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Abstract The photosynthetic rate is considered to be affected by individual biomass and limited by nutrients. Metabolic scaling models are often utilized to predict photosynthetic rates based on plant size and other factors, such as temperature and plant nutrient composition. However, the intrinsic regulatory mechanisms of the combined factors that affect the photosynthetic rates of living organisms are subject to debate. Here, we present a model developed from the metabolic scaling model, the Michaelis‐Menten equation and elemental stoichiometric models to precisely predict the relationship between plant photosynthetic rate and biomass. The developed model was verified against data for small woody and nonwoody plants, and in comparison with the typical metabolic scaling model, this model was shown to be more capable of explaining the photosynthesis‐biomass relationship. Moreover, the results showed that the combined factors affected photosynthesis via the regulatory effect of nutrients on photosynthesis‐biomass allometry. We highlight that nutrients have direct effects on the allocation of plant biomass and photosynthetic investment under stable and balanced growth states.

Here the authors report a simple method to create a solid electrolyte interphase that is tightly anchored onto the surface of lithium metal anode. This artificial structure suppresses dead and dendrite Li and stores Li via formation of alloys, enabling impressive battery performance.

Objective This experiment was designed to determine the effects of coated cysteamine hydrochloride (CC) on muscle fiber characteristics, amino acid composition and transporters gene expression in the longissimus dorsi muscle (LDM) of finishing pigs. Methods Two hundred and sixteen Duroc/Landrace/Yorkshire cross-bred male finishing pigs were fed with a corn-soybean basal diet supplemented with 0, 70, and 140 mg/kg cysteamine. Each group contained eight replicates of nine pigs per replicate. After 29 days, one pig was randomly selected from each replicate and slaughtered. Blood and LDM samples were collected and analyzed. Results The results showed that supplemental dietary CC increased (p

Abstract Background Cysteamine was coated to cover its odor and maintain the stability. However, coated cysteamine (CC) has not been clearly evaluated for its effects on the gastrointestinal mucosa status. We hypothesize that the appropriate CC supplementation in diet impacts the stomach and intestinal mucosa variously through regulating the morphology, apoptosis, and oxidative stress status in model of pigs. Results The results showed that villus height increased (P

Mn dissolution is dominantly responsible for capacity fading of most Mn-rich cathodes. Here the authors reveal that soluble Mn2+ species significantly destabilizes solvent and anion via its unique solvation sheath structure, providing insight into the failure mechanism of related cathode chemistries.

Range-extended Electric Vehicles (REVs) have become popular due to their lack of emissions while driving in urban areas, and the elimination of range anxiety when traveling long distances with a combustion engine as the power source. The fuel consumption performance of REVs depends greatly on the energy management strategy (EMS). This article proposes a practical energy management solution for REVs based on an Adaptive Equivalent Fuel Consumption Minimization Strategy (A-ECMS), wherein the equivalent factor is dynamically optimized by the battery’s State of Charge (SoC) and traffic information provided by Intelligent Transportation Systems (ITS). Furthermore, a penalty function is incorporated with the A-ECMS strategy to achieve the quasi-optimal start–stop control of the range extender. The penalty function is designed based on more precise vehicle velocity forecasting through a nonlinear autoregressive network with exogeneous input (NARX). A model of the studied REV is established in the AVL Cruise environment and the proposed energy management strategy is set up in Matlab/Simulink. Lastly, the performance of the proposed strategy is evaluated over multiple Worldwide Light-duty Test Cycles (WLTC) and real-world driving cycles through model simulation. The simulation conditions are preset such that the range extender must be switched on to finish the planned route. Compared with the basic Charge-Depleting and Charge-Sustaining (CD-CS) strategy, the proposed A-ECMS strategy achieves a fuel-consumption benefit of up to 9%. With the implementation of range extender start–stop optimization, which is based on velocity forecasting, the fuel saving rate can be further improved by 6.7% to 18.2% compared to the base A-ECMS. The proposed strategy is energy efficient, with a simple structure, and it is intended to be implemented on the studied vehicle, which will be available on the market at the end of October 2022.

A new control strategy is proposed to suppress earthquake-induced vibrations on uncertain building structures. The control strategy embeds fuzzy logic in a fractional-order (FO) proportional derivative (FOPD) controller. A new improved FO particle swarm optimization (IFOPSO) algorithm is derived to adjust the initial parameters of the FOPD controller. An original fuzzy logic-FOPD (FFOPD) controller is then designed by combining the advantages of the fuzzy logic and FOPD control, to deal with large displacements on structures under earthquake excitation. Simulation experiments are carried out on uncertain building structures subjected to the effects of different kinds of seismic signals, illustrating the validity and feasibility of the proposed method.

