Chemical short-range disorder in lithium oxide cathodes.

Ordered layered structures serve as essential components in lithium (Li)-ion cathodes1-3. However, on charging, the inherently delicate Li-deficient frameworks become vulnerable to lattice strain and structural and/or chemo-mechanical degradation, resulting in rapid capacity deterioration and thus short battery life2,4. Here we report an approach that addresses these issues using the integration of chemical short-range disorder (CSRD) into oxide cathodes, which involves the localized distribution of elements in a crystalline lattice over spatial dimensions, spanning a few nearest-neighbour spacings. This is guided by fundamental principles of structural chemistry and achieved through an improved ceramic synthesis process. To demonstrate its viability, we showcase how the introduction of CSRD substantially affects the crystal structure of layered Li cobalt oxide cathodes. This is manifested in the transition metal environment and its interactions with oxygen, effectively preventing detrimental sliding of crystal slabs and structural deterioration during Li removal. Meanwhile, it affects the electronic structure, leading to improved electronic conductivity. These attributes are highly beneficial for Li-ion storage capabilities, markedly improving cycle life and rate capability. Moreover, we find that CSRD can be introduced in additional layered oxide materials through improved chemical co-doping, further illustrating its potential to enhance structural and electrochemical stability. These findings open up new avenues for the design of oxide cathodes, offering insights into the effects of CSRD on the crystal and electronic structure of advanced functional materials.

Tracking cubic ice at molecular resolution.

Ice is present everywhere on Earth and has an essential role in several areas, such as cloud physics, climate change and cryopreservation. The role of ice is determined by its formation behaviour and associated structure. However, these are not fully understood1. In particular, there is a long-standing debate about whether water can freeze to form cubic ice-a currently undescribed phase in the phase space of ordinary hexagonal ice2-6. The mainstream view inferred from a collection of laboratory data attributes this divergence to the inability to discern cubic ice from stacking-disordered ice-a mixture of cubic and hexagonal sequences7-11. Using cryogenic transmission electron microscopy combined with low-dose imaging, we show here the preferential nucleation of cubic ice at low-temperature interfaces, resulting in two types of separate crystallization of cubic ice and hexagonal ice from water vapour deposition at 102 K. Moreover, we identify a series of cubic-ice defects, including two types of stacking disorder, revealing the structure evolution dynamics supported by molecular dynamics simulations. The realization of direct, real-space imaging of ice formation and its dynamic behaviour at the molecular level provides an opportunity for ice research at the molecular level using transmission electron microscopy, which may be extended to other hydrogen-bonding crystals.

Disorder-tuned conductivity in amorphous monolayer carbon.

Correlating atomic configurations-specifically, degree of disorder (DOD)-of an amorphous solid with properties is a long-standing riddle in materials science and condensed matter physics, owing to difficulties in determining precise atomic positions in 3D structures1-5. To this end, 2D systems provide insight to the puzzle by allowing straightforward imaging of all atoms6,7. Direct imaging of amorphous monolayer carbon (AMC) grown by laser-assisted depositions has resolved atomic configurations, supporting the modern crystallite view of vitreous solids over random network theory8. Nevertheless, a causal link between atomic-scale structures and macroscopic properties remains elusive. Here we report facile tuning of DOD and electrical conductivity in AMC films by varying growth temperatures. Specifically, the pyrolysis threshold temperature is the key to growing variable-range-hopping conductive AMC with medium-range order (MRO), whereas increasing the temperature by 25 °C results in AMC losing MRO and becoming electrically insulating, with an increase in sheet resistance of 109 times. Beyond visualizing highly distorted nanocrystallites embedded in a continuous random network, atomic-resolution electron microscopy shows the absence/presence of MRO and temperature-dependent densities of nanocrystallites, two order parameters proposed to fully describe DOD. Numerical calculations establish the conductivity diagram as a function of these two parameters, directly linking microstructures to electrical properties. Our work represents an important step towards understanding the structure-property relationship of amorphous materials at the fundamental level and paves the way to electronic devices using 2D amorphous materials.

