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Abstract Background Chronic obstructive pulmonary disease (COPD) is a widespread respiratory disease. This study examines extracellular vesicles (EVs) and proteins contained in EVs in COPD. Methods Blood samples were collected from 40 COPD patients and 10 health controls. Cytokines including IFN-γ, TNF-α, IL-1β, IL-6, IL-8, and IL-17, were measured by ELISA. Small EVs samples were extracted from plasma and identified by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA), and Western blot. Protein components contained in EVs were analyzed by Tandem Mass Tags (TMT) to identify differential proteins. Treg-derived EV was extracted and added to isolated CD8+, Treg, and Th17 subsets to assess its effect on T-lymphocytes. Results ELISA revealed higher levels of all cytokines and flow cytometry suggested a higher proportion of Treg and Th17 cells in COPD patients. After identification, TMT analysis identified 207 unique protein components, including five potential COPD biomarkers: BTRC, TRIM28, CD209, NCOA3, and SSR3. Flow cytometry revealed that Treg-derived EVs inhibited differentiation into CD8+, CD4+, and Th17 cells. Conclusion The study shows that cytokines, T-lymphocyte subsets differences in COPD and Treg-derived EVs influence T-lymphocyte differentiation. Identified biomarkers may assist in understanding COPD pathogenesis, prognosis, and therapy. The study contributes to COPD biomarker research.

Fibrosis is usually the final pathological state of many chronic inflammatory diseases and may lead to organ malfunction. Excessive deposition of extracellular matrix (ECM) molecules is a characteristic of most fibrotic tissues. The blood vessel wall contains three layers of membrane structure, including the intima, which is composed of endothelial cells; the media, which is composed of smooth muscle cells; and the adventitia, which is formed by the interaction of connective tissue and fibroblasts. The occurrence and progression of vascular remodeling are closely associated with cardiovascular diseases, and vascular remodeling can alter the original structure and function of the blood vessel. Dysregulation of the composition of the extracellular matrix in blood vessels leads to the continuous advancement of vascular stiffening and fibrosis. Vascular fibrosis reaction leads to excessive deposition of the extracellular matrix in the vascular adventitia, reduces vessel compliance, and ultimately alters key aspects of vascular biomechanics. The pathogenesis of fibrosis in the vasculature and strategies for its reversal have become interesting and important challenges. Ion channels are widely expressed in the cardiovascular system; they regulate blood pressure, maintain cardiovascular function homeostasis, and play important roles in ion transport, cell differentiation, proliferation. In blood vessels, different types of ion channels in fibroblasts, smooth muscle cells and endothelial cells may be relevant mediators of the development of fibrosis in organs or tissues. This review discusses the known roles of ion channels in vascular fibrosis remodeling and discusses potential therapeutic targets for regulating remodeling and repair after vascular injury.

Abstract A series of arecoline derivatives with amino acid moieties were designed and synthesised using an acylamide condensation strategy, taking arecoline as the foundational structure. The insecticidal efficacy of these compounds against Aphis craccivora and Tetranychus cinnabarinus was evaluated. Notably, derivatives 3h and 3i demonstrated superior insecticidal activity compared with arecoline. Additionally, 3h and 3i showed good fungicidal effectiveness against two types of plant fungi. Moreover, molecular docking analyses suggested that 3h and 3i could affect the nervous systems of A. craccivora and T. cinnabarinus by binding to neuronal nicotinic acetylcholine receptors. These findings suggest that compounds 3h and 3i represent promising leads for further development in insecticide and fungicide research.

