Regulating the Pore Structure of Biomass-Derived Hard Carbon for an Advanced Sodium-Ion Battery.

Biomass-derived hard carbon materials are attractive for sodium-ion batteries due to their abundance, sustainability, and cost-effectiveness. However, their widespread use is hindered by their limited specific capacity. Herein, a type of bamboo-derived hard carbon with adjustable pore structures is developed by employing a ball milling technique to modify the carbon chain length in the precursor. It is observed that the length of the carbon chain in the precursor can effectively control the rearrangement behavior of the carbon layers during the high-temperature carbonization process, resulting in diverse pore structures ranging from closed pores to open pores, which significantly impact the electrochemical properties. The optimized hard carbon with abundant closed pores exhibits a high specific capacity of 356 mAh g-1 at 20 mA g-1, surpassing that of bare hard carbon (243 mAh g-1) and hard carbon with abundant open pores (129 mAh g-1 at 20 mA g-1). However, the kinetic analysis reveals that hard carbon with open pores shows better sodium-ion diffusion kinetics, indicating that a balance between the closed and open pores should be considered. This research offers valuable insights into pore design and presents a promising approach for enhancing the performance of hard carbon anode materials derived from biomass precursors.

Optimizing the spatial immune landscape of CD103+CD8+ tissue-resident memory T cells in non-small cell lung cancer by neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy (NAC) combined with immunotherapy is increasingly used in non-small cell lung cancer (NSCLC). Tissue-resident memory T (TRM) cells are the primary subset responding to anti-cancer immunity. However, the immunomodulatory effects of NAC on TRM cells remain unknown. METHODS: We established two NSCLC cohorts including patients undergoing upfront surgery (US) and NAC followed by surgery. Beyond the unpaired comparison between the US cohort (n = 122) and NAC cohort (n = 141) with resection samples, 58 matched pre-NAC biopsy samples were available for paired comparisons. Using multiplex immunofluorescence, we characterized TRM cells (CD103+CD8+) and four heterogeneous TRM subsets, including naive TRM1 (PD-1-Tim-3-), pre-exhausted TRM2 (PD-1+Tim-3-), TRM3 (PD-1-Tim-3+), and terminally exhausted TRM4 (PD-1+Tim-3+). Cell density, cytotoxicity, and two spatial features were defined to evaluate the effect of NAC on TRM subsets. RESULTS: The cell densities, infiltration scores, and cancer-cell proximity scores of TRM cells, especially TRM1&2 subsets, were significantly increased after NAC and associated with better prognosis of patients. In Contrast, no significant change was observed in the TRM4 subset, which was associated with poor prognosis. Besides, the cytotoxicity of TRM subsets was unaltered after NAC. Compared with patients without major pathologic response (MPRs), patients with MPR had higher densities of TRM1&2 subsets and higher cancer-cell proximity scores of TRM2&3 subsets. Furthermore, increased density of CD31 + cancer microvessels was positively associated with both TRM and Tnon-RM cells after NAC. CONCLUSIONS: NAC may remodel the cell density and spatial distribution of TRM subsets, which is associated with favorable therapeutic effect and prognosis in patients with NSCLC.

Spatial cell interplay networks of regulatory T cells predict recurrence in patients with operable non-small cell lung cancer.

