METTL3 as a novel diagnosis and treatment biomarker and its association with glycolysis, cuproptosis and ceRNA in oesophageal carcinoma.

METTL3 has been shown to be involved in regulating a variety of biological processes. However, the relationship between METTL3 expression and glycolysis, cuproptosis-related genes and the ceRNA network in oesophageal carcinoma (ESCA) remains unclear. ESCA expression profiles from databases were obtained, and target genes were identified using differential analysis and visualization. Immunohistochemistry (IHC) staining assessed METTL3 expression differences. Functional enrichment analysis using GO, KEGG and GSEA was conducted on the co-expression profile of METTL3. Cell experiments were performed to assess the effect of METTL3 interference on tumour cells. Correlation and differential analyses were carried out to assess the relationship between METTL3 with glycolysis and cuproptosis. qRT-PCR was used to validate the effects of METTL3 interference on glycolysis-related genes. Online tools were utilized to screen and construct ceRNA networks based on the ceRNA theory. METTL3 expression was significantly higher in ESCA compared to the controls. The IHC results were consistent with the above results. Enrichment analysis revealed that METTL3 is involved in multiple pathways associated with tumour development. Significant correlations were observed between METTL3 and glycolysis-related genes and cuproptosis-related gene. Experiments confirmed that interfered with METTL3 significantly inhibited glucose uptake and lactate production in tumour cells, and affected the expression of glycolytic-related genes. Finally, two potential ceRNA networks were successfully predicted and constructed. Our study establishes the association between METTL3 overexpression and ESCA progression. Additionally, we propose potential links between METTL3 and glycolysis, cuproptosis and ceRNA, presenting a novel targeted therapy strategy for ESCA.

Programmable Optoelectronic Synaptic Transistors Based on MoS2/Ta2NiS5 Heterojunction for Energy-Efficient Neuromorphic Optical Operation.

The optoelectronic synaptic transistors with various functions, broad spectral perception, and low power consumption are an urgent need for the development of advanced optical neural network systems. However, it remains a great challenge to realize the functional diversification of the systems on a single device. 2D van der Waals (vdW) materials can combine unique properties by stacking with each other to form heterojunctions, which may provide a strategy for solving this problem. Herein, an all-2D vdW heterojunction-based programmable optoelectronic synaptic transistor based on MoS2/Ta2NiS5 heterojunctions is demonstrated. The device implements reconfigurable, multilevel non-volatile memory (NVM) states through sequential modulation of multiple optical and electrical stimuli to achieve broadband (532-808 nm), energy-efficient (17.2 fJ), hetero-synaptic functionality in a bionic manner. The intrinsic working mechanisms of the photogating effect caused by band alignment and the interfacial trapping defect modulation induced by gate voltage are revealed by Kelvin-probe force microscopy (KPFM) measurements and carrier transport analysis. Overall, the (opto)electronic synaptic weight controllability for combined in-sensor and in-memory logic processors is realized by the heterojunction properties. The proposed findings facilitate the technical realization of generic all 2D hetero-synapses for future artificial vision systems, opto-logical systems, and Internet of Things (IoT) entities.

Electrochemical Platform Based on the Bi2Te3 Family of Topological Insulators for the Detection of SARS-CoV-2 Pathogenic Factors.

Accurate and rapid detection of the causative agent of a disease is of great importance in controlling the spread of the disease. This work developed a biosensor with the Bi2Te3 family of topological insulators for detection of the SARS-CoV-2 virulence factor. The Bi2Te3 family is a three-dimensional topological insulator material with topologically protected surface states; the presence of these surface states facilitates charge transfer between the electrode and electrolyte interface. Compared with the detection performance of Bi2Se3, BiSbTeSe2, and a trivial insulator like Sb2Se3, Bi2Te3 exhibits superior characteristics. A Bi2Te3 electrochemical detection platform is utilized to fabricate a sensor that can detect SARS-CoV-2 DNA, RNA, and antigen for label-free target detection. The concentration range of DNA detection by the biosensor using Bi2Te3 is between 1.0 × 10-15 and 1.0 × 10-10 M, and the detection limit can reach 1.41 × 10-16 M. Furthermore, it exhibits excellent selectivity and maintains good stability even after being stored for 14 days. This study provides a new way to apply topological insulator materials in the field of biosensors and use their unique electronic structure to improve the accuracy and speed of disease detection and diagnosis.

eIF6 is potential diagnostic and prognostic biomarker that associated with 18F-FDG PET/CT features and immune signatures in esophageal carcinoma.