RNF20 contributes to epigenetic immunosuppression through CDK9-dependent LSD1 stabilization.

Cyclin-dependent kinase 9 (CDK9) plays a critical role in transcription initiation and is essential for maintaining gene silencing at heterochromatic loci. Inhibition of CDK9 increases sensitivity to immunotherapy, but the underlying mechanism remains unclear. We now report that RNF20 stabilizes LSD1 via K29-mediated ubiquitination, which is dependent on CDK9-mediated phosphorylation. This CDK9- and RNF20-dependent LSD1 stabilization is necessary for the demethylation of histone H3K4, then subsequent repression of endogenous retrovirus, and an interferon response, leading to epigenetic immunosuppression. Moreover, we found that loss of RNF20 sensitizes cancer cells to the immune checkpoint inhibitor anti-PD-1 in vivo and that this effect can be rescued by the expression of ectopic LSD1. Our findings are supported by the observation that RNF20 levels correlate with LSD1 levels in human breast cancer specimens. This study sheds light on the role of RNF20 in CDK9-dependent LSD1 stabilization, which is crucial for epigenetic silencing and immunosuppression. Our findings explore the potential importance of targeting the CDK9-RNF20-LSD1 axis in the development of new cancer therapies.

KGANSynergy: knowledge graph attention network for drug synergy prediction.

Combination therapy is widely used to treat complex diseases, particularly in patients who respond poorly to monotherapy. For example, compared with the use of a single drug, drug combinations can reduce drug resistance and improve the efficacy of cancer treatment. Thus, it is vital for researchers and society to help develop effective combination therapies through clinical trials. However, high-throughput synergistic drug combination screening remains challenging and expensive in the large combinational space, where an array of compounds are used. To solve this problem, various computational approaches have been proposed to effectively identify drug combinations by utilizing drug-related biomedical information. In this study, considering the implications of various types of neighbor information of drug entities, we propose a novel end-to-end Knowledge Graph Attention Network to predict drug synergy (KGANSynergy), which utilizes neighbor information of known drugs/cell lines effectively. KGANSynergy uses knowledge graph (KG) hierarchical propagation to find multi-source neighbor nodes for drugs and cell lines. The knowledge graph attention network is designed to distinguish the importance of neighbors in a KG through a multi-attention mechanism and then aggregate the entity's neighbor node information to enrich the entity. Finally, the learned drug and cell line embeddings can be utilized to predict the synergy of drug combinations. Experiments demonstrated that our method outperformed several other competing methods, indicating that our method is effective in identifying drug combinations.

Tunable Magnetism in Atomically Thin Itinerant Antiferromagnet with Room-Temperature Ferromagnetic Order.

Addressing the need for modulated spin configurations is crucial, as they serve as the foundational building blocks for next-generation spintronics, particularly in atomically thin structures and at room temperature. In this work, we realize intrinsic ferromagnetism in monolayer flakes and tunable ferro-/antiferromagnetism in (Fe0.56Co0.44)5GeTe2 antiferromagnets. Remarkably, the ferromagnetic ordering (≥1 L) and antiferromagnetic ordering (≥4 L) remain discernible up to room temperature. The TC (∼310 K) of the monolayer flakes sets a record high for known exfoliated monolayer van der Waals magnets. Within the framework of A-type antiferromagnetism, a notable odd-even layer-number effect at elevated temperatures (T = 150 K) is observed. Of particular interest is the strong ferromagnetic order in even-layer flakes at low temperatures. The intricate interplay among magnetic field strength, layer number, and temperature gives rise to a diverse array of phenomena, holding promise not only for new physics but also for practical applications.

Nucleolin lactylation contributes to intrahepatic cholangiocarcinoma pathogenesis via RNA splicing regulation of MADD.

BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (iCCA) is a fatal malignancy of the biliary system. The lack of a detailed understanding of oncogenic signaling or global gene expression alterations has impeded clinical iCCA diagnosis and therapy. The role of protein lactylation, a newly unraveled post-translational modification that orchestrates gene expression, remains largely elusive in the pathogenesis of iCCA. METHODS: Proteomics analysis of clinical iCCA specimens and adjacent tissues was performed to screen for proteins aberrantly lactylated in iCCA. Mass spectrometry, macromolecule interaction and cell behavioral studies were employed to identify the specific lactylation sites on the candidate protein(s) and to decipher the downstream mechanisms responsible for iCCA development, which were subsequently validated using a xenograft tumor model and clinical samples. RESULTS: Nucleolin (NCL), the most abundant RNA-binding protein in the nucleolus, was identified as a functional lactylation target that correlates with iCCA occurrence and progression. NCL was lactylated predominantly at lysine 477 by the acyltransferase P300 in response to a hyperactivity of glycolysis, and promoted the proliferation and invasion of iCCA cells. Mechanistically, lactylated NCL bound to the primary transcript of MAP kinase-activating death domain protein (MADD) and led to efficient translation of MADD by circumventing alternative splicing that generates a premature termination codon. NCL lactylation, MADD translation and subsequent ERK activation promoted xenograft tumor growth and were associated with overall survival in patients with iCCA. CONCLUSION: NCL is lactylated to upregulate MADD through an RNA splicing-dependent mechanism, which potentiates iCCA pathogenesis via the MAPK pathway. Our findings reveal a novel link between metabolic reprogramming and canonical tumor-initiating events, and uncover biomarkers that can potentially be used for prognostic evaluation or targeted treatment of iCCA. IMPACT AND IMPLICATIONS: Intrahepatic cholangiocarcinoma (iCCA) is a highly aggressive liver malignancy with largely uncharacterized pathogenetic mechanisms. Herein, we demonstrated that glycolysis promotes P300-catalyzed lactylation of nucleolin, which upregulates MAP kinase-activating death domain protein (MADD) through precise mRNA splicing and activates ERK signaling to drive iCCA development. These findings unravel a novel link between metabolic rewiring and canonical oncogenic pathways, and reveal new biomarkers for prognostic assessment and targeting of clinical iCCA.

CXCL12+ Tumor-associated Endothelial Cells Promote Immune Resistance in Hepatocellular Carcinoma.

BACKGROUND: The tumor microenvironment (TME) plays a crucial role in the limited efficacy of existing treatments for hepatocellular carcinoma (HCC), with tumor-associated endothelial cells (TECs) serving as fundamental TME components that substantially influence tumor progression and treatment efficacy. However, the precise roles and mechanisms of TECs in HCC remain inadequately understood. METHODS: We employed a multi-omics profiling strategy to investigate the single-cell and spatiotemporal evolution of TECs within the microenvironment of HCC tumors showcasing varied responses to immunotherapy. Through an analysis of a clinical cohort of HCC patients, we explored the correlation between TEC subpopulations and immunotherapy outcomes. The influence of TEC subsets on the immune microenvironment was confirmed through comprehensive in vitro and in vivo studies. To further explore the mechanisms of distinct TEC subpopulations in microenvironmental modulation and their impact on immunotherapy, we utilized TEC subset-specific knockout mouse models as well as humanized mouse models. RESULTS: In this research, we identified a new subset of CXCL12+ TECs that exert a crucial role in immune suppression within the HCC TME. Functionally, CXCL12+ TECs impede the differentiation of CD8+ naïve T cells into CD8+ cytotoxic T cells by secreting CXCL12. Furthermore, they attract myeloid-derived suppressor cells (MDSCs). A bispecific antibody was developed to target both CXCL12 and PD1 specifically, showing significant promise in bolstering anti-tumor immune responses and advancing HCC therapy. CONCLUSIONS: CXCL12+ TECs are pivotal in mediating immunosuppression within HCC microenvironment and targeting CXCL12+ TECs presents a promising approach to augment the efficacy of immunotherapies in HCC patients. IMPACT AND IMPLICATION: This investigation reveals a pivotal mechanism in the HCC TME, where CXCL12+ TECs emerge as crucial modulators of immune suppression. The discovery of CXCL12+ TECs as inhibitors of CD8+ naïve T cell activation and recruiters of MDSCs significantly advances our grasp of the dynamic between HCC and immune regulation. Moreover, the development and application of a bispecific antibody precisely targeting CXCL12 and PD1 has proven to enhance immune responses in a humanized mouse HCC model. This finding underscores a promising therapeutic direction for HCC, offering the potential to amplify the impact of current immunotherapies.