BACKGROUND: The interplay between regulatory T cells (Tregs) and neighboring cells, which is pivotal for anti-tumor immunity and closely linked to patient prognosis, remains to be fully elucidated. METHODS: Tissue microarrays of 261 operable NSCLC patients were stained by multiplex immunofluorescence (mIF) assay, and the interaction between Tregs and neighboring cells in the tumor microenvironment (TME) was evaluated. Employing various machine learning algorithms, we developed a spatial immune signature to predict the prognosis of NSCLC patients. Additionally, we explored the interplay between programmed death-1/programmed death ligand-1 (PD-1/PD-L1) interactions and their relationship with Tregs. RESULTS: Survival analysis indicated that the interplay between Tregs and neighboring cells in the invasive margin (IM) and tumor center was associated with recurrence in NSCLC patients. We integrated the intersection of the three algorithms to identify four crucial spatial immune features [P(CD8+Treg to CK) in IM, P(CD8+Treg to CD4) in IM, N(CD4+Treg to CK) in IM, N(CD4+Tcon to CK) in IM] and employed these characteristics to establish SIS, an independent prognosticator of recurrence in NSCLC patients [HR = 2.34, 95% CI (1.53, 3.58), P < 0.001]. Furthermore, analysis of cell interactions demonstrated that a higher number of Tregs contributed to higher PD-L1+ cells surrounded by PD-1+ cells (P < 0.001) with shorter distances (P = 0.004). CONCLUSION: We dissected the cell interplay network within the TME, uncovering the spatial architecture and intricate interactions between Tregs and neighboring cells, along with their impact on the prognosis of NSCLC patients.

Modified spatial architecture of regulatory T cells after neoadjuvant chemotherapy in non-small cell lung cancer patients.

It is crucial to decipher the modulation of regulatory T cells (Tregs) in tumor microenvironment (TME) induced by chemotherapy, which may contribute to improving the efficacy of neoadjuvant chemoimmunotherapy in resectable non-small cell lung cancer (NSCLC). We retrospectively collected specimens from patients with II-III NSCLC, constituting two cohorts: a neoadjuvant chemotherapy (NAC) cohort (N = 141) with biopsy (N = 58) and postoperative specimens (N = 141), and a surgery-only cohort (N = 122) as the control group. Then, the cell density (Dens), infiltration score (InS), and Treg-cell proximity score (TrPS) were conducted using a panel of multiplex fluorescence staining (Foxp3, CD4, CD8, CK, CD31, ɑSMA). Subsequently, the association of Tregs with cancer microvessels (CMVs) and cancer-associated fibroblasts (CAFs) was analyzed. Patients with NAC treatment have a higher density of Tregs in both paired (P < 0.001) and unpaired analysis (P = 0.022). Additionally, patients with NAC treatment showed higher infiltration score (paired, P < 0.001; unpaired, P = 0.014) and more CD8+T cells around Tregs (paired/unpaired, both P < 0.001). Subgroup analysis indicated that tumors with a diameter of ≤ 5 cm exhibited increase in both Dens(Treg) and InS(Treg), and gemcitabine, pemetrexed and taxel enhanced Dens(Treg) and TrPS(CD8) following NAC. Multivariate analysis identified that the Dens(Tregs), InS(Tregs) and TrPS(CD8) were significantly associated with better chemotherapy response [OR = 8.54, 95%CI (1.69, 43.14), P = 0.009; OR = 7.14, 95%CI (1.70, 30.08), P = 0.024; OR = 5.50, 95%CI (1.09, 27.75), P = 0.039, respectively] and positive recurrence-free survival [HR = 3.23, 95%CI (1.47, 7.10), P = 0.004; HR = 2.70; 95%CI (1.27, 5.72); P = 0.010; HR = 2.55, 95%CI (1.21, 5.39), P = 0.014, respectively]. Moreover, TrPS(CD8) and TrPS(CD4) were negatively correlated with the CMVs and CAFs. These discoveries have deepened our comprehension of the immune-modulating impact of chemotherapy and underscored that the modified spatial landscape of Tregs after chemotherapy should be taken into account for personalized immunotherapy, aiming to ultimately improve clinical outcomes in patients with NSCLC.

Dysfunction of CD8+ T cells around tumor cells leads to occult lymph node metastasis in NSCLC patients.

