Graphene nanoribbons grown in hBN stacks for high-performance electronics.

Van der Waals encapsulation of two-dimensional materials in hexagonal boron nitride (hBN) stacks is a promising way to create ultrahigh-performance electronic devices1-4. However, contemporary approaches for achieving van der Waals encapsulation, which involve artificial layer stacking using mechanical transfer techniques, are difficult to control, prone to contamination and unscalable. Here we report the transfer-free direct growth of high-quality graphene nanoribbons (GNRs) in hBN stacks. The as-grown embedded GNRs exhibit highly desirable features being ultralong (up to 0.25 mm), ultranarrow (<5 nm) and homochiral with zigzag edges. Our atomistic simulations show that the mechanism underlying the embedded growth involves ultralow GNR friction when sliding between AA'-stacked hBN layers. Using the grown structures, we demonstrate the transfer-free fabrication of embedded GNR field-effect devices that exhibit excellent performance at room temperature with mobilities of up to 4,600 cm2 V-1 s-1 and on-off ratios of up to 106. This paves the way for the bottom-up fabrication of high-performance electronic devices based on embedded layered materials.

Design of biologically active binary protein 2D materials.

Ordered two-dimensional arrays such as S-layers1,2 and designed analogues3-5 have intrigued bioengineers6,7, but with the exception of a single lattice formed with flexible linkers8, they are constituted from just one protein component. Materials composed of two components have considerable potential advantages for modulating assembly dynamics and incorporating more complex functionality9-12. Here we describe a computational method to generate co-assembling binary layers by designing rigid interfaces between pairs of dihedral protein building blocks, and use it to design a p6m lattice. The designed array components are soluble at millimolar concentrations, but when combined at nanomolar concentrations, they rapidly assemble into nearly crystalline micrometre-scale arrays nearly identical to the computational design model in vitro and in cells without the need for a two-dimensional support. Because the material is designed from the ground up, the components can be readily functionalized and their symmetry reconfigured, enabling formation of ligand arrays with distinguishable surfaces, which we demonstrate can drive extensive receptor clustering, downstream protein recruitment and signalling. Using atomic force microscopy on supported bilayers and quantitative microscopy on living cells, we show that arrays assembled on membranes have component stoichiometry and structure similar to arrays formed in vitro, and that our material can therefore impose order onto fundamentally disordered substrates such as cell membranes. In contrast to previously characterized cell surface receptor binding assemblies such as antibodies and nanocages, which are rapidly endocytosed, we find that large arrays assembled at the cell surface suppress endocytosis in a tunable manner, with potential therapeutic relevance for extending receptor engagement and immune evasion. Our work provides a foundation for a synthetic cell biology in which multi-protein macroscale materials are designed to modulate cell responses and reshape synthetic and living systems.

Amyloid-like amelogenin nanoribbons template mineralization via a low-energy interface of ion binding sites.

Protein scaffolds direct the organization of amorphous precursors that transform into mineralized tissues, but the templating mechanism remains elusive. Motivated by models for the biomineralization of tooth enamel, wherein amyloid-like amelogenin nanoribbons guide the mineralization of apatite filaments, we investigated the impact of nanoribbon structure, sequence, and chemistry on amorphous calcium phosphate (ACP) nucleation. Using full-length human amelogenin and peptide analogs with an amyloid-like domain, films of ß-sheet nanoribbons were self-assembled on graphite and characterized by in situ atomic force microscopy and molecular dynamics simulations. All sequences substantially reduce nucleation barriers for ACP by creating low-energy interfaces, while phosphoserines along the length of the nanoribbons dramatically enhance kinetic factors associated with ion binding. Furthermore, the distribution of negatively charged residues along the nanoribbons presents a potential match to the Ca­Ca distances of the multi-ion complexes that constitute ACP. These findings show that amyloid-like amelogenin nanoribbons provide potent scaffolds for ACP mineralization by presenting energetically and stereochemically favorable templates of calcium phosphate ion binding and suggest enhanced surface wetting toward calcium phosphates in general.

