The modulation of cAMP/PKA pathway by asiaticoside ameliorates high glucose-induced inflammation and apoptosis of retinal pigment epithelial cells.

Asiaticoside, the major bioactive constituent purified from Centella asiatica, is a pentacyclic triterpene saponin with sugar moieties (glucose-glucose-rhamnose). Its biological activities including anti-inflammation and antioxidant have been widely reported. This study aimed to investigate the role of asiaticoside in diabetic retinopathy (DR). Human retinal pigment epithelium (RPE) cells ARPE-19 were induced by high glucose. Then, cell survival rate, expression of inflammatory factors, oxidative stress, and apoptosis were measured by MTT method, western blot, oxidative stress detection kits and TUNEL respectively. To uncover the underlying mechanism, the levels of cyclic AMP (cAMP) and protein kinase A (PKA) were measured by Enzyme linked immunosorbent assay (ELISA) and PKA activities were detected by the Kemptide phosphorylation assay. Furthermore, cAMP inhibitor SQ22536 was also used to validate the mechanism. Asiaticoside suppressed the inflammation and apoptosis of ARPE-19 cells, and the activities of cAMP and PKA were inhibited upon HG induction while again released after further administration of asiaticoside. However, these effects were all abolished by SQ22536. In conclusion, we have demonstrated in this paper that asiaticoside ameliorates high glucose-induced inflammation and apoptosis of RPE cells by activating cAMP/PKA signaling pathway. asiaticoside-mediated activation of cAMP/PKA signaling pathway may serve as a potential target for the management of DR.

Mechanisms of Biochanin A Alleviating PM2.5 Organic Extracts-Induced EMT of A549 Cells through the PI3K/Akt Pathway.

Epithelial-mesenchymal transition (EMT) is an important step in tumor progression, which enables tumor cells to acquire migration and invasion characteristics. The aim of this study was to investigate the mechanism of biological biochanin A (BCA) in ameliorating fine particulate matter (PM2.5) lung injury. The results showed that PM2.5 could induce spindle-like changes in cell morphology, causing the ability of migration and invasion. However, they were significantly inhibited by BCA treatment (10/20/30 µm). After BCA treatment, the release and transcription of chemokine CXCL12 and its receptor gene CXCR4 were inhibited, and the release of growth inducer TGF-ß1 was significantly reduced. In addition, BCA promoted the transcription of E-cadherin and ß-catenin, inhibiting the expression of N-cadherin, vimentin, and fibronectin, and down-regulated the expression of MMP-2/9. We found that BCA effectively interfered with the PI3K/Akt signaling pathway activated by PM2.5. In conclusion, PM2.5 can induce EMT in lung cancer cells, and BCA may reverse this process by activating the PI3K/Akt signaling pathway.

Expression pattern and regulatory effect of lysine-specific demethylase 2A gene in clear cell renal cell carcinoma.

BACKGROUND: Our study aimed to explore the expression and the biological role of lysine-specific demethylase 2A (KDM2A) in clear cell renal cell carcinoma (ccRCC). METHODS: In vitro, KDM2A expression was measured by qRT-PCR and western blot. A total of 50 patients with ccRCC were included, and KDM2A expression in ccRCC tissues was assessed by qRT-PCR and immunohistochemistry. The effects of KDM2A expression on cell biological behavior were examined by cell counting kit-8 assay, transwell assay and flow cytometry, respectively. The prognostic value of KDM2A in ccRCC was evaluated by Kaplan-Meier method. RESULTS: The KDM2A expression was significantly upregulated in ccRCC cell line (P < 0.05). Compared with para cancer tissues, ccRCC samples showed a higher KMD2A mRNA level and a larger proportion of high KDM2A expression (all P < 0.05). High KDM2A mRNA expression was more likely to occur in ccRCC tissues with tumor size > 7 cm (P = 0.005) and T3-T4 stage (P = 0.047). Knockdown of KDM2A significantly suppressed the proliferation and invasion, and promoted the apoptosis of ccRCC cells (all P < 0.05). Moreover, Kaplan-Meier survival analysis revealed that higher level of KDM2A expression in ccRCC patients was associated with lower survival rate (P = 0.004). CONCLUSIONS: Our findings demonstrated a vital role of KDM2A in the pathogenesis of ccRCC, which provides a new perspective to understand the underlying molecular mechanisms in ccRCC.