Anomaly detection on time series data has been successfully used in power grid operation and maintenance, flow detection, fault diagnosis, and other applications. However, anomalies in time series often lack strict definitions and labels, and existing methods often suffer from the need for rigid hypotheses, the inability to handle high-dimensional data, and highly time-consuming calculation costs. Generative Adversarial Networks (GANs) can learn the distribution pattern of normal data, detecting anomalies by comparing the reconstructed normal data with the original data. However, it is difficult for GANs to extract contextual information from time series data. In this paper, we propose a new method, Transformer-based GAN for Anomaly Detection of Time Series Data (TGAN-AD), The transformer-based generators of TGAN-AD can extract contextual features of time series data to prompt the performance. TGAN-AD’s discriminator can also assist in determining abnormal data. Anomaly scores are calculated through both the generator and the discriminator. We have conducted comprehensive experiments on three public datasets. Experimental results show that our TGAN-AD has better performance in anomaly detection than the state-of-the-art anomaly detection techniques, with the highest Recall and F1 values on all datasets. Our experiments also demonstrate the high efficiency of the model and the optimal choice of hyperparameters.

In this study, we investigated the therapeutic effects and mechanism of atractylodin (ATL) on dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. We found that atractylodin could significantly reverse the effects of DSS-induced ulcerative colitis, such as weight loss, disease activity index score; shorten the colon length, and reverse the pathological changes in the colon of mice. Atractylodin could inhibit the activation of colonic macrophages by inhibiting the MAPK pathway and alleviate intestinal inflammation in the mouse model of ulcerative colitis. Moreover, it could protect the intestinal barrier by inhibiting the decrease of the tight junction proteins, ZO-1, occludin, and MUC2. Additionally, atractylodin could decrease the abundance of harmful bacteria and increase that of beneficial bacteria in the intestinal tract of mice, effectively improving the intestinal microecology. In an LPS-induced macrophage model, atractylodin could inhibit the MAPK pathway and expression of the inflammatory factors of macrophages. Atractylodin could also inhibit the production of lactate, which is the end product of glycolysis; inhibit the activity of GAPDH, which is an important rate-limiting enzyme in glycolysis; inhibit the malonylation of GAPDH, and, thus, inhibit the translation of TNF-α. Therefore, ours is the first study to highlight the potential of atractylodin in the treatment of ulcerative colitis and reveal its possible mechanism.

Background:Moutan cortex radicis (MCR), as a common traditional Chinese medicine, has been widely used as an antipyretic, antiseptic, and anti-inflammatory agent in China.Objectives: This study aimed to investigate the effects of dietary MCR supplementation on the antioxidant capacity and intestinal health of the pigs and to explore whether MCR exerts positive effects on intestinal health via regulating nuclear factor kappa-B (NF-κB) signaling pathway and intestinal microbiota.Methods: MCR powder was identified by LC-MS analysis. Selected 32 weaned piglets (21 d of age, 6.37 ± 0.10 kg average BW) were assigned (8 pens/diet, 1 pig/pen) to 4 groups and fed with a corn-soybean basal diet supplemented with 0, 2,000, 4,000, and 8,000 mg/kg MCR for 21 d. After the piglets were sacrificed, antioxidant indices, histomorphology examination, and inflammatory signaling pathway expression were assessed. The 16s RNA sequencing was used to analyze the effects of MCR on the intestinal microbiota structure of piglets.Results: Supplemental 4,000 mg/kg MCR significantly increased (P < 0.05) the average daily weight gain (ADG), average daily feed intake (ADFI), total antioxidative capability, colonic short-chain fatty acids (SCFA) concentrations, and the crypt depth in the jejunum but decreased (P < 0.05) the mRNA expression levels of interferon γ, tumor necrosis factor-α, interleukin-1β, inhibiting kappa-B kinase β (IKKβ), inhibiting nuclear factor kappa-B (IκBα), and NF-κB in the jejunum and ileum. Microbiota sequencing identified that MCR supplementation significantly increased the microbial richness indices (Chao1, ACE, and observed species, P < 0.05) and the relative abundances of Firmicutes and Lactobacillus (P < 0.05), decreased the relative abundances of Bacteroides, Parabacteroides, unidentified_Lachnospiraceae, and Enterococcus (P < 0.05) and had no significant effects on the diversity indices (Shannon and Simpson, P > 0.05). Microbial metabolic phenotypes analysis also showed that the richness of aerobic bacteria and facultative anaerobic bacteria, oxidative stress tolerance, and biofilm forming were significantly increased (P < 0.05), and the richness of anaerobic bacteria and pathogenic potential of gut microbiota were reduced (P < 0.05) by MCR treatment. Regression analysis showed that the optimal MCR supplemental level for growth performance, serum antioxidant capacity, and intestinal health of weaned piglets was 3,420 ~ 4,237 mg/kg.Conclusions: MCR supplementation improved growth performance and serum antioxidant capacity, and alleviated intestinal inflammation by inhibiting the IKKβ/IκBα/NF-κB signaling pathway and affecting intestinal microbiota in weaned piglets.

Tryptophan (Trp) has received increasing attention in the maintenance of intestinal function. In this study, improved triploid crucian carp (ITCC) fed diets containing 6.35 g kg−1 Trp had higher average daily gain (ADG) and improved villus height (VH) and crypt depth (CD) in the intestine compared to the control group. To elucidate the potential mechanisms, we used RNA sequencing (RNA-seq) to investigate changes in the intestinal transcriptome and 16S rRNA gene sequencing to measure the intestinal microbiota in response to 6.35 g kg−1 Trp feeding in ITCC. Dietary Trp altered intestinal gene expression involved in nutrient transport and metabolism. Differentially expressed transcripts (DETs) were highly enriched in key pathways containing protein digestion and absorption and the AMPK signaling pathway. 16S rRNA sequencing showed that 6.35 g kg−1 Trp significantly increased the abundance of the genus Cetobacterium, and the Firmicutes/Bacteroidetes ratio at the phylum level (P < 0.05). In addition, bacterial richness indices (Simpson index) significantly increased (P < 0.05) community evenness in response to 6.35 g kg−1 Trp. In conclusion, appropriate dietary Trp improves the growth performance, and influences the intestinal flora of ITCC. This study might be helpful to guide the supply of dietary exogenous Trp in ITCC breeding.

