RNA modification-related genes illuminate prognostic signature and mechanism in esophageal squamous cell carcinoma.

Emerging studies have demonstrated the link between RNA modifications and various cancers, while the predictive value and functional mechanisms of RNA modification-related genes (RMGs) in esophageal squamous cell carcinoma (ESCC) remain unclear. Here we established a prognostic signature for ESCC based on five RMGs. The analysis of ESCC clinical samples further verified the prognostic power of the prognostic signature. Moreover, we found that the knockdown of NSUN6 promotes ESCC progression in vitro and in vivo, whereas the overexpression of NSUN6 inhibits the malignant phenotype of ESCC cells. Mechanically, NSUN6 mediated tRNA m5C modifications selectively enhance the translation efficiency of CDH1 mRNA in a codon dependent manner. Rescue assays revealed that E-cadherin is an essential downstream target that mediates NSUN6's function in the regulation of ESCC progression. These findings offer additional insights into the link between ESCC and RMGs, as well as provide potential strategies for ESCC management and therapy.

Esterification of black bean anthocyanins with unsaturated oleic acid, and application characteristics of the product.

Esterification of anthocyanins with saturated fatty acids have been widely investigated, while that with unsaturated fatty acids is little understood. In this study, crude extract (purity âˆ¼ 35 %) of cyanidin-3-O-glucoside (C3G) from black bean seed coat was utilized as reaction substrate, and enzymatically acylated with unsaturated fatty acid (oleic acid). Optimization of various reaction parameters finally resulted in the highest acylation rate of 54.3 %. HPLC-MS/MS and NMR analyses elucidated the structure of cyanidin-3-O-glucoside-oleic acid ester (C3G-OA) to be cyanidin-3-O-(6″-octadecene)-glucoside. Introduction of oleic acid into C3G improved the lipophilicity, antioxidant ability, and antibacterial activity. Further, the color and substance stability analyses showed that the susceptibility of C3G and C3G-OA to different thermal, peroxidative, and illuminant treatments were highly pH dependent, which suggested individual application guidelines. Moreover, C3G-OA showed lower toxicity to normal cell (QSG-7701) and better inhibitory effect on the proliferation of HepG2 cells than C3G, which indicated its potential anti-tumor bioactivity.

Exosomes Derived from Astragaloside IV-pretreated Endothelial Progenitor Cells (AS-IV-Exos) Alleviated Endothelial Oxidative Stress and Dysfunction Via the miR-210/ Nox2/ROS Pathway.

BACKGROUND: Chronic hyperglycemia in diabetes induces oxidative stress, leading to damage to the vascular system. In this study, we aimed to evaluate the effects and mechanisms of AS-IV-Exos in alleviating endothelial oxidative stress and dysfunction caused by high glucose (HG). METHODS: Histopathological changes were observed using HE staining, and CD31 expression was assessed through immunohistochemistry (IHC). Cell proliferation was evaluated through CCK8 and EDU assays. The levels of ROS, SOD, and GSH-Px in the skin tissues of each group were measured using ELISA. Cell adhesion, migration, and tube formation abilities were assessed using adhesion, Transwell, and tube formation experiments. ROS levels in HUVEC cells were measured using flow cytometry. The levels of miR-210 and Nox2 were determined through quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of Nox2, SOD, GSH-Px, CD63, and CD81 was confirmed using WB. RESULTS: The level of miR-210 was reduced in diabetes-induced skin damage, while the levels of Nox2 and ROS increased. Treatment with AS-IV increased the level of miR-210 in EPC-Exos. Compared to Exos, AS-IV-Exos significantly reduced the proliferation rate, adhesion number, migration speed, and tube-forming ability of HGdamaged HUVEC cells. AS-IV-Exos also significantly decreased the levels of SOD and GSH-Px in HG-treated HUVEC cells and reduced the levels of Nox2 and GSH-Px. However, ROS levels and Nox2 could reverse this effect. CONCLUSION: AS-IV-Exos effectively alleviated endothelial oxidative stress and dysfunction induced by HG through the miR-210/Nox2/ROS pathway.

