Construction of a Near-Infrared Fluorescent Probe for Dynamic Monitoring and Early Diagnosis of Heart Failure.

Cardiac hypertrophy characterized by abnormal cardiomyocyte viscosity is a typical sign of heart failure (HF) with vital importance for early diagnosis. However, current biochemical and imaging diagnostic methods are unable to detect this subclinical manifestation. In this work, we developed a series of NIR-I fluorescence probes for detecting myocardial viscosity based on the pyridazinone scaffold. The probes showed weak fluorescence due to free intramolecular rotation under low-viscosity conditions, while they displayed strong fluorescence with limited intramolecular rotation in response to a high-viscosity environment. Among them, CarVis2 exhibited higher stability and photobleaching resistance than commercial dyes. Its specific response to viscosity was not influenced by the pH and biological species. Furthermore, CarVis2 showed rapid and accurate responses to the viscosity of isoproterenol (ISO)-treated H9C2 cardiomyocytes with good biocompatibility. More importantly, CarVis2 demonstrated excellent sensitivity in monitoring myocardial viscosity variation in HF mice in vivo, potentially enabling earlier noninvasive identification of myocardial abnormalities compared to traditional clinical imaging and biomarkers. These findings revealed that CarVis2 can serve as a powerful tool to monitor myocardial viscosity, providing the potential to advance insights into a pathophysiological mechanism and offering a new reference strategy for early visual diagnosis of HF.

Contrast-induced acute kidney injury: a review of definition, pathogenesis, risk factors, prevention and treatment.

Contrast-induced acute kidney injury (CI-AKI) has become the third leading cause of hospital-acquired AKI, which seriously threatens the health of patients. To date, the precise pathogenesis of CI-AKI has remained not clear and may be related to the direct cytotoxicity, hypoxia and ischemia of medulla, and oxidative stress caused by iodine contrast medium, which have diverse physicochemical properties, including cytotoxicity, permeability and viscosity. The latest research shows that microRNAs (miRNAs) are also involved in apoptosis, pyroptosis, and autophagy which caused by iodine contrast medium (ICM), which may be implicated in the pathogenesis of CI-AKI. Unfortunately, effective therapy of CI-AKI is very limited at present. Therefore, effective prevention of CI-AKI is of great significance, and several preventive options, including hydration, antagonistic vasoconstriction, and antioxidant drugs, have been developed. Here, we review current knowledge about the features of iodine contrast medium, the definition, pathogenesis, molecular mechanism, risk factors, prevention and treatment of CI-AKI.

TLFND: A Multimodal Fusion Model Based on Three-Level Feature Matching Distance for Fake News Detection.

In the rapidly evolving information era, the dissemination of information has become swifter and more extensive. Fake news, in particular, spreads more rapidly and is produced at a lower cost compared to genuine news. While researchers have developed various methods for the automated detection of fake news, challenges such as the presence of multimodal information in news articles or insufficient multimodal data have hindered their detection efficacy. To address these challenges, we introduce a novel multimodal fusion model (TLFND) based on a three-level feature matching distance approach for fake news detection. TLFND comprises four core components: a two-level text feature extraction module, an image extraction and fusion module, a three-level feature matching score module, and a multimodal integrated recognition module. This model seamlessly combines two levels of text information (headline and body) and image data (multi-image fusion) within news articles. Notably, we introduce the Chebyshev distance metric for the first time to calculate matching scores among these three modalities. Additionally, we design an adaptive evolutionary algorithm for computing the loss functions of the four model components. Our comprehensive experiments on three real-world publicly available datasets validate the effectiveness of our proposed model, with remarkable improvements demonstrated across all four evaluation metrics for the PolitiFact, GossipCop, and Twitter datasets, resulting in an F1 score increase of 6.6%, 2.9%, and 2.3%, respectively.

[Geochemical Background and Baseline Value of Soil Chemical Elements in Hebei Province].