Glioblastoma is a fatal primary malignant brain tumor, and the 5-year survival rate of treated glioblastoma patients still remains

Placental oxidative stress has been implicated as a main risk factor for placental dysfunction. Alleviation of oxidative stress and enhancement of antioxidant capacity of porcine trophectoderm (PTr2) cells are effective means to maintaining normal placental function. The present study was conducted to evaluate the protective effect of melatonin (MT) on H2O2-induced oxidative damage in PTr2 cells. Our data revealed that pretreatment with MT could significantly improve the decrease in cell viability induced by H2O2, and reduce intracellular reactive oxygen species (ROS) levels and the ratio of apoptotic cells. Here, we compared the transcriptomes of untreated versus melatonin-treated PTr2 cells by RNA-seq analysis and found that differentially expressed genes (DEGs) were highly enriched in the Wnt signaling, TGF-beta signaling and mTOR signaling pathways. Moreover, pretreatment with MT upregulated the antioxidant-related genes such as early growth response3 (EGR3), WAP four-disulfide core domain1 (WFDC1), heme oxygenase1 (HMOX1) and vimentin (VIM). These findings reveal that melatonin protects PTr2 cells from H2O2-induced oxidative stress damage.

Solid Electrolyte Interphase (SEI) has been identified as the most important and least understood component in lithium-ion batteries. Despite extensive studies in the past two decades, a few mysteries remain: what is the chemical form of and degree of mobility of Li+ in the interphase? What fraction of Li+ is permanently immobilized in the SEI, while the rest are still able to participate in the cell reactions via the ion-exchange process with Li+ in the electrolyte? This study attempted to answer, in part, these questions by using 6Li and 7Li-isotopes to label SEIs and electrolytes, and then quantifying the distribution of permanently immobilized and ion-exchangeable Li+ with solid-state NMR and ToF-SIMS. The results showed that the majority of Li+ were exchanged after one SEI formation cycle, and a complete exchange after 25 cycles. Ion exchange by diffusion based on concentration gradient in the absence of applied potential also occurred simultaneously. This knowledge will provide a foundation for not only understanding but also designing better SEIs for future battery chemistries.

With the development of various new intelligent materials, pneumatic artificial muscles are becoming widely used as actuators in industry, with their advantages of having a simple and compact structure, smooth action, fast response and movement closer to natural biological muscle movement. This paper introduced the concept of a fiber-constrained flexible actuator for direct ventricular assist devices. The structural parameters of the actuator were initially determined based on the morphology of the human heart; the model of the flexible body with fibers and strain limiting layer was then constructed using SOLIDWORKS; then, the model was imported into the ABAQUS finite element analysis software for simulation in order to determine the feasibility of the structural solution; finally, the structural parameters of the actuator were optimized based on the simulation results. In order to investigate whether the actuator could cause damage to myocardial tissue when squeezing the heart, the actuator was tested for the displacement and the output force. The results showed that fiber-constrained direct ventricular assist devices did not damage the myocardium while assisting the heart to pump blood; moreover, their blood output could meet the requirements of both types of heart failure patients. The annular flexible actuator can provide effective compression of the ventricle and twist at an angle during inflation. This twist adapts to the torsional requirements of the heart, and reduces sliding friction between the device and the heart surface, thereby reducing myocardial damage.

Omega-3 polyunsaturated fatty acids (omega-3 PUFAs), which are essential fatty acids that humans should obtain from diet, have potential benefits for human health. In addition to altering the structure and function of cell membranes, omega-3 PUFAs (docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), alpha-linolenic acid (ALA), and docosapentaenoic acid (DPA)) exert different effects on intestinal immune tolerance and gut microbiota maintenance. Firstly, we review the effect of omega-3 PUFAs on gut microbiota. And the effects of omega-3 PUFAs on intestinal immunity and inflammation were described. Furthermore, the important roles of omega-3 PUFAs in maintaining the balance between gut immunity and the gut microbiota were discussed. Additional factors, such as obesity and diseases (NAFLD, gastrointestinal malignancies or cancer, bacterial and viral infections), which are associated with variability in omega-3 PUFA metabolism, can influence omega-3 PUFAs–microbiome–immune system interactions in the intestinal tract and also play roles in regulating gut immunity. This review identifies several pathways by which the microbiota modulates the gut immune system through omega-3 PUFAs. Omega-3 supplementation can be targeted to specific pathways to prevent and alleviate intestinal diseases, which may help researchers identify innovative diagnostic methods.