Chemoselectivity of the CuAAC/Ring Cleavage/Cyclization Reaction between Enaminones and α-Acylketenimine.

Ketenimines represent an important class of reactive species, useful synthetic intermediates, and synthons. However, in general, ketenimines preferentially undergoes nucleophilic addition reactions with hydroxyl and amino groups, and carbon functional groups remain a less studied subset of such systems. Herein, we develop a straightforward syntheses of pyridin-4(1H)-imines that is achieved by cyclization of a reacting enaminone unit with α-acylketenimine which is generated from the reactions of sulfonyl azides and terminal ynones in situ (CuAAC/Ring cleavage reaction). The cascade process preferentially starts with the nucleophilic α-C of the enaminone unit instead of an amino group, attacking the electron-deficient central carbon of ketenimine, and the chemoselectivity unconventional products pyridin-4(1H)-imines were formed by intramolecular cyclization.

Remdesivir inhibits Porcine epidemic diarrhea virus infection in vitro.

Porcine Epidemic Diarrhea Virus (PEDV) is a highly contagious and pathogenic virus that causes symptoms such as diarrhea, vomiting, weight loss, and even death in piglets. Due to its high transmission rate, PEDV has resulted in significant global losses. Although some vaccines have been developed and utilized to prevent PEDV, their effectiveness is limited due to the virus's mutations. Therefore, it is imperative to investigate new strategies to combat PEDV. Remdesivir, a classic antiviral drug for coronaviruses, has been proven in our experiment to effectively suppress PEDV replication in Vero and LLC-PK1 cells. Additionally, the cell experiment demonstrated its direct inhibition of PEDV RNA-dependent RNA polymerase (RdRp) enzyme activity. Molecular docking simulations were employed to predict the binding site of remdesivir and PEDV RdRp. Moreover, we observed that remdesivir does not impact the production of inflammatory factors and exhibits antagonistic effects with exogenous nucleosides. Furthermore, we conducted RNA-Seq analysis to investigate the global changes in transcriptome of infected cells treated with remdesivir. Overall, our findings indicate that remdesivir holds promise as a potential candidate for the treatment of PEDV infection.

Nitrogen metabolism in mycobacteria: the key genes and targeted antimicrobials.

Nitrogen metabolism is an important physiological process that affects the survival and virulence of Mycobacterium tuberculosis. M. tuberculosis's utilization of nitrogen in the environment and its adaptation to the harsh environment of acid and low oxygen in macrophages are closely related to nitrogen metabolism. In addition, the dormancy state and drug resistance of M. tuberculosis are closely related to nitrogen metabolism. Although nitrogen metabolism is so important, limited research was performed on nitrogen metabolism as compared with carbon metabolism. M. tuberculosis can use a variety of inorganic or organic nitrogen sources, including ammonium salts, nitrate, glutamine, asparagine, etc. In these metabolic pathways, some enzymes encoded by key genes, such as GlnA1, AnsP2, etc, play important regulatory roles in the pathogenesis of TB. Although various small molecule inhibitors and drugs have been developed for different nitrogen metabolism processes, however, long-term validation is needed before their practical application. Most importantly, with the emergence of multidrug-resistant strains, eradication, and control of M. tuberculosis will still be very challenging.

Molnupiravir Inhibits Porcine Epidemic Diarrhea Virus Infection In Vitro.

