CD177 drives the transendothelial migration of Treg cells enriched in human colorectal cancer.

Objectives: Regulatory T (Treg) cells regulate immunity in autoimmune diseases and cancers. However, immunotherapies that target tumor-infiltrating Treg cells often induce unwanted immune responses and tissue inflammation. Our research focussed on exploring the expression pattern of CD177 in tumor-infiltrating Treg cells with the aim of identifying a potential target that can enhance immunotherapy effectiveness. Methods: Single-cell RNA sequencing (scRNA-seq) data and survival data were obtained from public databases. Twenty-one colorectal cancer patient samples, including fresh tumor tissues, peritumoral tissues and peripheral blood mononuclear cells (PBMCs), were analysed using flow cytometry. The transendothelial activity of CD177+ Treg cells was substantiated using in vitro experiments. Results: ScRNA-seq and flow cytometry results indicated that CD177 was exclusively expressed in intratumoral Treg cells. CD177+ Treg cells exhibited greater activation status and expressed elevated Treg cell canonical markers and immune checkpoint molecules than CD177- Treg cells. We further discovered that both intratumoral CD177+ Treg cells and CD177-overexpressing induced Treg (iTreg) cells had lower levels of PD-1 than their CD177- counterparts. Moreover, CD177 overexpression significantly enhanced the transendothelial migration of Treg cells in vitro. Conclusions: These results demonstrated that Treg cells with higher CD177 levels exhibited an enhanced activation status and transendothelial migration capacity. Our findings suggest that CD177 may serve as an immunotherapeutic target and that overexpression of CD177 may improve the efficacy of chimeric antigen receptor T (CAR-T) cell therapy.

Intrinsic Defect-Driven Synergistic Synaptic Heterostructures for Gate-Free Neuromorphic Phototransistors.

The optoelectronic synaptic devices based on two-dimensional (2D) materials offer great advances for future neuromorphic visual systems with dramatically improved integration density and power efficiency. The effective charge capture and retention are considered as one vital prerequisite to realizing the synaptic memory function. However, the current 2D synaptic devices are predominantly relied on materials with artificially-engineered defects or intricate gate-controlled architectures to realize the charge trapping process. These approaches, unfortunately, suffer from the degradation of pristine materials, rapid device failure, and unnecessary complication of device structures. To address these challenges, an innovative gate-free heterostructure paradigm is introduced herein. The heterostructure presents a distinctive dome-like morphology wherein a defect-rich Fe7S8 core is enveloped snugly by a curved MoS2 dome shell (Fe7S8@MoS2), allowing the realization of effective photocarrier trapping through the intrinsic defects in the adjacent Fe7S8 core. The resultant neuromorphic devices exhibit remarkable light-tunable synaptic behaviors with memory time up to ≈800 s under single optical pulse, thus demonstrating great advances in simulating visual recognition system with significantly improved image recognition efficiency. The emergence of such heterostructures foreshadows a promising trajectory for underpinning future synaptic devices, catalyzing the realization of high-efficiency and intricate visual processing applications.

Identification of AP002498.1 and LINC01871 as prognostic biomarkers and therapeutic targets for distant metastasis of colorectal adenocarcinoma.

BACKGROUND: Increasing evidence suggests that lncRNA (Long non-coding RNA, lncRNA)-mediated ceRNA (competing endogenous RNA, ceRNA) networks are involved in the occurrence and progression of colorectal cancer (CRC). However, the roles of the lncRNA-miRNA-mRNA ceRNA network in distant metastasis of CRC are still unclear. METHODS: In this study, we constructed a specific ceRNA network to identify potential biomarkers and therapeutic targets for distant metastasis of CRC. Specifically, RNA-Seq data from The Cancer Genome Atlas (TCGA) were used to screen for differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) related to metastasis. After validation and selection by qRT-PCR and univariate and multivariate analysis of the metastasis- and prognosis-related lncRNAs, the regulated microRNAs (miRNAs) and coexpressed mRNAs were used to construct a ceRNA network for distant metastasis of CRC. RESULTS: Two key distant metastasis-related DElncRNAs, AP002498.1 and LINC01871, were identified by univariate and multivariate analysis in combination with analyses of clinical data and expression levels. Furthermore, lncRNA-associated ceRNA subnetworks were constructed from the predicted miRNAs and 13 coexpressed DEmRNAs (SERPINA1, ITLN1, REG4, L1TD1, IGFALS, MUC5B, CIITA, CXCL9, CXCL10, GBP4, GNLY, IDO1, and NOS2). The AP002498.1- and LINC01871-associated ceRNA subnetworks regulated the expression of the target genes SERPINA1 and MUC5B and GNLY, respectively, through the associated miRNAs. CONCLUSION: The DElncRNA AP002498.1 and the LINC01871/miR-4644 and miR-185-5p/GNLY axes were identified as being closely associated with distant metastasis and could represent independent prognostic biomarkers or therapeutic targets in colorectal adenocarcinoma.

