Bulk and single-cell transcriptome reveal the immuno-prognostic subtypes and tumour microenvironment heterogeneity in HCC.

BACKGROUND & AIMS: Accumulating evidences suggest tumour microenvironment (TME) profoundly influence clinical outcome in hepatocellular carcinoma (HCC). Existing immune subtypes are susceptible to batch effects, and integrative analysis of bulk and single-cell transcriptome is helpful to recognize immune subtypes and TME in HCC. METHODS: Based on the relative expression ordering (REO) of 1259 immune-related genes, an immuno-prognostic signature was developed and validated in 907 HCC samples from five bulk transcriptomic cohorts, including 72 in-house samples. The machine learning models based on subtype-specific gene pairs with stable REOs were constructed to jointly predict immuno-prognostic subtypes in single-cell RNA-seq data and validated in another single-cell data. Then, cancer characteristics, immune landscape, underlying mechanism and therapeutic benefits between subtypes were analysed. RESULTS: An immune-related signature with 29 gene pairs stratified HCC samples individually into two risk subgroups (C1 and C2), which was an independent prognostic factor for overall survival. The machine learning models verified the immune subtypes from five bulk cohorts to two single-cell transcriptomic data. Integrative analysis revealed that C1 had poorer outcomes, higher CNV burden and malignant scores, higher sensitivity to sorafenib, and exhibited an immunosuppressive phenotype with more regulators, e.g., myeloid-derived suppressor cells (MDSCs), Mø_SPP1, while C2 was characterized with better outcomes, higher metabolism, more benefit from immunotherapy, and displayed active immune with more effectors, e.g., tumour infiltrating lymphocyte and dendritic cell. Moreover, both two single-cell data revealed the crosstalk of SPP1-related L-R pairs between cancer and immune cells, especially SPP1-CD44, might lead to immunosuppression in C1. CONCLUSIONS: The REO-based immuno-prognostic subtypes were conducive to individualized prognosis prediction and treatment options for HCC. This study paved the way for understanding TME heterogeneity between immuno-prognostic subtypes of HCC.

Evaluation and Prognostication of Gd-EOB-DTPA MRI and CT in Patients With Macrotrabecular-Massive Hepatocellular Carcinoma.

BACKGROUND: Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is highly aggressive. Comparing the diagnosis ability of CT and gadoxetate disodium (Gd-EOB-DTPA) MRI for MTM-HCC are lacking. PURPOSE: To compare the performance of Gd-EOB-DTPA MRI and CT for differentiating MTM-HCC from non-MTM-HCC, and determine the prognostic indicator. STUDY TYPE: Retrospective. SUBJECTS: Post-surgery HCC patients, divided into the training (N = 272) and external validation (N = 44) cohorts. FIELD STRENGTH/SEQUENCE: 3.0 T, T1-weighted imaging, in-opp phase, and T1-weighted volumetric interpolated breath-hold examination/liver acquisition with volume acceleration; enhanced CT. ASSESSMENT: Three radiologists evaluated clinical characteristics (sex, age, liver disease, liver function, blood routine, alpha-fetoprotein [AFP] and prothrombin time international normalization ratio [PT-INR]) and imaging features (tumor length, intratumor fat, hemorrhage, arterial phase peritumoral enhancement, intratumor necrosis or ischemia, capsule, and peritumoral hepatobiliary phase [HBP] hypointensity). Compared the performance of CT and MRI for diagnosing MTM-HCC. Follow-up occurred every 3-6 months, and nomogram demonstrated the probability of MTM-HCC. STATISTICAL TESTS: Fisher test, t-test or Wilcoxon rank-sum test, area under the curve (AUC), 95% confidence interval (CI), multivariable logistic regression, Kaplan-Meier curve, and Cox proportional hazards. Significance level: P < 0.05. RESULTS: Gd-EOB-DTPA MRI (AUC: 0.793; 95% CI, 0.740-0.839) outperformed CT (AUC: 0.747; 95% CI, 0.691-0.797) in the training cohort. The nomogram, incorporating AFP, PT-INR, and MRI features (non-intratumor fat, incomplete capsule, intratumor necrosis or ischemia, and peritumoral HBP hypointensity) demonstrated powerful performance for diagnosing MTM-HCC with an AUC of 0.826 (95% CI, 0.631-1.000) in the external validation cohort. Median follow-up was 347 days (interquartile range [IQR], 606 days) for the training cohort and 222 days (IQR, 441 days) for external validation cohort. Intratumor necrosis or ischemia was an independent indicator for poor prognosis. DATA CONCLUSION: Gd-EOB-DTPA MRI might assist in preoperative diagnosis of MTM-HCC, and intratumor necrosis or ischemia was associated with poor prognosis. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Multi-Channel Time-Domain Boring-Vibration-Enhancement Method Using RNN Networks.