Systematic construction and validation of an immune prognostic model for lung adenocarcinoma.

Lung adenocarcinoma (LUAD), the most common non-small-cell lung cancer, is characterized by a dense lymphocytic infiltrate, which indicates that the immune system plays an active role in the development and growth of this cancer. However, no investigations to date have proposed robust models for predicting survival outcome for patients with LUAD in terms of tumour immunology. A total of 761 LUAD patients were included in this study, in which the database of The Cancer Genome Atlas (TCGA) was utilized for discovery, and the Gene Expression Omnibus (GEO) database was utilized for validation. Bioinformatics analysis and R language tools were utilized to construct an immune prognostic model and annotate biological functions. Lung adenocarcinoma showed a weakened immune phenotype compared with adjacent normal tissues. Immune-related gene sets were profiled, an immune prognostic model based on 2 immune genes (ANLN and F2) was developed with the TCGA database to distinguish cases as having a low or high risk of unfavourable prognosis, and the model was verified with the GEO database. The model was prognostically significant in stratified cohorts, including stage I-II, stage III-IV and epidermal growth factor receptor (EGFR) mutant subsets, and was considered to be an independent prognostic factor for LUAD. Furthermore, the low- and high-risk groups showed marked differences in tumour-infiltrating leucocytes, tumour mutation burden, aneuploidy and PD-L1 expression. In conclusion, an immune prognostic model was proposed for LUAD that is capable of independently identifying patients at high risk for poor survival, suggesting a relationship between local immune status and prognosis.

Detection of carcinoembryonic antigen using a magnetoelastic nano-biosensor amplified with DNA-templated silver nanoclusters.

Here we develop a magnetoelastic (ME) nano-biosensor based on the competitive strategy for the detection of a carcinoembryonic antigen (CEA). Specifically, the gold-coated ME material provided a platform and the thiolated single-stranded DNA (HS-DNA) containing a half-complementary sequence towards the CEA aptamer was modified on the surface via Au-S bonding. DNA-templated silver nanoclusters (DNA-AgNCs) containing another half-complementary sequence towards the aptamer were used to amplify the signals by about 2.1 times, compared to those obtained using just the aptamer. CEA aptamers as a bio-recognition element were employed to link HS-DNA and DNA-AgNCs through DNA hybridization. The CEA aptamer preferentially combined with CEA rather than hybridized with DNA. Due to the magnetostrictive nature of the ME materials, the resonant frequency of the nano-biosensor would increase along with the release of DNA-AgNCs and CEA aptamers. The modification process was demonstrated by UV-vis spectra, x-ray photoelectron spectroscopy (XPS), Raman spectroscopy, transmission electron microscope (TEM) and an atomic force microscope (AFM). The nano-biosensor has a linear response to the logarithmic CEA concentrations ranging from 2 pg ml-1 to 6.25 ng ml-1, with a limit of detection (LOD) of 1 pg ml-1 and a sensitivity of 105.05 Hz/ng · ml-1. This study provides a low-cost, highly sensitive and wireless method for selective detection of CEA.

Rapid cancer diagnosis by highly fluorescent carbon nanodots-based imaging.

Carbon dots (Cdots) with bright green fluorescence were applied to the rapid and selective cell imaging for a variety of cell lines. Different labeling distributions of hepatoma cells (HepG2) and normal human liver cells (LO2) were achieved using Cdots as imaging agents. For HepG2 cells, the Cdots could rapidly permeate the cell membrane and diffuse into the cytoplasm and nucleus within 3 min, and retained their location in the targets for 24 h. However, the Cdots exhibited bright fluorescence only in the cytoplasm of LO2 cell lines. Moreover, the Cdots were almost non-cytotoxic and exhibited superior photostability over a wide range of pH. Therefore, these Cdots have great potential for rapid, luminous and selective bioimaging applications, and are expected to be used as a nucleus-staining agent in cancer diagnosis. Graphical abstract ᅟ.

