Systematic pan-cancer analysis insights into ICAM1 as an immunological and prognostic biomarker.

Intercellular adhesion molecule 1 (ICAM1) is a cell surface adhesion glycoprotein in the immunoglobulin supergene family. It is associated with several epithelial tumorigenesis processes, as well as with inflammation. However, the function of ICAM1 in the prognosis of tumor immunity is still unclear. This study aimed to examine the immune function of ICAM1 in 33 tumor types and to investigate the prognostic value of tumors. Using datasets from the Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), Cancer Cell Lines Encyclopedia (CCLE), Human Protein Atlas (HPA), and cBioPortal, we investigated the role of ICAM1 in tumors. We explored the potential correlation between ICAM1 expression and tumor prognosis, gene mutations, microsatellite instability, and tumor immune cell levels in various cancers. We observed that ICAM1 is highly expressed in multiple malignant tumors. Furthermore, ICAM1 is negatively or positively associated with different malignant tumor prognoses. The expression levels of ICAM1 were correlated with the tumor mutation burden (TMB) in 11 tumors and with MSI in eight tumors. ICAM1 is a gene associated with immune infiltrating cells, such as M1 macrophages and CD8+ T cells in gastric and colon cancer. Meanwhile, the expression of ICAM1 is associated with several immune-related functions and immune-regulation-related signaling pathways, such as the chemokine signaling pathway. Our study shows that ICAM1 can be used as a prognostic biomarker in many cancer types because of its function in tumorigenesis and malignant tumor immunity.

An Improved SSVEP-based Brain-Computer Interface with Low Contrast Visual Stimulation and its Application in UAV Control.

Efficient communication and regulation are crucial for advancing brain-computer interfaces (BCIs), with the steady-state visual evoked potential (SSVEP) paradigm demonstrating high accuracy and information transfer rates. However, the conventional SSVEP paradigm encounters challenges related to visual occlusion and fatigue. In this study, we propose an improved SSVEP paradigm that addresses these issues by lowering the contrast of visual stimuli. visual stimulation. The improved paradigms outperform the traditional paradigm in the experiments, significantly reducing the visual stimulation of the SSVEP paradigm. Furthermore, we apply this enhanced paradigm to a BCI navigation system, enabling two-dimensional navigation of Unmanned Aerial Vehicles (UAVs) through a first-person perspective. Experimental results indicate the enhanced SSVEP-based BCI system's accuracy in performing navigation and search tasks. Our findings highlight the feasibility of the enhanced SSVEP paradigm in mitigating visual occlusion and fatigue issues, presenting a more intuitive and natural approach for BCIs to control external equipment.

Assessment of arterial pulsatility of cerebral perforating arteries using 7T high-resolution dual-VENC phase-contrast MRI.

PURPOSE: Directly imaging the function of cerebral perforating arteries could provide valuable insight into the pathology of cerebral small vessel diseases (cSVD). Arterial pulsatility has been identified as a useful biomarker for assessing vascular dysfunction. In this study, we investigate the feasibility and reliability of using dual velocity encoding (VENC) phase-contrast MRI (PC-MRI) to measure the pulsatility of cerebral perforating arteries at 7 T. METHODS: Twenty participants, including 12 young volunteers and 8 elder adults, underwent high-resolution 2D PC-MRI scans with VENCs of 20 cm/s and 40 cm/s at 7T. The sensitivity of perforator detection and the reliability of pulsatility measurement of cerebral perforating arteries using dual-VENC PC-MRI were evaluated by comparison with the single-VENC data. The effects of temporal resolution in the PC-MRI acquisition and aging on the pulsatility measurements were investigated. RESULTS: Compared to the single VENCs, dual-VENC PC-MRI provided improved sensitivity of perforator detection and more reliable pulsatility measurements. Temporal resolution impacted the pulsatility measurements, as decreasing temporal resolution led to an underestimation of pulsatility. Elderly adults had elevated pulsatility in cerebral perforating arteries compared to young adults, but there was no difference in the number of detected perforators between the two age groups. CONCLUSION: Dual-VENC PC-MRI is a reliable imaging method for the assessment of pulsatility of cerebral perforating arteries, which could be useful as a potential imaging biomarker of aging and cSVD.