Effect of cyclophosphamide combined with glucocorticoid therapy on idiopathic membranous nephropathy: A multicenter open-label randomized controlled trial.

OBJECTIVE: We aimed to evaluate the effect of cyclophosphamide combined with glucocorticoid therapy on idiopathic membranous nephropathy through a multicenter open-label randomized controlled trial. MATERIALS AND METHODS: 92 patients with idiopathic membranous nephropathy admitted from March 2020 to September 2022 were included and assigned to a control group (n = 46) and a research group (n = 46) using a random number table. The control group was given glucocorticoid, and the research group was given cyclophosphamide combined with glucocorticoid. Clinical efficacy, renal function-related indicators (serum creatinine, blood urea nitrogen and albumin, and 24-hour urine protein quantification), inflammatory factors (interleukin (IL)-6, IL-18, transforming growth factor-ß, and tumor necrosis factor-α), immune function-related indicators (anti-phospholipase A2 receptor antibody, and T-lymphocyte subsets), oxidative stress-related indicators (heme oxygenase-1, superoxide dismutase, malondialdehyde, and nitric oxide), blood lipid-related indicators (total cholesterol, triacylglycerol, and low-density lipoprotein), and adverse reactions were compared. RESULTS: The overall remission rate of the research group was higher than that of the control group (93.48 vs. 78.26%, p < 0.05). After treatment, the research group had lower levels of 24-hour urine protein quantification, serum creatinine, blood urea nitrogen, IL-6, IL-18, transforming growth factor-ß, tumor necrosis factor-α, heme oxygenase-1, malondialdehyde, anti-phospholipase A2 receptor antibody, CD8+, total cholesterol, triacylglycerol and low-density lipoprotein, higher levels of albumin, superoxide dismutase, nitric oxide, and CD4+ and a higher CD4+/CD8+ ratio than the control group (p < 0.05). CONCLUSION: Cyclophosphamide combined with glucocorticoid therapy is effective for improving the overall remission rate and can suppress inflammatory responses and oxidative stress in patients with idiopathic membranous nephropathy.

Enhanced ferromagnetic properties achieved by F-doping in BaFe1-xMnxO3-δ.

Tailoring the crystal structure, spin, and charge state of perovskite oxides through fluorine ion doping is an attractive and effective strategy, which could significantly modify the physical and chemical properties of base oxides. Here, BaFe1-xMnxO3-δ (x = 0, 0.1, 0.2, 0.3) and BaFe1-xMnxO2.9-δF0.1 (x = 0.1, 0.2, 0.3), belonging to 6H-type BaFeO3-δ, are prepared and investigated to evaluate the impact of F- doping. The distortion of crystal structure and the reduced average valence of Mn and Fe confirm the preference for F- substitution in the hexagonal layer, which are found as the key factors for the improved magnetic properties, including ferromagnetic ordering temperature, coercive force, and remanent magnetization. Moreover, the valence reduction of B-site ions and the increased resistance distinctly indicate the expense of electron hole via fluorine doping. This work describes the adjustment of crystal structure, electronic configuration, and ferromagnetic performance by simple F- doping, which provides a prospect for practical magnetic materials.

Molecular scale behavior of xylan during solvent-controlled extraction and precipitation.