A fluorometric method for mercury(II) detection based on the use of pyrophosphate-modified carbon quantum dots.

Pyrophosphate-modified carbon quantum dots (PP-CDs) are demonstrated to be a viable fluorescent nanoprobe for mercury(II) (Hg2+) detection. Hg2+ reacts with the pyrophosphate groups on the surface of PP-CDs to form a non-fluorescent complex. This results in quenching of the green fluorescence which has excitation/emission peaks at 400/513 nm. Static quenching is shown to be the dominant mechanism. The probe works in 0.1 µM to 1.4 µM Hg2+ concentration range, and the limit of detection is 2 nM. The PP-CDs were also used to visualize Hg2+ inside human hepatocyte LO2 cells. Graphical abstract Schematic representation of pyrophosphate-modified carbon quantum dots (CDs) for selective and sensitive fluorometric determination of mercury(II). Hg(II) quenches the blue fluorescence of the CDs, and glutathione restores it. The method was used to detect Hg(II) in spiked tap water and inside cells.

Ultrasound Elastography for Differentiating Benign from Malignant Thickened Greater Omentum.

OBJECTIVES: To investigate whether ultrasound elastography (UE) is an effective non-invasive diagnostic procedure for evaluating benign and malignant thickened greater omentum. METHODS: Ultrasound elastographic images from 118 patients who underwent ultrasound-guided biopsy for thickened greater omentum from May 2012 to October 2013 were retrospectively analysed. The results were compared with the pathological findings from the biopsies, and evaluated by ROC curve analysis. RESULTS: A total of 93.6% of the benign thickened greater omentum had elasticity scoring of 1 or 2, whereas 93.0% of the malignant thickened greater omentum had elasticity scoring of 3 or 4. The elasticity strain ratios for malignant thickened greater omenta were higher than for benign thickened greater omenta using muscle or fat yielded as reference tissue (P < 0.01). The optimal cut-off point for elasticity strain ratios using fat as reference was 2.6. The sensitivity, specificity, accuracy, and positive and negative predictive values for determining elasticity strain ratios using fat as reference were 83.3%, 90.6%, 86.5%, 92.1%, and 80.6%, respectively, and for elasticity scoring were 95.2%, 96.9%, 95.9%, 97.6%, and 93.9%, respectively. CONCLUSIONS: UE using elasticity scoring or elasticity strain ratios is an effective new non-invasive method for differentiating benign from malignant thickened greater omentum. KEY POINTS: • Elasticity score is an objective method for differentiating greater omentum lesions. • Elasticity strain ratio is another method for differentiating greater omentum lesions. • Fat tissue is better than abdominal wall muscle as reference in elasticity imaging. • UE is a new effective, non-invasive method for diagnosing omental diseases.

Identifying the plasma metabolome responsible for mediating immune cell action in severe COVID-19: a Mendelian randomization investigation.

Introduction: The immune response regulates the severity of COVID-19 (sCOVID-19). This study examined the cause-and-effect relationship between immune cell traits (ICTs) and the risk of severe COVID-19. Additionally, we discovered the potential role of plasma metabolome in modulating this risk. Methods: Employing data from a genome-wide association study (GWAS), we conducted a two-sample Mendelian randomization (MR) assessment of 731 genetic ICTs and sCOVID-19 (5,101 cases, 1,383,241 controls) incidence. The MR analysis was utilized to further quantitate the degree of plasma metabolome-mediated regulation of immune traits in sCOVID-19. Results: The inverse variance weighted method recognized 2 plasma metabolites (PMs) responsible for casual associations between immune cells and sCOVID-19 risk. These included Tridecenedioate (C13:1-DC) which regulated the association between CD27 on IgD- CD38br (OR 0.804, 95% CI 0.699-0.925, p = 0.002) and sCOVID-19 risk (mediated proportion: 18.7%); arginine to citrulline ratio which controlled the relationship of CD39 on monocyte (OR 1.053, 95% CI 1.013-1.094, p = 0.009) with sCOVID-19 risk (mediated proportion: -7.11%). No strong evidence that genetically predicted sCOVID-19 influenced the aforementioned immune traits. Conclusion: In this study, we have successfully identified a cause-and-effect relationship between certain ICTs, PMs, and the likelihood of contracting severe COVID-19. Our findings can potentially improve the accuracy of COVID-19 prognostic evaluation and provide valuable insights into the underlying mechanisms of the disease.