Manipulations of Electronic and Spin States in Co-Quantum Dot/WS2 Heterostructure on a Metal-Dielectric Composite Substrate by Controlling Interfacial Carriers.

Charge and spin are two intrinsic attributes of carriers governing almost all of the physical processes and operation principles in materials. Here, we demonstrate the manipulation of electronic and spin states in designed Co-quantum dot/WS2 (Co-QDs/WS2) heterostructures by employing a metal-dielectric composite substrate and via scanning tunneling microscope. By repeatedly scanning under a unipolar bias, switching the bias polarity, or applying a pulse through nonmagnetic or magnetic tips, the Co-QDs morphologies exhibit a regular and reproducible transformation between bright and dark dots. First-principles calculations reveal that these tunable characters are attributed to the variation of density of states and the transition of magnetic anisotropy energy induced by carrier accumulation. It also suggests that the metal-dielectric composite substrate is successful in creating the interfacial potential for carrier accumulation and realizes the electrically controllable modulations. These results will promote the exploration of electron-matter interactions in quantum systems and provide an innovative way to facilitate the development of spintronics.

Tip Growth of Quasi-Metallic Bilayer Graphene Nanoribbons with Armchair Chirality.

Graphene nanoribbons (GNRs), quasi one-dimensional (1D) narrow strips of graphene, have shown promise for high-performance nanoelectronics due to their exceptionally high carrier mobility and structurally tunable bandgaps. However, producing chirality-uniform GNRs on insulating substrates remains a big challenge. Here, we report the successful growth of bilayer GNRs with predominantly armchair chirality and ultranarrow widths (<5 nm) on insulating hexagonal boron nitride (h-BN) substrates using chemical vapor deposition (CVD). The growth of GNRs is catalyzed by transition metal nanoparticles, including Fe, Co, and Ni, through a unique tip-growth mechanism. Notably, GNRs catalyzed by Ni exhibit a high purity (97.3%) of armchair chirality. Electron transport measurements indicate that the ultrathin bilayer armchair GNRs exhibit quasi-metallic behavior. This quasi-metallicity is further supported by density functional theory (DFT) calculations, which reveal a significantly reduced bandgap in bilayer armchair GNRs. The chirality-specific GNRs reported here offer promising advancements for the application of graphene in nanoelectronics.

Urinary microbiome dysbiosis is associated with an inflammatory environment and perturbed fatty acids metabolism in the pathogenesis of bladder cancer.

BACKGROUND: Bladder cancer is a common malignancy with high recurrence rate. Early diagnosis and recurrence surveillance are pivotal to patients' outcomes, which require novel minimal-invasive diagnostic tools. The urinary microbiome is associated with bladder cancer and can be used as biomarkers, but the underlying mechanism is to be fully illustrated and diagnostic performance to be improved. METHODS: A total of 23 treatment-naïve bladder cancer patients and 9 non-cancerous subjects were enrolled into the Before group and Control group. After surgery, 10 patients from the Before group were further assigned into After group. Void mid-stream urine samples were collected and sent for 16S rDNA sequencing, targeted metabolomic profiling, and flow cytometry. Next, correlations were analyzed between microbiota, metabolites, and cytokines. Finally, receiver operating characteristic (ROC) curves of the urinary biomarkers were plotted and compared. RESULTS: Comparing to the Control group, levels of IL-6 (p < 0.01), IL-8 (p < 0.05), and IL-10 (p < 0.05) were remarkably elevated in the Before group. The α diversity of urine microbiome was also significantly higher, with the feature microbiota positively correlated to the level of IL-6 (r = 0.58, p < 0.01). Significant differences in metabolic composition were also observed between the Before and Control groups, with fatty acids and fatty acylcarnitines enriched in the Before group. After tumor resection, cytokine levels and the overall microbiome structure in the After group remained similar to that of the Before group, but fatty acylcarnitines were significantly reduced (p < 0.05). Pathway enrichment analysis revealed beta-oxidation of fatty acids was significantly involved (p < 0.001). ROC curves showed that the biomarker panel of Actinomycetaceae + arachidonic acid + IL-6 had superior diagnostic performance, with sensitivity of 0.94 and specificity of 1.00. CONCLUSIONS: Microbiome dysbiosis, proinflammatory environment and altered fatty acids metabolism are involved in the pathogenesis of bladder cancer, which may throw light on novel noninvasive diagnostic tool development.

