 correspond to fine type cashmere (F) samples, C1, C2 and C3 correspond to coarse type cashmere (C) samples, respectively.

Additional file 12: Figure S8. The target bands and western blots of GPR142, VTN, GLB1, AEBP1. GAPDH was used as control.

Poly(ADP-ribose) polymerase-1 (PARP-1), a critical DNA repair enzyme in the base excision repair pathway, has been pursued as an attractive cancer therapeutic target. Intervention with PARP-1 has been proved to be more sensitive to cancer cells carrying BRCA1/2 mutations. Several PARP-1 inhibitors have been available on market for the treatment of breast, ovarian and prostatic cancer. Promisingly, the newly developed proteolysis targeting chimaeras (PROTACs) may provide a more potential strategy based on the degradation of PARP-1. Here we report the design, synthesis, and evaluation of a proteolysis targeting chimaera (PROTAC) based on the combination of PARP-1 inhibitor olaparib and the CRBN (cereblon) ligand lenalidomide. In SW620 cells, our probe-quality degrader compound 2 effectively induced PARP-1 degradation which results in anti-proliferation, cells apoptosis, cell cycle arresting, and cancer cells migratory inhibition. Thus, our findings qualify a new chemical probe for PARP-1 knockdown., Graphical Abstract

Inhibition of BET family of bromodomain is an appealing intervention strategy for several cancers and inflammatory diseases. This article highlights our work toward the identification of potent, selective, and efficacious BET inhibitors using a structure-based approach focused on improving potency. Our medicinal chemistry efforts led to the identification of compound 24, a novel phenanthridin-6(5H)-one derivative, as a potent (IC50 = 0.24 μM) and selective BET inhibitor with excellent cancer cell lines inhibitory activities and favorable oral pharmacokinetic properties.

In order to solve the problem of quality degradation of underwater image due to absorption and scattering of water body, this paper proposes a method of underwater image enhancement based on the combination of computational imaging and deep learning. The method has achieved good results in removing image blur and scattering noise. It can effectively enhance the target images in turbid water, which will allow underwater image applications to have a wider range of areas.

Compared with images taken in the air, underwater images are susceptible due to the adverse effects of complex water conditions, such as absorption, attenuation, scattering, various noises, and uneven lighting, etc. These effects severely reduce the quality of underwater imaging and give rise to many problems among which is image color distortion. To fully acknowledge the underwater scenes, it is important to acquire the images with accurate colors, especially for marine rescue, underwater target recognition, and marine ecological research. To address this problem, this paper proposes an underwater imaging technology based on a light field camera array. The application of this technology can not only perform accurate color correction processing on the captured images but also expand the dynamic range of underwater images, thereby obtain enhanced high-quality, true-color underwater images. The experimental system in this paper contains a 3*3 camera array that simultaneously captures images of underwater targets with different exposure times. As the light attenuation coefficient of different wavelengths in water varies with the wavelength, during the color restoration process, we measure the relative value of the underwater spectral power distribution concerning the air, calculate the tristimulus value change according to the colorimetric principle, and convert the tristimulus value change in the CIEXYZ color space to the CIE La*b* color space. The color on the underwater images obtained by the camera array is then compensated. Then, in the image fusion process, images with different exposure are used to recover the response function of the imaging process, and multiple images are fused into a single, high-dynamic-range radiance map using high quality tone mapping technique in the radiance value dynamic display high-contrast images on devices with limited range. Experimental results show that our light-field imaging color correction and dynamic range expansion processing methods have obvious advantages over single cameras in underwater color correction and underwater moving target imaging detection, which provide advanced technology and equipment for underwater in-situ applications.

The bromodomain and extra-terminal (BET) bromodomains, particularly BRD4, have been identified as promising therapeutic targets in the treatment of many human disorders such as cancer, inflammation, obesity, and cardiovascular disease. Recently, the discovery of novel BRD4 inhibitors has garnered substantial interest. Starting from scaffold hopping of the reported compound dihydroquinazolinone (PFI-1), a series of coumarin derivatives were designed and synthesised as a new chemotype of BRD4 inhibitors. Interestingly, the representative compounds 13 exhibited potent BRD4 binding affinity and cell proliferation inhibitory activity, and especially displayed a favourable PK profile with high oral bioavailability (F = 49.38%) and metabolic stability (T1/2 = 4.2 h), meaningfully making it as a promising lead compound for further drug development., Graphical Abstract