Tissue adaptation of regulatory T cells in adipose tissue.

Foxp3+ regulatory T (Treg) cells critically suppress over-activated immune responses and therefore maintain immune homeostasis. Adipose tissue-resident Treg (AT Treg) cells are known for modulating immunity and metabolism in adipose tissue microenvironment through various physiological signals, as well as their heterogeneous subsets, which potentially play disparate roles in aging and obesity. Recent single-cell studies of Treg cells have revealed specialized trajectories of their tissue adaptation and development in lymphoid tissues and at barrier sites. Here, we reviewed a T Cell Receptor (TCR)-primed environmental cue-boosted model of adipose Treg cells' tissue adaptation, especially in response to IL-33, IFN-α, insulin, and androgen signals, which trigger sophisticated transcriptional cascades and ultimately establish unique transcriptional modules in adipose Treg cell subsets. In addition, we further discuss potential therapeutic strategies against aging and obesity by blocking detrimental environmental cues, strengthening the functions of specific AT Treg subsets and modifying the communications between AT Treg subsets and adipocytes.

High-level of intratumoral GITR+ CD4 T cells associate with poor prognosis in gastric cancer.

Immunotherapy targeting glucocorticoid-induced TNFR-related protein (GITR) exhibited strong anti-tumor capacity in mouse model but poor efficacy in clinical trials. This may be attributed to the different GITR expression mode between human and mouse. In this study, we analyzed single-cell RNA sequencing (scRNA-seq) data of human gastric cancer (GC) and used flow to explore the GITR expression across T cell subsets and tissue types in GC patients. We revealed that GITR+ CD4 T cells, including regulatory CD4 T (Treg) cells and conventional CD4 T (Tconv) cells, might contribute to the immunosuppressive microenvironment in GC. The enrichment of these cells was associated with a worse prognosis. Moreover, we found the cellular distribution of GITR protein in Treg cells was microenvironment dependent. In conclusion, GITR is still an important immune checkpoint need to be studied.

High-Performance Thermoelectric α-Ag9 Ga1-x Te6 Compounds with Ultralow Lattice Thermal Conductivity Originating from Ag9 Te2 Motifs.

We have determined the complex atomic structure of high-temperature α-Ag9 GaTe6 phase with a hexagonal lattice (P63 mc space group, a=b=8.2766 Å, c=13.4349 Å). The structure has outer [GaTe4 ]5- tetrahedrons and inner [Ag9 Te2 ]5+ clusters. All of the Ag ions are disorderly distributed in the lattice. Seven types of the Ag atoms constitute the cage-like [Ag9 Te2 ]5+ clusters. The highly disordered Ag ions vibrate in-harmonically, producing strong coupling between low frequency optical phonons and acoustic phonons. This in conjunction with a low sound velocity of 1354 m s-1 leads to an ultralow thermal conductivity of 0.20 W m-1 K-1 at 673 K. Meanwhile, the deficiency of Ga in Ag9 Ga1-x Te6 compounds effectively optimizes the electronic transport properties. Ag9 Ga0.91 Te6 attains a highest power factor of 0.40 mW m-1 K-2 at 673 K. All these contribute to a much-improved ZT value of 1.13 at 623 K for Ag9 Ga0.95 Te6 , which is 41 % higher than that of the pristine Ag9 GaTe6 sample.

Cell cycle arrest is an important mechanism of action of compound Kushen injection in the prevention of colorectal cancer.