Occult lymph node metastasis (OLNM) is one of the main causes of regional recurrence in inoperable N0 non-small cell lung cancer (NSCLC) patients following stereotactic ablation body radiotherapy (SABR) treatment. The integration of immunotherapy and SABR (I-SABR) has shown preliminary efficiency in mitigating this recurrence. Therefore, it is necessary to explore the functional dynamics of critical immune effectors, particularly CD8+ T cells in the development of OLNM. In this study, tissue microarrays (TMAs) and multiplex immunofluorescence (mIF) were used to identify CD8+ T cells and functional subsets (cytotoxic CD8+ T cells/predysfunctional CD8+ T cells (CD8+ Tpredys)/dysfunctional CD8+ T cells (CD8+ Tdys)/other CD8+ T cells) among the no lymph node metastasis, OLNM, and clinically evident lymph node metastasis (CLNM) groups. As the degree of lymph node metastasis escalated, the density of total CD8+ T cells and CD8+ Tdys cells, as well as their proximity to tumor cells, increased progressively and remarkably in the invasive margin (IM). In the tumor center (TC), both the density and proximity of CD8+ Tpredys cells to tumor cells notably decreased in the OLNM group compared with the group without metastasis. Furthermore, positive correlations were found between the dysfunction of CD8+ T cells and HIF-1α+CD8 and cancer microvessels (CMVs). In conclusion, the deterioration in CD8+ T cell function and interactive dynamics between CD8+ T cells and tumor cells play a vital role in the development of OLNM in NSCLC. Strategies aimed at improving hypoxia or targeting CMVs could potentially enhance the efficacy of I-SABR.

Attention-guided graph structure learning network for EEG-enabled auditory attention detection.

Objective: Decoding auditory attention from brain signals is essential for the development of neuro-steered hearing aids. This study aims to overcome the challenges of extracting discriminative feature representations from electroencephalography (EEG) signals for auditory attention detection (AAD) tasks, particularly focusing on the intrinsic relationships between different EEG channels.Approach: We propose a novel attention-guided graph structure learning network, AGSLnet, which leverages potential relationships between EEG channels to improve AAD performance. Specifically, AGSLnet is designed to dynamically capture latent relationships between channels and construct a graph structure of EEG signals.Main result: We evaluated AGSLnet on two publicly available AAD datasets and demonstrated its superiority and robustness over state-of-the-art models. Visualization of the graph structure trained by AGSLnet supports previous neuroscience findings, enhancing our understanding of the underlying neural mechanisms.Significance: This study presents a novel approach for examining brain functional connections, improving AAD performance in low-latency settings, and supporting the development of neuro-steered hearing aids.

The STING-mediated antiviral effect of fucoidan from Durvillaea antarctica.

Fucoidans have attracted increasing attention due to their minimal toxicity and various biological activities, such as antioxidant, anti-inflammatory, anti-tumor and immunomodulatory effects. In this study, the antiviral effect and mechanism of fucoidan (FU) derived from Durvillaea antarctica were explored in vitro. The results demonstrated that FU effectively inhibited the infection of both RNA virus (VSV) and DNA virus (HSV-1). The potential antiviral mechanism of FU is to trigger the production of type I IFN (IFN-I) and IFN-stimulated genes dependent on the cytoplasmic DNA adaptor STING (stimulator of interferon genes), and to enhance innate immune response via activating the STING-TBK1-IRF3 pathway. FU possesses the potential to be an antiviral and immunomodulatory agent in the future.

Clustered surface amino acid residues modulate the acid stability of GH10 xylanase in fungi.

Acidic xylanases are widely used in industries such as biofuels, animal feeding, and fruit juice clarification due to their tolerance to acidic environments. However, the factors controlling their acid stability, especially in GH10 xylanases, are only partially understood. In this study, we identified a series of thermostable GH10 xylanases with optimal temperatures ranging from 70 to 90 °C, and among these, five enzymes (Xyn10C, Xyn10RE, Xyn10TC, Xyn10BS, and Xyn10PC) exhibited remarkable stability at pH 2.0. Our statistical analysis highlighted several factors contributing to the acid stability of GH10 xylanases, including electrostatic repulsion, π-π stacking, ionic bonds, hydrogen bonds, and Van der Waals interactions. Furthermore, through mutagenesis studies, we uncovered that acid stability is influenced by a complex interplay of amino acid residues. The key amino acid sites determining the acid stability of GH10 xylanases were thus elucidated, mainly concentrated in two surface regions behind the enzyme active center. Notably, the critical residues associated with acid stability markedly enhanced Xyn10RE's thermostability by more than sixfold, indicating a potential acid-thermal interplay in GH10 xylanases. This study not only reported a series of valuable genes but also provided a range of modification targets for enhancing the acid stability of GH10 xylanases. KEY POINTS: • Five acid stable and thermostable GH10 xylanases were reported. • The key amino acid sites, mainly forming two enriched surface regions behind the enzyme active center, were identified responsible for acid stability of GH10 xylanases. • The finding revealed interactive amino acid sites, offering a pathway for synergistic enhancement of both acid stability and thermostability in GH10 xylanase modifications.