Transcription factors KNAT3 and KNAT4 are essential for integument and ovule formation in Arabidopsis.

Integuments form important protective cell layers surrounding the developing ovules in gymno- and angiosperms. Although several genes have been shown to influence the development of integuments, the transcriptional regulatory mechanism is still poorly understood. In this work, we report that the Class II KNOTTED1-LIKE HOMEOBOX (KNOX II) transcription factors KNOTTED1-LIKE HOMEBOX GENE 3 (KNAT3) and KNAT4 regulate integument development in Arabidopsis (Arabidopsis thaliana). KNAT3 and KNAT4 were co-expressed in inflorescences and especially in young developing ovules. The loss-of-function double mutant knat3 knat4 showed an infertility phenotype, in which both inner and outer integuments of the ovule are arrested at an early stage and form an amorphous structure as in the bell1 (bel1) mutant. The expression of chimeric KNAT3- and KNAT4-EAR motif repression domain (SRDX repressors) resulted in severe seed abortion. Protein-protein interaction assays demonstrated that KNAT3 and KNAT4 interact with each other and also with INNER NO OUTER (INO), a key transcription factor required for the outer integument formation. Transcriptome analysis showed that the expression of genes related with integument development is influenced in the knat3 knat4 mutant. The knat3 knat4 mutant also had a lower indole-3-acetic acid (IAA) content, and some auxin signaling pathway genes were downregulated. Moreover, transactivation analysis indicated that KNAT3/4 and INO activate the auxin signaling gene IAA INDUCIBLE 14 (IAA14). Taken together, our study identified KNAT3 and KNAT4 as key factors in integument development in Arabidopsis.

Azobenzene-based colorimetric and fluorometric chemosensor for nitroxyl releasing.

The precise release and characterization of nitroxyl (HNO) gas signaling molecule remain a challenge due to its short lifetime to date. To solve this issue, an azobenzene-based HNO donor (Azo-D1) was proposed as a colorimetric and fluorometric chemosensor for HNO releasing, to release both HNO and an azobenzene fluorescent reporter together. Specifically, the Azo-D1 has an HNO release half-life of ∼68 min under physiological conditions. The characteristic color change from the original orange to the yellow color indicated the decomposition of the donor molecule. In addition, the stoichiometry release of HNO was qualitatively and quantitatively verified through the classical phosphine compound trap. As compared with the donor molecule by itself, the decomposed product demonstrates a maximum fluorescence emission at 424 nm, where the increase of fluorescence intensity by 6.8 times can be applied to infer the real-time concentration of HNO. Moreover, cellular imaging can also be achieved using this Azo-D1 HNO donor through photoexcitation at 405 and 488 nm, where the real-time monitoring of HNO release was achieved without consuming the HNO source. Finally, the Azo-D1 HNO donor would open a new platform in the exploration of the biochemistry and the biology of HNO.

Causal role of myeloid cells in Parkinson's disease: Mendelian randomization study.