Abstract Myocardial infarction (MI) is a leading cause of death worldwide. Few drugs hold the ability to depress cardiac electrical and structural remodeling simultaneously after MI, which is crucial for the treatment of MI. The aim of this study is to investigate an effective therapy to improve both electrical and structural remodeling of the heart caused by MI. Here, an “ion cocktail therapy” is proposed to simultaneously reverse cardiac structural and electrical remodeling post‐MI in rats and minipigs by applying a unique combination of silicate, strontium (Sr) and copper (Cu) ions due to their specific regulatory effects on the behavior of the key cells involved in MI including angiogenesis of endothelial cells, M2 polarization of macrophages and apoptosis of cardiomyocyte. The results demonstrate that ion cocktail treatment attenuates structural remodeling post‐MI by ameliorating infarct size, promoting angiogenesis in both peri‐infarct and infarct areas. Meantime, to some extent, ion cocktail treatment reverses the deteriorative electrical remodeling by reducing the incidence rate of early/delayed afterdepolarizations and minimizing the heterogeneity of cardiac electrophysiology. This ion cocktail therapy reveals a new strategy to effectively treat MI with great clinical translation potential due to the high effectiveness and safety of the ion cocktail combination.

Abstract Background Rubber plant (Hevea brasiliensis) is one of the major sources of latex. Somatic embryogenesis (SE) is a promising alterative to its propagation by grafting and seed. Phytohormones have been shown to influence SE in different plant species. However, limited knowledge is available on the role of phytohormones in SE in Hevea. The anther cultures of two Hevea genotypes (Yunyan 73477-YT and Reken 628-RT) with contrasting SE rate were established and four stages i.e., anthers (h), anther induced callus (y), callus differentiation state (f), and somatic embryos (p) were studied. UPLC-ESI-MS/MS and transcriptome analyses were used to study phytohormone accumulation and related expression changes in biosynthesis and signaling genes. Results YT showed higher callus induction rate than RT. Of the two genotypes, only YT exhibited successful SE. Auxins, cytokinins (CKs), abscisic acid (ABA), jasmonic acid (JA), salicylic acid (SA), gibberellins (GAs), and ethylene (ETH) were detected in the two genotypes. Indole-3-acetic acid (IAA), CKs, ABA, and ETH had notable differences in the studied stages of the two genotypes. The differentially expressed genes identified in treatment comparisons were majorly enriched in MAPK and phytohormone signaling, biosynthesis of secondary metabolites, and metabolic pathways. The expression changes in IAA, CK, ABA, and ETH biosynthesis and signaling genes confirmed the differential accumulation of respective phytohormones in the two genotypes. Conclusion These results suggest potential roles of phytohormones in SE in Hevea.

Estimating the impact of pesticide residue bioaccessibility in fruits on dietary exposure is a complex task in human health risk assessment. This research investigated the bioaccessibility of ten commonly used and detected pesticides in bananas and mangoes, as well as the factors influencing it, using an in vitro model. The highest bioaccessibility was observed at pH levels of 2.5 and 6.5 in the gastric and intestinal stages, respectively. Bioaccessibility decreased significantly with increasing solid/liquid ratios for most pesticides. The consumption of protein and four dietary components (carbohydrates, protein, lipids, and dietary fiber) could significantly reduce pesticide bioaccessibility by 9.89–48.32% (p < 0.05). Bioaccessibility in oral and gastric stages among four populations followed the order of adults/the elderly > children > infants, due to decreasing concentrations of α-amylase and pepsin. Pesticides in bananas generally exhibited a higher bioaccessibility (18.65–82.97%) compared to that in mangoes (11.68–87.57%). Bioaccessibility showed a negative correlation with the Log P values of the target pesticide, while no clear relationship was found between bioaccessibility and initial pesticide concentrations. Incorporating bioaccessible pesticide concentrations into risk assessments could lower dietary risk estimates by 11.85–79.57%. Assessing human exposure to pesticides based on bioaccessibility would greatly improve the accuracy of the risk assessment.

This study presents a method for analyzing dimethomorph residues in lychee using QuEChERS extraction and HPLC-MS/MS. The validation parameters for this method, which include accuracy, precision, linearity, and recovery, indicate that it meets standard validation requirements. Following first-order kinetics, the dissipation dynamic of dimethomorph in lychee was determined to range from 6.4 to 9.2 days. Analysis of terminal residues revealed that residues in whole lychee were substantially greater than those in the pulp, indicating that dimethomorph residues are predominantly concentrated in the peel. When applied twice and thrice at two dosage levels with pre-harvest intervals (PHIs) of 5, 7, and 10 days, the terminal residues in whole lychee ranged from 0.092 to 1.99 mg/kg. The terminal residues of the pulp ranged from 0.01 to 0.18 mg/kg, with the residue ratio of whole lychee to pulp consistently exceeding one. The risk quotient (RQ) for dimethomorph, even at the recommended dosage, was less than one, indicating that the potential for damage was negligible. This study contributes to the establishment of maximum residue limits (MRLs) in China by providing essential information on the safe application of dimethomorph in lychee orchards.