Association of mitochondrial homeostasis and dynamic balance with malignant biological behaviors of gastrointestinal cancer.

Mitochondria determine the physiological status of most eukaryotes. Mitochondrial dynamics plays an important role in maintaining mitochondrial homeostasis, and the disorder in mitochondrial dynamics could affect cellular energy metabolism leading to tumorigenesis. In recent years, disrupted mitochondrial dynamics has been found to influence the biological behaviors of gastrointestinal cancer with the potential to be a novel target for its individualized therapy. This review systematically introduced the role of mitochondrial dynamics in maintaining mitochondrial homeostasis, and further elaborated the effects of disrupted mitochondrial dynamics on the cellular biological behaviors of gastrointestinal cancer as well as its association with cancer progression. We aim to provide clues for elucidating the etiology and pathogenesis of gastrointestinal cancer from the perspective of mitochondrial homeostasis and disorder.

Three-dimensional echo-shifted EPI with simultaneous blip-up and blip-down acquisitions for correcting geometric distortion.

PURPOSE: EPI with blip-up/down acquisition (BUDA) can provide high-quality images with minimal distortions by using two readout trains with opposing phase-encoding gradients. Because of the need for two separate acquisitions, BUDA doubles the scan time and degrades the temporal resolution when compared to single-shot EPI, presenting a major challenge for many applications, particularly fMRI. This study aims at overcoming this challenge by developing an echo-shifted EPI BUDA (esEPI-BUDA) technique to acquire both blip-up and blip-down datasets in a single shot. METHODS: A 3D esEPI-BUDA pulse sequence was designed by using an echo-shifting strategy to produce two EPI readout trains. These readout trains produced a pair of k-space datasets whose k-space trajectories were interleaved with opposite phase-encoding gradient directions. The two k-space datasets were separately reconstructed using a 3D SENSE algorithm, from which time-resolved B0 -field maps were derived using TOPUP in FSL and then input into a forward model of joint parallel imaging reconstruction to correct for geometric distortion. In addition, Hankel structured low-rank constraint was incorporated into the reconstruction framework to improve image quality by mitigating the phase errors between the two interleaved k-space datasets. RESULTS: The 3D esEPI-BUDA technique was demonstrated in a phantom and an fMRI study on healthy human subjects. Geometric distortions were effectively corrected in both phantom and human brain images. In the fMRI study, the visual activation volumes and their BOLD responses were comparable to those from conventional 3D echo-planar images. CONCLUSION: The improved imaging efficiency and dynamic distortion correction capability afforded by 3D esEPI-BUDA are expected to benefit many EPI applications.

Expression characteristics and their functional role of IGFBP gene family in pan-cancer.

BACKGROUND: Insulin-like growth factor binding proteins (IGFBPs) are critical regulators of the biological activities of insulin-like growth factors. The IGFBP family plays diverse roles in different types of cancer, which we still lack comprehensive and pleiotropic understandings so far. METHODS: Multi-source and multi-dimensional data, extracted from The Cancer Genome Atlas (TCGA), Oncomine, Cancer Cell Line Encyclopedia (CCLE), and the Human Protein Atlas (HPA) was used for bioinformatics analysis by R language. Immunohistochemistry and qRT-PCR were performed to validate the results of the database analysis results. Bibliometrics and literature review were used for summarizing the research progress of IGFBPs in the field of tumor. RESULTS: The members of IGFBP gene family are differentially expressed in various cancer types. IGFBPs expression can affect prognosis of different cancers. The expression of IGFBPs expression is associated with multiple signal transduction pathways. The expression of IGFBPs is significantly correlated with tumor mutational burden, microsatellite instability, tumor stemness and tumor immune microenvironment. The qRT-PCR experiments verified the lower expression of IGFBP2 and IGFBP6 in gastric cancer and the lower expression of IGFBP6 in colorectal cancer. Immunohistochemistry validated a marked downregulation of IGFBP2 protein in gastric cancer tissues. The keywords co-occurrence analysis of IGFBP related publications in cancer showed relative research have been more concentrating on the potential of IGFBPs as tumor diagnostic and prognostic markers and developing cancer therapies. CONCLUSIONS: These findings provide frontier trend of IGFBPs related research and new clues for identifying novel therapeutic targets for various cancers.