Solvent-controlled extraction and precipitation are the most fundamental methods for obtaining hemicellulose from lignocellulosic biomass and purification processes. However, the dissolution and precipitation mechanisms involved have scarcely been mentioned. In this study, the molecular scale behavior of xylan-type hemicellulose during solvent-controlled extraction and precipitation is investigated using molecular dynamics (MD) simulations and density functional theory (DFT) calculations. To bring the model closer to the real extracted xylan, a high degree of polymerization (DP100) of xylan is established, and hemicelluloses with low DP (DP15 and DP50) are also investigated. Four phenomena are explained at the molecular level, including the influence of the polymerization degree and side chain on the solubility of xylan in water, the improvement of the xylan's solubility in NaOH, the precipitation of xylan in ethanol, and the acetyl group preservation of xylan in DMSO. This study contributes to an increased understanding of the dissolution and precipitation mechanisms of hemicellulose and provides a resource for the simulation of high DP hemicellulose, which gives a theoretical basis for the efficient extraction of high-purity hemicellulose as well as economic biorefining.

White Matter Functional Connectivity in Resting-State fMRI: Robustness, Reliability, and Relationships to Gray Matter.

A comprehensive characterization of the spatiotemporal organization in the whole brain is critical to understand both the function and dysfunction of the human brain. Resting-state functional connectivity (FC) of gray matter (GM) has helped in uncovering the inherent baseline networks of brain. However, the white matter (WM), which composes almost half of brain, has been largely ignored in this characterization despite studies indicating that FC in WM does change during task and rest functional magnetic resonance imaging (fMRI). In this study, we identify 9 white matter functional networks (WM-FNs) and 9 gray matter functional networks (GM-FNs) of resting fMRI. Intraclass correlation coefficient (ICC) was calculated on multirun fMRI data to estimate the reliability of static functional connectivity (SFC) and dynamic functional connectivity (DFC). Associations between SFC, DFC, and their respective ICCs are estimated for GM-FNs, WM-FNs, and GM-WM-FNs. SFC of GM-FNs were stronger than that of WM-FNs, but the corresponding DFC of GM-FNs was lower, indicating that WM-FNs were more dynamic. Associations between SFC, DFC, and their ICCs were similar in both GM- and WM-FNs. These findings suggest that WM fMRI signal contains rich spatiotemporal information similar to that of GM and may hold important cues to better establish the functional organization of the whole brain.

A recombinant capripoxvirus expressing the F protein of peste des petits ruminants virus and the P12A3C of foot-and-mouth disease virus.

BACKGROUND: Peste des petits ruminants (PPR), foot-and-mouth disease (FMD) and sheep pox and goat pox are three important infectious diseases that infect goats, sheep and other small ruminants. It is well-known that the prevention of three diseases rely mainly on their individual vaccines. However, the vaccines have a variety of different disadvantages, such as short duration of immunity, increasing the number of vaccinations, and poor thermal stability. The purpose of this study is to construct a recombinant goat pox virus (rGPV) capable of expressing the F gene of PPRV and the P12A3C gene of FMDV as a live vector vaccine. RESULTS: The IRES, FMDV P12A3C and PPRV F genes into the multi-cloning site of the universal transfer plasmid pTKfpgigp to construct a recombinant transfer plasmid pTKfpgigpFiP12A3C, and transfected GPV-infected lamb testis (LT) cells with liposomes and produced by homologous recombination Recombinant GPV (rGPV/PPRVF-FMDVP12A3C, rGPV). The rGPV was screened and purified by green florescence protein (GFP) and xanthine-guanine-phosphoribosyltransferase gene (gpt) of Escherichia coli as selective markers, and the expression of rGPV in LT cells was detected by RT-PCR and immunofluorescence techniques. The results showed that the virus strain rGPV/PPRVF-FMDVP12A3C containing FMDV P12A3C and PPRV F genes was obtained. The exogenous genes FMDV P12A3C and PPRV F contained in rGPV were normally transcribed and translated in LT cells, and the expression products could specifically react with PPRV and FMDV antiserum. Then, the rGPV was intradermally inoculated with goats, the animal experiments showed that rGPV/PPRVF-FMDVP12A3C could induce high levels of specific antibodies against GPV, PPRV and FMDV. CONCLUSIONS: The constructed rGPV induced high levels of specific antibodies against GPV, PPRV and FMDV. The study provides a reference for " one vaccine with multiple uses " of GPV live vector vaccine.