Geochemical background and baseline values are important parameters for understanding the geochemical characteristics of soil elements, but the research degree of these two parameters is lacking in Hebei Province. Therefore, data from the multi-purpose regional geochemical survey and land quality geochemical assessment in Hebei Province from 2004 to 2018 were collected, covering approximately 71% of the land area of the whole province. Based on the data of surface soil and deep soil, scientific and robust methods including median value and median absolute deviation were used to calculate the geochemical background values, geochemical baseline values, as well as variation ranges of 54 indexes (Ag, Al2O3, As, Au, B, Ba, Be, Bi, Br, CaO, Cd, Ce, Cl, Co, Cr, Cu, F, Fe2O3, Ga, Ge, Hg, I, K2O, La, Li, MgO, Mn, Mo, N, Na2O, Nb, Ni, P, Pb, pH, Rb, S, Sb, Sc, Se, SiO2, Sn, Sr, Th, Ti, Tl, U, V, W, Y, Zn, Zr, total carbon (TC), and organic carbon (Corg)) in Hebei Province and 11 prefecture-level cities. The change rate in geochemical background for each index was also calculated. The results showed that the geochemical background and baseline values of most soil chemical elements in Hebei Province were lower than those nationwide, but the values of Ba, Br, Cl, MgO, Na2O, P, pH, S, Sr, and TC were higher, with CaO being the highest. Compared with those in north China, there was no significant difference in the geochemical background and baseline values for the 54 indexes, with the ratios of 0.83-1.17 and 0.79-1.19, respectively. Significant changes in the geochemical background for Corg, Hg, N, P, S, and Se were observed in Hebei Province, indicating that these indexes were greatly influenced by human factors. Preliminary analysis suggests that coal burning emissions and agricultural chemical use were two very important inducing factors.

Baicalin Alleviates Contrast-Induced Acute Kidney Injury Through ROS/NLRP3/Caspase-1/GSDMD Pathway-Mediated Proptosis in vitro.

Purpose: To investigate the effect of baicalin on the reactive oxygen species (ROS)/ NOD-like receptor protein 3 (NLRP3)/Caspase-1/gasdermin-D (GSDMD) inflammasome pathway and its related mechanism in regulating pyroptosis of human renal tubular epithelial cells (HK-2) induced by contrast media. Methods: Iohexol was used to act on HK-2 cells to establish a renal tubular cell pyroptosis model; and the signal pathway genes were silenced, cytokines were detected by enzyme-linked immunosorbent assay (ELISA), and cell viability, gene expression, and protein expression were evaluated by double fluorescence staining and flow cytometry. To assess the cytotoxicity caused by the contrast agent; cells were pretreated with different concentrations of baicalin; and then the cells were exposed to iohexol again, and the relevant indicators were tested again. Results: After HK-2 cells were exposed to iohexol, the NLRP3 inflammasome pathway markers NLRP3, interleukin (IL)-1ß, and IL-18 mRNA levels as well as the protein expression levels of NLRP3, ASC, Caspase-1, and GSDMD were up-regulated. In addition, the effect also significantly increased the IL-18, IL-1ß, lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA) release, and cellular ROS levels. The results of Annexin V-FITC/PI flow cytometry showed that the level of apoptosis was increased. However, after the intervention of baicalin, the changes in the above indexes caused by iohexol stimulation of HK-2 cells were inhibited. Conclusion: Exposure to iohexol can induce pyroptosis of HK-2 cells through the ROS/NLRP3/Caspase-1/GSDMD signaling pathway. Baicalin ameliorated iohexol-induced pyroptosis in HK-2 cells by regulating the NLRP3 inflammasome pathway.

Glutamatergic synapses from the insular cortex to the basolateral amygdala encode observational pain.