BACKGROUND: Although eukaryotic initiation factor 6 (eIF6) is a novel therapeutic target, data on its importance in the development of esophageal carcinoma (ESCA) remains limited. This study evaluated the correlation between eIF6 expression and metabolic analysis using fluorine-18 fluorodeoxyglucose (18F-FDG) -Positron emission tomography (PET) and immune gene signatures in ESCA. METHODS: This study employed The Cancer Genome Atlas (TCGA) to analyze the expression and prognostic value of eIF6, as well as its relationship with the immune gene signatures in ESCA patients. The qRT-PCR and Western blot analyses were used to profile the expression of eIF6 in ESCA tissues and different ESCA cell lines. The expression of tumor eIF6 and glucose transporter 1 (GLUT1) was examined using immunohistochemical tools in fifty-two ESCA patients undergoing routine 18F-FDG PET/CT before surgery. In addition, the cellular responses to eIF6 knockdown in human ESCA cells were assessed via the MTS, EdU, flow cytometry and wound healing assays. RESULTS: Our data demonstrated that compared with the normal esophageal tissues, eIF6 expression was upregulated in ESCA tumor tissues and showed a high diagnostic value with an area under curve of 0.825 for predicting ESCA. High eIF6 expression was significantly correlated with shorter overall survival of patients with esophagus adenocarcinoma (p = 0.038), but not in squamous cell carcinoma of the esophagus (p = 0.078). In addition, tumor eIF6 was significantly associated with 18F-FDG PET/CT parameters: maximal and mean standardized uptake values (SUVmax and SUVmean) and total lesion glycolysis (TLG) (rho = 0.458, 0.460, and 0.300, respectively, p < 0.01) as well as GLUT1 expression (rho = 0.453, p < 0.001). A SUVmax cutoff of 18.2 led to prediction of tumor eIF6 expression with an accuracy of 0.755. Functional analysis studies demonstrated that knockdown of eIF6 inhibited ESCA cell growth and migration, and fueled cell apoptosis. Moreover, the Bulk RNA gene analysis revealed a significant inverse association between eIF6 and the tumor-infiltrating immune cells (macrophages, T cells, or Th1 cells) and immunomodulators in the ESCA microenvironment. CONCLUSION: Our study suggested that eIF6 might serve as a potential prognostic biomarker associated with metabolic variability and immune gene signatures in ESCA tumor microenvironment.

Immune synergistic mechanism of recombinant plasmid adjuvant containing chicken IL-4 and IL-2 fusion genes on chicken coccidia live vaccine.

The recombinant plasmid pCI-IL-4-IL-2-EGFP containing fusion genes of chicken IL-4 and IL-2 can be used as an adjuvant to enhance the anticoccidiosis effect of the chicken coccidia live vaccine. The chickens were divided into 3 groups: blank control group, vaccine + pCI-IL-4-IL-2-EGFP adjuvant coimmunization group, and vaccine-only group to investigate the immune synergy mechanism of recombinant plasmid adjuvant pCI-IL-4-IL-2-EGFP. The expressions of IL-2, IL-4, TNF-α, and IFN-γ in chicken sera and tissues were detected by ELISA and RT-qPCR, and the proliferation of T and B lymphocytes and antigen presenting cells (APC) in chicken immune organs and intestines were detected by acid alpha-naphthalase (ANAE) staining, methyl green pyronine (MGP) staining, and immunofluorescence (IF) staining, respectively. Results showed that the mRNA expression of IL-2, IL-4, IFN-γ and the number of activated T and B lymphocytes were significantly upregulated in the spleen and cecum tonsils of chickens in vaccine + pCI-IL-4-IL-2-EGFP group compared with the vaccine-only group on 7 d after vaccination (P < 0.05). Protein contents of IL-2, IL-4 and TNF-α in vaccine + pCI-IL-4-IL-2-EGFP group were significantly increased compared to vaccine-only group on 28 d of inoculation (P < 0.05). The number of T and B lymphocytes and APC in chickens of the vaccine+ pCI-IL-4-IL-2-EGFP group was significantly higher than that of the vaccine-only group in cecum tonsils, thymus and spleen after 14 and 28 d of inoculation (P < 0.05). All results revealed that pCI-IL-4-IL-2-EGFP adjuvant enhanced the immune response of chicken coccidia live vaccine by upregulating the expression of IL-2, IL-4, TNF-α, and IFN-γ and promoting the proliferation of T, B lymphocytes and APCs in chicken intestines and immune organ sites. Moreover, our study provides a theoretical basis for the clinical application of cytogenic plasmids as adjuvants.