Sclerostin antibody promotes bone formation through the Wnt/ß-catenin signaling pathway in femoral trochlear after patellar instability.

PURPOSE: The molecular mechanism of patellar instability (PI) remains unknown. The purpose of this study was to explore the function of SOST/sclerostin in PI and examine the effect of sclerostin antibody (Scl-Ab). MATERIALS AND METHODS: We randomly divided 60 male 3-week-old C57Bl/6 mice into four groups: sham, PI, Scl-Ab intraperitoneal injection (Scl-Ab IP), Scl-Ab intraarticular injection (Scl-Ab IA). PI was established in the latter three groups. The Scl-Ab IP/IA groups were administered with an intraperitoneal/intraarticular Scl-Ab injection (100 mg/kg, 20 µl), respectively, at 5-day intervals. Distal femurs were collected 30 days after the surgery. The SOST/sclerostin, ß-catenin, ALP, OPG and RANKL expression in distal femur were determined. Trochlear morphology and structural parameters of the trabecular and cortical bone compartments were determined by micro-CT. Further sub-regional analysis was performed. HE staining and Masson's trichrome staining were performed to evaluate cartilage changes. RESULTS: PI increased the expression of SOST/sclerostin and RANKL, and decreased ß-catenin, ALP and OPG levels, while Scl-Ab IP reversed these changes. Scl-Ab IP brought trochlear morphology closer to normality. Additionally, Scl-Ab IP significantly improved most of the bone parameters. Importantly, both PI and Scl-Ab IP acted mainly on trabecular bone. Histological analysis showed that Scl-Ab IP protected cartilage from degeneration. However, Scl-Ab IA did not protect against bone loss or cartilage degradation. CONCLUSIONS: SOST/sclerostin plays an important role in PI and systemic Scl-Ab use promotes bone formation through the Wnt/ß-catenin signaling pathway in the femoral trochlear after PI.

Predicting the Probability of Recurrence Based on Individualized Risk Factors After Primary Lateral Patellar Dislocation Treated Nonoperatively.

PURPOSE: To develop a comprehensive and effective personalized scoring system on the basis of demographic and clinical characteristics for predicting recurrence probability in patients with primary lateral patellar dislocation (LPD). METHODS: Participants included 261 primary patients with LPD with 2-year minimum follow-up from our hospital across 2013 to 2020. Demographic and clinical characteristics were collected retrospectively. The backward stepwise method was performed to identify independent predictors and construct a nomogram to predict the probability of recurrence. The predictive performance was assessed by receiver operating characteristic curves, calibration plots, and decision curve analysis. RESULTS: After variables selection, 6 independent predictors of recurrence (skeletal maturity, trochlear dysplasia, tibial tuberosity-trochlear groove distance, mechanical axis deviation, Insall-Salvati index, and patellar tilt) were enrolled in our model. Validation of this nomogram in both training and validation cohort revealed powerful predictive ability, with an area under the curve of 0.962 and 0.977, respectively. The nomogram also showed great calibration and good clinical practicability. CONCLUSIONS: Our study presented a nomogram that incorporates 6 independent risk factors (skeletal maturity, trochlear dysplasia, tibial tuberosity-trochlear groove distance, mechanical axis deviation, Insall-Salvati index, and patellar tilt), which can be conveniently used to accurately predicts the risk of recurrence after primary LPD in individual cases. LEVEL OF EVIDENCE: Level III, retrospective comparative prognostic study.

Isolated medial patellofemoral ligament reconstruction is valid to stabilize patellofemoral joint but uncertain to reduce patellar height in setting of lateral patellar dislocation and patella alta.