Porcine epidemic diarrhea virus (PEDV) is a swine coronavirus that is highly infectious and prone to variation. Vaccines derived from traditional PEDV strains provide less protection against PEDV-variant strains. Furthermore; there is a complex diversity of sequences among various PEDV-variant strains. Therefore; there is an urgent need to develop alternative antiviral strategies to defend against PEDV. Molnupiravir is a nucleotide analogue that could replace natural nucleosides to restrain viral RNA replication. Our study provided evidence for the dose-dependent inhibition of PEDV replication by molnupiravir in Vero cells. Molnupiravir also exhibited a strong inhibitory effect on viral RNA and protein production. Our results demonstrated that molnupiravir inhibits PEDV RNA-dependent RNA polymerase (RdRp) activity and induces a high frequency of mutations in the PEDV genome. Further studies revealed that molnupiravir can reverse changes in the transcriptome caused by viral infection. In conclusion, our results indicated that molnupiravir has the potential to be an effective treatment for PEDV infection.

In situ cyclodextrin metal-organic framework/electrospun composite fibers with biosafety for the removal of volatile organic compounds.

Volatile organic compounds (VOCs) are one of the most common air pollutants, which threaten human health seriously. Fibrous textile is one of the most popular matrices for VOC removal in daily life. In this study, biosafe cyclodextrin metal-organic framework/polycaprolactone (CD-MOF/PCL) electrospun fibers were prepared via a CD precursor doping method, followed by hydrothermal treatment in methanol vapor diffusion. In situ CD-MOF crystals with a high loading of more than 50 wt% densely covered the surface of the electrospun fibers. The CD-MOF/PCL composite fibers show similar stress-strain behavior to the electrospun PCL fibers. The analysis of the fractured zone indicated that the compatibility of CD-MOF/PCL fibers was excellent, and CD-MOF showed no obvious peeling-off, even at low temperatures. The hemolysis rate of less than 1% confirms the biosafety of the composite materials. Further, the CD-MOF crystals anchored onto the fibers promote their VOC uptakes significantly. The CD-MOF/PCL fibrous matrix, which demonstrated compatibility, excellent strength, and biosafety would be beneficial to develop novel equipment to purify air pollution.

State- and stimulus-specific dynamics of SMAD signaling determine fate decisions in individual cells.

SMAD-mediated signaling regulates apoptosis, cell cycle arrest, and epithelial-to-mesenchymal transition to safeguard tissue homeostasis. However, it remains elusive how the relatively simple pathway can determine such a broad range of cell fate decisions and how it differentiates between varying ligands. Here, we systematically investigate how SMAD-mediated responses are modulated by various ligands of the transforming growth factor ß (TGFß) family and compare these ligand responses in quiescent and proliferating MCF10A cells. We find that the nature of the phenotypic response is mainly determined by the proliferation status, with migration and cell cycle arrest being dominant in proliferating cells for all tested TGFß family ligands, whereas cell death is the major outcome in quiescent cells. In both quiescent and proliferating cells, the identity of the ligand modulates the strength of the phenotypic response proportional to the dynamics of induced SMAD nuclear-to-cytoplasmic translocation and, as a consequence, the corresponding gene expression changes. Interestingly, the proliferation state of a cell has little impact on the set of genes induced by SMAD signaling; instead, it modulates the relative cellular sensitivity to TGFß superfamily members. Taken together, diversity of SMAD-mediated responses is mediated by differing cellular states, which determine ligand sensitivity and phenotypic effects, while the pathway itself merely serves as a quantitative relay from the cell membrane to the nucleus.

Bile Acid Derivatives Effectively Prevented High-Fat Diet-Induced Colonic Barrier Dysfunction.