Background Idiopathic pulmonary fibrosis is a lethal fibrosing interstitial pneumonia characterized by progressive worsening of dyspnea and lung function with poor prognosis. Since pirfenidone was approved for IPF treatment, the search for more effective candidates has been greatly intensified. Methods In this study, the antifibrotic effects and mechanisms of compound PBD-617 , the ideal candidate discovered in our previous work, were investigated on transforming growth factor-β1 (TGF-β1)-induced human embryonic lung fibroblasts (HELF) and on bleomycin (BLM)-induced pulmonary fibrotic rats. Results Oral administration with PBD-617 decreased the levels of collagen I, collagen III and matrix metalloproteinase 7 , and inhibited the protein expression of α-smooth muscle actin in BLM-induced pulmonary fibrosis rats. Furthermore, PBD-617 suppressed the expression of TGF-β1 , phosphorylated Smad3, phosphorylated p38 and activator protein 1 on TGF-β1-induced HELF, while the regulation could be rescued by using p38 agonist p79350. Conclusion PBD-617 not only inhibited TGF-β1-induced HELF proliferation, but also attenuated BLM-induced pulmonary fibrosis in rats, with efficacy to some extent higher than that of pirfenidone at the same effective dosage. PBD-617 attenuated pulmonary fibrosis effectively by suppressing activation of TGF-β1/Smad3 and p38 signaling pathways .

Early-onset gastric cancer (EOGC) is a serious social burden. For patients with EOGC, typically considered as those aged

Huachao Guo, Hao Liang, Jiaguang Wang, Shuo Wen, Yong Wang, Yushe Wang, Zhen Ma Department of Neurosurgery, Henan University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of ChinaCorrespondence: Yushe Wang; Zhen MaDepartment of Neurosurgery, Henan University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, 450000, People’s Republic of ChinaEmail ghchdsy2018@sina.com; mzilyhdsy@163.comBackground: Intraparenchymal meningiomas without dural attachment are extremely rare, especially in female children. To our knowledge, fibrous intraparenchymal meningioma located in the temporal lobe has never been reported in female children. The significance in the differential diagnosis of lesions in the temporal lobe should be emphasized.Case Presentation: A 12-year-old girl was admitted to our hospital, complaining of recurrent generalized seizures for 2 months. Magnetic resonance imaging demonstrated a solid lesion located in the temporal lobe. The lesion underwent gross total resection. Histopathological examination indicated that the lesion was a fibrous meningioma. Postoperative rehabilitation was uneventful.Conclusion: This case report presents an extremely unusual intraparenchymal fibrous meningioma of the temporal lobe with peritumoral edema and reviewed 21 intraparenchymal meningioma cases in children and to discuss the clinical presentation and treatment, differential diagnosis, and radiological features.Keywords: meningioma, fibrous, temporal lobe, intraparenchymal

Additional file 5: A discrimination is relied on 2 statistical evidences, upper panel, ROC analysis, and lower panel, averages of feature importance in a RF model with 17 features. A total of 7 subgroups upon the clinical parameters are selected, (A) the patient ages < 35, (B) the patient ages ��� 35, (C) the patients received long protocol, (D) the patients received ultralong protocol, (E) the patients received GnRH-ant protocol. The representativeness of X-axis and Y-axis is as same as Figure 3D and E.

Additional file 6: Further dimensional reduction of the features consisting of metabolites and clinical parameters with rfFuncs in each subgroup. A total of 7 subgroups upon the clinical parameters are selected, (A) the patient ages < 35, (B) the patient ages ��� 35, (C) the patients received long protocol, (D) the patients received ultralong protocol, (E) the patients received GnRH-ant protocol. The representativeness of X-axis and Y-axis is as same as Figure 3C.

Additional file 3:. Further dimensional reduction of the features consisting of metabolites and clinical parameters rfFuncs. Y-axis represents the average AUC value of ROC in RF models, error bar represents the standard derivation of AUCs, and X-axis denotes the selected features.

Additional file 1:. Assessment of batch effect with PCA plot in each LC-MS/MS method. The batch effect of amino acid, fat-soluble vitamin, water-soluble vitamin, hormone and P180 method is represented in a-e, respectively.

As new structural and functional materials, porous materials have unparalleled advantages compared to dense materials because of their special pore structure. The powder metallurgy technique was utilized to prepare titanium foams by adding space holders to generate pores and FeV80 to modify the structure and properties of the materials. The results show that the TixVy (x + y = 1) phase exists in the sintering product after adding FeV80 powder. The content of FeV80 increases from 0% to 12%, resulting in the initial yield strength increasing from 190.08 MPa to 380.82 MPa; when the content of FeV80 is increased to 16%, the initial yield strength decreases to 331.77 MPa. Therefore, the improvement created in the mechanical properties of the porous titanium by adding ferrovanadium alloy is highly significant.

Additional file 4:. The frequency of metabolites selected in 17 features pattern.

Additional file 7: The morphology of the embryos on day 3 after fertilization. (A) The morphology of the embryo evaluated as G group on day 3 after fertilization (8C-I); (B) The morphology of the embryo evaluated as P group on day 3 after fertilization (IV).

The teaching methods of vocational college teachers can not only reflect the comprehensive quality and professional level of teachers, but also highlight the innovative ability of teachers. Good teaching methods can not only help students learn professional knowledge, but also affect students' professional employment development. This article analyzes the teaching methods of vocational college teachers under the background of big data.