Abstract In this work a simple, rapid, and environmentally friendly method has been established for the determination of chlorpyrifos residue in green tea by dispersive liquid–liquid microextraction and gas chromatography-flame photometric detection. Some experimental parameters that influence extraction efficiency, such as the kind and volume of disperser solvents and extraction solvents, extraction time, addition of salt and pH, were investigated. And the optimal experimental conditions were obtained, quantitative analysis was carried out using external standard method. The correlation coefficient of the calibration curves was 0.999 with in 0.05 mg/kg to 5 mg/kg. The results showed that under the optimum conditions, the enrichment factors of the chlorpyrifos was about 554.51, the recoveries for standard addition fell in the range from 91.94 to 104.70% and the relative standard deviations was 4.61%. The limit of quantification of chlorpyrifos in green tea was 0.02 μg/mL at the signal/noise ratio of 3.

BackgroundThoracic aortic aneurysm (TAA) occurs due to pathological aortal dilation, and both individuals with normal tricuspid aortic valves (TAV) or abnormal bicuspid aortic valves (BAV), the latter being a congenital condition, are at risk. However, some differences are present between TAA/BAV and TAA/TAV with respect to their pathophysiological processes and molecular mechanisms, but their exact nature is still mostly unknown. Therefore, it is necessary to elucidate TAA developmental differences among BAV vs. TAV patients.MethodsPublically-available gene expression datasets, aortic tissue derived from TAA/BAV and TAA/TAV individuals, were analyzed by weighted gene co-expression network analysis (WGCNA) to identify gene modules associated with those conditions. Gene Ontology (GO) enrichment analysis was performed on those modules to identify the enriched genes within those modules, which were verified by Gene Set Variation Analysis (GSVA) on a dataset derived from aortic smooth muscle cell gene expression between TAA/TAV and TAV/BAV patients. Immune cell infiltration patterns were then analyzed by CIBERSORT, and a protein-protein interaction (PPI) network was constructed based on WGCNA and enrichment analysis results to identify hub genes, followed by validation via stepwise regression analysis. Three signatures most strongly associated with TAA/TAV were confirmed by receiver operating characteristic (ROC) and decision curve analyses (DCA) between prior-established training and testing gene sets.ResultsWGCNA delineated 2 gene modules being associated with TAA/TAV vs. TAA/BAV; both were enriched for immune-associated genes, such as those relating to immune responses, etc., under enrichment analysis. TAA/TAV and TAA/BAV tissues also had differing infiltrating immune cell proportions, particularly with respect to dendritic, mast and CD4 memory T cells. Identified three signatures, CD86, integrin beta 2 (ITGB2) and alpha M (ITGAM), as yielding the strongest associations with TAA/TAV onset, which was verified by areas under the curve (AUC) at levels approximating 0.8 or above under ROC analysis, indicating their predictive value for TAA/TAV onset. However, we did not examine possible confounding variables, so there are many alternative explanations for this association.ConclusionsTAA/TAV pathogenesis was found to be more associated with immune-related gene expression compared to TAA/BAV, and the identification of three strongly-associated genes could facilitate their usage as future biomarkers for diagnosing the likelihood of TAA/TAV onset vs. TAA/BAV, as well as for developing future treatments.