The larvae of certain wood-boring beetles typically inhabit the interior of trees and feed on the wood, leaving almost no external traces during the early stages of infestation. Acoustic techniques are commonly employed to detect the vibrations produced by these larvae while they feed on wood, significantly increasing detection efficiency compared to traditional methods. However, this method's accuracy is greatly affected by environmental noise interference. To address the impact of environmental noise, this paper introduces a signal separation system based on a multi-channel attention mechanism. The system utilizes multiple sensors to receive wood-boring vibration signals and employs the attention mechanism to adjust the weights of relevant channels. By utilizing beamforming techniques, the system successfully removes noise from the wood-boring vibration signals and separates the clean wood-boring vibration signals from the noisy ones. The data used in this study were collected from both field and laboratory environments, ensuring the authenticity of the dataset. Experimental results demonstrate that this system can efficiently separate the wood-boring vibration signals from the mixed noisy signals.

Genomic analysis reveals a cryptic pangolin species.

Eight extant species of pangolins are currently recognized. Recent studies found that two mitochondrial haplotypes identified in confiscations in Hong Kong could not be assigned to any known pangolin species, implying the existence of a species. Here, we report that two additional mitochondrial haplotypes identified in independent confiscations from Yunnan align with the putative species haplotypes supporting the existence of this mysterious species/population. To verify the new species scenario we performed a comprehensive analysis of scale characteristics and 138 whole genomes representing all recognized pangolin species and the cryptic new species, 98 of which were generated here. Our morphometric results clearly attributed this cryptic species to Asian pangolins (Manis sp.) and the genomic data provide robust and compelling evidence that it is a pangolin species distinct from those recognized previously, which separated from the Philippine pangolin and Malayan pangolin over 5 Mya. Our study provides a solid genomic basis for its formal recognition as the ninth pangolin species or the fifth Asian one, supporting a new taxonomic classification of pangolins. The effects of glacial climate changes and recent anthropogenic activities driven by illegal trade are inferred to have caused its population decline with the genomic signatures showing low genetic diversity, a high level of inbreeding, and high genetic load. Our finding greatly expands current knowledge of pangolin diversity and evolution and has vital implications for conservation efforts to prevent the extinction of this enigmatic and endangered species from the wild.

A CNN-Based Method for Enhancing Boring Vibration with Time-Domain Convolution-Augmented Transformer.

Recording vibration signals induced by larvae activity in the trunk has proven to be an efficient method for detecting trunk-boring insects. However, the accuracy of the detection is often limited because the signals collected in real-world environments are heavily disrupted by environmental noises. To deal with this problem, we propose a deep-learning-based model that enhances trunk-boring vibration signals, incorporating an attention mechanism to optimize its performance. The training data utilized in this research consist of the boring vibrations of Agrilus planipennis larvae recorded within trunk sections, as well as various environmental noises that are typical of the natural habitats of trees. We mixed them at different signal-to-noise ratios (SNRs) to simulate the realistically collected sounds. The SNR of the enhanced boring vibrations can reach up to 17.84 dB after being enhanced by our model, and this model can restore the details of the vibration signals remarkably. Consequently, our model's enhancement procedure led to a significant increase in accuracy for VGG16, a commonly used classification model. All results demonstrate the effectiveness of our approach for enhancing the detection of larvae using boring vibration signals.

Tumor-selective Blockade of CD47 Signaling with CD47 Antibody for Enhanced Anti-tumor Activity in Malignant Meningioma.