First description study on molecular characterization of Hemiclepsis khankiana (Hirudinea: Glossiphoniidae) in China.

BACKGROUND: Leeches are an integral component of aquatic biocenosis and can be found in a wide range of ecosystems such as freshwater, saltwater, flowing, and still-water ecosystems. It especially plays an important role in the freshwater benthic community and is an important part of the food web. In this study, a leech species was found in the mantle cavity of wild freshwater mussels in Zigong City, Sichuan Province, China, and its identity was determined through morphological analysis and molecular biological analysis. RESULTS: The leech is Hemiclepsis khankiana, a new species of Hemiclepsis that has been discovered in Russia in recent years. Through morphological analysis, the current survey observed that the morphological characteristics of Hemiclepsis khankiana eyespots were significantly different from the first reported description. The first pair of eyespots on the leech were separated and clear, while it had been reduced to unclear shadows in the previous report. The phylogenetic tree based on the COI gene showed that the COI gene sequence obtained in this study was in the same evolutionary branch as Hemiclepsis khankiana (MN295420, MN295421). Genetically, it was most closely related to Hemiclepsis kasmiana (mean COI p-distance = 3.98%). CONCLUSIONS: The current study reported on the new distribution range of Hemiclepsis khankiana, which was initially discovered in China. This study indicates that the distribution range of the leech species has expanded, laying a foundation for further studies in China.

Comprehensive Analysis of Microbiome, Metabolome, and Transcriptome Revealed the Mechanisms of Intestinal Injury in Rainbow Trout under Heat Stress.

Global warming is one of the most common environmental challenges faced by cold-water fish farming. Intestinal barrier function, gut microbiota, and gut microbial metabolites are significantly altered under heat stress, posing serious obstacles to the healthy artificial culture of rainbow trout. However, the molecular mechanisms underlying intestinal injury in rainbow trout under heat stress remain unclear. In the present study, the optimal growth temperature for rainbow trout (16 °C) was used for the control group, and the maximum temperature tolerated by rainbow trout (24 °C) was used for the heat stress group, which was subjected to heat stress for 21 days. The mechanism of intestinal injury in rainbow trout under heat stress was explored by combining animal histology, 16S rRNA gene amplicon sequencing, ultra-high performance liquid chromatography-mass spectrometry, and transcriptome sequencing. The results showed that the antioxidant capacity of rainbow trout was enhanced under heat stress, the levels of stress-related hormones were significantly increased, and the relative expression of genes related to heat stress proteins was significantly increased, indicating that the heat stress model of rainbow trout was successfully established. Secondly, the intestinal tract of rainbow trout showed inflammatory pathological characteristics under heat stress, with increased permeability, activation of the inflammatory factor signaling pathway, and increased relative expression of inflammatory factor genes, suggesting that the intestinal barrier function was impaired. Thirdly, heat stress caused an imbalance of intestinal commensal microbiota and changes in intestinal metabolites in rainbow trout, which participated in the stress response mainly by affecting lipid metabolism and amino acid metabolism. Finally, heat stress promoted intestinal injury in rainbow trout by activating the peroxisome proliferator-activated receptor-α signaling pathway. These results not only expand the understanding of fish stress physiology and regulation mechanisms, but also provide a scientific basis for healthy artificial culture and the reduction of rainbow trout production costs.

Clarifying the Relationship between the Lithium Deposition Coverage and Microstructure in Lithium Metal Batteries.