Spatial features of specific CD103+CD8+ tissue-resident memory T cell subsets define the prognosis in patients with non-small cell lung cancer.

BACKGROUND: Tissue-resident memory T (TRM) cells can reside in the tumor microenvironment and are considered the primary response cells to immunotherapy. Heterogeneity in functional status and spatial distribution may contribute to the controversial role of TRM cells but we know little about it. METHODS: Through multiplex immunofluorescence (mIF) (CD8, CD103, PD-1, Tim-3, GZMB, CK), the quantity and spatial location of TRM cell subsets were recognized in the tissue from 274 patients with NSCLC after radical surgery. By integrating multiple machine learning methods, we constructed a TRM-based spatial immune signature (TRM-SIS) to predict the prognosis. Furthermore, we conducted a CD103-related gene set enrichment analysis (GSEA) and verified its finding by another mIF panel (CD8, CD103, CK, CD31, Hif-1α). RESULTS: The density of TRM cells was significantly correlated with the expression of PD-1, Tim-3 and GZMB. Four types of TRM cell subsets was defined, including TRM1 (PD-1-Tim-3-TRM), TRM2 (PD-1+Tim-3-TRM), TRM3 (PD-1-Tim-3+TRM) and TRM4 (PD-1+Tim-3+TRM). The cytotoxicity of TRM2 was the strongest while that of TRM4 was the weakest. Compare with TRM1 and TRM2, TRM3 and TRM4 had better infiltration and stronger interaction with cancer cells. The TRM-SIS was an independent prognostic factor for disease-free survival [HR = 2.43, 95%CI (1.63-3.60), P < 0.001] and showed a better performance than the TNM staging system for recurrence prediction. Furthermore, by CD103-related GSEA and mIF validation, we found a negative association between tumor angiogenesis and infiltration of TRM cells. CONCLUSIONS: These findings reveal a significant heterogeneity in the functional status and spatial distribution of TRM cells, and support it as a biomarker for the prognosis of NSCLC patients. Regulating TRM cells by targeting tumor angiogenesis may be a potential strategy to improve current immunotherapy.

Shared and malignancy-specific functional plasticity of dynamic brain properties for patients with left frontal glioma.

The time-varying brain activity may parallel the disease progression of cerebral glioma. Assessment of brain dynamics would better characterize the pathological profile of glioma and the relevant functional remodeling. This study aims to investigate the dynamic properties of functional networks based on sliding-window approach for patients with left frontal glioma. The generalized functional plasticity due to glioma was characterized by reduced dynamic amplitude of low-frequency fluctuation of somatosensory networks, reduced dynamic functional connectivity between homotopic regions mainly involving dorsal attention network and subcortical nuclei, and enhanced subcortical dynamic functional connectivity. Malignancy-specific functional remodeling featured a chaotic modification of dynamic amplitude of low-frequency fluctuation and dynamic functional connectivity for low-grade gliomas, and attenuated dynamic functional connectivity of the intrahemispheric cortico-subcortical connections and reduced dynamic amplitude of low-frequency fluctuation of the bilateral caudate for high-grade gliomas. Network dynamic activity was clustered into four distinct configuration states. The occurrence and dwell time of the weakly connected state were reduced in patients' brains. Support vector machine model combined with predictive dynamic features achieved an averaged accuracy of 87.9% in distinguishing low- and high-grade gliomas. In conclusion, dynamic network properties are highly predictive of the malignant grade of gliomas, thus could serve as new biomarkers for disease characterization.