INTRODUCTION: Medial patellofemoral ligament reconstruction (MPFLR) is the most commonly used surgical treatment for patients with lateral patellar dislocation (LPD). It is still poorly understood whether or not MPFLR has a contributory effect on decreasing patellar height. MATERIALS AND METHODS: Forty-five patients who underwent isolated MPFLR for LPD and patella alta were evaluated with a mean follow-up period of 24 months (22-25 months). Knee joint functions were evaluated by Banff patellofemoral instability instrument (BPII) 2.0 scores and Kujala scores. Patellofemoral engagement and stability were assessed by the patella tilt angle (PTA) and patellar congruence angle (PCA) measured by CT scans, and the patellar-glide test. Patellar height was calculated on lateral radiographs according to three methods: Caton-Deschamps ratios (CDR), Insall-Salvati ratios (ISR), and Blackburne-Peel ratios (BPR). A threshold value of p < 0.05 denoted a statistically significant difference. RESULTS: Significant improvements were found in both BPII 2.0 scores, which increased from 41.7 to 77.8 (p < 0.001) and Kujala scores, which increased from 49.2 to 85.5 (p < 0.001). Post-operative PTAs and PCA decreased from 19.6 ± 8.8 to - 3.4 ± 6.2, and from 24.6 ± 7.3 to 13.1 ± 3.8 degrees respectively (p < 0.001). No patients showed lateral translation more than grade II in the patellar-glide test. Regarding patellar height, a tiny reduction (Δ = 0.02, Δ max = 0.09) was discovered in using CDR (p = 0.027), rather than ISR or BPR. All measurements of radiographic indices had an excellent intra- and inter-rater reliability (ICC > 0.75). CONCLUSIONS: Isolated anatomic MPFLR is sufficient to achieve good clinical outcomes, as well as patellofemoral stability and high rates of return-to-sport. However, it is unclear if the reconstructed MPFL has a contributory effect on reducing patellar height.

Optimization of pseudo-continuous arterial spin labeling at 7T with parallel transmission B1 shimming.

PURPOSE: To optimize pseudo-continuous arterial spin labeling (pCASL) for 7 T, and to further improve the labeling efficiency with parallel RF transmission transmit B1 ( B1+ ) shimming. METHODS: pCASL parameters were optimized based on B1+/B0 field distributions at 7 T with simulation. To increase labeling efficiency, the B1+ amplitude at inflowing arteries was increased with parallel RF transmission B1+ shimming. The "indv-shim" with shimming weights calculated for each individual subject, and the "univ-shim" with universal weights calculated on a group of 12 subjects, were compared with circular polarized (CP) shim. The optimized pCASL sequences with three B1+ shimming modes (indv-shim, univ-shim, and CP-shim) were evaluated in 6 subjects who underwent two repeated scans 24 hours apart, along with a pulsed ASL sequence. Quantitative metrics including mean B1+ amplitude, perfusion, and intraclass correlation coefficient were calculated. The optimized 7T pCASL was compared with standard 3T pCASL on 5 subjects, using spatial SNR and temporal SNR. RESULTS: The optimal pCASL parameter set (RF duration/gap = 300/250 us, Gave=0.6mT/m,gRatio=10 ) achieved robust perfusion measurement in the presence of B1+/B0 inhomogeneities. Both indv-shim and univ-shim significantly increased B1+ amplitude compared with CP-shim in simulation and in vivo experiment (P < .01). Compared with CP-shim, perfusion signal was increased by 9.5% with indv-shim (P < .05) and by 5.3% with univ-shim (P = .35). All three pCASL sequences achieved fair to good repeatability (intraclass correlation coefficient ≥ 0.5). Compared with 3T pCASL, the optimized 7T pCASL achieved 78.3% higher spatial SNR and 200% higher temporal SNR. CONCLUSION: The optimized pCASL achieved robust perfusion imaging at 7 T, while both indv-shim and univ-shim further increased labeling efficiency.

Recent Technical Developments in ASL: A Review of the State of the Art.

This review article provides an overview of a range of recent technical developments in advanced arterial spin labeling (ASL) methods that have been developed or adopted by the community since the publication of a previous ASL consensus paper by Alsop et al. It is part of a series of review/recommendation papers from the International Society for Magnetic Resonance in Medicine Perfusion Study Group. Here, we focus on advancements in readouts and trajectories, image reconstruction, noise reduction, partial volume correction, quantification of nonperfusion parameters, fMRI, fingerprinting, vessel selective ASL, angiography, deep learning, and ultrahigh field ASL. We aim to provide a high level of understanding of these new approaches and some guidance for their implementation, with the goal of facilitating the adoption of such advances by research groups and by MRI vendors. Topics outside the scope of this article that are reviewed at length in separate articles include velocity selective ASL, multiple-timepoint ASL, body ASL, and clinical ASL recommendations.