A Method based on Evolutionary Algorithms and Channel Attention Mechanism to Enhance Cycle Generative Adversarial Network Performance for Image Translation.

A Generative Adversarial Network (GAN) can learn the relationship between two image domains and achieve unpaired image-to-image translation. One of the breakthroughs was Cycle-consistent Generative Adversarial Networks (CycleGAN), which is a popular method to transfer the content representations from the source domain to the target domain. Existing studies have gradually improved the performance of CycleGAN models by modifying the network structure or loss function of CycleGAN. However, these methods tend to suffer from training instability and the generators lack the ability to acquire the most discriminating features between the source and target domains, thus making the generated images of low fidelity and few texture details. To overcome these issues, this paper proposes a new method that combines Evolutionary Algorithms (EAs) and Attention Mechanisms to train GANs. Specifically, from an initial CycleGAN, binary vectors indicating the activation of the weights of the generators are progressively improved upon by means of an EA. At the end of this process, the best-performing configurations of generators can be retained for image generation. In addition, to address the issues of low fidelity and lack of texture details on generated images, we make use of the channel attention mechanism. The latter component allows the candidate generators to learn important features of real images and thus generate images with higher quality. The experiments demonstrate qualitatively and quantitatively that the proposed method, namely, Attention evolutionary GAN (AevoGAN) alleviates the training instability problems of CycleGAN training. In the test results, the proposed method can generate higher quality images and obtain better results than the CycleGAN training methods present in the literature, in terms of Inception Score (IS), Fréchet Inception Distance (FID) and Kernel Inception Distance (KID).

A panel of seven protein tumour markers for effective and affordable multi-cancer early detection by artificial intelligence: a large-scale and multicentre case-control study.

Background: Early detection of cancer aims to reduce cancer deaths. Unfortunately, many established cancer screening technologies are not suitable for use in low- and middle-income countries (LMICs) due to cost, complexity, and dependency on extensive medical infrastructure. We aimed to assess the performance and robustness of a protein assay (OncoSeek) for multi-cancer early detection (MCED) that is likely to be more practical in LMICs. Methods: This observational study comprises a retrospective analysis on the data generated from the routine clinical testings at SeekIn and Sun Yat-sen Memorial Hospital. 7565 participants (954 with cancer and 6611 without) from the two sites were divided into training and independent validation cohort. The second validation cohort (1005 with cancer and 812 without) was from Johns Hopkins University School of Medicine. Patients with cancer prior to therapy were eligible for inclusion in the study. Individuals with no history of cancer were enrolled from the participating sites as the non-cancer group. One tube of peripheral blood was collected from each participant and quantified a panel of seven selected protein tumour markers (PTMs) by a common clinical electrochemiluminescence immunoassay analyser. An algorithm named OncoSeek was established using artificial intelligence (AI) to distinguish patients with cancer from those without cancer by calculating the probability of cancer (POC) index based on the quantification results of the seven PTMs and clinical information including sex and age of the individuals and to predict the possible affected tissue of origin (TOO) for those who have been detected with cancer signals in blood. Findings: Between November 2012 and May 2022, 7565 participants were enrolled at SeekIn and Sun Yat-sen Memorial Hospital. The conventional clinical method, which relies only on a single threshold for each PTM, would suffer from a high false positive rate that accumulates as the number of markers increased. OncoSeek was empowered by AI technology to significantly reduce the false positive rate, increasing the specificity from 56.9% (95% confidence interval [CI]: 55.8-58.0) to 92.9% (92.3-93.5). In all cancer types, the overall sensitivity of OncoSeek was 51.7% (49.4-53.9), resulting in 84.3% (83.5-85.0) accuracy. The performance was generally consistent in the training and the two validation cohorts. The sensitivities ranged from 37.1% to 77.6% for the detection of the nine common cancer types (breast, colorectum, liver, lung, lymphoma, oesophagus, ovary, pancreas, and stomach), which account for ∼59.2% of global cancer deaths annually. Furthermore, it has shown excellent sensitivity in several high-mortality cancer types for which routine screening tests are lacking in the clinic, such as the sensitivity of pancreatic cancer which was 77.6% (69.3-84.6). The overall accuracy of TOO prediction in the true positives was 66.8%, which could assist the clinical diagnostic workup. Interpretation: OncoSeek significantly outperforms the conventional clinical method, representing a novel blood-based test for MCED which is non-invasive, easy, efficient, and robust. Moreover, the accuracy of TOO facilitates the follow-up diagnostic workup. Funding: The National Key Research and Development Programme of China.