BACKGROUND: Previous studies have observed elevated myeloid cells in the peripheral blood of patients with Parkinson's disease (PD), but the causal relationship between them remains to be elucidated. We investigated whether there is a causal relationship between different subtypes of peripheral blood myeloid cells and PD using Mendelian randomization (MR) combined with bioinformatics analysis. Exploring the etiology of PD from the perspective of genetics can remove confounding factors and provide a more reliable theoretical basis for elucidating the pathogenesis of PD. METHODS: Comprehensive two-sample MR analysis and sensitivity analyses were conducted to explore the causal associations between 64 myeloid cell signatures and PD risk. The Venn diagram and protein-protein interaction network analysis of instrumental variables (IV) corresponding genes were used to further investigate the potential mechanism of myeloid cells influencing the pathogenesis of PD. RESULTS: We investigated the impact of four immunophenotypes on the risk of PD, including Im MDSC% CD33dim HLA DR- CD66b- (relative count), CD33dim HLA DR+ CD11b+% CD33dim HLA DR+ (relative count), and CD11b on Mo MDSC (MFI) and CD11b on CD33br HLA DR+ CD14dim (MFI), while an immunophenotype's protective effect on PD was observed CD45 on Im MDSC (MFI). The results of bioinformatics analysis showed that CD33, NTRK2, PLD2, GRIK2 and RELN had protein interactions with the risk genes of PD. CONCLUSIONS: Our study has demonstrated a close genetic correlation between different subtypes of myeloid cells and PD, providing guidance for early identification and immunotherapeutic development in patients with PD.

Protein Biomarkers for the Identification of Forensically Relevant Human Hair from Different Body Parts in Intimate Contact Cases.

Correctly identifying the human hair anatomic location found at crime scenes can link biological sample donors with the actual crime event, thus providing significant insight into the crime scene reconstruction. Forensic proteomic studies on human hairs can facilitate the development of new biomarkers for hair identification while compensating for the limitations of the conventional morphologic hair comparison and DNA analysis. Herein, the LC-MS/MS platform was used to find differentially expressed protein biomarkers in hairs from different body sites. The findings indicated that a total of 296 protein biomarkers with statistically significant differences in body sites were initially identified, and hair samples from the scalp, pubic, and armpit parts were distinguished from each other, which were validated by multiple bioinformatic methods. Fewer differences in protein patterns between armpit and pubic hairs while larger differences between hair and armpit as well as pubic hairs provided reasonable evidence of sexual or close intimate contact in crimes. This study lays the foundation for the development of a more reliable strategy to distinguish human hairs of various body areas from Chinese and will also support microscopic hair comparison analysis and assist in the proper handling of legal proceedings in relative cases by judicial officers, deserving special attention and further in-depth investigation. The MS proteomics data have been deposited to the ProteomeXchange Consortium via the iProX partner repository with the dataset identifier PXD038173.

Total Synthesis of Vilmoraconitine.

Vilmoraconitine belongs to one of the most complex skeleton types in the C19-diterpenoid alkaloids, which architecturally features an unprecedented heptacyclic core possessing a rigid cyclopropane unit. Here, we report the first total synthesis of vilmoraconitine relying on strategic use of efficient ring-forming reactions. Key steps include an oxidative dearomatization-induced Diels-Alder cycloaddition, a hydrodealkenylative fragmentation/Mannich sequence, and an intramolecular Diels-Alder cycloaddition.

Research Development on Exosome Separation Technology.

Exosomes are special extracellular vesicles secreted by cells, which are of great significance in the basic research of life science and clinical application and has become a hot research field with rapid development in recent 10 years. Therefore, the isolation and separation of exosomes is particularly important for the research and application of exosomes. This paper aims to review the research progress of exosome isolation and separation methods in recent years, including ultracentrifugation, ultrafiltration, size­exclusion chromatography, precipitation, immunomagnetic bead capture method, aptamer-based isolation, and isolation methods based on microfluidic technology. It is generally accepted that most of the existing methods have limitations, for example, ultracentrifugation is time-consuming and laborious, and immunomagnetic bead capture method and aptamer-based separation method have small sample processing capacity and high cost. As a result, we also introduce some common situations in which two or more methods are combined for use. Finally, the separation and isolation methods including all those presented in this review were compared and summarized.

Causal relationships between birth weight, childhood obesity and age at menarche: A two-sample Mendelian randomization analysis.