SCOPE: Bile acids (BAs) have recently emerged as important regulators of many physiological and pathological processes. However, the change of colonic BAs induced by high-fat diet (HFD) and their effects on colonic barrier function remain to be further elucidated. METHODS AND RESULTS: C57BL/6 mice are divided into two groups and feed 12 weeks with diets differing for fat content. Higher levels of serum diamine oxidase (DAO) activity, endotoxin (ET), and d-lactate (d-LA) are observed in HFD-fed mice, indicating an increase in intestinal permeability. Real-time quantitative PCR and western blot analyses demonstrate that HFD downregulates tight junction proteins (TJs, including zonula-occludens 1 [ZO-1], Occludin, and Claudin1) and Muc2 expression in the colon. The colonic BA profiles are analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). HFD induces an increase in primary BAs but a decrease in secondary BAs. In human colonic cell line Caco-2, secondary BAs (deoxycholic acid [DCA], lithocholic acid [LCA], their 3-oxo- and iso- derivates) upregulate the expression of TJs and counteract DSS-induced increase in intestinal permeability at physiological concentrations. IsoDCA and isoLCA are the most effective ones. Moreover, supplementation of isoDCA or isoLCA also effectively prevents HFD-induced colonic barrier dysfunction in mice. CONCLUSION: These results demonstrate that secondary BAs (especially isomerized derivatives) may be important protectors for the colonic barrier function.

Passivity and passification of fractional-order memristive neural networks with time delays.

A class of fractional-order memristive neural networks (FMNNs) with time delays is studied. At first, the original network system is converted to fractional-order uncertain one to simplify the analysis by a variable transformation. Successively, some new LMIs-based passivity criteria are derived by differential inclusions, set-valued maps, inequality techniques and linear matrix inequality approach. Furthermore, a feedback control protocol is designed to solve the passification problem for the considered system, whose feedback control effect on different neurons can be changed artificially, which can be better applied to neural networks. The obtained results include some existing ones as special cases. A numerical example is proposed to illustrate the theoretical results.

The value of dual-energy spectral CT in differentiating solitary pulmonary tuberculosis and solitary lung adenocarcinoma.

Background: To explore the value of dual-energy spectral CT in distinguishing solitary pulmonary tuberculosis (SP-TB) from solitary lung adenocarcinoma (S-LUAD). Methods: A total of 246 patients confirmed SP-TB (n = 86) or S-LUAD (n = 160) were retrospectively included. Spectral CT parameters include CT40keV value, CT70keV value, iodine concentration (IC), water concentration (WC), effective atomic number (Zeff), and spectral curve slope (λ70keV). Data were measured during the arterial phase (AP) and venous phase (VP). Chi-square test was used to compare categorical variables, Wilcoxon rank-sum test was used to compare continuous variables, and a two-sample t-test was used to compare spectral CT parameters. ROC curves were used to calculate diagnostic efficiency. Results: There were significant differences in spectral CT quantitative parameters (including CT40keV value [all P< 0.001] , CT70keV value [all P< 0.001], λ70keV [P< 0.001, and P = 0.027], Zeff [P =0.015, and P = 0.001], and IC [P =0.002, and P = 0.028]) between the two groups during the AP and VP. However, WC (P = 0.930, and P = 0.823) was not statistically different between the two groups. The ROC curve analysis showed that the AUC in the AP and VP was 90.9% (95% CI, 0.873-0.945) and 83.4% (95% CI, 0.780-0.887), respectively. The highest diagnostic performance (AUC, 97.6%; 95% CI, 0.961-0.991) was achieved when all spectral CT parameters were combined with clinical variables. Conclusion: Dual-energy spectral CT has a significant value in distinguishing SP-TB from S-LUAD.

Imaging Stars with Quantum Error Correction.

The development of high-resolution, large-baseline optical interferometers would revolutionize astronomical imaging. However, classical techniques are hindered by physical limitations including loss, noise, and the fact that the received light is generally quantum in nature. We show how to overcome these issues using quantum communication techniques. We present a general framework for using quantum error correction codes for protecting and imaging starlight received at distant telescope sites. In our scheme, the quantum state of light is coherently captured into a nonradiative atomic state via stimulated Raman adiabatic passage, which is then imprinted into a quantum error correction code. The code protects the signal during subsequent potentially noisy operations necessary to extract the image parameters. We show that even a small quantum error correction code can offer significant protection against noise. For large codes, we find noise thresholds below which the information can be preserved. Our scheme represents an application for near-term quantum devices that can increase imaging resolution beyond what is feasible using classical techniques.

Optical quantum super-resolution imaging and hypothesis testing.