Summary: Circular RNAs (circRNAs) have been identified as naturally occurring RNAs that are highly represented in the eukaryotic transcriptome. Although a large number of circRNAs have been reported, the underlying regulatory mechanism of circRNAs biogenesis remains largely unknown. Here, we integrated in-depth multi-omics data including epigenome, transcriptome, and non-coding RNA and identified candidate circRNAs in six cellular contexts. Next, circRNAs were divided into two classes (high versus low) with different expression levels. Machine learning models were constructed that predicted circRNA expression levels based on 11 different histone modifications and host gene expression. We found that the models achieve great accuracy in predicting high versus low expressed circRNAs. Furthermore, the expression levels of host genes of circRNAs, H3k36me3, H3k79me2, and H4k20me1 contributed greatly to the classification models in six cellular contexts. In summary, all these results suggest that epigenetic modifications, particularly histone modifications, can effectively predict expression levels of circRNAs.

Atractylodes lancea (Thunb.) DC. (AL) is used in traditional Chinese medicine for the treatment of spleen-deficiency syndrome (SDS). Bran-processed Atractylodes lancea (BAL) has been found to be more effective than unprocessed AL. However, the compound in BAL active against SDS remains unclear. The pharmacological efficacy of BAL and its mechanism of action against SDS were investigated by HPLC-ELSD. Candidate compound AA (atractyloside A) in AL and BAL extracts was identified by HPLC-MS analysis. AA was tested in a rat model of SDS in which body weight, gastric residual rate, and intestinal propulsion were measured, and motilin (MTL), gastrin (GAS), and c-Kit were quantified by enzyme-linked immunosorbent assay. Potential targets and associated pathways were identified based on network pharmacology analysis. mRNA expression levels were measured by qRT-PCR and protein expression levels were measured by Western blot analysis and immunohistochemistry. AA increased body weight, intestinal propulsion, MTL, GAS, and c-Kit levels, while decreasing gastric residual volume and intestinal tissue damage, as same as Epidermal Growth Factor Receptor and Proliferating Cell Nuclear Antigen levels. Seventy-one potential pharmacologic targets were identified. Analysis of protein interaction, Gene Ontology (GO) functional analysis, pathway enrichment analysis, and docking and molecular interactions highlighted MAPK signaling as the potential signal transduction pathway. Validation experiments indicated that treatment with AA increased MTL, GAS, ZO-1, and OCLN levels, while reducing AQP1, AQP3, and FGF2 levels. In addition, phosphorylation of p38 and myosin light-chain kinase (MLCK) expression were inhibited. AA improved gastrointestinal function by protecting the intestinal mucosal barrier via inhibition of the p38 MAPK pathway. The results have clinical implications for the therapy of SDS.

Ningaloo Niño is a well-known ocean-atmosphere coupled climate event in the southeastern Indian Ocean that interacts with large-scale atmospheric circulations at the interannual time scale. When a Ningaloo Niño develops, remarkably enhanced precipitation anomalies occur primarily off the coast of northwestern Australia (NWA) rather than over the offshore area of western Australia (WA), where the most significant sea surface temperature warming prevails. This enhanced NWA precipitation manifests as jointly intensified stratiform and convective precipitation accompanied by an increase in high cloud cover. Further analyses of the column-integrated moist static energy (MSE) budget reveal that during Ningaloo Niño events, positive vertical MSE transport moistens and heats the atmosphere in the WA region. However, these moistening and heating effects are mostly offset by the inhibitory effect of the negative horizontal MSE advection, leading to the relatively weak and nonsignificant variation in local precipitation anomalies off the WA coastal region. In contrast, off the coast of the NWA region, the recharge of column-integrated MSE, which is induced by the significant positive radiative and surface heating, horizontal MSE advection, and vertical MSE advection, contributes to the heaviest austral summer precipitation associated with Ningaloo Niño. Therefore, the distinct MSE transport processes result in the particular rainfall pattern in which the most enhanced rainfall is associated with Ningaloo Niño events over the NWA region.

The limited availability of nitrogen (N) is a fundamental challenge for many crop plants. We have hypothesized that the relative crop photosynthetic rate (P) is exponentially constrained by certain plant-specific enzyme activities, such as ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), NADP-glyceraldehyde-3-phosphate dehydrogenase (NADP-G3PDH), 3-phosphoglyceric acid (PGA) kinase, and chloroplast fructose-1,6-bisphosphatase (cpFBPase), in Triticum aestivum and Oryza sativa. We conducted a literature search to compile information from previous studies on C3 and C4 crop plants, to examine the photosynthetic rate responses to limited leaf [N] levels. We found that in Zea mays, NADP-malic enzyme (NADP-ME), PEP carboxykinase (PCK), and Rubisco activities were positively correlated with P. A positive correlation was also observed between both phosphoenolpyruvate carboxylase (PEPC) and Rubisco activity with leaf [N] in Sorghum bicolor. Key enzyme activities responded differently to P in C3 and C4 plants, suggesting that other factors, such as leaf [N] and the stage of leaf growth, also limited specific enzyme activities. The relationships followed the best fitting exponential relationships between key enzymes and the P rate in both C3 and C4 plants. It was found that C4 species absorbed less leaf [N] but had higher [N] assimilation rates (Arate) and higher maximum photosynthesis rates (Pmax), i.e., they were able to utilize and invest more [N] to sustain higher carbon gains. All C3 species studied herein had higher [N] storage (Nstore) and higher absorption of [N], when compared with the C4 species. Nstore was the main [N] source used for maintaining photosynthetic capacity and leaf expansion. Of the nine C3 species assessed, rice had the greatest Pmax, thereby absorbing more leaf [N]. Elevated CO2 (eCO2) was also found to reduce the leaf [N] and Pmax in rice but enhanced the leaf [N] and N use efficiency of photosynthesis in maize. We concluded that eCO2 affects [N] allocation, which directly or indirectly affects Pmax. These results highlight the need to further study these physiological and biochemical processes, to better predict how crops will respond to eCO2 concentrations and limited [N].