BACKGROUND: Patients with WHO grade III meningioma have a poor prognosis with a median survival of less than two years and a high risk of recurrence. However, traditional treatment options have failed to improve prognosis. Therefore, development of novel immunotherapy targets is urgently needed. CD47 acting as a "don't eat me" signal to macrophages can trigger tumor immune escape. However, the role of CD47 in malignant meningioma is not well understood. METHODS: We collected 190 clinical meningioma samples and detected the expression of CD47 and immune infiltration in WHO grade I-III by immunohistochemistry, western blot, qPCR. We also examined the functional effects of anti-CD47 on cell proliferation, migration and invasion, macrophagemediated phagocytosis and tumorigenicity both in vitro and in vivo. RESULTS: We found that the expression of CD47 was increased in malignant meningioma along with a decreased number of T cells and an increase in CD68+ macrophages. Blocking CD47 with anti-CD47 antibody (B6H12) suppressed tumor cell growth, motility and promoted macrophage-mediated phagocytosis in IOMM-Lee cells in vitro. In vivo experiments showed that anti-CD47 antibody (B6H12 or MIAP301) significantly inhibited the tumor growth and this effect was partly blocked by the depletion of macrophages. Finally, p-ERK and EGFR showed higher expression in malignant meningioma with high expression of CD47, which was verified by western blot. CONCLUSION: Our results demonstrated that CD47 maybe involved in the meningioma progression and prognosis and offered a novel therapeutic option by targeting CD47 in malignant meningioma.

Value of susceptibility-weighted imaging in differentiating benign from malignant portal vein thrombosis.

Background: Many diseases are accompanied by portal vein thrombosis (PVT), and its nature is closely related to its prognosis and treatment. It is important to evaluate magnetic resonance imaging (MRI) parameters, including susceptibility-weighted imaging (SWI) and qualitative diffusion-weighted imaging (DWI), in the differentiation between benign and malignant PVT. Methods: In this retrospective study, we collected clinical imaging data from 140 patients with PVTs characterized as benign or malignant based on enhanced MRI between January 2011 and April 2016 and retrospectively analyzed PVTs using SWI and DWI. There were 37 benign and 103 malignant PVTs. Image review was performed by 2 radiologists blinded to clinical information. The signal intensity (SI) of PVTs was recorded on SWI. The apparent diffusion coefficient (ADC) and the ratio of signal intensity (SIR) on SWI (SIRSWI) and ADC (SIRADC) between the PVTs and the spinal cord were calculated. Finally, we generated receiver operating characteristic (ROC) curves to evaluate the efficacy of SIRSWI and SIRADC for distinguishing benign and malignant PVTs. Results: On SWI and DWI, 100.0% (36/36) and 80.5% (29/36) of benign PVTs were hypointense, respectively. For malignant PVTs on SWI and DWI, 99.0% (103/104) and 89.4% (93/104) were hyperintense, respectively. The SIRSWI values of benign and malignant PVTs were 0.58±0.13 and 0.88±0.06, respectively, representing a significant difference (P<0.001). The SIRADC values of benign and malignant PVTs were 0.72±0.32 and 0.62±0.17, respectively, representing a significant difference (P=0.034). The area under the ROC curve (AUROC) for SIRSWI [0.990; 95% confidence interval (CI): 0.971-1.000] was significantly higher than that for SIRADC (0.619; 95% CI: 0.500-0.737; P<0.001). The SIRSWI had a sensitivity of 100.0% and a specificity of 97.3% with a cutoff value of 0.749, while the SIRADC had a sensitivity of 45.9% and specificity of 83.3% with a cutoff value of 0.791. Conclusions: The diagnostic performance of SWI is superior to that of DWI in the differentiation of benign and malignant PVTs.

Identification reproducible microbiota biomarkers for the diagnosis of cirrhosis and hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignant tumor with high incidence in China, which is mainly related to chronic hepatitis B (CHB) and liver cirrhosis (LC) caused by hepatitis B virus (HBV) infection. This study aimed to identify reproducible gut microbial biomarkers across Chinese population for LC and HCC diagnosis. In this study, a group of 21 CHB, 25 LC, 21 HCC and 15 healthy control (HC) were examined, and used as the training data. Four published faecal datasets from different regions of China were collected, totally including 121 CHB, 33 LC, 70 HCC and 96 HC. Beta diversity showed that the distribution of community structure in CHB, LC, HCC was significantly different from HC. Correspondingly, 14 and 10 reproducible differential genera across datasets were identified in LC and HCC, respectively, defined as LC-associated and HCC-associated genera. Two random forest (RF) models based on these reproducible genera distinguished LC or HCC from HC with an area under the curve (AUC) of 0.824 and 0.902 in the training dataset, respectively, and achieved cross-region validations. Moreover, AUCs were greatly improved when clinical factors were added. A reconstructed random forest model on eight genera with significant changes between HCC and non-HCC can accurately distinguished HCC from LC. Conclusively, two RF models based on 14 reproducible LC-associated and 10 reproducible HCC-associated genera were constructed for LC and HCC diagnosis, which is of great significance to assist clinical early diagnosis.