Estimating the angular separation between two incoherent thermal sources is a challenging task for direct imaging, especially at lengths within the diffraction limit. Moreover, detecting the presence of multiple sources of different brightness is an even more severe challenge. We experimentally demonstrate two tasks for super-resolution imaging based on hypothesis testing and quantum metrology techniques. We can significantly reduce the error probability for detecting a weak secondary source, even for small separations. We reduce the experimental complexity to a simple interferometer: we show (1) our set-up is optimal for the state discrimination task, and (2) if the two sources are equally bright, then this measurement can super-resolve their angular separation. Using a collection baseline of 5.3 mm, we resolve the angular separation of two sources placed 15 µm apart at a distance of 1.0 m with a 1.7% accuracy - an almost 3-orders-of-magnitude improvement over shot-noise limited direct imaging.

Oxidative stress-induced lncRNA CYLD-AS1 promotes RPE inflammation via Nrf2/miR-134-5p/NF-κB signaling pathway.

Oxidative stress-induced damage to and dysfunction of retinal pigment epithelium (RPE) cells are important pathogenetic factors of age-related macular degeneration (AMD); however, the underlying molecular mechanism is not fully understood. Long noncoding RNAs (lncRNAs) have important roles in various biological processes. In this study, using an oxidative damage model in RPE cells, we identified a novel oxidation-related lncRNA named CYLD-AS1. We further revealed that the expression of CYLD-AS1 was increased in RPEs during oxidative stress. Depletion of CYLD-AS1 promoted cell proliferation and mitochondrial function and protected RPE cells against hydrogen peroxide (H2 O2 )-induced damage. Mechanistically, CYLD-AS1 also regulated the expression of NRF2, which is related to oxidative stress, and NF-κB signaling pathway members, which are related to inflammation. Remarkably, these two signaling pathways were mediated by the CYLD-AS1 interactor miR-134-5p. Moreover, exosomes secreted by CYLD-AS1 knockdown RPE cells had a lower proinflammatory effect than those secreted by control cells. In summary, our study revealed that CYLD-AS1 affects the oxidative stress-related and inflammatory functions of RPE cells by sponging miR-134-5p to mediate NRF2/NF-κB signaling pathway activity, suggesting that targeting CYLD-AS1 could be a promising strategy for the treatment of AMD and related diseases.

Human Pulse Detection by a Soft Tactile Actuator.

Soft sensing technologies offer promising prospects in the fields of soft robots, wearable devices, and biomedical instruments. However, the structural design, fabrication process, and sensing algorithm design of the soft devices confront great difficulties. In this paper, a soft tactile actuator (STA) with both the actuation function and sensing function is presented. The tactile physiotherapy finger of the STA was fabricated by a fluid silica gel material. Before pulse detection, the tactile physiotherapy finger was actuated to the detection position by injecting compressed air into its chamber. The pulse detecting algorithm, which realized the pulse detection function of the STA, is presented. Finally, in actual pulse detection experiments, the pulse values of the volunteers detected by using the STA and by employing a professional pulse meter were close, which illustrates the effectiveness of the pulse detecting algorithm of the STA.

Generating Somatic Knockout Cell Lines with CRISPR-Cas9 Technology to Investigate SMAD Signaling.

Genome engineering provides a powerful tool to explore TGF-ß/SMAD signaling by enabling the deletion and modification of critical components of the pathway. Over the past years, CRISPR-Cas9 technology has matured and can now be used to routinely generate knockout cell lines. Here, we describe a method to design and generate deletions of genes from the SMAD pathway in somatic human cell lines based on homologous recombination.

Quantum Hypothesis Testing for Exoplanet Detection.