Calcific aortic valve disease (CAVD) occurs via a pathophysiological process that includes inflammation-induced osteoblastic differentiation of aortic valvular interstitial cells (AVICs). Here, we investigated the role of the anti-inflammatory compound caffeic acid phenethyl ester (CAPE) in inhibiting CAVD. Human AVICs were isolated and cultured in osteogenic induction medium (OM) with or without 10 μM CAPE. Cell viability was assessed using CCK8 assays and calcified transformation of AVICs was evaluated by Alizarin Red staining and osteogenic gene/protein expression. RNA-sequencing was conducted to identify differentially expressed genes (DEGs) and enrichment in associated pathways, as potential molecular targets through which CAPE inhibits osteogenic induction. The regulatory effects of CAPE on activation of the AKT/NF-κB and NLRP3 inflammasome were evaluated by Western blot analysis and immunofluorescent staining. CAPE slowed the growth of AVICs cultured in OM but did not show significant cytotoxicity. In addition, CAPE markedly suppressed calcified nodule formation and decreased gene/protein expression of RUNX2 and ALP in AVICs. Gene expression profiles of OM-induced AVICs cultured with or without CAPE revealed 518 common DEGs, which were highly enriched in the NOD-like receptor, PI3K-AKT, and NF-κB signaling pathways. Furthermore, CAPE inhibited phosphorylation of AKT, ERK1/2, and NF-κB, and suppressed NLRP3 inflammasome activation in AVICs cultured in OM. Thus, CAPE is implicated as a potent natural product for the prevention of CAVD by inhibiting activation of the AKT/NF-κB pathway and NLRP3 inflammasome.

The consistency test is a vital component of pairwise comparison matrices if meaningful results are to be guaranteed, and it has been studied extensively, since the analytic hierarchy process was developed by Saaty. However, how to deal with the consistency of a probability-hesitant analytic hierarchy process with different probability values is a specific problem which needs to be studied further. This paper provides a direct consistency test and an improvement method for the probability-hesitant analytic hierarchy process. A paradox in Saaty's consistency test is first proposed, and then a direct consistency improvement method is suggested for dealing with the consistency of a probability-hesitant analytic hierarchy process with different probability values, from the perspective of three tuples, rather than carrying out matrix operations. In our method, only simple mathematical calculations are needed and there is no need for matrix operations. By using a partial correction, the proposed method can retain most of the information provided by the original comparison matrix, and simultaneously indicate the modification direction and provide the optimal values. At the same time, using the proposed method, the inconsistent elements in the probability-hesitant pairwise comparison matrix can be found rapidly and with a high degree of accuracy. Moreover, our proposed iterative algorithm is a method that is both very quick and leads to good results being obtained.

This study aimed to investigate the effects of leucine (Leu) and its metabolites (α-ketoisocaproate (KIC) and β-hydroxy-β-methylbutyrate (HMB)) on muscle protein metabolism in growing pigs fed low-protein diets. 32 pigs (Large White × Landrace, 9.55 ± 0.19 kg) were divided into four groups (basal diet, L-Leu, KIC-Ca, HMB-Ca). Results showed that compared to the control, dietary supplementation of KIC and excess Leu significantly decreased the weight of soleus muscle (SM, P 0.05). In conclusion, HMB, but not KIC or excess Leu, might act as a nutrient signal to stimulate positive protein balance especially in muscles of oxidative fiber-types of growing pigs fed low-protein diets, and these effects might be associated with the Akt signaling.

We describe a biodegradable amphiphilic polyurethane (PU) with disulfide bonds in the main chain [PEtOz-b-PU(SS)-b-PEtOz]. This multi-block PU was synthesized using poly (ε-caprolactone) diol (PCL-SS-PCL) and poly (2-ethyl-2-oxazoline) (PEtOz-OH) as soft segments, and bis (2-isocyanatoethyl) disulfide as the hard segment. Acid-sensitive PEtOz-OH was used as a hydrophilic segment for pH sensitivity. And reduction sensitivity was induced via disulfide bonds incorporated into the hydrophobic poly (ε-caprolactone) segment of the amphiphilic PUs. The system can self-assemble to form micelles responsive to pH and reducing conditions. The properties of the micelle were studied with dynamic light scattering and scanning electron microscopy. Doxorubicin (DOX) was chosen as a model drug. The in vitro release studies showed that PEtOz-b-PU(SS)-b-PEtOz micelle could degrade more rapidly and completely in a reductive and acidic environment [10 mM dl-Dithiothreitol, pH 5.0]. The methyl tetrazolium (MTT) assay and fluorescent microscopy confirmed the cytotoxicity of the DOX-loaded micelles. This work provides a promising dual-responsive drug carrier based on amphiphilic PU to achieve efficient drug delivery.