Electro-Acupuncture Pretreatment Ameliorates Anesthesia and Surgery-Induced Cognitive Dysfunction Via Inhibiting Mitochondrial Injury and nEuroapoptosis in Aged Rats.

Postoperative cognitive dysfunction (POCD) remains one of the most common complications following anesthesia and surgery (AS) in the elderly population. Calcium-mediated mitochondrial injury has been proved to induce cognitive impairment in a variety of neurologic diseases. In the current study we determined whether electro-acupuncture (EA) pretreatment ameliorated AS-induced POCD in aged rats, as well as the underlying mechanism. Eighty SD rats (18 months, male) were randomly assigned into four groups (n = 20): C, C + EA, POCD and EA + POCD. Rats in Group POCD and EA + POCD were subjected to exploratory laparotomy under sevoflurane anesthesia. Rats of Group C + EA and EA + POCD received a 5-day EA stimulation at Hegu, Neiguan and Zusanli acupoints before AS. At 3rd day after AS, open field test along with Morris water maze test were employed to examine the cognitive function of aged rats. Then hippocampal tissues were stripped and hippocampal neuronal amount, expression level of cleaved caspase-9 level, cytochrome c (Cyt C), cleaved caspase-3 level, Bcl-2, Bax, ROS expression level, apoptosis rate, mitochondrial membrane potential (MMP), cytosolic calcium concentration ([Ca2+]c), opening level of mitochondrial permeability transition pore (mPTP) and ultrastructure of hippocampal neurons were detected separately. EA pretreatment inhibited AS-induced cognitive dysfunction. Furthermore, EA pretreatment decreased level of [Ca2+]c, MMP, mPTP, ROS and hippocampal mitochondrial disruption and enhanced neuronal amount. In addition, EA pretreatment notably reduced the AS-induced increased level of cleaved caspase-9, cleaved caspase-3 and expression of Cyt c, Bax/Bcl-2 ratio, as well as neuronal apoptosis rate in aged rats. EA pretreatment ameliorates AS-induced POCD in aged rats, the potential mechanism may be associated with inhibiting calcium overload and ameliorating mitochondrial injury and neuroapoptosis in hippocampal neurons.

RNA-sequencing reveals the expression profiles of tsRNAs and their potential carcinogenic role in cholangiocarcinoma.

BACKGROUND: Recently, the incidence of cholangiocarcinoma (CCA) has gradually increased. As CCA has a poor prognosis, the ideal survival rate is scarce for patients. The abnormal expressed tsRNAs may regulate the progression of a variety of tumors, and tsRNAs is expected to become a new diagnostic biomarker of cancer. However, the expression of tsRNAs is obscure and should be elucidated in CCA. METHODS: High-throughput RNA sequencing technology (RNA-seq) was utilized to determine the overall expression profiles of tsRNAs in three pairs CCA and adjacent normal tissues and to screen the tsRNAs that were differentially expressed. The target genes of dysregulated tsRNAs were predicted and the biological effects and potential signaling pathways of these target genes were explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate 11 differentially expressed tRFs with 12 pairs CCA and adjacent normal tissues. RESULTS: High-throughput RNA-seq totally demonstrated 535 dysregulated tsRNAs, of which 241 tsRNAs were upregulated, such as tRF-21-YLKZKWE5D，tRF-16-9NF5W8B，tRF-27-78YLKZKWE52，tRF-19-RLXN48KP，tRF-33-IK9NJ4S2I7L7DV，tRF-19-F8DHXYIV, and 294 tsRNAs were downregulated (tRF-20-739P8WQ0, tRF-34-JJ6RRNLIK898HR, tRF-17-VL8RPY5, tRF-23-YP9LON4VDP, tRF-39-EH623K76IR3DR2I2, tRF-17-18YKISM, tRF-19-Q1Q89PJZ, etc.) in CCA compared with adjacent normal tissues (|log2 [fold change] | ≥ 1 and p value <0.05). GO and KEGG enrichment analyses indicated that the target genes of dysregulated tRFs (tRF-34-JJ6RRNLIK898HR, tRF-38-0668K87SERM492V, and tRF-39-0668K87SERM492E2) were mainly enriched in the Notch signaling pathway, Hippo signaling pathway, cAMP signaling pathway and in growth hormone synthesis, secretion and action, etc. qRT-PCR result showed that tRF-34-JJ6RRNLIK898HR/tRF-38-0668K87SERM492V/tRF-39-0668K87SERM492E2 was downregulated (p = 0.021), and tRF-20-LE2WMK81 was upregulated in CCA (p = 0.033). CONCLUSION: Differentially expressed tRFs in CCA are enriched in many pathways associated with neoplasms, which may impact the tumor progression and have potential to be diagnostic biomarkers and therapeutic targets of CCA.