Environmental-Friendly Ag2S QD-Multilayer MoSe2 van Der Waals Heterostructure for High-Performance Broadband Photodetection.

Broadband photodetectors have drawn intensive attention owing to their wide application prospects in optical communication, imaging, astronomy, and so on. Two-dimensional transition-metal dichalcogenides (TMDs) are considered as highly potential candidates for photodetection applications, benefiting from their excellent photoelectric properties. However, most of the photodetectors based on TMDs suffer from low performance in the near-infrared (NIR) region due to the weak optical absorption efficiency near their absorption band edge, which severely constrains their usage for broadband optoelectronics. Here, by taking advantage of the high absorption coefficient and environment-friendly property of Ag2S quantum dots (QDs), the hybrid of multilayer MoSe2/Ag2S QDs is demonstrated with a high-performance broadband photodetection capability (532-1270 nm). The favorable energy band alignment of MoSe2/Ag2S QDs facilitates effective separation and collection of photogenerated carriers, and the heterostructure device exhibits significant enhancement of performance compared to the bare MoSe2 device. High responsivity, detectivity, and external quantum efficiency of 25.5 A/W, 1.45 × 1011 Jones, and 1070% are obtained at a low working voltage of 1 V under 980 nm illumination. The responsivity of the device can reach up to 1.2 A/W at 1270 nm wavelength, which is competitive to the commercial NIR photodetectors. Meanwhile, broadband imaging capability is demonstrated. Our work may open up a facile and eco-friendly approach to construct high-performance broadband photodetectors for next-generation compact optoelectronic applications.

Pan-cancer analysis reveals correlation between RAB3B expression and tumor heterogeneity, immune microenvironment, and prognosis in multiple cancers.

RAB3B is essential for the transportation and secretion within cells. Its increased expression is linked to the development and progression of various malignancies. However, understanding of RAB3B's involvement in carcinogenesis is mostly limited to specific cancer subtypes. Hence, exploring RAB3B's regulatory roles and molecular mechanisms through comprehensive cancer datasets might offer innovative approaches for managing clinical cancer. To examine the potential involvement of RAB3B in the development of cancer, we analyzed data from various sources including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), cBioPortal, HPA, UALCAN, and tissue microarray (TAM). Using bioinformatics techniques, we examined the correlation between RAB3B expression and prognosis, tumor heterogeneity, methylation modifications, and immune microenvironment across different cancer types. Our findings indicate that elevated RAB3B expression can independently predict prognosis in many tumors and has moderate accuracy for diagnosing most cancers. In most cancer types, we identified RAB3B mutations that showed a significant correlation with tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and microsatellite instability (MSI). Abnormal DNA methylation patterns were also observed in most cancers compared to normal tissues. Additionally, we found significant correlations between RAB3B expression, immune cell infiltration, and immune scores across various cancers. Through pan-cancer analysis, we observed significant differences in RAB3B expression levels between tumors and normal tissues, making it a potential primary factor for cancer diagnosis and prognosis. The IHC results revealed that the expression of RAB3B in six types of tumors was consistent with the results of the pan-cancer analysis of the database. Furthermore, RAB3B showed potential associations with tumor heterogeneity and immunity. Thus, RAB3B can be utilized as an auxiliary diagnostic marker for early tumor detection and a prognostic biomarker for various tumor types.

