ThCr2Si2C: An Antiferromagnetic Metal with a Cr2C Square Lattice.

A quaternary compound, ThCr2Si2C, was synthesized by using the arc-melting technique. The compound adopts a tetragonal CeCr2Si2C-type crystal structure. The electronic resistivity and specific heat data exhibit metallic behavior, while the magnetic susceptibility displays a pronounced broad peak at around 370 K, indicating the antiferromagnetic phase transition. The first-principles calculations suggest A-type antiferromagnetic ordering of the Cr sublattice, which is confirmed by neutron diffraction experiments. By comparing the crystal structure of ThCr2Si2C with the isostructural Cr-based compounds, the magnetic state of Cr 3d orbital is discussed in terms of the band-filling effects and indirect spin exchange interaction.

Developmental Process and Symmetry of Fetal Sulci in the Mesial Area Assessed by Ultrasound: A Cohort Study in Chinese Population.

OBJECTIVE: We aimed to investigate the progression of cortical development in Chinese population and to determine the rate of isolated asymmetric cortical development. We also explored the outcomes of these fetuses and determined whether cortical asymmetry represents normal individual physiological variation. METHODS: Our observational cohort study included 456 healthy singleton pregnant women who visited Peking University First Hospital between September 2020 and December 2021. We evaluated the progression and symmetry of the parieto-occipital sulcus, calcarine sulcus, and cingulate sulcus using a scoring system during routine fetal ultrasound examinations. The outcomes of the included fetuses after birth were assessed using the Ages and Stages Questionnaire, Third Edition (ASQ-3). RESULTS: The median gestational ages at which the parieto-occipital, calcarine, and cingulate sulci reached grade 1 were 22, 22, and 26 weeks, respectively. Among 456 included fetuses, 426 showed symmetric cortical development and 30 showed asymmetric cortical development during ultrasound examination. Fetuses with asymmetric cortical development underwent 'catch-up growth' and developed to the same grade in 2-6 weeks. All fetuses with symmetric or asymmetric cortical development had normal neurodevelopment after birth according to ASQ-3 assessment. CONCLUSION: The gestational age at which the parieto-occipital, calcarine, and cingulate sulci can be detected using ultrasound varies in different studies. Racial differences may be present in cortical development. Normal fetuses may physiologically have mildly asymmetric cortical development in the mesial area.

Construction of a predictive model for immunotherapy efficacy in lung squamous cell carcinoma based on the degree of tumor-infiltrating immune cells and molecular typing.

BACKGROUND: To construct a predictive model of immunotherapy efficacy for patients with lung squamous cell carcinoma (LUSC) based on the degree of tumor-infiltrating immune cells (TIIC) in the tumor microenvironment (TME). METHODS: The data of 501 patients with LUSC in the TCGA database were used as a training set, and grouped using non-negative matrix factorization (NMF) based on the degree of TIIC assessed by single-sample gene set enrichment analysis (GSEA). Two data sets (GSE126044 and GSE135222) were used as validation sets. Genes screened for modeling by least absolute shrinkage and selection operator (LASSO) regression and used to construct a model based on immunophenotyping score (IPTS). RNA extraction and qPCR were performed to validate the prognostic value of IPTS in our independent LUSC cohort. The receiver operating characteristic (ROC) curve was constructed to determine the predictive value of the immune efficacy. Kaplan-Meier survival curve analysis was performed to evaluate the prognostic predictive ability. Correlation analysis and enrichment analysis were used to explore the potential mechanism of IPTS molecular typing involved in predicting the immunotherapy efficacy for patients with LUSC. RESULTS: The training set was divided into a low immune cell infiltration type (C1) and a high immune cell infiltration type (C2) by NMF typing, and the IPTS molecular typing based on the 17-gene model could replace the results of the NMF typing. The area under the ROC curve (AUC) was 0.82. In both validation sets, the IPTS of patients who responded to immunotherapy were significantly higher than those who did not respond to immunotherapy (P = 0.0032 and P = 0.0451), whereas the AUC was 0.95 (95% CI = 1.00-0.84) and 0.77 (95% CI = 0.58-0.96), respectively. In our independent cohort, we validated its ability to predict the response to cancer immunotherapy, for the AUC was 0.88 (95% CI = 1.00-0.66). GSEA suggested that the high IPTS group was mainly involved in immune-related signaling pathways. CONCLUSIONS: IPTS molecular typing based on the degree of TIIC in the TME could well predict the efficacy of immunotherapy in patients with LUSC with a certain prognostic value.