Empathic pain has attracted the interest of a substantial number of researchers studying the social transfer of pain in the sociological, psychological, and neuroscience fields. However, the neural mechanism of empathic pain remains elusive. Here, we establish a long-term observational pain model in mice and find that glutamatergic projection from the insular cortex (IC) to the basolateral amygdala (BLA) is critical for the formation of observational pain. The selective activation or inhibition of the IC-BLA projection pathway strengthens or weakens the intensity of observational pain, respectively. The synaptic molecules are screened, and the upregulated synaptotagmin-2 and RIM3 are identified as key signals in controlling the increased synaptic glutamate transmission from the IC to the BLA. Together, these results reveal the molecular and synaptic mechanisms of a previously unidentified neural pathway that regulates observational pain in mice.

Social media study of public opinions on potential COVID-19 vaccines: informing dissent, disparities, and dissemination.

Background The current development of vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unprecedented. Little is known, however, about the nuanced public opinions on the vaccines on social media. Methods We adopted a human-guided machine learning framework using more than six million tweets from almost two million unique Twitter users to capture public opinions on the vaccines for SARS-CoV-2, classifying them into three groups: pro-vaccine, vaccine-hesitant, and anti-vaccine. After feature inference and opinion mining, 10,945 unique Twitter users were included in the study population. Multinomial logistic regression and counterfactual analysis were conducted. Results Socioeconomically disadvantaged groups were more likely to hold polarized opinions on coronavirus disease 2019 (COVID-19) vaccines, either pro-vaccine ( B = 0.40 , SE = 0.08 , P < 0.001 , OR = 1.49 ; 95 % CI = 1.26 -- 1.75 ) or anti-vaccine ( B = 0.52 , SE = 0.06 , P < 0.001 , OR = 1.69 ; 95 % CI = 1.49 -- 1.91 ). People who have the worst personal pandemic experience were more likely to hold the anti-vaccine opinion ( B = - 0.18 , SE = 0.04 , P < 0.001 , OR = 0.84 ; 95 % CI = 0.77 -- 0.90 ). The United States public is most concerned about the safety, effectiveness, and political issues regarding vaccines for COVID-19, and improving personal pandemic experience increases the vaccine acceptance level. Conclusion Opinion on COVID-19 vaccine uptake varies across people of different characteristics.

Value of multiphase contrast-enhanced CT with three-dimensional reconstruction in detecting depth of infiltration, lymph node metastasis, and extramural vascular invasion of gastric cancer.

BACKGROUND: Multiphase contrast-enhanced computed tomography (CECT) can reveal the location, morphology, size, and enhancement pattern of gastric cancer (GC), whereas the three-dimensional reconstruction (3DR) technique can better display the relationships of the lesions with surrounding structures, the feeding vessels, and lymph node metastasis. Here, we investigated the value of multi-phase CECT with 3DR in detecting depth of infiltration, lymph node metastasis, and extramural vascular invasion (EMVI) of GC. METHODS: The clinical and imaging data of 132 GC patients admitted to the Chongqing Hospital of Traditional Chinese Medicine and the Third Affiliated Hospital of Chongqing Medical University during the period from January 2012 to October 2019 were collected. All patients received plain and multiphase contrast-enhanced CT scans. The agreement between the results of preoperative CT evaluation and the surgical/pathological findings was compared. RESULTS: (I) CT findings of GC of 3 differentiation levels: on the multiphase CECT, the peak enhancement percentage was highest in the portal venous phase. The CT values significantly differed among the arterial, portal venous, and equilibrium phases (P<0.05); the differences in the arterial, portal venous, and equilibrium phases were statistically significant among the well-, moderately, and poorly differentiated groups (all P<0.05); finally, the difference in the equilibrium phase was statistically significant between the well- and moderately differentiated groups (P<0.05). (II) Preoperative CT and postoperative pathology had good consistency in T staging (Kappa =0.667). (III) The Kappa values between the preoperative CT-diagnosed lymph node metastasis and postoperative pathologically showing an increasing consistency with the increase of CT enhancement differences. (IV) Preoperative CT and postoperative pathology had good consistency in N staging (Kappa =0.779). (V) Preoperative CT in displaying arterial supply to the stomach. The rate of positive EMVI was 32.6% (43/132) on preoperative CT. The positive EMVI diagnosed by preoperative CT was correlated with tumor size, growth pattern, tissue differentiation degree, T stage, and N stage (all P<0.05). CONCLUSIONS: Multiphase CECT combined with 3DR has high diagnostic performance in detecting the depth of infiltration, lymph node metastasis, and EMVI of GC.