Electrochemical biosensor for sensitive detection of SARS-CoV-2 gene fragments using Bi2Se3 topological insulator.

In this study, we have designed an electrochemical biosensor based on topological material Bi2Se3 for the sensitive detection of SARS-CoV-2 in the COVID-19 pandemic. Flake-shaped Bi2Se3 was obtained directly from high-quality single crystals using mechanical exfoliation, and the single-stranded DNA was immobilized onto it. Under optimal conditions, the peak current of the differential pulse voltammetry method exhibited a linear relationship with the logarithm of the concentration of target-complementary-stranded DNA, ranging from 1.0 × 10-15 to 1.0 × 10-11 M, with a detection limit of 3.46 × 10-16 M. The topological material Bi2Se3, with Dirac surface states, enhanced the signal-to-interference plus noise ratio of the electrochemical measurements, thereby improving the sensitivity of the sensor. Furthermore, the electrochemical sensor demonstrated excellent specificity in recognizing RNA. It can detect complementary RNA by amplifying and transcribing the initial DNA template, with an initial DNA template concentration ranging from 1.0 × 10-18 to 1.0 × 10-15 M. Furthermore, the sensor also effectively distinguished negative and positive results by detecting splitting-synthetic SARS-CoV-2 pseudovirus with a concentration of 1 copy/µL input. Our work underscores the immense potential of the electrochemical sensing platform based on the topological material Bi2Se3 in the detection of pathogens during the rapid spread of acute infectious diseases.

EtROP38 suppresses apoptosis of host cells infected with Eimeria tenella by inhibition of the p38MAPK pathway.

Coccidiosis is an important parasitic disease that has serious adverse effects on the global poultry industry. The mechanism by which the pathogenic factors of Eimeria tenella damage host cells is unknown. Some kinases from the rhoptry compartment can regulate apoptosis of host cells. This study focused on revealing the role and critical nodes of E. tenella rhoptry protein (EtROP) 38 in controlling the apoptosis of host cells via the P38 mitogen-activated protein kinase (MAPK) signaling pathway. The cells were treated with EtROP38 protein, siRNA p38MAPK, or both. The rate of infection, apoptosis, and the dynamic changes in the expression and activation of key factor genes of the P38MAPK signaling pathway in host cells infected with E. tenella were measured. The results showed that the addition of EtROP38 and/or knockdown of the host cells p38 gene reduced the apoptosis rate of cecal epithelial cells (CECS), decreased the mRNA expressions of p38, p53, c-myc, c-fos, and c-jun and increased the expression of p65, decreased the protein expressions of c-myc, c-fos, and c-jun, decreased the p38 protein phosphorylation level, and increased the p65 protein phosphorylation level in CECS. When E. tenella was inoculated for 4-96 h, the addition of Et ROP38 and/or host cell p38 knockdown both increased the infection rate of host cells, and this effect was more pronounced with the addition of EtROP38 with the host cell p38 knockdown. These observations indicate that E. tenella can inhibits the activation of the p38MAPK signaling pathway in host cells via EtROP38, which suppresses apoptosis in host cells.

Prevention and control of chicken coccidiosis construction of recombinant Lactococcus lactis expressing chicken IL-4 and IL-2 fusion protein and its immune synergistic effect on chicken coccidia live vaccine.