Background The rubber tree (Hevea brasiliensis) is the only species capable of producing high-quality natural rubber for commercial use, and is often subjected to various abiotic stresses in non-traditional rubber plantation areas. Superoxide dismutase (SOD) is a vital metalloenzyme translated by a SOD gene family member and acts as a first-line of protection in plant cells by catalysing the disproportionation of reactive oxygen species (ROS) to produce H2O2 and O2. However, the SOD gene family is not reported in rubber trees. Methods Here, we used hidden markov model (HMM) and BLASTP methods to identify SOD genes in the H. brasiliensis genome. Phylogenetic tree, conserved motifs, gene structures, cis elements, and gene ontology annotation (GO) analyses were performed using MEGA 6.0, MEME, TBtools, PlantCARE, and eggNOG database, respectively. HbSOD gene expression profiles were analysed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results We identified nine HbSOD genes in the rubber tree genome, including five HbCSDs, two HbFSDs, and two HbMSDs. Phylogenetic relationship analysis classified the SOD proteins from the rubber tree and other related species into three subfamilies. The results of gene structure and conserved motif analysis illustrated that most HbSOD genes have similar exon-intron numbers and conserved motifs in the same evolutionary branch. Five hormone-related, four stress-related, and light-responsive elements were detected in the HbSODs’ promoters. HbSODs were expressed in different tissues, gradually increased with leaf development, and were abundantly expressed in mature leaves. HbCSD2 and HbCSD4 was significantly upregulated under low and high temperatures, and salt stress, except for HbCSD2, by heat. Furthermore, most HbSOD genes were significantly upregulated by drought, except HbMSD2. These findings imply that these genes may play vital roles in rubber tree stress resistance. Our results provide a basis for further studies on the functions of HbSOD genes in rubber trees and stress response mechanisms.

Geranylgeranylacetone (GGA) exerts cytoprotective activity against various toxic stressors via the thioredoxin (TRX) redox system; however, its effect on skin inflammation and molecular mechanism on inducing the TRX of GGA is still unknown. We investigated the effects of GGA in a murine irritant contact dermatitis (ICD) model induced by croton oil. Both a topical application and oral administration of GGA induced TRX production and Nrf2 activation. GGA ameliorated ear swelling, neutrophil infiltration, and inhibited the expression of TNF-α, IL-1β, GM-CSF, and 8-OHdG. GGA’s cytoprotective effect was stronger orally than topically in mice. In vitro studies also showed that GGA suppressed the expression of NLRP3, TNF-α, IL-1β, and GM-CSF and scavenged ROS in PAM212 cells after phorbol myristate acetate stimulation. Moreover, GGA induced endogenous TRX production and Nrf2 nuclear translocation in PAM212 cells (dependent on the presence of ROS) and activated the PI3K-Akt signaling pathway. GGA significantly downregulated thioredoxin-interacting protein (TXNIP) levels in PAM212 cells treated with or without Nrf2 siRNA. After knocking down Nrf2 in PAM212 cells, the effect of GGA on TRX induction was significantly inhibited. This suggests that GGA suppress ICD by inducing endogenous TRX, which may be regulated by PI3K/Akt/Nrf2 mediation of the TRX redox system.

Thioredoxin-1 (Trx1) is an important regulator of cellular redox homeostasis that comprises a redox-active dithiol. Trx1 is induced in response to various stress conditions, such as oxidative damage, infection or inflammation, metabolic dysfunction, irradiation, and chemical exposure. It has shown excellent anti-inflammatory and immunomodulatory effects in the treatment of various human inflammatory disorders in animal models. This review focused on the protective roles and mechanisms of Trx1 in allergic diseases, such as allergic asthma, contact dermatitis, food allergies, allergic rhinitis, and drug allergies. Trx1 plays an important role in allergic diseases through processes, such as antioxidation, inhibiting macrophage migration inhibitory factor (MIF), regulating Th1/Th2 immune balance, modulating allergic inflammatory cells, and suppressing complement activation. The regulatory mechanism of Trx1 differs from that of glucocorticoids that regulates the inflammatory reactions associated with immune response suppression. Furthermore, Trx1 exerts a beneficial effect on glucocorticoid resistance of allergic inflammation by inhibiting the production and internalization of MIF. Our results suggest that Trx1 has the potential for future success in translational research.