Perioperative stroke in patients undergoing spinal surgery: a retrospective cohort study.

BACKGROUND: The incidence of perioperative stroke following spinal surgery, including ischemic and hemorrhagic stroke, has not been fully investigated in the Chinese population. Whether specific spinal or emergency/elective procedures are associated with perioperative stroke remains controversial. This study aimed to investigate the incidence of perioperative stroke, health economic burden, clinical outcomes, and associated risk factors. METHOD: A retrospective cohort study using an electronic hospital information system database was conducted from Jan 1, 2015, to Jan 1, 2021, in a tertiary hospital in China. Patients aged ≥18 years who had undergone spinal surgery were included in the study. We recorded patient demographics, comorbidities, and health economics data. Clinical outcomes included perioperative stroke during hospitalization and associated risk factors. The patients' operative data, anesthetic data, and clinical manifestations were recorded. RESULT: A total of 17,408 patients who had undergone spinal surgery were included in this study. Twelve patients had perioperative stroke, including seven ischemic stroke (58.3%) and five hemorrhagic stroke (41.7%). The incidence of perioperative stroke was 0.07% (12/17,408). In total, 12 stroke patients underwent spinal fusion. Patients with perioperative stroke were associated with longer hospital stay (38.33 days vs. 9.78 days, p < 0.001) and higher hospital expenses (RMB 175,642 vs. RMB 81,114, p < 0.001). On discharge, 50% of perioperative patients had severe outcomes. The average onset time of perioperative stroke was 1.3 days after surgery. Stroke history (OR 146.046, 95% CI: 28.102-759.006, p < 0.001) and hyperlipidemia (OR 4.490, 95% CI: 1.182-17.060, p = 0.027) were associated with perioperative stroke. CONCLUSION: The incidence of perioperative stroke of spinal surgery in a tertiary hospital in China was 0.07%, with a high proportion of hemorrhagic stroke. Perioperative stroke patients experienced a heavy financial burden and severe outcomes. A previous stroke history and hyperlipidemia were associated with perioperative stroke.

Emergency Braking Evoked Brain Activities during Distracted Driving.

Electroencephalogram (EEG) was used to analyze the mechanisms and differences in brain neural activity of drivers in visual, auditory, and cognitive distracted vs. normal driving emergency braking conditions. A pedestrian intrusion emergency braking stimulus module and three distraction subtasks were designed in a simulated experiment, and 30 subjects participated in the study. The common activated brain regions during emergency braking in different distracted driving states included the inferior temporal gyrus, associated with visual information processing and attention; the left dorsolateral superior frontal gyrus, related to cognitive decision-making; and the postcentral gyrus, supplementary motor area, and paracentral lobule associated with motor control and coordination. When performing emergency braking under different driving distraction states, the brain regions were activated in accordance with the need to process the specific distraction task. Furthermore, the extent and degree of activation of cognitive function-related prefrontal regions increased accordingly with the increasing task complexity. All distractions caused a lag in emergency braking reaction time, with 107.22, 67.15, and 126.38 ms for visual, auditory, and cognitive distractions, respectively. Auditory distraction had the least effect and cognitive distraction the greatest effect on the lag.