Intestinal mucosa injury and loss of weight gain are unavoidable while using live vaccine strain to prevent chicken coccidiosis. In this study, recombinant Lactococcus lactis NZ3900/pNZ8149-IL-4-IL-2, expressing the fusion protein of chicken IL-4 and IL-2, was constructed using food-grade NICE expression system, trying to develop a possible oral immune adjuvant to enhance the immune effect of the live vaccine against chicken coccidiosis and minimize its adverse effects. Chickens were given different doses of recombinant L. lactis together with the live vaccine, then experimently attacked with coccidia virulent strains. Results showed that weight gains of co-immunization groups, given both 1 × 109 or 1 × 1010 CFU recombinant L. lactis and the live vaccine, were significantly higher than the vaccine-only group (P<0.05), while intestinal lesion scores of duodenum, jejunum, and cecum were significantly lower than the vaccine-only group (P<0.05), so was the oocyst shedding. The anticoccidial indexes (ACI) of the co-immunized groups given 1 × 109 and 1 × 1010 CFU recombinant L. lactis were 187.85 and 193.33, respectively, higher than 174.61 of the vaccine-only group. In addition, chickens in co-immunization groups gained more body weight than the vaccine-only group before being challenged with the virulent strains (P<0.05). All the results indicated that the constructed recombinant L. lactis NZ3900/ pNZ8149-IL-4-IL-2 exhibited an immune synergistic function to coccidiosis live vaccine, and could alleviate its adverse effect affecting weight gain. The application of the recombinant L. lactis showed the potency to lift the anticoccidial efficiency of the live vaccine from a medium level to a high level.

SLC17A9 as a prognostic biomarker correlated with immune infiltrates in human non-small cell lung cancer.

The vesicular nucleotide transporter (SLC17A9) has been overexpressed in various cancers. Nonetheless, little is known about its influence on non-small cell lung cancer (NSCLC), including human lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Integrative bioinformatics analysis was performed to investigate the prognostic significance and underlying mechanisms of SLC17A9 in patients with NSCLC. Here, we found that SLC17A9 up-regulation was significantly correlated with overall survival in LUAD and LUSC (P < 0.05). Gene set enrichment analysis and protein-protein interaction results revealed that SLC17A9 up-regulation was linked to metabolic process, the hallmark of MYC targets, DNA repair, coagulation and complement. SLC17A9 expression was negatively associated with overall survival and positively related to most LUSC immune cells and immunoinhibitor (20/23), particularly immuno A2aR, PD-1, and CTLA-4 (P < 0.001). High SLC17A9 was associated with infiltrating levels of B cells, CD4+ T cells, M1 macrophages, and T cell exhaustion checkpoints such as PD-1, CTLA4, and LAG3 in LUAD. Moreover, Real-time PCR, MTS assay, EdU assay, ATP production assays and cell cycle analysis were performed to validate SLC17A9 knockdown in LUAD cells. SLC17A9 knockdown significantly inhibited cell proliferation and ATP levels by affecting P2X1, Cytochrome C, and STAT3 expression in lung cancer cells. In conclusion, the present study suggested that SLC17A9 could potentially serve as a prognostic biomarker and correlated with immune infiltrates in LUAD and LUSC.

Microstructure abnormalities of the diffusion quantities in children with attention-deficit/hyperactivity disorder: an AFQ and TBSS study.

Objective: To explore the specific alterations of white matter microstructure in children with attention-deficit/hyperactivity disorder (ADHD) by automated fiber quantification (AFQ) and tract-based spatial statistics (TBSS), and to analyze the correlation between white matter abnormality and impairment of executive function. Methods: In this prospective study, a total of twenty-seven patients diagnosed with ADHD (20 males, 7 females; mean age of 8.89 ± 1.67 years) and twenty-two healthy control (HC) individuals (11 males, 11 females, mean age of 9.82 ± 2.13 years) were included. All participants were scanned with diffusion kurtosis imaging (DKI) and assessed for executive functions. AFQ and TBSS analysis methods were used to investigate the white matter fiber impairment of ADHD patients, respectively. Axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD) and fractional anisotropy (FA) of 17 fiber properties were calculated using the AFQ. The mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), mean diffusivity (MDDKI), axial diffusivity (ADDKI), radial diffusivity (RDDKI) and fractional anisotropy (FADKI) of DKI and AD, RD, MD, and FA of diffusion tensor imaging (DTI) assessed the integrity of the white matter based on TBSS. Partial correlation analyses were conducted to evaluate the correlation between white matter abnormalities and clinical test scores in ADHD while taking age, gender, and education years into account. The analyses were all family-wise error rate (FWE) corrected. Results: ADHD patients performed worse on the Behavior Rating Inventory of Executive Function (BRIEF) test (p < 0.05). Minor variances existed in gender and age between ADHD and HC, but these variances did not yield statistically significant distinctions. There were no significant differences in TBSS for DKI and DTI parameters (p > 0.05, TFCE-corrected). Compared to HC volunteers, the mean AD value of right cingulum bundle (CB_R) fiber tract showed a significantly higher level in ADHD patients following the correction of FWE. As a result of the point-wise comparison between groups, significant alterations (FWE correction, p < 0.05) were mainly located in AD (nodes 36-38, nodes 83-97) and MD (nodes 92-95) of CB_R. There was no significant correlation between white matter diffusion parameters and clinical test scores in ADHD while taking age, gender, and education years into account. Conclusion: The AFQ method can detect ADHD white matter abnormalities in a specific location with greater sensitivity, and the CB_R played a critical role. Our findings may be helpful in further studying the relationship between focal white matter abnormalities and ADHD.