Research progress on neonatal Fc receptor and its application.

Neonatal Fc receptor (FcRn) is a specific receptor for immunoglobulin G (IgG) and albumin, which binds to them in a pH-dependent manner and prevents them from lysosomal degradation to keep a long plasma half-life. In addition, FcRn plays an important role in transmembrane transport of IgG and albumin and in antigen presentation. In autoimmune diseases, anti-FcRn antibody can promote the degradation of pathogenic IgG by competitive binding to FcRn. In infectious diseases, the half-life of drugs can be prolonged by increasing the affinity between therapeutic antibody and FcRn, while the combination of viral antigen and Fc fragment of IgG can cause local immune response of mucosa for disease prevention and treatment. In cancer, albumin as a carrier of anticancer drugs can achieve efficient drug delivery, and FcRn itself may be used as a predictor of the prognosis of cancer patients. This review details the functions of FcRn, highlights its role in autoimmune diseases, infectious diseases and cancer, as well as the mechanism of drug development based on FcRn, to provide a reference for the clinical application and drug development of FcRn.

Pressure-stabilized polymerization of nitrogen in alkaline-earth-metal strontium nitrides.

High-pressure technology can help us to obtain excellent materials. We have explored alkaline-earth-metal strontium nitrides under different pressures, theoretically. A variety of stable Sr-N structures were predicted by the structure searching method using CALYPSO code. Six new stoichiometries, SrN, Sr2N3, SrN2, SrN3, SrN4, and SrN5, were predicted. And our calculation proved that all these compounds were stable existing under ambient pressure up to 100 GPa. A rich variety of poly-nitrogen forms appeared in the newly predicted SrNx compounds, including four nitrogen polymerization forms: ranging from N2, N3, N4, and N5 molecules, to zig-zag nitrogen chains and extended chains connected by puckered "N6" rings. Significantly, the 1D extended polymeric chain of puckered "N6" rings was firstly identified in the P1[combining macron]-SrN3 structure at 60 GPa. Another N-rich C2/c-SrN4 was stable only under the relatively high-pressure of 20 GPa, but this phase can be quenched under atmospheric pressure. The N-rich phase SrN5 maintained structural stability when the pressure reached 50-70 GPa. The delocalization of π electrons from N atoms was the principal cause for its metallicity in SrN5. In this paper, our calculated results indicated that the energetic poly-nitrides in alkaline-earth-metal nitrides can be obtained by the high-pressure method.

Cervical Cancer Detection and Diagnosis Based on Saliency Single Shot MultiBox Detector in Ultrasonic Elastography.

Cervical cancer is increasingly threatening the health of women, then early screening and prevention of cervical cancer is very necessary. A traditional saliency cervical cancer detection method in Ultrasound image, assuming that there is only one salient object, is not conductive to practical application. Their effects are dependent on saliency threshold. Object detection model provides a kind of new solutions for multiple salient objects. Shot multiBox detector can accurately detect multi-objects with different scales simultaneously except for small cervical cancer regions. To overcome this drawback, this paper presents a new multi-saliency objects detection model, appending deconvolution module embedded within attention residual module. Experiments show that our proposed diagnosis algorithm achieves higher detection accuracy than comparison algorithms. Also, it improves detection performance for mult-saliency cervical cancer objects with small scales, which greatly improve the diagnosis accuracy of cervical cancer.

Insights into Antibonding Induced Energy Density Enhancement and Exotic Electronic Properties for Germanium Nitrides at Modest Pressures.