Study of SO2 measurement based on a dual optical path Fabry-Perot correlation spectroscopy.

This paper investigates a method for measuring SO2 concentration using Fabry-Perot interferometer correlation spectroscopy. In this method, the experimental system is designed as a separated beam, with the beam entering the F-P cavity at two incidence angles simultaneously to match the peak and valley positions of the SO2 absorption cross-section. The system achieves a 2σ detection limit of 28.2 ppm·m(15 cm) at a sampling frequency of 10 Hz. An outfield comparison experiment with the differential optical absorption spectroscopy method shows good agreement for the simultaneous measurement of SO2 concentration from sulfur combustion, with a correlation coefficient of R2 = 0.93. This study introduces a non-dispersive, highly accurate, and fast gas detection technique.

Inhibition of integrated stress response protects against lipid-induced senescence in hypothalamic neural stem cells in adamantinomatous craniopharyngioma.

BACKGROUND: Adamantinomatous craniopharyngioma (ACP) is a benign tumor with malignant clinical manifestations. ACP adjacent to the hypothalamus often presents with more severe symptoms and higher incidence of hypothalamic dysfunction. However, the mechanism underlying hypothalamic dysfunction remains unclear. METHODS: Immunostaining was performed to determine the nerve damage to the floor of the third ventricle (3VF) adjacent to ACP and to examine the recruitment and senescence of hypothalamic neural stem cells (htNSCs). The accumulation of lipid droplets (LDs) in htNSCs was evaluated via BODIPY staining, oil red O staining, and transmission electron microscopy. In vitro and in vivo assays were used to evaluate the effect of cystic fluid or oxidized low-density lipoprotein and that of oxytocin (OXT) on htNSC senescence and the hypothalamic function. The protein expression levels were analyzed using western blotting. RESULTS: htNSCs with massive LD accumulation were recruited to the damaged 3VF adjacent to ACP. The LDs in htNSCs induced senescence and reduced neuronal differentiation; however, htNSC senescence was effectively prevented by inhibiting either CD36 or integrated stress response (ISR) signaling. Furthermore, OXT pretreatment reduced lipotoxicity via the inhibition of ISR signaling and the repair of the blood-brain barrier. CONCLUSIONS: Reduced LD aggregation or ISR signaling inhibition prevented senescence in htNSCs and identified molecular pathways and potential therapeutic targets that may improve hypothalamic dysfunction in ACP patients.

Microbiome analysis reveals universal diagnostic biomarkers for colorectal cancer across populations and technologies.

The gut microbial dysbiosis is a risk of colorectal cancer (CRC) and some bacteria have been reported as potential markers for CRC diagnosis. However, heterogeneity among studies with different populations and technologies lead to inconsistent results. Here, we investigated six metagenomic profiles of stool samples from healthy controls (HC), colorectal adenoma (CA) and CRC, and six and four genera were consistently altered between CRC and HC or CA across populations, respectively. In FengQ cohort, which composed with 61 HC, 47 CA, and 46 CRC samples, a random forest (RF) model composed of the six genera, denoted as signature-HC, distinguished CRC from HC with an area under the curve (AUC) of 0.84. Similarly, another RF model composed of the four universal genera, denoted as signature-CA, discriminated CRC from CA with an AUC of 0.73. These signatures were further validated in five metagenomic sequencing cohorts and six independent 16S rRNA gene sequencing cohorts. Interestingly, three genera overlapped in the two models (Porphyromonas, Parvimonas and Peptostreptococcus) were with very low abundance in HC and CA, but sharply increased in CRC. A concise RF model on the three genera distinguished CRC from HC or CA with AUC of 0.87 and 0.67, respectively. Functional gene family analysis revealed that Kyoto Encyclopedia of Genes and Genomes Orthogroups categories which were significantly correlated with markers in signature-HC and signature-CA were mapped into pathways related to lipopolysaccharide and sulfur metabolism, which might be vital risk factors of CRC development. Conclusively, our study identified universal bacterial markers across populations and technologies as potential aids in non-invasive diagnosis of CRC.