Self-Assembled and Multilayer-Overlapped ESM-PDA@rGO Nanofilm-Based Flexible Wearable Sensor for Real-Time Body Temperature Monitoring.

There is an urgent need for wearable sensors that continuously monitor human physiological conditions in real time. Herein, an ESM-PDA@rGO-based flexible wearable temperature sensor was successfully constructed by integrating an eggshell membrane (ESM) with reduced graphene oxide (rGO) through dopamine (DA) polymerization. Depending on the "bridge effect" of diversified polydopamine (PDA) chains, on the one hand, a staggered arrangement of PDA-rGO frameworks and a lot of conductive pathways were produced and acted as an active layer. On the other hand, PDA-rGO frameworks were linked with ESM by PDA chains as a flexible sensing nanofilm. As a result, these mechanical merits of the ESM-PDA@rGO exhibited a 1.8-fold increase in Young' s modulus and 1.4-fold increase in tensile strength. Thereby, the conformability and performance of the temperature sensor were greatly enhanced, showing excellent sensitivity (-2.23%/°C), good linearity (R2 = 0.979), as well as stability. Especially, the flexible sensing nanofilm is evolved from the staggered arrangement of PDA-rGO frameworks, which endows it with rapid response (only 4-8 s), high resolution (0.1 °C), as well as excellent long-term durability (10 weeks). More importantly, the temperature sensor demonstrates insensitivity to bending deformation, ensuring reliable wearing stability. The sensor allows for online, real-time monitoring of human body temperature, encompassing both core (forehead, temple, cochlea, and exhale gas) and shell (palm and back of the hand, fingertip, and instep) temperatures. Particularly, it can accurately assess minor changes in peripheral body temperature before and after exercise, and it is capable of mapping daily patterns of body temperatures. The developed temperature sensor will provide us new materials design concepts and holds considerable promise in the fields of e-skin, disease surveillance, prediction, and diagnose.

The Accurate Interpretation and Clinical Significance of Morphological Features of Fine Needle Aspiration Cells in Papillary Thyroid Carcinoma.