Abstract Background Vascular grafts are widely used as a treatment in coronary artery bypass surgery, hemodialysis, peripheral arterial bypass and congenital heart disease. Various types of synthetic and natural materials were experimented to produce tissue engineering vascular grafts. In this study, we investigated in vivo tissue engineering technology in miniature pigs to prepare decellularized autologous extracellular matrix-based grafts that could be used as vascular grafts for small-diameter vascular bypass surgery. Methods Autologous tissue conduits (3.9 mm in diameter) were fabricated by embedding Teflon tubings in the subcutaneous pocket of female miniature pigs (n = 8, body weight 25–30 kg) for 4 weeks. They were then decellularized by CHAPS decellularization solution. Heparin was covalently-linked to decellularized tissue conduits by Sulfo-NHS/EDC. We implanted these decellularized, completely autologous extracellular matrix-based grafts into the carotid arteries of miniature pigs, then sacrificed the pigs at 1 or 2 months after implantation and evaluated the patency rate and explants histologically. Results After 1 month, the patency rate was 100% (5/5) while the inner diameter of the grafts was 3.43 ± 0.05 mm (n = 5). After 2 months, the patency rate was 67% (2/3) while the inner diameter of the grafts was 2.32 ± 0.14 mm (n = 3). Histological staining confirmed successful cell infiltration, and collagen and elastin deposition in 2-month samples. A monolayer of endothelial cells was observed along the inner lumen while smooth muscle cells were dominant in the graft wall. Conclusion A completely autologous acellular conduit with excellent performance in mechanical properties can be remodeled into a neoartery in a minipig model. This proof-of-concept study in the large animal model is very encouraging and indicates that this is a highly feasible idea worthy of further study in non-human primates before clinical translation.

Long non-coding RNAs (lncRNAs), as important ncRNA regulators, play crucial roles in the regulation of various biological processes, and their aberrant expression is related to the occurrence and development of diseases, which is gradually validated by more and more studies. Alzheimer’s disease (AD) is a chronic neurodegenerative disease that often develops slowly and gradually deteriorates over time. However, which functions the lncRNAs perform in AD are almost unknown. In this study, we performed transcriptome analysis in AD, containing 12,892 known lncRNAs and 19,053 protein-coding genes (PCGs). Further, 14 down-regulated and 39 up-regulated lncRNAs were identified, compared with normal brain samples, which indicated that these lncRNAs might play critical roles in the pathogenesis of AD. In addition, 19 down-regulated and 28 up-regulated PCGs were also detected. Using the differentially expressed lncRNAs and PCGs through the WGCNA method, an lncRNA–mRNA co-expressed network was constructed. The results showed that lncRNAs RP3-522J7, MIR3180-2, and MIR3180-3 were frequently co-expressed with known AD risk PCGs. Interestingly, PCGs in the network are significantly enriched in brain- or AD-related biological functions, including the brain renin–angiotensin system, cell adhesion, neuroprotective role of THOP1 in AD, and so on. Furthermore, it was shown that 18 lncRNAs and 7 PCGs were highly expressed in normal brain tissue relative to other normal tissue types, suggesting their potential as diagnostic markers of AD, especially RP3-522J7, MIR3180-2, MIR3180-3, and CTA-929C8. In total, our study identified a compendium of AD-related dysregulated lncRNAs and characterized the corresponding biological functions of these lncRNAs in AD, which will be helpful to understand the molecular basis and pathogenesis of AD.

Poor electrochemical reversibility of the conversion-type cathode materials remains an important challenge for their practical applications. Here, the authors report a highly reversible fluoride cathode material with low hysteresis through concerted doping of cobalt and oxygen into iron fluoride.

Abstract Increasing evidence suggests that PRMT5, a protein arginine methyltransferase, has roles in cell growth regulation and cancer development. However, the role of PRMT5 in hepatocellular carcinoma (HCC) progression remains unclear. Here, we showed that PRMT5 expression was frequently upregulated in HCC tissues, and its expression was inversely correlated with overall survival in HCC patients. PRMT5 knockdown markedly inhibited in vitro HCC proliferation and in vivo tumorigenesis. We revealed that the mechanism of PRMT5‐induced proliferation was partially mediated by BTG downregulation, leading to cell cycle arrest during the G1 phase in HCC cells. Ectopic BTG2 overexpression decreased HCC growth, caused cell cycle arrest at the G1 phase, and downregulated Cyclin D1 and Cyclin E1 protein expression. Furthermore, we found that PRMT5‐induced ERK phosphorylation regulated BTG2 expression in HCC cells, whereas pretreatment with a selective ERK1/2 inhibitor (PD184352) significantly reversed the effect of PRMT5 on BTG2 expression. Our results indicated that PRMT5 promotes HCC proliferation by downregulating BTG2 expression via the ERK pathway.