CCSDS LDPC code cannot effectively solve the problems of communication interruptions and high communication error rates in deep space communication. An application scheme of digital fountain code for deep space communication is thoroughly studied in this paper. First, an improved joint coding and decoding algorithm for LT code is proposed by adjusting the probability of the source symbol selection to achieve a nonuniform selection coding algorithm and by introducing the idea of real-time decoding on the basis of combining the BP and GE decoding algorithms to disperse the decoding complexity. Second, to ensure that the LT code can be reliably transmitted under different channel conditions, a feedback information extraction method and a retransmission coding method are designed, and an LT code transmission scheme based on key information feedback is proposed. Finally, the concatenation of the LDPC code with the LT code based on key information feedback is proposed. The LDPC code processing can be equivalently run on deep-space channels as erasure channels so that the advantage of the LT code being rateless can still be exploited in deep-space communication. Through simulation experiments, the performance of the cascade codes is analyzed from the two aspects of decoding efficiency and decoding overhead, and the performance of the cascade codes and CCSDS LDPC codes are compared from the perspective of the bit error rate. Simulation results show that the decoding efficiency of the cascade code increases, the decoding overhead decreases, and the communication bit error rate is lower in deep space communication compared with the CCSDS LDPC code. Therefore, the cascade code can improve the reliability of deep space communication.

BackgroundCompared with bone marrow mesenchymal stem cells (BMSCs), decidual mesenchymal stem cells (DMSCs) are easy to obtain and exhibit excellent angiogenic effects, but their role in cell transplantation after myocardial infarction (MI) remains unclear.MethodsBMSCs and DMSCs were harvested from healthy donors. The effects of both cell types on angiogenesis were observed in vitro. Metabonomics analysis was performed to compare different metabolites and screen critical metabolic pathways. A murine model of acute myocardial infarction (AMI) was established, which was randomized into five groups (control, BMSC, DMSC, DMSC + ODCshRNA and BMSC + ODC consisting of 50 animals, equally divided into each group). The therapeutic effect of DMSCs on MI in rats was assessed based on neovascularization and cardiac remodeling.ResultsDMSCs exhibited a better angiogenic effect on human umbilical vein endothelial cells (HUVECs) than BMSCs in vitro. In addition, ornithine metabolism, which is associated with vascularization, was significantly increased in DMSCs. The transplantation of DMSCs in the rat MI model significantly enhanced angiogenesis of the infarct border area and improved cardiac remodeling and dysfunction postinfarction compared with BMSCs. Furthermore, inhibition of ornithine metabolism by silencing ornithine decarboxylase (ODC) in DMSCs partly abolished the benefits of DMSC transplantation.ConclusionCompared with BMSCs, DMSCs exhibited better efficacy in improving revascularization and heart remodeling post-MI via the activation of ODC-associated ornithine metabolism.

The formation and dynamic process analysis of the rockslide avalanche in mountainous areas are one of the consequences of the catastrophic accident. Such loose accumulation in upslope may saturate partially or completely when the stability of their accumulation dam is distributed or affected by rainfall. We present a case study with respect to the southern Wuyi Mountain located in eastern China, where the wet and rainy climate has led to dozens of similar rockslide hazards. The purpose of this paper was to analyse the mechanism and dynamic characteristics of the rockslide influenced by the same geological conditions and to predict the outburst susceptibility of similar landslides in the future. Detail field surveys, 3D laser scanning, and high-density electrical methods were used to collect the geotechnical information of the complex landslide, to identify the discontinuity between the landslide material and the bedrock, and to investigate the deformation characterization and dynamic process of the rockslide. Based on remote sensing interpretation and field investigation of the deformation process of a landslide in different times and different parts, the background, mechanism, and cause of the landslide were demonstrated. The landslide is controlled by the characteristics of the geological structure, including collapse, circular sliding, plane sliding, and debris flow. In addition, there are rock avalanches on the rear edge of the slope subjected to the combined action of rainfall and gravity. Moreover, there are some resistance anomaly areas of the aquifer and soil between 2 and 50 m where the resistivity is less than 120 ohm-m, and they were deduced to be full of water, confirming a “bathtub” type structure. The mechanism of the catastrophic landslide was a combination of the upper pushing deformation induced by rainfall line uplift and rotational; due to the ancient landslide reactivation in the transposition area, the velocity of the rockslide reached 40.11 m/s.