The Study of Short-Term Plastic Visual Perceptual Training Based on Virtual and Augmented Reality Technology in Amblyopia.

Backgrounds: The treatment for amblyopia can have a substantial impact on quality of life. Conventional treatments for amblyopia have some limitations, then we try to explore a new and effective method to treat amblyopia. This study aimed to determine the potential effect of short-term plastic visual perceptual training based on VR and AR platforms in amblyopic patients. Methods: All observers were blinded to patient groupings. A total of 145 amblyopic children were randomly assigned into 2 groups: VR group (71 patients) and AR group (74 patients). In the VR group, each subject underwent a 20-min short-term plastic visual perceptual training based on a VR platform, and in the AR group, based on an AR platform. The best-corrected visual acuity (BCVA), fine stereopsis, and contrast sensitivity function (CSF) were measured before and after training. Results: The BCVA (P < 0.001) and fine stereopsis (P < 0.05) were improved significantly both in VR and AR group after training. Moreover, in the AR group, the CSF showed the value of all spatial frequencies had a statistically significant improvement after training (P < 0.05), while in the VR group, only the value of spatial frequency 12 improved significantly (P = 0.008). Conclusions: This study showed that the short-term plastic visual perceptual training based on VR and AR technology can improve BCVA, fine stereopsis and CSF of refractive amblyopia. It was suggested that the visual perceptual training based on the VR and AR platforms may be potentially applied in treatment for amblyopia and provided a high-immersing alternative.

Metabolic assessment of cerebral palsy with normal clinical MRI using 18F-FDG PET imaging: A preliminary report.

To explore the cerebral metabolic patterns of cerebral palsy (CP) patients without structural abnormalities by brain magnetic resonance imaging (MRI) scans, we evaluated 18F-fluoro-deoxyglucose positron emission tomography (18F-FDG PET) imaging features in patients. Thirty-one children with CP [Gross Motor Function Classification System (GMFCS) levels II-V] showing no structural abnormalities by MRI were enrolled in this study. Regional glucose metabolic activity values were calculated using Scenium software and compared between the right and left cerebral hemispheres. These comparisons revealed asymmetric metabolic reductions in the central region, cerebellum, frontal lobe, and parietal lobe (p < 0.01). We next determined whether averaged brain metabolic activity values in different brain regions correlated with GMFCS levels. The metabolic activity values of basal ganglia, left temporal lobe, and cerebellum correlated negatively with GMFCS scores (all p < 0.05). This method was applied to the left cerebellum, which showed higher metabolic activity values than those in the right cerebellum in most patients (83.8%), and these values also correlated negatively with GMFCS scores (Spearman's r = -0.36, p = 0.01). Differential cortical glucose metabolism by 18F-FDG PET, may help to distinguish between different CP diagnoses that are not detected by MRI.

Situs Inversus Totalis on 18F-FDG PET/CT: A Case Report and a Literature Review.