Papillary thyroid carcinoma (PTC) is the most common malignant neoplasm of the thyroid gland; fine needle aspiration cytology is the most basic and reliable diagnostic method before PTC operation. However, it is not clear which cell morphological changes can be used as a reliable standard for the diagnosis of PTC. A retrospective analysis was performed on 337 patients with PTC confirmed by postoperative histology. An additional 197 randomly selected patients with benign thyroid lesions were included in the study and used as a control group. True papillary arrangements, swirl arrangements, and escape arrangements had high specificity, all of which were 100%, but only swirl arrangements had ideal sensitivity (77.61%). The nuclear volume characteristics had a high sensitivity of more than 90%, but the specificities of both nuclear crowding and nuclear overlap were too low, only 16.34% and 23.35%. The sensitivities of five nuclear structural characteristics were more than 90%, but only the specificity of intranuclear cytoplasmic pseudoinclusions (INCIs) reached 100%, nuclear contour irregularity and pale nuclei with powdery chromatin also had ideal interpretation value except for grooves and marginally placed micronucleoli. Although the sensitivity of psammoma bodies (PBs) was low, the specificity was 100%. In terms of preparation methods, the method of liquid-based preparation (LBP) is obviously better than that of conventional smears. The diagnostic efficiency by the combined detection method of parallel tests showed that without reducing the specificity, the sensitivity increased with the increase of the number of morphological characteristics and finally reached 98.81%. The INCIs and swirl arrangements are the most common and important indicators for the diagnosis of PTC, whereas papillary-like arrangements, the crowding and overlap of nuclear, grooves, marginally placed micronucleoli, and multinucleated giant cells are of little significance for the diagnosis of PTC.

Pseudomyxoma peritonei: some different sonographic findings.

OBJECTIVES: The purpose of our study was to assess the sonographic features of pseudomyxoma peritonei (PMP). MATERIALS AND METHODS: All records of peritoneal biopsies under the guidance of ultrasound in our institutional database from April 2007 to June 2011 were retrospectively reviewed. 19 cases of PMP and 279 cases of other peritoneal lesions were included in the study. The sonograms of peritoneum, ascites, and parenchymal organs involved by PMP were evaluated, respectively, and compared with sonograms of other peritoneal lesions. RESULTS: Anechoic areas were found in 89.5% cases of PMP at high frequency of insonation and the sensitivity in indicating PMP was 100%. In the pelvic cavity, echogenic foci in ascites of PMP in 52.6% cases were mobile. The specificity of "starburst" appearance and sensitivity of scalloping of the liver margin were relatively high (82.3 and 88.1%), but the sensitivity and specificity (57.9 and 42.1%) of these two signs were relatively low. CONCLUSION: Anechoic area in the thickened peritoneum was a specific sign in indicating the diagnosis of PMP and high-frequency transducer could reveal these tiny anechoic areas more explicitly. In the pelvic cavity, echogenic foci in ascites of PMP could be observed to be mobile and scalloping of the liver margin and "starburst" appearance also played a significant role in indicating PMP.

Visceral adiposity measures are strongly associated with cardiovascular disease among female participants in Southwest China: A population-based prospective study.

Background and aims: Controversy remains regarding the prediction effects of different adiposity measure indicators for the risk of cardiovascular disease (CVD). Our study aimed to assess the associations of three traditional anthropometric indicators, namely, waist circumference (WC), waist-to-height ratio (WHtR), and body mass index (BMI) as well as three non-traditional anthropometric indicators, namely, the Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP), and body shape index (ABSI), with the risk of CVD among Southwest Chinese population. Methods: Our study was based on the Guizhou Population Health Cohort Study (GPHCS) conducted from 2010 to 2020. A total of 9,280 participants were recruited from 12 areas in Guizhou Province, China, from November 2010 to December 2012, and followed up for major chronic diseases until December 2020. A total of 7,837 individuals with valid data were included in this analysis. The gender-specific associations of WC, WHtR, BMI, CVAI, LAP, and ABSI with CVD were evaluated using Cox proportional hazards models. Receiver operating characteristic (ROC) curve analysis was used to estimate the prediction powers of different indicators for CVD. Results: No association of six indicators with CVD was observed among male participants. Female participants with either WC-based central obesity (HR: 1.82, 95% CI: 1.12-2.97) or WHtR-based central obesity (HR: 1.68, 95% CI: 1.07-2.64) had a higher risk of CVD, after adjusted for age, area, ethnic group, smoking, alcohol drinking, MET, previous history of diabetes, hypertension and dyslipidemia, medication use, and nutraceutical intake. Compared with female participants in the lowest quartile (Q1), those in the highest quartile (Q4) of WHtR (HR: 2.24, 95% CI: 1.17-4.27), CVAI (HR: 3.98, 95% CI: 1.87-8.49), and ABSI (HR: 1.94, 95% CI: 1.06-3.52) had an increased risk for incident CVD. CAVI showed the maximum predictive power of CVD with the biggest AUC of 0.687 (95% CI: 0.654-0.720) compared to other indicators in female participants. Conclusions: Visceral adiposity measures, especially CVAI, are stronger predictive indicators of CVD among female and not male participants in Southwest China. Different anthropometric indexes need to be combined to comprehensively assess health risks.