OBJECTIVES: Observational studies suggest birth weight and childhood obesity are closely associated with age at menarche. However, the relationships between them are currently inconsistent and it remains elusive whether such associations are causal. Therefore, the aim of the study was to investigate whether there existed causal relationships between birth weight, childhood obesity and age at menarche. DESIGN, PATIENTS AND MEASUREMENTS: A two-sample Mendelian randomization (MR) study. The standard inverse variance weighted MR analyses were adopted to evaluate the causal effects of birth weight (n = 143,677), childhood body mass index (BMI) (n = 39,620) on age at menarche (n = 182,416) with summary statistics from large-scale genome-wide association studies (GWASs). Meanwhile, we validated our MR results with some sensitivity analyses including maximum likelihood, weighted-median and MR pleiotropy residual sum and outlier methods. RESULTS: The present study showed that each one standard deviation (1-SD) lower birth weight was predicted to result in a 0.1479 years earlier of age at menarche (ß = .1479, 95% confidence interval [CI] = 0.0422-0.2535; p = 0.0061). We also found that genetically predicted 1-SD increase in childhood BMI was causally associated with early age at menarche (ß = -.3966, 95% CI = -0.5294 to -0.2639; p = 4.73E-09). CONCLUSIONS: Our MR study suggests the causal effect of lower birth weight and higher childhood BMI on the increased risk of earlier menarche. It may be the opportune time to carry out weight control intervention in prenatal and early childhood development periods to prevent early menarche onset, thus decreasing the future adverse consequences.

Synthesis and nitroxyl (HNO) donating properties of benzoxadiazole-based Piloty's acids.

Developing functional nitroxyl (HNO) donors play a significant role in the further exploration of endogenous HNO in biochemistry and pharmacology. In this work, two novel Piloty's acids (SBD-D1 and SBD-D2) were proposed by incorporating benzoxadiazole-based fluorophores, in order to achieve the dual-function of releasing both HNO and a fluorophore in situ. Under physiological conditions, both SBD-D1 and SBD-D2 efficiently donated HNO (t1/2 = 10.96 and 8.18 min, respectively). The stoichiometric generation of HNO was determined by both Vitamin B12 and phosphine compound trap. Interestingly, due to the different substitution groups on the aromatic ring, SBD-D1 with the chlorine showed no fluorescence emission, but SBD-D2 was strongly fluorescent due to the presence of the dimethylamine group. Specifically, the fluorescent signal would decrease during the release process of HNO. Moreover, theoretical calculations were performed to understand the emission difference. A strong radiation derived from benzoxadiazole with dimethylamine group due to the large transition dipole moment (∼4.3 Debye), while the presence of intramolecular charge transfer process in the donor with chlorine group caused a small transition dipole moment (<0.1 Debye). Finally, these studies would contribute to the future design and application of novel functional HNO donors for the exploration of HNO biochemistry and pharmacology.

Case report: durable complete response to pembrolizumab plus lenvatinib in a metastatic upper tract urothelial carcinoma patient with high tumor mutational burden and an immune-active tumor microenvironment.

Immune checkpoint inhibitors (ICIs) have been approved as an emerging first-line treatment option for advanced and metastatic urothelial carcinoma whose tumors express programmed death-ligand 1 (PD-L1). However, the efficacy of immunotherapy in PD-L1-negative urothelial carcinoma patients remains unclear, and biomarkers beyond PD-L1 expression to predict response to immunotherapy need investigation. Here, we report a metastatic renal pelvis urothelial carcinoma patient with PD-L1 negative expression that responded dramatically to first-line pembrolizumab plus lenvatinib. By the recent follow-up in March 2022, the patient had a complete radiological response for 3.4 years, with no recurrence even during the 23-month drug-withdrawal period. The results of the next-generation sequencing using the tumor sample revealed a high tumor mutational burden (TMB), which may be independently driven by the pathogenic mutation in TP53 , TERT , NCOR1 , and TSC2 genes. Besides, the tumor microenvironment exhibited an immune-active signature with relatively abundant CD8+ cells and M1 tumor-associated macrophages but scarce regulatory T cells may also explain the great benefit of the combination therapy. Our case provides a direction for identifying biomarkers beyond PD-L1 expression to screen urothelial carcinoma patients who benefit from ICI as well as ICI-based therapy.