Here, the electronic and bonding features in ground-state structures of germanium nitrides under different components that not accessible at ambient conditions have been systematically studied. The forming essence of weak covalent bonds between the Ge and N atom in high-pressure ionic crystal Fd-3 m-Ge3N4 is induced by the binding effect of electronic clouds originated from the Ge_ p orbitals. Hence, it helps us to understand the essence of covalent bond under high pressure, profoundly. As an excellent reducing agent, germanium transfer electrons to the antibonding state of the N2 dimer in Pa-3-GeN2 phase at 20 GPa, abnormally, weakening the bonding strength considerably than nitrogen gap (N≡N) at ambient pressure. Furthermore, the common cognition that the atomic distance will be shortened under the high pressures has been broken. Amazingly, with a lower range of synthetic pressure (∼15 GPa) and nitrogen contents (28%), its energy density is up to 2.32 kJ·g-1, with a similar order of magnitude than polymeric LiN5 (nonmolecular compound, 2.72 kJ·g-1). It breaks the universal recognition once again that nitrides just containing polymeric nitrogen were regarded as high energy density materials. Hence, antibonding induced energy density enhancement mechanism for low nitrogen content and pressure has been exposed in view of electrons. Both the highest occupied molecular orbitals (HOMO) and the lowest unoccupied molecular orbitals (LUMO) are usually the separated orbitals of N_π* and N_σ*, which are the key to stabilization. Besides, the sp2 hybridizations that exist in N4 units are responsible for the stability of the R-3 c-GeN4 structure and restrict the delocalization of electrons, exhibiting nonmetallic properties.

Bonding Properties of Aluminum Nitride at High Pressure.

Exploring the bonding properties and polymerization mechanism of stable polymeric nitrogen phases is the main goal of our high-pressure study. The pressure versus composition phase diagram of the Al-N system is established. In addition to the known Fm3̅m phase of AlN, a notable monoclinic phase with N66- anion polymeric nitrogen chains for AlN3 in the pressure range from 43 to 85 GPa is predicted. Its energy density is up to 2.75 kJ·g-1, and the weight ratio of nitrogen is nearly 61%, which make it potentially interesting for the industrial applications as a high energy density material. The high-pressure studies of atomic and electronic structures in this predicted phase reveal that the formation of N66- anion is driven by the sp2 hybridization of nitrogen atoms. The resonance effect between alternating π-bonds and σ-bonds in polymeric nitrogen chains are all responsible for the structural stability. Because of the electrons transfer from aluminums to polymeric nitrogen chains, there is a pseudogap in the electronic structures of AlN3. The N_p electrons form π-type chemical bonds with the neighboring atoms, resulting in the delocalization of π electrons and charge transfer in polymeric nitrogen chains. Furthermore, disparities of charge density distribution between nitrogen atoms in polymeric nitrogen chains are the principal reason for the metallicity.

Alkaline-earth metal (Mg) polynitrides at high pressure as possible high-energy materials.

The high-pressure structural evolutionary behaviors of magnesium polynitrides were studied up to 100 GPa using first-principles calculations. Using the unbiased structure searching method, five stable chemical stoichiometries of magnesium polynitrides (MgN, Mg2N3, MgN2, MgN3, and MgN4) were theoretically predicted at high pressures. The predicted MgNx compounds contain a rich variety of polynitrogen forms ranging from charged molecules (one-dimensional bent molecules N3, planar triangle N4 to benzene-like rings N6) to extended polymeric chains (N∞). To the best of our knowledge, this is the first time that stable bent molecules N3, planar triangle N4, and polymeric chains (N∞) were predicted in alkaline-earth metal polynitrides. The decomposition of P1[combining macron]-MgN3 and P1[combining macron]-MgN4 are expected to be highly exothermic, releasing an energy of approximately 2.83 kJ g-1 and 2.01 kJ g-1, respectively. Furthermore, P1[combining macron]-MgN4 can be synthesized at several GPa. The results of the present study suggest that it is possible to obtain energetic polynitrogen in main-group nitrides under high pressure.

Ground state structures of tantalum tetraboride and triboride: an ab initio study.