RNF31 mediated ubiquitination of A20 aggravates inflammation and hepatocyte apoptosis through the TLR4/MyD88/NF-κB signaling pathway.

Inflammatory cytokine storm is one of the main pathogenesis of acute liver injury, and accumulating evidence suggests that the E3 ubiquitin ligase ring finger protein 31 (RNF31) plays an important regulatory role in the activation of inflammatory pathways. We found that RNF31 expression was up-regulated in lipopolysaccharide (LPS)-treated HL-7702 cells. Western blotting results showed decreased expression of RNF31 and total ubiquitinated proteins after transfection of si-RNF31. The results of MTT assay indicated that cell viability was enhanced. Flow cytometry analysis showed that cell apoptosis and ROS content was decreased, and ELISA assay results exhibited that the inflammatory factors secretion was reduced. Interestingly, A20 protein expression was inhibited as RNF31 expression was upregulated. On this basis, we performed co-immunoprecipitation assays and found that RNF31 could interact with A20. Actinomycin tracing and proteasome inhibition experiments showed that RNF31 degrades A20 through the proteasome pathway. Furthermore, overexpression of A20 enhanced cell viability, reduced apoptosis, and inhibited ROS generation and inflammatory factor secretion. Mechanistic studies revealed that RNF31 was able to degrade A20, which affected the inflammatory response and hepatocyte apoptosis mediated by the toll like receptor 4 (TLR4)/myeloid differentiation factor88 (MyD88)/nuclear transcription factor-κB (NF-κB) signaling pathway. Moreover, knockdown of RNF31 attenuated the inflammatory response induced by d-Gal/LPS in mice with acute liver injury. In conclusion, RNF31 degrades A20 by ubiquitination and activates the TLR4/MyD88/NF-κB signaling pathway to aggravate acute liver injury.

Early Diagnosis of Cerebral Ischemia Reperfusion Injury and Revelation of Its Regional Development by a H3R Receptor-Directed Probe.

In vivo imaging of cerebral hydrogen peroxide (H2O2) may facilitate early diagnosis of cerebral ischemia reperfusion injury (CIRI) and a revelation of its pathological progression. In this study, we report our rational design of a brain-targeting fluorescent probe using the basis of a pyridazinone scaffold. A structure-activity relationship study reveals that PCAB is the best candidate (Ki = 15.8 nM) for a histamine H3 receptor (H3R), which is highly expressed in neurons of the central nervous system. As a two-photon fluorescent probe, PCAB exhibits a fast, selective reaction toward both extra- and intracellular H2O2 in SH-SY5Y cells under oxygen glucose deprivation and resupply. In vivo fluorescent imaging of a middle cerebral artery occlusion mouse confirms that PCAB is an ultrasensitive probe with potent blood-brain barrier penetration, precise brain targeting, and fast detection of CIRI.

Neurotensin Attenuates Nociception by Facilitating Inhibitory Synaptic Transmission in the Mouse Spinal Cord.