Improving the reversibility of lithium metal batteries is one of the challenges in current battery research. This requires better fundamental understanding of the evolution of the lithium deposition morphology, which is very complex due to the various parameters involved in different systems. Here, we clarify the fundamental origins of lithium deposition coverage in achieving highly reversible and compact lithium deposits, providing a comprehensive picture in the relationship between the lithium microstructure and solid electrolyte interphase (SEI) for lithium metal batteries. Systematic variation of the salt concentration offers a framework that brings forward the different aspects that play a role in cycling reversibility. Higher nucleation densities are formed in lower concentration electrolytes, which have the advantage of higher lithium deposition coverage; however, it goes along with the formation of an organic-rich instable SEI which is unfavorable for the reversibility during (dis)charging. On the other hand, the growth of large deposits benefiting from the formation of an inorganic-rich stable SEI is observed in higher concentration electrolytes, but the initial small nucleation density prevents full coverage of the current collector, thus compromising the plated lithium metal density. Taking advantages of the paradox, a nanostructured substrate is rationally applied, which increases the nucleation density realizing a higher deposition coverage and thus more compact plating at intermediate concentration (∼1.0 M) electrolytes, leading to extended reversible cycling of batteries.

Genetic diversity and pathogenicity of novel chicken astrovirus in China.

Five novel chicken astrovirus (CAstV) strains, designated ZDF, MHC, WSC, WSW and MHW, were successfully isolated from chickens with gout, and were subjected to full genome sequencing characterization and tested for their pathogenic effects in specific pathogen-free (SPF) chicken embryos and chickens. The complete genomes of the five isolated strains were approximately 7436 nt to 7511 nt in length. Phylogenetic analysis revealed that strains ZDF and MHC were clustered in a clade with strains isolated in China and that the others were clustered with strains from other countries. Based on the amino acids of ORF2, strains MHW and WSW belonged to subgroup Ai, strain WSC belonged to Bii, and strains ZDF and MHC belonged to Bi. The pathogenicity of strains MHW, MHC and WSC, all belonging to different subgroups was studied. The results showed that the mortality of the chicken embryos was 100% when infected with any strain at a dose of more than 103 TCID50, 35% in SPF chickens infected with strain WSC, 25% with MHC and 15% with MHW. The body weights of chickens and embryos infected with 0.2 ml 10 TCID50 were significantly reduced after hatching. SPF chickens infected with any of the strains had similar lesions characterized by urate deposits on the epicardium and kidney, and necrotic spots on the liver. This study identified the three types of genotypic CAstV prevalent in China, with high mortality in embryonated chicken eggs and leading to white chick syndrome, retarded growth and visceral gout in infected chicks.

Veratramine ameliorates pain symptoms in rats with diabetic peripheral neuropathy by inhibiting activation of the SIGMAR1-NMDAR pathway.

CONTEXT: Veratramine may have a potential therapeutic effect for diabetic peripheral neuropathy (DPN). OBJECTIVE: To evaluate whether veratramine ameliorates neuropathic pain in a rat diabetic model. MATERIALS AND METHODS: Sprague-Dawley rats were used for a diabetic model induced by a streptozotocin + high-fat diet. Two months after the induction of the diabetic model, the rats with DPN were screened according to the mechanical pain threshold. The rats with DPN were divided into a model group (n = 12) and a treated group (n = 12). Rats with diabetes, but without peripheral neuropathy, were used in the vehicle group (n = 9). The treatment group received 50 µg/kg veratramine via the tail vein once a day for 4 weeks. During modelling and treatment, rats in all three groups were fed a high-fat diet. RESULTS: The mechanical withdrawal threshold increased from 7.5 ± 1.9 N to 17.9 ± 2.6 N in DPN rats treated with veratramine. The tolerance time of the treated group to hot and cold ectopic pain increased from 11.8 ± 4.2 s and 3.4 ± 0.8 s to 20.4 ± 4.1 s and 5.9 ± 1.7 s, respectively. Veratramine effectively alleviated L4-L5 spinal cord and sciatic nerve pathological injury. Veratramine inhibited the expression of SIGMAR1 and the phosphorylation of the N-methyl-d-aspartate receptor (NMDAR) Ser896 site in spinal cord tissue, as well as inhibited the formation of SIGMAR1-NMDAR and NMDAR-CaMKII complexes. DISCUSSION AND CONCLUSIONS: Veratramine may alleviate the occurrence of pain symptoms in rats with DPN by inhibiting activation of the SIGMAR1-NMDAR pathway.