Brain Topology Modeling With EEG-Graphs for Auditory Spatial Attention Detection.

OBJECTIVE: Despite recent advances, the decoding of auditory attention from brain signals remains a challenge. A key solution is the extraction of discriminative features from high-dimensional data, such as multi-channel electroencephalography (EEG). However, to our knowledge, topological relationships between individual channels have not yet been considered in any study. In this work, we introduced a novel architecture that exploits the topology of the human brain to perform auditory spatial attention detection (ASAD) from EEG signals. METHODS: We propose EEG-Graph Net, an EEG-graph convolutional network, which employs a neural attention mechanism. This mechanism models the topology of the human brain in terms of the spatial pattern of EEG signals as a graph. In the EEG-Graph, each EEG channel is represented by a node, while the relationship between two EEG channels is represented by an edge between the respective nodes. The convolutional network takes the multi-channel EEG signals as a time series of EEG-graphs and learns the node and edge weights from the contribution of the EEG signals to the ASAD task. The proposed architecture supports the interpretation of the experimental results by data visualization. RESULTS: We conducted experiments on two publicly available databases. The experimental results showed that EEG-Graph Net significantly outperforms the state-of-the-art methods in terms of decoding performance. In addition, the analysis of the learned weight patterns provides insights into the processing of continuous speech in the brain and confirms findings from neuroscientific studies. CONCLUSION: We showed that modeling brain topology with EEG-graphs yields highly competitive results for auditory spatial attention detection. SIGNIFICANCE: The proposed EEG-Graph Net is more lightweight and accurate than competing baselines and provides explanations for the results. Also, the architecture can be easily transferred to other brain-computer interface (BCI) tasks.

RGCnet: An Efficient Recursive Gated Convolutional Network for EEG-based Auditory Attention Detection.

Humans are able to listen to one speaker and disregard others in a speaking crowd, referred to as the "cocktail party effect". EEG-based auditory attention detection (AAD) seeks to identify whom a listener is listening to by decoding one's EEG signals. Recent research has demonstrated that the self-attention mechanism is effective for AAD. In this paper, we present the Recursive Gated Convolutional network (RGCnet) for AAD, which implements long-range and high-order interactions as a self-attention mechanism, while maintaining a low computational cost. The RGCnet expands the 2nd order feature interactions to a higher order to model the complex interactions between EEG features. We evaluate RGCnet on two public datasets and compare it with other AAD models. Our results demonstrate that RGCnet outperforms other comparative models under various conditions, thus potentially improving the control of neuro-steered hearing devices.

Natural recombination of the torque teno canis virus within the ORF1, -2, and -3 genes and the untranslated region.

The torque teno canis virus (TTCaV) was first reported in 2001 and it shares similarities with the known Torque teno virus (TTV) in terms of genomic organization and putative transcriptional features. It is a single-stranded DNA virus characterized by high rates of recombination and nucleotide substitution, like RNA viruses. Studies reported recombination events in torque teno virus; however, there is limited reporting of TTCaV reorganization events. This study screened fecal samples from domestic dogs in Henan Province. There was a positivity rate of 16.5% (19/115) for TTCaV. Four nearly complete TTCaV genomes, namely Canine/HeNan/4, 5, 6, and 13/2019, were obtained from the 19 positive fecal samples, whose genome sequence was obtained using gap-filling PCR. Sequence analysis revealed two unique amino acid mutation sites in the TTCaV strains, K278Q (compared with the first isolate Cf-TTV10 in Japan) and V/L268I (compared with the TTCaV strain from southern China). Subsequently, 17 near full-length TTCaV genome sequences were subjected to phylogenetic and recombination detection program analyzes. We obtained evidence supporting recombination events in the Chinese TTCaV strains. These findings suggest that mutation and recombination occurred in the three individual gene segments (ORF1, ORF2, ORF3) and the untranslated region, an area of major recombination in the Chinese TTCaV strain GX265 genome. Interestingly, the TTCaV strain (Canine/HeNan/6/2019) was a major parent involved in the genetic recombination of the GX265 strain. This study provides insights into the genetic variability and evolution of TTCaV.