Tantalum-boron compounds, which are potential candidates for superhard multifunctional materials, may possess multiple stoichiometries and structures under pressure. Using first-principle methods, ground-state TaB3 with the monoclinic C2/m space group and high-pressure TaB4 with the orthorhombic Amm2 space group have been found. They are more stable than the previously proposed structures. High-pressure boron-rich Amm2-TaB4 can be quenched to ambient pressure. The ground-state C2/m-TaB3 and high-pressure Amm2-TaB4 are two potential ultra-incompressible and hard materials with a calculated hardness of 17.02 GPa and 30.02 GPa at ambient pressure, respectively. Detailed electronic structure and chemical bonding analysis proved that the high hardness value of Amm2-TaB4 mainly stems from the strong covalent boron-boron bonds in graphene-like B layers as well as B-B bonds between layers.

A Multi-Omics Analysis Revealed the Diversity of the MYB Transcription Factor Family's Evolution and Drought Resistance Pathways.

The MYB transcription factor family can regulate biological processes such as ABA signal transduction to cope with drought stress, but its evolutionary mechanism and the diverse pathways of response to drought stress in different species are rarely reported. In this study, a total of 4791 MYB family members were identified in 908,757 amino acid sequences from 12 model plants or crops using bioinformatics methods. It was observed that the number of MYB family members had a linear relationship with the chromosome ploidy of species. A phylogenetic analysis showed that the MYB family members evolved in subfamily clusters. In response to drought stress, the pathways of MYB transcription factor families exhibited species-specific diversity, with closely related species demonstrating a higher resemblance. This study provides abundant references for drought resistance research and the breeding of wheat, soybean, and other plants.

Altered serum levels of cytokines in patients with myasthenia gravis.

Background: Myasthenia gravis (MG) is an autoimmune disease characterized by generalized skeletal muscle contraction weakness due to autoantibodies targeting neural-muscular junctions. Here, we investigated the relationship between key cytokines and MG type, disease course, antibodies, and comorbidities. Method: Cytokine levels in serum samples collected from MG (n = 45) and healthy control (HC, n = 38) patients from January 2020 to June 2022 were quantified via flow cytometry. Results: Levels of IL-6 were higher in the MG group versus healthy individuals (p = 0.026) and in patients with generalized versus ocular MG (p = 0.019). IL-6 levels were positively correlated with QMG score. In patients with MG with both AChR and Titin antibodies, serum levels of sFas and granulysin were higher than in those with AChR alone (p = 0.036, and p = 0.028, respectively). LOMG had a reduction in serum levels of IL-2 compared to EOMG (p = 0.036). LOMG patients with diabetes had lower serum levels of IL-2, IL-4, and IFN-γ (p = 0.044, p = 0.038, and p = 0.047, respectively) versus those without diabetes. sFas in the MG with Abnormal thymus were reduced compared to those in MG with Normal thymus (p = 0.008). Conclusions: This study revealed a positive correlation between IL-6 level and MG status. Serum cytokine levels of the AChR + Titin MG group differed from those of the AChR group. LOMG had a lower IL-2 level. Comorbidities affect some cytokines in peripheral blood in MG serum.

A newly predicted stable calcium argon compound byab initiocalculations under high pressure.

High pressure can change the valence electron arrangement of the elements, and it can be as a new method for the emergence of unexpected new compounds. In this paper, the Ca-Ar compounds at 0-200 GPa are systematically investigated by using CALYPSO structure prediction methods combined with first principles calculations. The study of the Ca-Ar system can provide theoretical guidance for the exploration of new structures of inert elemental Ar compounds under high pressure. A stable structure:P63/mmc-CaAr and six metastable structures:Rm-CaAr2,P4/mmm-CaAr2,Pm1-CaAr3,P4/mmm-CaAr3,P21/m-CaAr4andPm1-CaAr5were obtained. Our calculations show that the only stable phaseP63/mmc-CaAr can be synthesized at high pressure of 90 GPa. All the structures are ionic compounds of metallic nature, and surprisingly all Ar atoms attract electrons and act as an oxidant under high pressure conditions. The calculation results ofab initiomolecular dynamics show thatP63/mmc-CaAr compound maintains significant thermodynamic stability at high temperatures up to 1000 K. The high-pressure structures and electronic behaviors of the Ca-Ar system are expected to expand the understanding of the high-pressure chemical reactivity of compounds containing inert elements, and provide important theoretical support for the search of novel anomalous alkaline-earth metal inert element compounds.