Detecting the faint emission of a secondary source in the proximity of the much brighter one has been the most severe obstacle for using direct imaging in searching for exoplanets. Using quantum state discrimination and quantum imaging techniques, we show that one can significantly reduce the probability of error for detecting the presence of a weak secondary source, especially when the two sources have small angular separations. If the weak source has intensity ε≪1 relative to the bright source, we find that the error exponent can be improved by a factor of 1/ε. We also find linear-optical measurements that are optimal in this regime. Our result serves as a complementary method in the toolbox of optical imaging, with applications ranging from astronomy to microscopy.

Dietary Protein From Different Sources Exerted a Great Impact on Lipid Metabolism and Mitochondrial Oxidative Phosphorylation in Rat Liver.

Associations between meat diets and human health have been widely considered. In this study, we focused on long-term effects of different sources of meat protein on liver metabolic enzymes. For 90 days, rats were fed with semisynthetic diets that differed only with protein source. Casein was used as a reference and isolated soybean, fish, chicken, pork, and beef proteins were compared. Changes in liver proteome were determined by isobaric tag for relative and absolute quantitation (iTRAQ) labeling and liquid chromatography electrospray ionization tandem mass spectrometry/mass spectrometry (LC-ESI-MS/MS). Fish and pork protein diets upregulated the gene expression involved in cholesterol synthesis and esterification, and pork protein diet also upregulated the gene expression of high-density lipoprotein receptor and low-density lipoprotein receptor. Chicken, pork, and beef protein diets upregulated the gene expression involved in cholesterol reverse transport and bile acid production, which increased the total cholesterol level in the fish protein diet group. Total cholesterol levels in liver were lower in the pork and beef protein diet groups. Triglyceride levels in liver were lower in chicken, pork, and beef protein diet groups. Peroxisomal proliferator-activated receptor-gamma coactivator-1 was upregulated by chicken, pork and beef protein diets, and promoted the degradation and metabolism of triglyceride, resulting in lower triglyceride in the three diet groups. Meat proteins at a recommended level could be more conducive to cholesterol degradation, triglyceride decomposition, and energy balance maintenance at a healthy level. The findings give a new insight into the associations between meat diet intake and human health.

Validation of an 8-item Recovery Assessment Scale (RAS-8) for people with schizophrenia in China.

BACKGROUND: The 24-item Recovery Assessment Scale (RAS) is the most widely-used and well-validated tool for measuring recovery for people with mental illness. The current study aims to assess the reliability and validity of an 8-item short form of RAS (RAS-8) among a Chinese sample of people living with schizophrenia. METHODS: A sample of 400 people living with schizophrenia were recruited for scale validation. Internal consistency was tested by calculating Cronbach's α. Test-retest reliability was calculated using the intraclass correlation coefficient (ICC) for the total score and weighted kappa for each item. Factor structure was tested with confirmatory factor analysis, and concurrent validity was examined by investigating the correlation of the RAS-8 with patient symptoms, disability, depression, anxiety, patient functioning, quality of life and general health. RESULTS: The RAS-8 full scale and subscales showed good internal consistency with Cronbach's alpha ranging from 0.87 to 0.92. ICC of 0.99 and weighted kappa ranged from 0.62 to 0.88, which generally indicates good test-retest reliability. The findings supported an a priori two-factor structure, χ2/df = 2.93, CFI = 0.98, TLI = 0.98, RMSEA = 0.07, SRMR = 0.035. Concurrent validity of the RAS-8 was further supported by its significant negative correlations with patient symptoms (r = -0.24, p < 0.01), disability (r = -0.30, p < 0.01), depression (r = -0.16, p < 0.05), and anxiety (r = -0.14, p < 0.05), and its significant positive relationships with patient functioning (r = 0.26, p < 0.01), quality of life (r = 0.39, p < 0.01) and general health (r = 0.34, p < 0.01). CONCLUSIONS: This study confirmed the reliability and validity of an 8-item short-form RAS for people living with schizophrenia in Chinese communities. The validation of the RAS-8 allows for its use as an alternative for the full RAS as a rapid assessment tool in clinical and research settings. The findings are discussed for their implications for application and validation with other populations and in other countries.