[Correlations of 18F-FDG PET/CT Metabolic Parameters and Metabolic Heterogeneity with Human Epidermal Growth Factor Receptor 2 Expression in Patients with Gastric Cancer].

Objective To investigate the value of 18F-FDG PET/CT metabolic parameters and metabolic heterogeneity for predicting the expression of human epidermal growth factor receptor 2 (HER2) in patients with gastric cancer. Methods A total of 45 patients with gastric cancer confirmed by surgical pathology between September 2016 and May 2021 were enrolled in this study.All the patients underwent 18F-FDG PET/CT examination before surgery.The maximum standardized uptake value (SUVmax),metabolic tumor volume (MTV),and total lesion glycolysis (TLG) of primary gastric cancer were measured,and the linear regression slope of MTV corresponding to different SUVmax thresholds (40% SUVmax and 80% SUVmax) was calculated.The absolute value of the slope was deemed to represent the metabolic heterogeneity of primary gastric cancer,termed the heterogeneity index (HI).Univariate and multivariate Logistic regression analyses were conducted to evaluate the correlations of 18F-FDG PET/CT metabolic parameters and HI with HER2 expression. Results The 45 patients included 10 with positive HER2 expression and 35 with negative result.The MTV (P=0.043) and HI (P=0.048) were lower in the patients with positive HER2 expression than in the patients with negative HER2 expression.The MTV and HI had the optimal thresholds of 12.10 cm3 and 3.71,respectively,which respectively showed the accuracy of 62.2% and 57.8% for predicting HER2 expression.The univariate Logistic regression showed that the tumor differentiation degree,MTV,and HI were correlated with HER2 expression,while the multivariate Logistic regression showed that only the tumor differentiation degree (OR=20.130,95%CI=1.843-219.860,P=0.014) was an independent predictor for HER2 expression.A further stratified analysis of the tumor differentiation degree showed that HER2 expression only varied among different MTV threshold groups in patients with moderately/well differentiated gastric cancer (P=0.031). Conclusions MTV and HI were associated with HER2 expression in gastric cancer,whereas neither played an independent predictive role.Therefore,these factors should be combined with clinicopathological characteristics of patients to jointly guide treatment decisions.

Structural and functional connectivity mapping of the human corpus callosum organization with white-matter functional networks.

The corpus callosum serves as a crucial organization for understanding the information integration between the two hemispheres. Our previous study explored the functional connectivity between the corpus callosum and white-matter functional networks (WM-FNs), but the corresponding physical connectivity remains unknown. The current study uses the resting-state fMRI of Human Connectome Project data to identify ten WM-FNs in 108 healthy subjects, and then independently maps the structural and functional connectivity between the corpus callosum and above WM-FNs using the diffusion tensor images (DTI) tractography and resting-state functional connectivity (RSFC). Our results demonstrated that the structural and functional connectivity between the human corpus callosum and WM-FNs have the following high overall correspondence: orbitofrontal WM-FN, DTI map = 89% and RSFC map = 92%; sensorimotor middle WM-FN, DTI map = 47% and RSFC map = 77%; deep WM-FN, DTI map = 50% and RSFC map = 79%; posterior corona radiata WM-FN, DTI map = 82% and RSFC map = 73%. These findings reinforce the notion that the corpus callosum has unique spatial distribution patterns connecting to distinct WM-FNs. However, important differences between the structural and functional connectivity mapping results were also observed, which demonstrated a synergy between DTI tractography and RSFC toward better understanding the information integration of primary and higher-order functional systems in the human brain.