Neutrophil infiltration and myocarditis in patients with severe COVID-19: A post-mortem study.

Aims: To investigate cardiac pathology in critically ill patients with coronavirus disease 2019 (COVID-19) and identify associations between pathological changes and clinical characteristics. Methods: The present autopsy cohort study included hearts from 26 deceased patients hospitalized in intensive care units due to COVID-19, and was conducted at four sites in Wuhan, China. Cases were divided into a neutrophil infiltration group and a no-neutrophil group based on the presence or absence of histopathologically identified neutrophilic infiltrates. Results: Among the 26 patients, histopathological examination identified active myocarditis in four patients. All patients with myocarditis exhibited extensive accompanying neutrophil infiltration, and all patients without myocarditis did not. The neutrophil infiltration group exhibited significantly higher rates of detection of interleukin-6 (100 vs. 4.6%) and tumor necrosis factor-alpha (100 vs. 31.8%) than the no-neutrophil group (both p < 0.05). On admission, four patients with neutrophil infiltration in myocardium had significantly higher baseline levels of aspartate aminotransferase, D dimer, and high-sensitivity C reactive protein than the other 22 patients (all p < 0.05). During hospitalization, patients with neutrophil infiltration had significantly higher maximum creatine kinase-MB (median 280.0 IU/L vs. 38.7 IU/L, p = 0.04) and higher troponin I (median 1.112 ng/ml vs. 0.220 ng/ml, p = 0.56) than patients without neutrophil infiltration. Conclusion: Active myocarditis was frequently associated with neutrophil infiltration in the hearts of deceased patients with severe COVID-19. Patients with neutrophil-infiltrated myocarditis had a series of severely abnormal laboratory test results on admission, and high maximum creatine kinase-MB during hospitalization. The role of neutrophils in severe heart injury and systemic conditions in patients with COVID-19 should be emphasized.

Metabolism-Related Gene Pairs to Predict the Clinical Outcome and Molecular Characteristics of Early Hepatocellular Carcinoma.

Recurrence is the main factor affecting the prognosis of early hepatocellular carcinoma (HCC), which is not accurately evaluated by clinical indicators. The metabolic heterogeneity of HCC hints at the possibility of constructing a stratification model to predict the clinical outcome. On the basis of the relative expression orderings of 2939 metabolism-related genes, an individualized signature with 10 metabolism-related gene pairs (10-GPS) was developed from 250 early HCC samples in the discovery datasets, which stratified HCC patients into the high- and low-risk subgroups with significantly different survival rates. The 10-GPS was validated in 311 public transcriptomic samples from two independent validation datasets. A nomogram that included the 10-GPS, age, gender, and stage was constructed for eventual clinical evaluation. The low-risk group was characterized by lower proliferation, higher metabolism, increased activated immune microenvironment, and lower TIDE scores, suggesting a better response to immunotherapy. The high-risk group displayed hypomethylation, higher copy number alterations, mutations, and more overexpression of immune-checkpoint genes, which might jointly lead to poor outcomes. The prognostic accuracy of the 10-GPS was further validated in 47 institutional transcriptomic samples and 101 public proteomic samples. In conclusion, the 10-GPS is a robust predictor of the clinical outcome for early HCC patients and could help evaluate prognosis and characterize molecular heterogeneity.

C-H Fluoroalkylsulfinylation/Intramolecular Rearrangement for Precise Synthesis of Fluoroalkyl Sulfoxides.

An efficient methodology to access various fluoroalkyl sulfoxides bearing ortho/para-functionalized amine scaffolds from arylhydroxylamines is described. The transformation was featured with new electrophilic trifluoromethylthiolated reagents, good functional group tolerance, and late-stage modification of complex bioactive scaffolds, providing a rapid access to prepare numerous trifluoromethyl- and difluoromethyl-substituted sulfoxides. Mechanism studies and density functional theory calculations suggest this reaction goes through a nucleophilic trifluoromethylthiolation of arylhydroxylamine and subsequent internal 2,3-sigmatropic rearrangement involving a sulfur and oxygen transfer process.