Compound Kushen injection (CKI) is the most widely used traditional Chinese medicine preparation for the comprehensive treatment of colorectal cancer (CRC) in China, but its underlying molecular mechanisms of action are still unclear. The present study employed a network pharmacology approach, in which we constructed a "bioactive compound-target-pathway" network. Experimental RNA sequencing (RNA-Seq) analysis was performed to identify a key "bioactive compound-target-pathway" network for subsequent experimental validation. Cell cycle, proliferation, autophagy, and apoptosis assays and a model of azoxymethane/dextran sodium sulfate-induced colorectal carcinogenesis in mice were employed to detect the biological effect of CKI on CRC. Real-time reverse-transcription polymerase chain reaction, Western blot, and immunohistochemistry were performed to verify the selected targets and pathways. We constructed a predicted network that included 82 bioactive compounds, 34 targets, and 33 pathways and further screened an anti-CRC CKI "biological compound (hesperetin 7-O-rutinoside, genistein 7-O-rutinoside, and trifolirhizin)-target (p53 and checkpoint kinase 1 [CHEK1])" network that targeted the "cell cycle pathway". Validation experiments showed that CKI effectively induced the cell-cycle arrest of CRC cells in vitro and suppressed the development of CRC in vivo by downregulating the expression of p53 and CHEK1. Our findings confirmed that inducing cell-cycle arrest by CKI is an important mechanism of its anti-CRC action, which provides a direct and scientific experimental basis for the clinical application of CKI.

Fast ion transport for synthesis and stabilization of ß-Zn4Sb3.

Mobile ion-enabled phenomena make ß-Zn4Sb3 a promising material in terms of the re-entry phase instability behavior, mixed electronic ionic conduction, and thermoelectric performance. Here, we utilize the fast Zn2+ migration under a sawtooth waveform electric field and a dynamical growth of 3-dimensional ionic conduction network to achieve ultra-fast synthesis of ß-Zn4Sb3. Moreover, the interplay between the mobile ions, electric field, and temperature field gives rise to exquisite core-shell crystalline-amorphous microstructures that self-adaptively stabilize ß-Zn4Sb3. Doping Cd or Ge on the Zn site as steric hindrance further stabilizes ß-Zn4Sb3 by restricting long-range Zn2+ migration and extends the operation temperature range of high thermoelectric performance. These results provide insight into the development of mixed-conduction thermoelectric materials, batteries, and other functional materials.

The roles and prognostic significance of ABI1-TSV-11 expression in patients with left-sided colorectal cancer.

Abnormally expressed and/or phosphorylated Abelson interactor 1 (ABI1) participates in the metastasis and progression of colorectal cancer (CRC). ABI1 presents as at least 12 transcript variants (TSVs) by mRNA alternative splicing, but it is unknown which of them is involved in CRC metastasis and prognosis. Here, we firstly identified ABI1-TSV-11 as a key TSV affecting the metastasis and prognosis of left-sided colorectal cancer (LsCC) and its elevated expression is related to lymph node metastasis and shorter overall survival (OS) in LsCC by analyzing data from The Cancer Genome Atlas and TSVdb. Secondly, ABI1-TSV-11 overexpression promoted LoVo and SW480 cells adhesion and migration in vitro, and accelerated LoVo and SW480 cells lung metastasis in vivo. Finally, mechanism investigations revealed that ABI1-isoform-11 interacted with epidermal growth factor receptor pathway substrate 8 (ESP8) and regulated actin dynamics to affect LoVo and SW480 cells biological behaviors. Taken together, our data demonstrated that ABI1-TSV-11 plays an oncogenic role in LsCC, it is an independent risk factor of prognosis and may be a potential molecular marker and therapeutic target in LsCC.

The Gut Microbial Signature of Gestational Diabetes Mellitus and the Association With Diet Intervention.

Gestational diabetes mellitus (GDM) is a high-risk pregnancy complication that is associated with metabolic disorder phenotypes, such as abnormal blood glucose and obesity. The link between microbiota and diet management contributes to metabolic homeostasis in GDM. Therefore, it is crucial to understand the structure of the gut microbiota in GDM and to explore the effect of dietary management on the microbiota structure. In this study, we analyzed the composition of the gut microbiota between 27 GDM and 30 healthy subjects at two time points using Illumina HiSeq 2500 platform. The taxonomy analyses suggested that the overall bacteria clustered by diabetes status, rather than diet intervention. Of particular interest, the phylum Acidobacteria in GDM was significantly increased, and positively correlated with blood glucose levels. Moreover, Partial least-squares discriminant analysis (PLS-DA) revealed that certain genera in the phyla Firmicutes, Bacteroidetes, Proteobacteria, and Lentisphaerae characterized the GDM gut microbiota. Correlation analysis indicated that blood glucose levels and BMI index were correlated with the relative abundance of SCFAS-producing genera. Through the comparison between the GDM and healthy samples with or without diet intervention, we discovered that the role of short-term diet management in GDM processes is associated with the change in the Firmicutes/Bacteroidetes ratio and some specific taxa, rather than an alternative gut microbial pattern. Our study have important implications for understanding the beneficial effects of diet intervention on the specific gut microbiota and thus possibly their metabolism in pregnant women with GDM.