A 62-year-old female patient with pathologically confirmed left lung small cell neuroendocrine carcinoma. The patient was referred to our positron emission tomography (PET)/CT center to look for possible metastatic diseases. After fasting for 8 h, the fasting blood glucose level of the patient was 7.1 mmol/L. The patient was intravenously injected with a 6.42 mCi (238 MBq) 18F-fluorodeoxyglucose (FDG) imaging agent. After the patient rested for 1 h, we scanned the patient with SIEMENS Biograph mCT 64 PET/CT camera. In addition to lung tumors and lymph node diseases, abnormal tracer uptake in the patient's thyroid was also found. PET/CT also showed situs inversus totalis of the patient, including the dextrocardia, liver on the left side, stomach, and spleen on the right side of the patient's body. The identification of anatomical variations and abnormalities by PET/CT imaging is very important to develop the best treatment for lung cancer.

Nucleophosmin 1 is a prognostic marker of gastrointestinal cancer and is associated with m6A and cuproptosis.

Background: NPM1 is highly expressed in a variety of solid tumors and promotes tumor development. However, there are few comprehensive studies on NPM1 analysis in gastrointestinal cancer. Methods: We used bioinformatics tools to study the expression difference of NPM1 between gastrointestinal cancer and control group, and analyzed the relationship between its expression level and the diagnosis, prognosis, functional signaling pathway, immune infiltration, m6A and cuproptosis related genes of gastrointestinal cancer. At the same time, the expression difference of NPM1 between esophageal carcinoma (ESCA) samples and control samples was verified by in vitro experiments. Results: NPM1 was overexpressed in gastrointestinal cancer. In vitro experiments confirmed that the expression of NPM1 in ESCA samples was higher than that in normal samples. The expression of NPM1 has high accuracy in predicting the outcome of gastrointestinal cancer. The expression of NPM1 is closely related to the prognosis of multiple gastrointestinal cancers. Go and KEGG enrichment analysis showed that NPM1 co-expressed genes involved in a variety of biological functions. NPM1 expression is potentially associated with a variety of immune cell infiltration, m6A and cuproptosis related genes in gastrointestinal cancers. Conclusion: NPM1 can be used as a diagnostic and prognostic marker of gastrointestinal cancer, which is related to the immune cell infiltration and the regulation of m6A and cuproptosis.

Comprehensive Analysis of Hexokinase 2 Immune Infiltrates and m6A Related Genes in Human Esophageal Carcinoma.

Background: Hexokinase 2 not only plays a role in physiological function of human normal tissues and organs, but also plays a vital role in the process of glycolysis of tumor cells. However, there are few comprehensive studies on HK2 in esophageal carcinoma (ESCA) needs further study. Methods: Oncomine, Tumor Immune Estimation Resource (TIMER), The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were used to analyze the expression differences of HK2 in Pan-cancer and ESCA cohort, and to analyze the correlation between HK2 expression level and clinicopathological features of TCGA ESCA samples. GO/KEGG, GGI, and PPI analysis of HK2 was performed using R software, LinkedOmics, GeneMANIA and STRING online tools. The correlation between HK2 and ESCA immune infiltration was analyzed TIMER and TCGA ESCA cohort. The correlation between HK2 expression level and m6A modification of ESCA was analyzed by utilizing TCGA ESCA cohort. Results: HK2 is highly expressed in a variety of tumors, and its high expression level in ESCA is closely related to the weight, cancer stages, tumor histology and tumor grade of ESCA. The analysis results of GO/KEGG showed that HK2 was closely related to cell adhesion molecule binding, cell-cell junction, ameboidal-type cell migration, insulin signaling pathway, hif-1 signaling pathway, and insulin resistance. GGI showed that HK2 associated genes were mainly involved in the glycolytic pathway. PPI showed that HK2 was closely related to HK1, GPI, and HK3, all of which played an important role in tumor proliferation. The analysis results of TIMER and TCGA ESCA cohort indicated that the HK2 expression level was related to the infiltration of various immune cells. TCGA ESCA cohort analyze indicated that the HK2 expression level was correlated with m6A modification genes. Conclusion: HK2 is associated with tumor immune infiltration and m6A modification of ESCA, and can be used as a potential biological target for diagnosis and therapy of ESCA.

The Study of Perceptual Eye Position Examination and Visual Perceptual Training in Postoperative Intermittent Exotropes.