Preoperative Assessment of Abdominal Adipose Tissue to Predict Microvascular Invasion in Small Hepatocellular Carcinoma.

Background and Aims: Microvascular invasion (MVI) affects recurrence after treatment of small hepatocellular carcinoma (sHCC) of ≤3 cm in size. The present study aimed to investigate whether abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and intermuscular adipose tissue (IMAT) are associated with MVI in patients with sHCC. Methods: A total of 124 patients with pathologically-confirmed sHCC diagnosed on surgical resection at the First Hospital Affiliated to Army Military University were recruited and divided into two groups according to MVI classification criteria (i.e., MVI-positive or MVI-negative). The SAT, VAT, and IMAT areas at the lumbar 3 vertebral level were imaged with abdominal computed tomography and measured using ImageJ software. Their association with MVI in sHCC was analyzed. Results: Of the 124 patients with sHCC, 67 were MVI-positive and 57 were MVI-negative. Univariate analysis revealed a significant difference in the abdominal VAT and SAT between the MVI-positive and MVI-negative groups (p<0.05), with an area under the receiver operating characteristic curve of 0.76 and 0.65, respectively. Conclusions: The results of this study suggest that the areas of abdominal SAT and VAT are of significant clinical value because they can effectively predict the MVI status in patients with sHCC.

Macrotrabecular-Massive Hepatocellular Carcinoma: What Should We Know?

Hepatocellular carcinoma is one of the most common malignancies globally. Recently, a newly identified histological subtype, designated as "macrotrabecular-massive hepatocellular carcinoma" (MTM-HCC), has been associated with an aggressive phenotype and has received extensive attention. MTM-HCC was a strong independent prognostic predictor of early and overall recurrence because it is closely related to tumor molecular subclass, gene mutation, carcinogenesis pathways, and immunohistochemical markers. In addition, preoperative imaging examination can potentially provide an essential clue for diagnosing MTM-HCC, intratumor necrosis or ischemia is an independent predictor for MTM-HCC on Gd-EOB-DTPA enhanced MRI or CT. Early diagnosis and appropriate treatment of MTM-HCC could prove beneficial for preventing early recurrence and could improve outcomes.

CD47 promotes the proliferation and migration of adamantinomatous craniopharyngioma cells by activating the MAPK/ERK pathway, and CD47 blockade facilitates microglia-mediated phagocytosis.

AIMS: CD47 is overexpressed in multiple tumours and plays an important role in immune escape and other biological processes of tumours. However, its role in adamantinomatous craniopharyngioma (ACP) remains unclear. Therefore, we explored the functions of CD47 in ACP. METHODS: In this study, the expression of CD47 and the infiltration of immune cells in ACP was determined by immunohistochemistry (IHC) or immunofluorescence. Microglia-mediated phagocytosis was analysed using an in vitro phagocytosis assay. Using lentivirus transfection, CD47 was either silenced or overexpressed in primary ACP cells and the biological effects of CD47 on these cells were evaluated in vitro using cell viability, flow cytometry, wound healing, Transwell migration and 3D hydrogel assays. The protein expression levels were analysed by western blotting. RESULTS: Finger-like protrusions, which may be the key factor in the recurrence of ACP, were primarily found in the region of hypothalamic involvement. The expression of CD47 was higher in palisading epithelium compared with stellate reticulum and epithelial whorls. An in vitro phagocytosis assay showed that CD47 blockade could promote microglia-mediated phagocytosis. Functional assays revealed that CD47 promoted the growth, migration and invasion of ACP cells in vitro. Our mechanistic investigations showed that CD47 activated the MAPK/ERK pathway, thereby facilitating the biological behaviour of ACP cells. CONCLUSIONS: Here, we demonstrated that CD47 plays an important role in ACP cells, suggesting that CD47 could be a new potential therapeutic target for ACP, and adding to the body of literature a role for the inhibition of MAPK/ERK in ACP.