Screening and genome-wide analysis of lignocellulose-degrading bacteria from humic soil.

Crop straw contains huge amounts of exploitable energy, and efficient biomass degradation measures have attracted worldwide attention. Mining strains with high yields of cellulose-degrading enzymes is of great significance for developing clean energy and industrial production of related enzymes. In this study, we reported a high-quality genome sequence of Bacillus velezensis SSF6 strain using high-throughput sequencing technology (Illumina PE150 and PacBio) and assessed its lignocellulose degradation potential. The results demonstrated that the genome of B. velezensis SSF6 was 3.89 Mb and contained 4,015 genes, of which 2,972, 3,831 and 158 genes were annotated in the COGs (Clusters of Orthologous Groups), KEGG (Kyoto Encyclopedia of Genes and Genomes) and CAZyme (Carbohydrate-Active enZymes) databases, respectively, and contained a large number of genes related to carbohydrate metabolism. Furthermore, B. velezensis SSF6 has a high cellulose degradation capacity, with a filter paper assay (FPA) and an exoglucanase activity of 64.48 ± 0.28 and 78.59 ± 0.42 U/mL, respectively. Comparative genomic analysis depicted that B. velezensis SSF6 was richer in carbohydrate hydrolase gene. In conclusion, the cellulose-degrading ability of B. velezensis SSF6 was revealed by genome sequencing and the determination of cellulase activity, which laid a foundation for further cellulose degradation and bioconversion.

Drought Sensitivity of Spring Wheat Cultivars Shapes Rhizosphere Microbial Community Patterns in Response to Drought.

Drought is the most important natural disaster affecting crop growth and development. Crop rhizosphere microorganisms can affect crop growth and development, enhance the effective utilization of nutrients, and resist adversity and hazards. In this paper, six spring wheat varieties were used as research material in the dry farming area of the western foot of the Greater Khingan Mountains, and two kinds of water control treatments were carried out: dry shed rain prevention (DT) and regulated water replenishment (CK). Phenotypic traits, including physiological and biochemical indices, drought resistance gene expression, soil enzyme activity, soil nutrient content, and the responses of potential functional bacteria and fungi under drought stress, were systematically analyzed. The results showed that compared with the control (CK), the leaf wilting, drooping, and yellowing of six spring wheat varieties were enhanced under drought (DT) treatment. The plant height, fresh weight (FW), dry weight (DW), net photosynthetic rate (Pn) and stomatal conductance (Gs), soil total nitrogen (TN), microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), microbial biomass phosphorus (MBP), organic carbon (SOC), and soil alkaline phosphatase (S-ALP) contents were significantly decreased, among which, FW, Gs and MBC decreased by more than 7.84%, 17.43% and 11.31%, respectively. By contrast, the soil total phosphorus (TP), total potassium (TK), and soil catalase (S-CAT) contents were significantly increased (p < 0.05). TaWdreb2 and TaBADHb genes were highly expressed in T.D40, T.L36, and T.L33 and were expressed at low levels in T.N2, T.B12, and T.F5. Among them, the relative expression of the TaWdreb2 gene in T.L36 was significantly increased by 2.683 times compared with CK. Soil TN and TP are the most sensitive to drought stress and can be used as the characteristic values of drought stress. Based on this, a drought-tolerant variety (T.L36) and a drought-sensitive variety (T.B12) were selected to further analyze the changes in rhizosphere microorganisms. Drought treatment and cultivar differences significantly affected the composition of the rhizosphere microbial community. Drought caused a decrease in the complexity of the rhizosphere microbial network, and the structure of bacteria was more complex than that of fungi. The Shannon index and network modular number of bacteria in these varieties (T.L36) increased, with rich small-world network properties. Actinobacteria, Chloroflexi, Firmicutes, Basidiomycota, and Ascomycota were the dominant bacteria under drought treatment. The beneficial bacteria Bacillus, Penicillium, and Blastococcus were enriched in the rhizosphere of T.L36. Brevibacillus and Glycomyce were enriched in the rhizosphere of T.B12. In general, drought can inhibit the growth and development of spring wheat, and spring wheat can resist drought hazards by regulating the expression of drought-related genes, regulating physiological metabolites, and enriching beneficial microorganisms.