Involvement of CXCL17 and GPR35 in Gastric Cancer Initiation and Progression.

The expression of CXC motif chemokine 17 (CXCL17) and its reported membrane receptor G-protein-coupled receptor 35 (GPR35) in different gastric pathological lesions and their clinical implications are largely unknown. In this study, a total of 860 pathological sections were immune-stained with either anti-CXCL17 or anti-GPR35 antibodies. Their expression was scored within the area of the normal gastric gland of non-atrophic gastritis (NAG-NOR), intestinal metaplasia of atrophic gastritis (AG-IM), IM adjacent to GC (GC-IM), and GC tissue. The clinical significance and potential function of CXCL17 and GPR35 were explored using multiple methods. Our results suggested that CXCL17 expression was gradually upregulated during the pathological progress of gastric diseases (NAG-NOR < AG-IM < GC-IM), but significantly downregulated when GC occurred. GPR35 had a similar expression pattern but its expression in GC remained abundant. High CXCL17 expression in GC was associated with less malignant behavior and was an independent biomarker of favorable prognosis. Overexpressing CXCL17 in HGC27 cells significantly upregulated CCL20 expression. TCGA analysis identified that CXCL17 was negatively correlated with some cancer-promoting pathways and involved in inflammatory activities. CTRP analysis revealed that gastric cell lines expressing less CXCL17 and were more sensitive to the CXCR2 inhibitor SB-225002.

Hyperbranched Polyborate: A Non-conjugated Fluorescent Polymer with Unanticipated High Quantum Yield and Multicolor Emission.

Non-conjugated fluorescent polymers have attracted great attention due to their excellent biocompatibility and environmental friendliness. However, it remains a huge challenge to obtain a polymer with high fluorescence quantum yield (QY) and multicolor emission simultaneously. Herein, we reported three kinds of nonaromatic hyperbranched polyborates (P1-P3) with multicolor emission, surprisingly, P2 also exhibits an unanticipated high QY (54.1 %). The natural bond orbital (NBO) analysis and density functional theory (DFT) calculation results revealed that the synergistic effect of rigid BO3 planar and flexible carbon chain, as well as the through-space dative bond in supramolecular aggregate, were the key factors contributing to the ultrahigh QY of P2. Moreover, the applications of P2 in Fe3+ ions detection and cell imaging were also investigated. This work provides a new perspective for designing non-conjugated fluorescent polymers with both high QY and multicolor emission.

Laminar perfusion imaging with zoomed arterial spin labeling at 7 Tesla.

Laminar fMRI based on BOLD and CBV contrast at ultrahigh magnetic fields has been applied for studying the dynamics of mesoscopic brain networks. However, the quantitative interpretations of BOLD/CBV fMRI results are confounded by different baseline physiology across cortical layers. Here we introduce a novel 3D zoomed pseudo-continuous arterial spin labeling (pCASL) technique at 7T that offers the capability for quantitative measurements of laminar cerebral blood flow (CBF) both at rest and during task activation with high spatial specificity and sensitivity. We found arterial transit time in superficial layers is ∼100 ms shorter than in middle/deep layers revealing the time course of labeled blood flowing from pial arteries to downstream microvasculature. Resting state CBF peaked in the middle layers which is highly consistent with microvascular density measured from human cortex specimens. Finger tapping induced a robust two-peak laminar profile of CBF increases in the superficial (somatosensory and premotor input) and deep (spinal output) layers of M1, while finger brushing task induced a weaker CBF increase in superficial layers (somatosensory input). This observation is highly consistent with reported laminar profiles of CBV activation on M1. We further demonstrated that visuospatial attention induced a predominant CBF increase in deep layers and a smaller CBF increase on top of the lower baseline CBF in superficial layers of V1 (feedback cortical input), while stimulus driven activity peaked in the middle layers (feedforward thalamic input). With the capability for quantitative CBF measurements both at baseline and during task activation, high-resolution ASL perfusion fMRI at 7T provides an important tool for in vivo assessment of neurovascular function and metabolic activities of neural circuits across cortical layers.