The aim of this study was to investigate perceptual eye position (PEP) and to evaluate the effect of dichoptic visual perceptual training in postoperative intermittent exotropia [X(T)]. We enrolled 30 non-strabismus children (control group) and 54 postoperative X(T) children [divided into training group (33 patients) and non-training group (21 patients)]. All subjects received measurements of PEP, and the postoperative X(T) children were measured both in the third postoperative day and the third postoperative month. All patients in training group received 3-month dichoptic visual perceptual training based on a unique virtual reality platform. The results showed that the postoperative X(T) children with normal eye position still had an abnormal PEP. After a period of visual perceptual training, the PEP pixels in postoperative children dramatically decreased. The results revealed that PEP could evaluate fixation disparity and binocular visual function perceptively and precisely, and the dichoptic visual perceptive training may rebuild binocular visual function.

Associated risk factors in the early stage of diabetic retinopathy.

BACKGROUND: To investigate the retinal capillary density (RCD) of the macula using optical coherence tomography angiography (OCT-A) in type 2 diabetic patients and to further determine the association with risk factors. METHODS: A total of 212 eyes from 212 subjects were recruited; subjects included diabetics with no retinopathy (NDR, n = 90 eyes), diabetics with mild retinopathy DR (MDR, n = 36 eyes), and healthy participants (Control, n = 86 eyes). All participants underwent OCT-A scanning. RCD was quantified by superficial and deep retinal capillary layers (SRCL and DRCL) from OCT-A images. RESULTS: RCD in SRCL and DRCL was lower in NDR (P < 0.001) as well as in MDR (P < 0.001) when compared with control eyes. Diabetic patients were subdivided according to individual risk factors, complications related to diabetes, and hyperglycemia. Diabetic patients showed lower RCD in both the SRCL and DRCL when compared with healthy controls. Diabetics with age > 55y, HbA1c > 7% had significantly reduced DRCL (P < 0.05) when compared with the other group of diabetics (age < 55y, HbA1c < 7%). Diabetics with a blood urea nitrogen (BUN) > 8.2 mmol/L had significantly reduced SRCL and DRCL when compared to the other group of diabetics. CONCLUSIONS: Risk factors including older age, higher level of HbA1c, LDL-C and BUN, were associated with lower RCDs found in type 2 diabetic patients with and without mild DR by OCT-A. The impairment of retinal capillary by OCT-A may play a key role in the early monitoring of management in diabetes.

Dexmedetomidine Attenuates Orthotopic Liver Transplantation-Induced Acute Gut Injury via α 2-Adrenergic Receptor-Dependent Suppression of Oxidative Stress.

Patients with orthotopic liver transplantation (OLT) frequently develop acute gut injury (AGI), and dexmedetomidine (Dex) has been reported to exert a protective effect against AGI. We investigated whether Dex protects against AGI through antioxidative stress effects by the Nrf2/HO-1 antioxidative signaling pathway. Rats were randomly allocated into a sham group and six orthotopic autologous liver transplantation (OALT) groups receiving different doses of Dex together with/without α 2-adrenergic receptor (AR) blockers. Intestinal tissues were collected to visualize the barrier damage and to measure the indexes of oxidative stress. For in vitro studies, rat intestinal recess epithelial cells (IEC-6) underwent hypoxia/reoxygenation (H/R), and the protective role of Dex was evaluated after α 2A-AR siRNA silencing. OALT resulted in increased oxidative stress, significant intestinal injury, and barrier dysfunction. Dex attenuated OALT-induced oxidative stress and intestinal injury, which was abolished by the pretreatment with the nonspecific α 2A-AR siRNA blocker atipamezole and the specific α 2A-AR siRNA blocker BRL-44408, but not by the specific 2B/C-AR siRNA blocker ARC239. Silencing of α 2A-AR siRNA also attenuated the protective role of Dex on alleviating oxidative stress in IEC-6 cells subjected to H/R. Dex exerted its protective effects by activating Nrf2/HO-1 antioxidative signaling. Collectively, Dex attenuates OALT-induced AGI via α 2A-AR-dependent suppression of oxidative stress, which might be a novel potential therapeutic target for OALT-induced AGI.