Preparation and In Vitro Characterization of Gelatin Methacrylate for Corneal Tissue Engineering.

BACKGROUND: Corneal disease is second only to cataract considered as the leading cause of blindness in the world, with high morbidity. Construction of corneal substitutes in vitro by tissue engineering technology to achieve corneal regeneration has become a research hotspot in recent years. We conducted in-depth research on the biocompatibility, physicochemical and mechanical properties of rat bone marrow mesenchymal stem cells (rBM-MSCs)-seeded gelatin methacrylate (GelMA) as a bioengineered cornea. METHODS: Four kinds of GelMA with different concentrations (7, 10, 15 and 30%) were prepared, and their physic-chemical, optical properties, and biocompatibility with rBM-MSCs were characterized. MTT, live/dead staining, cell morphology, immunofluorescence staining and gene expression of keratocyte markers were performed. RESULTS: 7%GelMA hydrogel had higher equilibrium water content and porosity, better optical properties and hydrophilicity. In addition, it is more beneficial to the growth and proliferation of rBM-MSCs. However, the 30%GelMA hydrogel had the best mechanical properties, and could be more conducive to promote the differentiation of rBM-MSCs into keratocyte-like cells. CONCLUSION: As a natural biological scaffold, GelMA hydrogel has good biocompatibility. And it has the ability to promote the differentiation of rBM-MSCs into keratocyte-like cells, which laid a theoretical and experimental foundation for further tissue-engineered corneal stromal transplantation, and provided a new idea for the source of seeded cells in corneal tissue engineering.

Toxicology of respiratory system: Profiling chemicals in PM10 for molecular targets and adverse outcomes.

Numerous studies have shown that the increasing trend of respiratory diseases have been closely associated with the endogenous toxic chemicals (polycyclic aromatic hydrocarbons, heavy metal ions, etc.) in PM10. In the present study, we aim to determine the strong correlations between the chemicals in PM10 and the adverse consequences. We used the ChemView DB, the ToxRef DB and a comprehensive literature analysis to collect, identify, and evaluate the chemicals in PM10 and their adverse effects on respiratory system, and then used the ToxCast DB to analyze their bioactivity and key targets through 1192 molecular targets and cell characteristic endpoints. Meanwhile, the bioinformatics analysis were carried out on the molecular targets to screen out prevention and treatment targets. A total of 310 chemicals related to the respiratory system were identified. An unsupervised two-directional heatmap was constructed based on hierarchical clustering of 227 chemicals by their effect scores. A subset of 253 chemicals with respiratory system toxicity had in vitro bioactivity on 318 molecular targets that could be described, clustered and annotated in the heatmap and bipartite network, which were analyzed based on the protein information in UniProt KB database and the software of GO, STRING, and KEGG. These results showed that the chemicals in PM10 have strong correlation with different types of respiratory system injury. The main pathways of respiratory system injury caused by PM10 are the Calcium signaling pathway, MAPK signaling pathway, and PI3K-AKT signaling pathway, and the core proteins in which are likely to be the molecular targets for the prevention and treatment of damage caused by PM10.

The Relationship Between Cord Blood Cytokine Levels and Perinatal Characteristics and Bronchopulmonary Dysplasia: A Case-Control Study.