A Bio-Inspired Spiking Attentional Neural Network for Attentional Selection in the Listening Brain.

Humans show a remarkable ability in solving the cocktail party problem. Decoding auditory attention from the brain signals is a major step toward the development of bionic ears emulating human capabilities. Electroencephalography (EEG)-based auditory attention detection (AAD) has attracted considerable interest recently. Despite much progress, the performance of traditional AAD decoders remains to be improved, especially in low-latency settings. State-of-the-art AAD decoders based on deep neural networks generally lack the intrinsic temporal coding ability in biological networks. In this study, we first propose a bio-inspired spiking attentional neural network, denoted as BSAnet, for decoding auditory attention. BSAnet is capable of exploiting the temporal dynamics of EEG signals using biologically plausible neurons and an attentional mechanism. Experiments on two publicly available datasets confirm the superior performance of BSAnet over other state-of-the-art systems across various evaluation conditions. Moreover, BSAnet imitates realistic brain-like information processing, through which we show the advantage of brain-inspired computational models.

Functional status and spatial architecture of tumor-infiltrating CD8+ T cells are associated with lymph node metastases in non-small cell lung cancer.

BACKGROUND: Anti-PD-(L)1 immunotherapy has been recommended for non-small cell lung cancer (NSCLC) patients with lymph node metastases (LNM). However, the exact functional feature and spatial architecture of tumor-infiltrating CD8 + T cells remain unclear in these patients. METHODS: Tissue microarrays (TMAs) from 279 IA-IIIB NSCLC samples were stained by multiplex immunofluorescence (mIF) for 11 markers (CD8, CD103, PD-1, Tim3, GZMB, CD4, Foxp3, CD31, αSMA, Hif-1α, pan-CK). We evaluated the density of CD8 + T-cell functional subsets, the mean nearest neighbor distance (mNND) between CD8 + T cells and neighboring cells, and the cancer-cell proximity score (CCPS) in invasive margin (IM) as well as tumor center (TC) to investigate their relationships with LNM and prognosis. RESULTS: The densities of CD8 + T-cell functional subsets, including predysfunctional CD8 + T cells (Tpredys) and dysfunctional CD8 + T cells (Tdys), in IM predominated over those in TC (P < 0.001). Multivariate analysis identified that the densities of CD8 + Tpredys cells in TC and CD8 + Tdys cells in IM were significantly associated with LNM [OR = 0.51, 95%CI (0.29-0.88), P = 0.015; OR = 5.80, 95%CI (3.19-10.54), P < 0.001; respectively] and recurrence-free survival (RFS) [HR = 0.55, 95%CI (0.34-0.89), P = 0.014; HR = 2.49, 95%CI (1.60-4.13), P = 0.012; respectively], independent of clinicopathological factors. Additionally, shorter mNND between CD8 + T cells and their neighboring immunoregulatory cells indicated a stronger interplay network in the microenvironment of NSCLC patients with LNM and was associated with worse prognosis. Furthermore, analysis of CCPS suggested that cancer microvessels (CMVs) and cancer-associated fibroblasts (CAFs) selectively hindered CD8 + T cells from contacting with cancer cells, and were associated with the dysfunction of CD8 + T cells. CONCLUSION: Tumor-infiltrating CD8 + T cells were in a more dysfunctional status and in a more immunosuppressive microenvironment in patients with LNM compared with those without LNM.

Functional Connectivity of White Matter and Its Association with Sleep Quality.