D-allulose, a versatile rare sugar: recent biotechnological advances and challenges.

D-Allulose is the C-3 epimer of D-fructose, and widely regarded as a promising substitute for sucrose. It's an excellent low-calorie sweetener, with 70% sweetness of sucrose, 0.4 kcal/g dietary energy, and special physiological functions. It has been approved as GRAS by the U.S. Food and Drug Administration, and is allowed to be excluded from total and added sugar counts on the food labels. Therefore, D-allulose gradually attracts more public attention. Owing to scarcity in nature, the bioproduction of D-allulose by using ketose 3-epimerase (KEase) has become the research hotspot. Herein, we give a summary of the physicochemical properties, physiological function, applications, and the chemical and biochemical synthesis methods of D-allulose. In addition, the recent progress in the D-allulose bioproduction using KEases, and the possible solutions for existing challenges in the D-allulose industrial production are comprehensively discussed, focusing on the molecular modification, immobilization, food-grade expression, utilizing low-cost biomass as feedstock, overcoming thermodynamic limitation, as well as the downstream separation and purification. Finally, Prospects for further development are also proposed.

Mechanoluminescence Affected by Trap Types and Excitation State Positions in Mg3Ca3(PO4)4:Eu2+/Mn2+/Ce3+ for Multimode Anticounterfeiting.

Mechanoluminescence (ML) materials with tunable emissions can serve in many practical applications; however, their underlying mechanism still needs further clarification. Herein, we developed Eu2+-/Mn2+-/Ce3+-activated Mg3Ca3(PO4)4 (MCP) phosphors and studied their luminescence properties by device fabrication. The intense blue ML is obtained by fabricating MCP:Eu2+ into the polydimethylsiloxane elastomer matrix. The red ML of relatively weak intensity is received in Mn2+ activator, but the ML for the Ce3+ dopant is nearly quenched in the same host. The possible reason is proposed from the analysis of the relative positions between the excitation state and conduction band, together with the trap types. The appropriate location of the excited energy levels in the band gap allows for a larger probability of efficient ML when shallow traps near the excitation states are created synchronously as an effective energy transfer (ET) channel. The concentration-dependent ML for the MCP:Eu2+,Mn2+-based devices indicates that the emitting light color can be tailored, where several ET processes among oxygen vacancies, Eu2+, Ce3+, and Mn2+, occur. The luminescence manipulation with dopants and excitation sources demonstrates the potential applications in visualized multimode anticounterfeiting. These findings open up many possibilities for constructing new ML materials by introducing appropriate traps into the band structures.

In Situ Visualization of Membrane Fouling Evolution during Ultrafiltration Using Label-Free Hyperspectral Light Sheet Fluorescence Imaging.

Profound understanding of fouling behaviors and underlying mechanisms is fundamentally important for fouling control in membrane-based environmental applications. Therefore, it entails novel noninvasive analytical approaches for in situ characterizing the formation and development of membrane fouling processes. This work presents a characterization approach based on hyperspectral light sheet fluorescence microscopy (HSPEC-LSFM), which is capable of discriminating various foulants and providing their 2-dimensional/3-dimensional spatial distributions on/in membranes in a label-free manner. A fast, highly sensitive and noninvasive imaging platform was established by developing a HSPEC-LSFM system and further extending it to incorporate a laboratory-scale pressure-driven membrane filtration system. Hyperspectral data sets with a spectral resolution of ∼1.1 nm and spatial resolution of ∼3 µm as well as the temporal resolution of ∼8 s/plane were obtained, and the fouling formation and development process of foulants onto membrane surfaces, within the pores and on the pore walls were clearly observed during the ultrafiltration of protein and humic substances solutions. Pore blocking/constriction at short times while cake growth/concentration polarization at longer times was found to have coupled effects for the flux decline in these filtration tests, and yet the contribution of each effect as well as the transition of the governing mechanisms was found distinct. These results demonstrate in situ label-free characterization of membrane fouling evolution with the recognition of foulant species during filtration and provide new insights into membrane fouling. This work offers a powerful tool to investigate dynamic processes for a wide range of membrane-based explorations.