Dynamic changes of soil microorganisms in rotation farmland at the western foot of the Greater Khingan range.

Crop rotation and other tillage systems can affect soil microbial communities and functions. Few studies have reported the response of soil spatial microbial communities to rotation under drought stress. Therefore, the purpose of our study was to explore the dynamic changes of the soil space microbial community under different drought stress-rotation patterns. In this study, two water treatments were set up, control W1 (mass water content 25%-28%), and drought W2 (mass water content 9%-12%). Four crop rotation patterns were set in each water content, spring wheat continuous (R1), spring wheat-potato (R2), spring wheat-potato-rape (R3) and spring wheat-rape (R4), for a total of eight treatments (W1R1, W1R2, W1R3, W1R4, W2R1, W2R2, W2R3, W2R4). Endosphere, rhizosphere and bulk soil of spring wheat in each treatment were collected, and root space microbial community data were generated. The soil microbial community changed under different treatments and their relationship with soil factors were analyzed using a co-occurrence network, mantel test, and other methods. The results revealed that the alpha diversity of microorganisms in the rhizosphere and bulk soil did not differ significantly, but it was significantly greater than in the endosphere. The bacteria community structure was more stable, fungi alpha-diversity significant changes (p < 0.05), that were more sensitive to the response of various treatments than bacteria. The co-occurrence network between fungal species was stable under rotation patterns (R2, R3, R4), while the community stability was poor under continuous cropping pattern (R1), and interactions were strengthened. Soil organic matter (SOM), microbial biomass carbon (MBC), and pH value were the most important factors dominating the bacteria community structural changed in the endosphere, rhizosphere, and bulk soil. The dominant factor that affected the fungal community structural changed in the endosphere, rhizosphere, and bulk soil was SOM. Therefore, we conclude that soil microbial community changes under the drought stress-rotation patterns are mainly influenced by soil SOM and microbial biomass content.

Methylglyoxal suppresses microglia inflammatory response through NRF2-IκBζ pathway.

Methylglyoxal (MGO) is a highly reactive metabolite generated by glycolysis. Although abnormal accumulation of MGO has been reported in several autoimmune diseases such as multiple sclerosis and rheumatoid arthritis, the role of MGO in autoimmune diseases has not yet been fully investigated. In this study, we found that the intracellular MGO levels increased in activated immune cells, such as microglia and lymphocytes. Treatment with MGO inhibited inflammatory cell accumulation in the spinal cord and ameliorated the clinical symptoms in EAE mice. Further analysis indicated that MGO suppressed M1-polarization of microglia cells and diminished their inflammatory cytokine production. MGO also inhibited the ability of microglial cells to recruit and activate lymphocytes by decreasing chemokine secretion and expression of co-stimulatory molecules. Furthermore, MGO negatively regulated glycolysis by suppressing glucose transporter 1 expression. Mechanically, we found that MGO could activate nuclear factor erythroid 2-related factor 2 (NRF2) pathway and NRF2 could bind to the promoter of IκBζ gene and suppressed its transcription and subsequently pro-inflammatory cytokine production. In conclusion, our results showed that MGO acts as an immunosuppressive metabolite by activating the NRF2-IκBζ.

Character variation of root space microbial community composition in the response of drought-tolerant spring wheat to drought stress.