Pepsinogen C expression-related lncRNA/circRNA/mRNA profile and its co-mediated ceRNA network in gastric cancer.

The expression of pepsinogen C (PGC) is considered an ideal negative biomarker of gastric cancer, but its pathological mechanisms remain unclear. This study aims to analyze competing endogenous RNA (ceRNA) networks related to PGC expression at a post-transcriptional level and build an experimental basis for studying the role of PGC in the progression of gastric cancer. RNA sequencing technology was used to detect the differential expression (DE) profiles of PGC-related long non-coding (lnc)RNAs, circular (circ)RNAs, and mRNAs. Ggcorrplot R package and online database were used to construct DElncRNAs/DEcircRNAs co-mediated PGC expression-related ceRNA networks. In vivo and in vitro validations were performed using quantitative reverse transcription-PCR (qRT-PCR). RNA sequencing found 637 DEmRNAs, 698 DElncRNAs, and 38 DEcircRNAs. The PPI network of PGC expression-related mRNAs consisted of 503 nodes and 1179 edges. CFH, PPARG, and MUC6 directly interacted with PGC. Enrichment analysis suggested that DEmRNAs were mainly enriched in cancer-related pathways. Eleven DElncRNAs, 13 circRNAs, and 35 miRNA-mRNA pairs were used to construct ceRNA networks co-mediated by DElncRNAs and DEcircRNAs that were PGC expression-related. The network directly related to PGC was as follows: SNHG16/hsa_circ_0008197-hsa-mir-98-5p/hsa-let-7f-5p/hsa-let-7c-5p-PGC. qRT-PCR validation results showed that PGC, PPARG, SNHG16, and hsa_circ_0008197 were differentially expressed in gastric cancer cells and tissues: PGC positively correlated with PPARG (r = 0.276, P = 0.009), SNHG16 (r = 0.35, P = 0.002), and hsa_circ_0008197 (r = 0.346, P = 0.005). PGC-related DElncRNAs and DEcircRNAs co-mediated complicated ceRNA networks to regulate PGC expression, thus affecting the occurrence and development of gastric cancer at a post-transcriptional level. Of these, the network directly associated with PGC expression was a SNHG16/hsa_circ_0008197-mir-98-5p/hsa-let-7f-5p/hsa-let-7c-5p - PGC axis. This study may form a foundation for the subsequent exploration of the possible regulatory mechanisms of PGC in gastric cancer.

Optimization of adiabatic pulses for pulsed arterial spin labeling at 7 tesla: Comparison with pseudo-continuous arterial spin labeling.

PURPOSE: To optimize and evaluate adiabatic pulses for pulsed arterial spin labeling at ultrahigh field 7 tesla. METHODS: Four common adiabatic inversion pulses, including hyperbolic secant, wideband uniform rate smooth truncation, frequency offset corrected inversion, and time-resampled frequency offset corrected inversion pulses, were optimized based on a custom-defined loss function that included labeling efficiency and inversion band uniformity. The optimized pulses were implemented in flow-sensitive alternating inversion recovery sequences and tested on phantom and 11 healthy volunteers with 2 constraints: 1) specific absorption rate normalized; and 2) equal peak RF amplitude, respectively. A pseudo-continuous arterial spin labeling sequence was implemented for comparison. Quantitative metrics such as perfusion and relative labeling efficiency versus residual tissue signal were calculated. RESULTS: Among the 4 pulses, the wideband uniform rate smooth truncation pulse yielded the lowest loss in simulation and achieved a good balance between labeling efficiency and residual tissue signal from both phantom and in vivo experiments. Wideband uniform rate smooth truncation-pulsed arterial spin labeling showed significantly higher relative labeling efficiency compared to the other sequences (P < .01), whereas the perfusion signal was increased by 40% when the highest B1+ amplitude was used. The 4 pulsed arterial spin labeling sequences yielded comparable perfusion signals compared to pseudo-continuous arterial spin labeling but with less than half the specific absorption rate. CONCLUSION: Optimized wideband uniform rate smooth truncation pulse with the highest B1+ amplitude allowed was recommended for 7 tesla pulsed arterial spin labeling.