The relationship between the baseline geriatric nutritional risk index (GNRI) and neurological function at the convalescence stage in patients with stroke: a cross-sectional study.

BACKGROUND: Malnutrition is a common complication after stroke and may worsen neurological outcomes for patients. There are still no uniform tools for screening nutritional status for the patients with stroke. We aimed to explore the relationship between the baseline geriatric nutritional risk index (GNRI) and neurological function at the convalescence stage for patients with stroke and assessed the predictive value of the GNRI for adverse neurological outcomes. METHODS: A total of 311 patients with stroke were enrolled retrospectively. Basic information and laboratory results on admission since onset of stroke were collected. The GNRI on admission was calculated and neurological outcomes evaluated by the Barthel index at 1 month after the onset of stroke. Statistical analyses, including correlation coefficient tests, multivariate regression analyses, and receiver operating characteristic (ROC) analyses, were applied in this study. RESULTS: Compared with the good outcome group, the poor outcome group showed a significantly lower GNRI on admission (P < 0.05). GNRI was associated with Barthel index (r = 0.702, P < 0.01). The GNRI was independently correlated with the Barthel index (Standardization ß = 0.721, P < 0.01) and poor outcome 0.885 (95% CIs, 0.855-0.917, P < 0.01) after adjusting for covariates. Compared with no nutritional risk grades (Q4), the OR of GNRI to poor neurological outcome increased across increasing nutritional risk grades of GNRI (OR = 2.803, 95% CIs = 1.330-5.909 in Q3, 7.992, 95% CIs = 3.294-19.387 in Q2 and 14.011, 95% CIs = 3.972-49.426 in Q1, respectively, P for trend < 0.001). The area under ROC curves (AUC) of the GNRI was 0.804, which was larger than that of the NIHSS, BMI, or Albumin (P < 0.01), with an optimal cut-off value of 97.69, sensitivity of 69.51% and specificity of 77.27%. Combined GNRI with NIHSS gained the largest AUC among all the variables (all P < 0.05), with an AUC of 0.855, sensitivity of 84.75 and specificity of 72.73%. CONCLUSIONS: For patients with stroke, higher nutritional risk grades at baseline indicated worse neurological function at the convalescence stage. Compared with NIHSS, BMI, and Albumin, GNRI was a competitive indicator for the risk of poor neurological outcome. The predictive property of GNRI for adverse neurological outcomes might be more powerful when combined with NIHSS.

Identification of cuproptosis-related lncRNAs for prognosis and immunotherapy in glioma.

Glioma is a highly invasive primary brain tumour, making it challenging to accurately predict prognosis for glioma patients. Cuproptosis is a recently discovered cell death attracting significant attention in the tumour field. Whether cuproptosis-related genes have prognostic predictive value has not been clarified. In this study, uni-/multi-variate Cox and Lasso regression analyses were applied to construct a risk model based on cuproptosis-related lncRNAs using TCGA and CGGA cohorts. A nomogram was constructed to quantify individual risk, including clinical and genic characteristics and risk. GO and KEGG analyses were used to define functional enrichment of DEGs. Tumour mutation burden (TMB) and immune checkpoint analyses were performed to evaluate potential responses to ICI therapy. Ten prognostic lncRNAs were obtained from Cox regression. Based on the median risk score, patients were divided into high- and low-risk groups. Either for grade 2-3 or for grade 4, glioma patients with high-risk exhibited significant poorer prognoses. The risk was an independent risk factor associated with overall survival. The high-risk group was functionally associated with immune responses and cancer-related pathways. The high-risk group was associated with higher TMB scores. The expression levels of many immune checkpoints in the high-risk group were significantly higher than those in the low-risk group. Differentiated immune pathways were primarily enriched in the IFN response, immune checkpoint and T-cell co-stimulation pathways. In conclusion, we established a risk model based on cuproptosis-related lncRNAs showing excellent prognostic prediction ability but also indicating the immuno-microenvironment status of glioma.