Drought is the most prevalent environmental stress in crop production, posing a significant danger to food security. Microorganisms in the crop root zone affect crop growth and development, enhance effective nutrient use, and resist adversity hazards. To analyze the changes and functional differences of root space microbial (endosphere-rhizosphere-bulk soil) communities in spring wheat under drought stress. In this study, the root, rhizosphere, and bulk soil of the drought-tolerant group (DTG, three varieties) and drought-sensitive group (DSG, three varieties) were collected. The control (CK, 25-28%), moderate drought (MD, 15-18%), and severe drought (SD, 9-12%) were analyzed by high-throughput sequencing and bioinformatics. The results showed significant differences in the diversity of Bacteria and Fungi in the root space of spring wheat under drought stress (P < 0.05), with the drought-tolerant group exhibiting higher microbial diversity. The microbial community change in spring wheat root space was mainly determined by the niche differentiation of endosphere, rhizosphere, and bulk soil and declined from endosphere to bulk soil due to drought. The antagonism between microbial and root-space species increased, and the community's complexity and stability deteriorated. Enriching drought-resistant preference groups like Actinobaciota, Variovorax, Streptomyces, and Conocybe altered the structure and function of the microbial community in the root space of spring wheat. Spring wheat's root space Bacteria and Fungi have different strategies to respond to drought.

Case Report: Short-Term Response to First-Line Crizotinib Monotherapy in a Metastatic Lung Adenocarcinoma Patient Harboring a Novel TPR-ROS1 Fusion.

ROS1-rearranged patients account for 1-2% of non-small cell lung cancer (NSCLC) cases. Approximately 10 fusion partners have been discovered, while clinical practice is actively generating knowledge of new ones and their therapeutic responses. Herein, we report a patient with stage IV NSCLC that harbored a novel TPR-ROS1 fusion, which demonstrated a rapid but short partial response to first line crizotinib and primary resistance to subsequent ceritinib. Computed tomography detected a pulmonary nodule in a 53-year-old woman who presented with persistent cough. Histopathologic and molecular examination of the tissue biopsy indicated a poorly differentiated adenocarcinoma staining negative for PD-L1 but harbored a novel translocated promoter region (TPR)-ROS1 (T4:R35) gene fusion. Frontline crizotinib monotherapy elicited a rapid partial response after 1 month, although the disease progressed another 2 months later. After another 3 months of continued crizotinib treatment, the patient manifested newly emerged and enlarged lung and brain lesions. Genomic profiling still identified TPR-ROS1 as the only aberration, while a lymph node biopsy indicated PD-L1 immunopositivity. The patient was then treated with ceritinib and progressed within 1 month. She was started on chemotherapy with pemetrexed plus carboplatin and has achieved rapid partial response as of the latest follow-up. In summary, we provided clinical evidence of a novel TPR-ROS1 fusion and its roles as an oncogenic driver in metastatic NSCLC. To the best of our knowledge, ours is the first case to report this fusion in NSCLC. This case was characterized by a rapid yet short-term response to first line crizotinib and primary resistance to subsequent ceritinib, while no known genetic resistance mechanism was identified and other mechanisms including histologic transformation were unlikely. Future research is needed to unveil the resistance mechanism and formulate effective treatment strategies.

A novel high-pressure phase of ScN5with higher stability predicted from first-principles calculations.

For binary compounds of Sc-N, the stable structures and stoichiometries were studied from ambient condition to high pressure of 100 GPa, adopting CALYPSO method. The newly predictedP21/c-ScN5compound was more energetically stable under high pressureP= 62 GPa comparing with the three previously reported phases ofP1-ScN5,Cm-ScN5andC2/m-ScN5. Furthermore, the high-pressure phase ofP21/c-ScN5was dynamically stable at ambient condition, so the ambient-pressure recovery is possible. In this paper, the study suggested that the energetic polynitrides can be obtained in transition metal nitrides under high pressure. And we identified one novel 3D extended puckered poly-nitrogen network in theP21/c-ScN5structure, which is similar to theC2/m-ScN5. The decomposition ofP21/c-ScN5to ScN and N2under ambient pressure was estimated to release 5.02 eV energy per formula unit (f.u.), corresponding to 4.19 kJ g-1in energy density, which was expected to be highly exothermic. The present results can conduce to obtain more polynitrogen forms and theoretically encourages experimental discovery in these promising materials.