This paper studies an adaptive coding scheme for B5G (beyond 5th generation) mobile system-enhanced transmission technology. Different from the existing works, the authors develop a class of rate-compatible, non-binary, low-density parity check (RC-NB-LDPC) codes, which expresses the strong connection between the algebra-based and graph-theoretic-based constructions. The constructed codes can not only express rate-compatible (RC) features, but also possess a quasi-cyclic (QC) structure that facilitates the encoding implementation. Further, in order to achieve the code rate-adaptive allocation scheme, the authors propose using the K-means++ clustering algorithm to cluster different channel environments, considering various factors that affect channel characteristics. Finally, in order to present the advantages of the adaptive coding scheme, the authors construct a coding scheme for image transmission. The numerical results demonstrate that the developed code can obtain better waterfall performance in a larger code rate range, which is more suitable for data transmission; the adaptive coding transmission scheme can obtain higher reconstructed image quality compared to the fixed code rate-coding scheme. Moreover, when considering unequal error protection (UEP), the proposed scheme can further improve the reconstructed image quality.

In order to improve the performance of non-binary low-density parity check codes (LDPC) hard decision decoding algorithm and to reduce the complexity of decoding, a sum of the magnitude for hard decision decoding algorithm based on loop update detection is proposed. This will also ensure the reliability, stability and high transmission rate of 5G mobile communication. The algorithm is based on the hard decision decoding algorithm (HDA) and uses the soft information from the channel to calculate the reliability, while the sum of the variable nodes’ (VN) magnitude is excluded for computing the reliability of the parity checks. At the same time, the reliability information of the variable node is considered and the loop update detection algorithm is introduced. The bit corresponding to the error code word is flipped multiple times, before this is searched in the order of most likely error probability to finally find the correct code word. Simulation results show that the performance of one of the improved schemes is better than the weighted symbol flipping (WSF) algorithm under different hexadecimal numbers by about 2.2 dB and 2.35 dB at the bit error rate (BER) of 10−5 over an additive white Gaussian noise (AWGN) channel, respectively. Furthermore, the average number of decoding iterations is significantly reduced.

After a myocardial infarction (MI), an increase in the cardiac ratio of matrix metalloproteinases (MMPs) relative to their inhibitors (TIMPs) causes extracellular matrix modulation that leads to ventricular dilatation and congestive heart failure. Cell therapy can mitigate these effects. In this study, we tested whether increasing MMP inhibition via cell-based gene transfer of Timp-3 further preserved ventricular morphometry and cardiac function in a rat model of MI. We also measured the effect of treatment timing. We generated MI (coronary artery ligation) in adult rats. Three or 14 days later, we implanted medium (control) or vascular smooth muscle cells transfected with empty vector (VSMCs) or Timp-3 (C-TIMP-3) into the peri-infarct region ( n = 15—24/group). We assessed MMP-2 and −9 expression and activity, TIMP-3, and TNF-α expression, cell apoptosis, infarct size and thickness, ventricular morphometry, and cardiac function (by echocardiography). Relative to medium, VSMCs delivered at either time point significantly reduced cardiac expression and activity of MMP-2 and −9, reduced expression of TNF-α, and increased expression of TIMP-3. Cell therapy also reduced apoptosis and scar area, increased infarct thickness, preserved ventricular structure, and reduced functional loss. All these effects were augmented by C-TIMP-3 treatment. Survival and cardiac function were significantly greater when VSMCs or C-TIMP-3 were delivered at 3 (vs. 14) days after MI. Upregulating post-MI cardiac TIMP-3 expression via cell-based gene therapy contributed additional regulation of MMP, TIMP, and TNF-α levels, thereby boosting the structural and functional effects of VSMCs transplanted at 3 or 14 days after an MI in rats. Early treatment may be superior to late, though both are effective.