Purpose: Functional magnetic resonance imaging (fMRI) has been widely adopted to investigate the neural activity in gray matter (GM) in the field of sleep research, but the neural activity in white matter (WM) has received much less attention. The current study set out to test our hypothesis that WM functional abnormality is associated with poor sleep quality. Participants and Methods: K-means clustering analysis was performed on 78 healthy adults drawn from the Human Connectome Project dataset to extract stable WM functional networks (WM-FNs) and GM-FNs. The differences in functional connectivity within WM-FNs and between WM- and GM-FNs, as well as the power spectrum between good sleep quality group (Pittsburgh Sleep Quality Index (PSQI) <6, daytime dysfunction = 0) and poor sleep quality group (PSQI >6, daytime dysfunction >0) were examined between groups with good and poor sleep quality. Additionally, linear relationships between sleep quality and altered functional characteristics of WM-FNs were evaluated. Results: Functional connectivity between middle and superficial WM-FNs, short- and long-range functional connectivity between WM- and GM-FNs were decreased in poor sleepers and negatively correlated with PSQI score. The mean amplitudes of right sensorimotor WM networks at whole, high and low frequency bands were higher in poor sleepers and were positively correlated with PSQI score. Conclusion: WM functional abnormality is associated with poor sleep quality. The neurobiological mechanisms that underlie the functional alterations of WM-FNs in poor sleepers need to be investigated in future studies.

RNAi-mediated CrebA silencing inhibits reproduction and immunity in Locusta migratoria manilensis.

Locusta migratoria manilensis is a major agricultural pest that causes severe direct and indirect damage to several crops. Thus, to provide a theoretical foundation for pest control, the role of CrebA in the reproduction and immune regulation of L. migratoria was investigated. CrebA is a bZIP transcription factor that critically regulates intracellular protein secretion. In this study, CrebA was widely expressed in the brain, fat body, integument, midgut, and reproductive tissues of different maturity stages of adult locusts, especially in the female fat body. RNA interfering (RNAi)-mediated silencing of CrebA inhibited locusts ovarian development, and key reproduction gene expressions, Vgs, VgRs, Chico, and JHAMT were downregulated. After the locusts were injected with Micrococcus luteus or Escherichia coli, M. luteus activated lysozyme expression, while the E. coli activated both phenol oxidase cascade and lysozyme expression. Furthermore, both bacteria stimulated the upregulation of the antimicrobial peptide genes DEF3 and DEF4. However, CrebA silencing is fatal to locusts infection with E. coli, with a mortality rate of up to 96.3%, and resulted in a significant decrease in the expression of DEF3 and DEF4 and changes in the activities of phenol oxidase and lysozyme of locusts infected by bacteria. Collectively, CrebA may be involved in diverse biological processes, including reproduction and immunity. CrebA inhibited locusts reproduction by regulating JH signaling pathway and inhibits the expression of immune genes TLR6, IMD, and AMPs. These results demonstrate CrebA seems to play a crucial role in reproduction and innate immunity.

Identification of Two Isoforms of Canine Tetherin in Domestic Dogs and Characterization of Their Antiviral Activity against Canine Influenza Virus.

Canine influenza virus (CIV) significantly threatens the canine population and public health. Tetherin, an innate immune factor, plays an important role in the defense against pathogen invasion and has been discovered to restrict the release of various enveloped viruses. Two isoforms of canine tetherin (tetherin-X1 and tetherin-X2) were identified in peripheral blood leukocytes of mixed-breed dogs using reverse transcription polymerase chain reaction (RT-PCR). Amino acid alignment revealed that relative to full-length tetherin (tetherin-X1) and truncated canine tetherin (tetherin-X2) exhibited deletion of 34 amino acids. The deletion occurred at the C-terminus of the coiled-coiled ectodomain and the N-terminus of the glycosylphosphatidylinositol (GPI)-anchor domain. Tetherin-X2 was localized subcellularly at the cell membrane, which was consistent with the localization of tetherin-X1. In addition, canine tetherin-X1 and tetherin-X2 restricted the release of H3N2 CIV. However, canine tetherin-X1 had higher antiviral activity than canine tetherin-X2, indicating that the C-terminus of the coiled-coiled ectodomain and the N-terminus of the GPI-anchor domain of canine tetherin (containing the amino acids deleted in tetherin-X2) are critical for its ability to restrict H3N2 CIV release. This study provides insights for understanding the key functional domains of tetherin that restrict CIV release.