Neurotensin (NT) is an endogenous tridecapeptide in the central nervous system. NT-containing neurons and NT receptors are widely distributed in the spinal dorsal horn (SDH), indicating their possible modulatory roles in nociception processing. However, the exact distribution and function of NT, as well as NT receptors (NTRs) expression in the SDH, have not been well documented. Among the four NTR subtypes, NTR2 is predominantly involved in central analgesia according to previous reports. However, the expression and function of NTR2 in the SDH has not yet been directly elucidated. Specifically, it remains unclear how NT-NTR2 interactions contribute to NT-mediated analgesia. In the present study, by using immunofluorescent histochemical staining and immunohistochemical staining with in situ hybridization histochemical staining, we found that dense NT- immunoreactivity (NT-ir) and moderate NTR2-ir neuronal cell bodies and fibers were localized throughout the superficial laminae (laminae I-II) of the SDH at the light microscopic level. In addition, γ-aminobutyric acid (GABA) and NTR2 mRNA were colocalized in some neuronal cell bodies, predominantly in lamina II. Using confocal and electron microscopy, we also observed that NT-ir terminals made both close contacts and asymmetrical synapses with the local GABA-ir neurons. Second, electrophysiological recordings showed that NT facilitated inhibitory synaptic transmission but not glutamatergic excitatory synaptic transmission. Inactivation of NTR2 abolished the NT actions on both GABAergic and glycinergic synaptic release. Moreover, a behavioral study revealed that intrathecal injection of NT attenuated thermal pain, mechanical pain, and formalin induced acute inflammatory pain primarily by activating NTR2. Taken together, the present results provide direct evidence that NT-containing terminals and fibers, as well as NTR2-expressing neurons are widely distributed in the spinal dorsal horn, GABA-containing neurons express NTR2 mainly in lamina II, GABA coexists with NTR2 mainly in lamina II, and NT may directly increase the activity of local inhibitory neurons through NTR2 and induce analgesic effects.

The effect of Malus doumeri leaf flavonoids on oxidative stress injury induced by hydrogen peroxide (H2O2) in human embryonic kidney 293 T cells.

BACKGROUND: In this study, Malus doumeri leaf flavonoids (MDLF) were used as the research object to observe their in vitro antioxidant stress ability. Hydrogen peroxide (H2O2) was used to induce oxidative stress in 293 T cells. METHODS: MTT, flow cytometry, and qPCR were used to verify the effect of MDLF. RESULTS: In vitro cell experiments showed that at a concentration of 0-160 µg/mL, MDLF did not affect the normal proliferation of human embryonic kidney 293 T cells (HEK 293 T cells), and MDLF had no cytotoxic effect in this concentration range. It was found that MDLF could maintain the survival of HEK 293 T cells (82.6%) at a high concentration (160 µg/mL). Morphological observation also found that MDLF can inhibit the cell structure imperfection caused by H2O2. It was also observed that MDLF could significantly increase the levels of catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) and reduce the level of malondialdehyde (MDA). The results of quantitative polymerase chain reaction (qPCR) showed that MDLF could significantly up-regulate the mRNA expression levels of CAT, SOD, GSH, GSH-Px, B-cell lymphoma-2 (Bcl-2) and downregulate the expression levels of B-cell lymphoma-2 associated x protein (Bax), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa-B (NF-κB) in oxidative stress-injured cells. The HPLC analysis showed that MDLF contained hyperin, isoquercetin, quercitrin, hesperidin, myricetin, baicalin and quercetin. CONCLUSION: From the experimental results, it was observed that MDLF has a strong anti-oxidation ability in vitro, and it can interfere with the oxidative stress damage caused by H2O2 in 293 T cells. Therefore, MDLF is a type of natural substance with good anti-oxidant effect, and it has the potential to interfere with many diseases.

A Smart Fluorescent Probe for NO Detection and Application in Myocardial Fibrosis Imaging.

On the basis of the pyridazinone scaffold and photoinduced electron transfer (PET) mechanism, we designed a smart nitric oxide (NO) probe, PYSNO, with high sensitivity and selectivity. PYSNO exhibited a rapid response to both exogenous and endogenous NO. This probe can also be used in tracking and investigating NO generation in animal tissue. In the myocardial fibrosis model for mice, PYSNO exhibited a powerful imaging property in vivo as a result of unravelling the progressive relationship between the generation of myocardial NO and the occurrence of myocardial fibrosis.