(1) Background: The white Hypsizygus marmoreus is a popular edible mushroom in East Asia markets. Research on the systematic investigation of the protein expression changes in the cultivation process of this mushroom are few. (2) Methods: Label-free LC-MS/MS quantitative proteomics analysis technique was adopted to obtain the protein expression profiles of six groups of samples collected in different growth stages. A total of 3468 proteins were identified. The UpSetR plot analysis, Pearson correlation coefficient (PCC) analysis, and principal component (PC) analysis were performed to reveal the correlation among the six groups of samples. The differentially expressed proteins (DEPs) were organised by One-way ANOVA test and divided into four clusters. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed to divide the DEPs into different metabolic processes and pathways in each cluster. (3) Results: The DEPs in cluster 1 are of the highest abundance in the mycelium and are mainly involved in protein biosynthesis, biosynthesis of cofactors, lipid metabolism, spliceosome, cell cycle regulation, and MAPK signaling pathway. The DEPs in cluster 2 are enriched in the stem and are mainly associated with protein biosynthesis, biosynthesis of cofactors, carbon, and energy metabolism. The DEPs in cluster 3 are highly expressed in the primordia and unmatured fruiting bodies and are related to amino acids metabolism, carbon and carbohydrate metabolism, protein biosynthesis and processing, biosynthesis of cofactors, cell cycle regulation, MAPK signaling pathway, ubiquitin-mediated proteolysis, and proteasome. The DEPs in cluster 4 are of the highest abundance in the cap and are mainly associated with spliceosome, endocytosis, nucleocytoplasmic transport, protein processing, oxidative phosphorylation, biosynthesis of cofactors, amino acids metabolism, and lipid metabolism. (4) Conclusions: This research reports the proteome analysis of different developmental stages during the cultivation of the commercially relevant edible fungi the white H. marmoreus. In the mycelium stage, most of the DEPs are associated with cell proliferation, signal response, and mycelium growth. In the primordia and unmatured fruiting bodies stage, the DEPs are mainly involved in biomass increase, cell proliferation, signal response, and differentiation. In the mature fruiting body stage, the DEPs in the stem are largely associated with cell elongation and increase in biomass, and most of the DEPs in the cap are mainly related to pileus expansion. Several carbohydrate-active enzymes, transcription factors, heat shock proteins, and some DEPs involved in MAPK and cAMP signaling pathways were determined. These proteins might play vital roles in metabolic processes and activities. This research can add value to the understanding of mechanisms concerning mushroom development during commercial production.

In order to explore the effect of okra on the cloudy and flavor characteristics of wheat beer, fresh okra and dried okra were added separately into boiling wort. The beer without okra was used as control sample. Aroma characteristics were analyzed using gas chromatography (GC), high-performance liquid chromatography, headspace–solid-phase microextraction–GC–mass spectrometry (HS-SPME-GC-MS), and electronic nose. The results showed that okra addition significantly increased the turbidity and viscosity. Principal components analysis reflected that three beers were apart from each other. After adding okra, the higher alcohols decreased, while the esters increased. In conclusion, okra can be used to improve stability and aroma characteristics.

Recently, thousands of circular RNAs have been reported in different pig breeds. However, researches on the temporal and spatial expression patterns of circRNA over the period of animal growth are limited. Here, we systematically analyzed circRNAs in skeletal muscle and subcutaneous fat in four growth time points (30 days, 90 days, 150 days and 210 days after birth) of a Chinese native pig breed, Ningxiang pigs. A total of 1171 differentially expressed (DE) circRNAs between muscle and fat were identified, including 562 upregulated and 609 downregulated circRNAs. KEGG pathway enrichment analysis of these DE circRNAs revealed that host genes were mainly involved in glycogen metabolism signaling pathways, muscle development signaling pathways such as ErbB pathway and adipocytokine signaling pathways and AMPK signaling pathways and fatty acid biosynthesis. The circRNAs have striking spatiotemporal specificity in the form of dynamic expression at 90 d. Short Time-Series Expression Miner analysis showed multiple model spectra that are significantly enriched with time changes in muscle and fat. Our findings provide new ideas and perspectives about the role of circular RNAs and their targeting relations with mRNA and miRNA in skeletal muscle and fat tissue during pig growth.

The research and application of airborne gravimetry technology has become one of the hottest topics in gravity field in recent years. Downward continuation is one of the key steps in airborne gravimetry data processing, and the quality of continuation results directly influence the further application of surveying data. The Poisson integral iteration method is proposed in this paper, and the modified Poisson integral discretization formulae are also introduced in the downward continuation of airborne gravimerty data. For the test area in this paper, compared with traditional Poisson integral discretization formula, the continuation result of modified formulae is improved by 10.8 mGal, and the precision of Poisson integral iteration method is in the same amplitude as modified formulae. So the Poisson integral iteration method can reduce the discretization error of Poisson integral formula effectively. Therefore, the research achievements in this paper can be applied directly in the data processing of our country's airborne scalar and vector gravimetry.