The role of spatial interplay patterns between PD-L1-positive tumor cell and T cell in recurrence of locally advanced non-small cell lung cancer.

PURPOSE: To explore the relationship between the spatial interaction of programmed death-ligand 1(PD-L1)-positive tumor cell and T cell with specific functions and the recurrence of non-small cell lung cancer (NSCLC) and optimize prognostic stratification. MATERIALS AND METHODS: This study retrospectively included 104 patients with locally advanced NSCLC who underwent radical surgery. Tissue microarrays were constructed including tumor center (TC) and invasion margin (IM), and CK/CD4/CD8/PD-L1/programmed death-1 (PD-1) was labeled using multiplex immunofluorescence to decipher the counts and spatial distribution of tumor cells and T cells. The immune microenvironment and recurrence stratification were characterized using the Mann-Whitney U test and Cox proportional hazards model. RESULT: Compared with the IM, the proportion of tumor cells (especially PD-L1+) was increased in the TC, while T cells (especially PD-1+) were decreased. An increase in TC PD-1+ CD8 T cells promoted relapse (HR = 2.183), while PD-L1+ tumor cells alone or in combination with T cells had no predictive value for relapse. In addition, in both TC and IM, CD8 were on average closer to PD-L1+ tumor cells than CD4, especially exhausted CD8. The effective density and percentage of PD-1+ CD4 T cells interacting with PD-L1+ tumor cells in the IM were both associated with recurrence, and the HRs increased sequentially (HRs were 2.809 and 4.063, respectively). Patients with low PD-1+CD4 count combined high PD-1+CD4 effective density showed significantly poorer RFS compared to those with high PD-1+CD4 count combined low PD-1+CD4 effective density, in both the TC and IM regions (HRs were 5.810 and 8.709, respectively). CONCLUSION: Assessing the relative spatial proximity of PD-1/PD-L1 contributes to a deeper understanding of tumor immune escape and generates prognostic information in locally advanced NSCLC patients.

P130cas-FAK interaction is essential for YAP-mediated radioresistance of non-small cell lung cancer.

Based on the RNA-sequencing data, previous studies revealed that extracellular matrix receptor interaction and focal adhesion signaling pathways were enriched in radioresistant non-small cell lung cancer (NSCLC) cell lines. As the principal members of these signaling pathways, recent studies showed that FAK controlled YAP's nuclear translocation and activation in response to mechanical activation. However, the underlying mechanisms are largely unknown. This study was designed to determine whether P130cas plays a role in FAK-YAP axis-mediated radioresistance. We found that P130cas promoted proliferation, altered the cell cycle profile, and enhanced tumor growth using cell lines and xenograft mouse models. After treating the cell lines and xenograft models with a single dose of 5 Gy irradiation, we observed that P130cas effectively induced radioresistance in vitro and in vivo. We confirmed that P130cas interacted with and promoted YAP stabilization, thereby facilitating YAP's activation and nuclear translocation and downregulating the radiosensitivity of NSCLC. Our data also revealed that P130cas and FAK directly interacted with each other and worked together to regulate YAP's activation and nuclear translocation. Furthermore, the present study identified that P130cas, FAK and YAP formed a triple complex to induce radioresistance. Using P130cas-ΔSH3, FAK- P712/715A mutant, YAP-ΔSH3bm and YAP-ΔWW mutant, our results showed that targeting P130cas-FAK interaction may be a more cost-effective way to overcome the YAP activation mediated radioresistance in NSCLC. Using the data of the public database and our clinical samples, the present study suggested that the expression of P130cas correlated with YAP expression and indicated a poor overall response rate of NSCLC patients who underwent radiation therapy. Overall, our study extends the knowledge of FAK-YAP interaction and provides new insight into understanding the underlying mechanisms to overcome the radioresistance of NSCLC.