Objective: To establish the association between serial levels of inflammatory cytokines in cord blood and perinatal characteristics and bronchopulmonary dysplasia (BPD) in preterm infants. Methods: 147 premature infants with gestational age ≤32 weeks who were born and hospitalized in the First Affiliated Hospital of Zhengzhou University between July 2019 and August 2021 were enrolled in this retrospective case-control study. Multiple microsphere flow immunofluorescence was used to detect seven cytokines in cord blood collected within 24 h of birth. Demographics, delivery characteristics, maternal factors, neonatal characteristics, and clinical outcomes were collected for the two groups. An unconditional logistic regression model was used in this study to assess the clinical variables. Results: IL-6 cord blood levels at birth were significantly higher in the BPD group than in the non-BPD group, but the odds ratio (OR) was very small (OR = 1). No differences in other cytokine concentrations were observed between the two groups. Multivariable logistic regression analysis demonstrated that increased maternal white blood cell (WBC) count on admission and lower birth weight increased the risk of BPD progression. Conclusions: Increased IL-6 cord blood levels at birth in preterm infants may have trivial significance for predicting BPD. Furthermore, higher maternal WBC count on admission and lower birth weight increased the risk of BPD.

Peritoneal metastases: evaluation with contrast-enhanced ultrasound.

OBJECTIVES: The aim of this study is to evaluate the contrast-enhanced ultrasound (CEUS) features of peritoneal metastases. MATERIALS AND METHODS: Unenhanced ultrasound and CEUS were conducted in 25 patients who had confident diagnoses of peritoneal metastases after ultrasound-guided biopsies of peritoneum. B-mode sonograms, color Doppler, CEUS pattern and quantitative analysis of blood perfusion in peritoneal metastases were successively evaluated. RESULTS: Peritoneum became markedly thickened and was well seen as a heterogeneous omental cake at B-mode ultrasound. Color Doppler only detected dotted or strip-like blood flow scattered in the thickened peritoneum and no blood signal was found in any metastatic nodule. At CEUS, the thickened peritoneum enhanced diffusely and parameters of time-intensity curves did not show any significant difference among variant metastases groups. All the metastatic nodules in the peritoneum showed fast radial enhancement and became homogeneous with adjacent parenchyma. These nodules soon became hypoechoic and the contour of the nodule was clearly shown during the wash-out phase. In all the nodules, the time to peak was shorter and peak intensity was higher compared with the peripheral tissue. CONCLUSION: CEUS played a good role in the evaluation of microcirculation and angiogenesis of peritoneal metastases and metastatic nodules in thickened peritoneum.

Reduction of IgG in nonhuman primates by a peptide antagonist of the neonatal Fc receptor FcRn.

The neonatal Fc receptor FcRn provides IgG molecules with their characteristically long half-lives in vivo by protecting them from intracellular catabolism and then returning them to the extracellular space. Other investigators have demonstrated that mice lacking FcRn are protected from induction of various autoimmune diseases, presumably because of the accelerated catabolism of pathogenic IgGs in the animals. Therefore, targeting FcRn with a specific inhibitor may represent a unique approach for the treatment of autoimmune disease or other diseases where the reduction of pathogenic IgG will have a therapeutic benefit. Using phage display peptide libraries, we screened for ligands that bound to human FcRn (hFcRn) and discovered a consensus peptide sequence that binds to hFcRn and inhibits the binding of human IgG (hIgG) in vitro. Chemical optimization of the phage-identified sequences yielded the 26-amino acid peptide dimer SYN1436, which is capable of potent in vitro inhibition of the hIgG-hFcRn interaction. Administration of SYN1436 to mice transgenic for hFcRn induced an increase in the rate of catabolism of hIgG in a dose-dependent manner. Treatment of cynomolgus monkeys with SYN1436 led to a reduction of IgG by up to 80% without reducing serum albumin levels that also binds to FcRn. SYN1436 and related peptides thus represent a previously uncharacterized family of potential therapeutic agents for the treatment of humorally mediated autoimmune and other diseases.