Can a molecular switch exist in both superalkali electride and superalkalide forms?

To combine both electride and alkalide characteristics in one molecular switch, it is shown herein that the phenalenyl radical and the M3 ring (M3-PHY, M = Li, Na, and K) stacked with parallel and vertical geometries are good candidates. The former geometry is the superalkali electride e-⋯M3+-PHY while the latter geometry is the superalkalide Mδ--M2(1-δ)+-PHY-. The superalkalide Mδ--M2(1-δ)+-PHY- may isomerize to the superalkali electride e-⋯M3+-PHY (M = Li, Na, and K) using suitable long-wavelength irradiation, while the latter may isomerize to the former with suitable short-wavelength irradiation. Also, applying suitable oriented external electric fields can drive the superalkalide Mδ-M2(1-δ)+-PHY- to change into the superalkali electride e-⋯M3+-PHY (M = Li, Na, and K). The differences in the static and dynamic first hyperpolarizability (ß0) values between them were also studied.

Expression of Insulin-Like Growth Factor Type 1 Receptor Is Linked to Inflammation in Adamantinomatous Craniopharyngioma.

INTRODUCTION: Insulin-like growth factor type 1 receptor (IGF1R) is overexpressed in various malignant tumors, which relates to their transformation and recurrence. Craniopharyngioma is a benign tumor with malignant results, often accompanied by a severe inflammatory reaction. However, the relationship between IGF1R expression and the inflammatory response of craniopharyngioma is unclear. METHODS: We enrolled 85 patients with adamantinomatous craniopharyngioma (ACP) in a study to explore the relationship between IGF1R expression and clinical features of this disease. RESULTS: Patients in the IGF1R high-expression group had a significantly higher incidence of hypopituitarism, higher recurrence rate, and lower progression-free survival. ß-Catenin can further regulate expression of the stem cell marker, CD44, by regulating IGF1R. Using immunofluorescence, we found that tumor stem cell-like cells did not express phosphorylated (p)-ERK, although p-ERK activation was evident in the surrounding cells. Picropodophyllin, a specific inhibitor of IGF1R, increased the expression of p-ERK protein and decreased the transcription level of interleukin-6. CONCLUSIONS: High expression of IGF1R might promote inflammation of ACP, which might be an unfavorable factor for pituitary function and prognosis. The high expression of IGF1R in tumor stem cell-like cells might inhibit the expression of p-ERK and promote the generation of inflammatory factors. IGF1R plays a stemness maintenance role in ACP and regulates the production of inflammatory factors through a p-ERK pathway, which suggests that targeting IGF1R and p-ERK might provide a new direction for alleviating tumor inflammation.

Preoperative prediction of early recurrence of HBV-related hepatocellular carcinoma (≤5†cm) by visceral adipose tissue index.

Background: This study aimed to investigate whether visceral adipose tissue index (VATI) is a significant risk factor for the early recurrence (ER) of HBV-related hepatocellular carcinoma (HCC) (≤5 cm) after hepatectomy. Methods: The recruited cohort patients who were positive for hepatitis B virus, presented with surgically confirmed HCC (≤5 cm) from Army Medical University (internal training cohort: n = 192) and Chongqing Medical University (external validation group: n = 46). We measured VATI, subcutaneous adipose tissue index (SATI) via computed tomography (CT). ER was defined as recurrence within 2 years after hepatectomy. The impact of parameters on outcome after hepatectomy for HCC was analyzed. Results: Univariate analysis showed that alpha-fetoprotein levels (p = 0.044), body mass index (BMI) (p < 0.001), SATI (p < 0.001), and VATI (p < 0.001) were significantly different between ER and non-ER groups in internal training cohort. Multivariate analysis identified VATI as an independent risk factor for ER (odds ratio = 1.07, 95% confidence interval: 1.047-1.094, p < 0.001), with a AUC of 0.802, based on the cut-off value of VATI, which was divided into high risk (≥37.45 cm2/m2) and low risk (<37.45 cm2/m2) groups. The prognosis of low risk group was significantly higher than that of high risk group (p < 0.001). The AUC value of VATI in external validation group was 0.854. Conclusion: VATI was an independent risk factor for the ER, and higher VATI was closely related to poor outcomes after hepatectomy for HBV-related HCC (≤5 cm).