Infantile diarrhea is a serious public health problem around worldwide and results in millions of deaths each year. The levels and sources of dietary protein are potential sources of diarrhea, but the relationship between the pathogenesis causes of infantile diarrhea and protein intake remains poorly understood. Many studies have indicated that the key to understanding the relationship between the protein in the diet and the postweaning diarrhea of piglets is to explore the influences of protein sources and levels on the mammalian digestion system. The current study was designed to control diarrhea control by choosing different protein levels in the diet and aimed at providing efficient regulatory measures for infantile diarrhea by controlling the protein levels in diets using a postweaning piglets model. To avoid influences from other protein sources, casein was used as the only protein source in this study. Fourteen piglets (7.98±0.14 kg, weaned at 28 d) were randomly allotted to two dietary treatments: a control group (Cont, containing 17% casein) and a high protein group (HP, containing 30% casein). The experiment lasted for two weeks and all animals were free to eat and drink water ad libitum. The diarrhea score (1=normal; 3=watery diarrhea) and growth performance were recorded daily. The results showed that the piglets in HP group had persistent diarrhea during the whole study, while no diarrhea was noticed in the control groups. Also, the feed intake and body weights were reduced in the HP groups compared with the other group (P

Immunotherapy has received increasing attention due to its low potential side effects and high specificity. For instance, cancer immunotherapy has achieved great success. CpG is a well-known and commonly used immunotherapeutic and vaccine adjuvant, but it has the disadvantage of being unstable and low in efficacy and needs to be transported through an effective nanocarrier. With perfect structural programmability, permeability, and biocompatibility, DNA nanostructures are one of the most promising candidates to deliver immune components to realize immunotherapy. However, the instability and low capability of the payload of ordinary DNA assemblies limit the relevant applications. Consequently, DNA nanostructure with a firm structure, high drug payloads is highly desirable. In the paper, the latest progress of biostable, high-payload DNA nanoassemblies of various structures, including cage-like DNA nanostructure, DNA particles, DNA polypods, and DNA hydrogel, are reviewed. Cage-like DNA structures hold drug molecules firmly inside the structure and leave a large space within the cavity. These DNA nanostructures use their unique structure to carry abundant CpG, and their biocompatibility and size advantages to enter immune cells to achieve immunotherapy for various diseases. Part of the DNA nanostructures can also achieve more effective treatment in conjunction with other functional components such as aPD1, RNA, TLR ligands.

This study aimed to explore the effects of dietary coated cysteamine on oxidative stress and inflammation in diquat-induced weaning pigs. Twenty-four pigs were randomly assigned to three dietary groups with eight replicates: the control (fed base diet), diquat (fed base diet), and coated cysteamine + diquat groups (fed 80 mg/kg cysteamine). The experiment was conducted for 21 d, and consisted of a pre-starter period (14 d) and a starter period (7 d). Coated cysteamine treatment significantly increased (p < 0.05) the final weight and average daily gain (ADG) in pigs. The contents of alkaline phosphatase (ALP), immunoglobulin G (IgG), serine (Ser), and isoleucine (Ile) were elevated (p < 0.05) while the contents of albumin (ALB) and aspartic acid (Asp) were reduced (p < 0.05) in the serum after coated cysteamine supplementation. Coated cysteamine supplementation resulted in greater (p < 0.05) serum superoxide dismutase (SOD) activity, the expression of interleukin-10 (IL-10) mRNA in the colon, and the CuSOD mRNA expression in the jejunum (p < 0.05) and colon (p = 0.073). Coated cysteamine supplementation showed an increasing trend in villus height (p = 0.060), villus height/crypt depth (V/C) (p = 0.056), the expression levels of zonula occludens-1 (ZO-1) mRNA (p = 0.061), and Occludin mRNA (p = 0.074) in the jejunum. In summary, dietary supplementation with coated cysteamine improves the intestinal barrier function of the jejunum by increasing the immunoglobulin content and the relative expression of intestinal immune factor mRNA in pigs while alleviating oxidative stress and inflammatory reactions caused by diquat.

Ningxiang pigs, a Chinese bred pig known for its tender meat and high quality unsaturated fatty acids. This study discovers the transcription profiles and functional networks in long non-coding RNA (lncRNA) and messenger RNA (mRNA) in subcutaneous adipose tissue. Subcutaneous adipose tissue was collected from piglet, nursery pig, early fattening, and late fattening stage of Ningxiang piglets, and lncRNA and mRNA transcription of each stage was profiled. A total of 339,204,926 (piglet), 315,609,246 (nursery), 266,798,202 (early fattening), and 343,740,308 (late fattening) clean reads were generated, and 2872 novel lncRNAs were identified. Additionally, 10,084 differential mRNAs (DEmRNAs) and 931 differential lncRNAs were determined. Most DEmRNAs were up-regulated in the piglet stage, while they were down-regulated in late fattening stage. A complicated interaction between mRNAs and lncRNAs was identified via STEM and WGCNA, demonstrated that lncRNAs are a significant regulatory component in mRNAs. The findings showed that modules 2 and 5 have a similar mode of transcription for both mRNA and lncRNA, and were mainly participated in steroid biosynthesis, glycosphingolipid biosynthesis, metabolic pathways, and glycerolipid metabolism. The mRNAs and lncRNAs transcription levels of both modules was higher in the early and late fattening stage, which may be due to the active activity of the metabolism in relation to fatty acids, sterols, steroids, and lipids in the subcutaneous adipose tissue during the early and late fattening stage. These findings could be expected to result in further research of the functional properties of lncRNA from subcutaneous adipose tissue at different stages of development in Ningxiang pigs.

When the use of optical images is not practical due to cloud cover, Synthetic Aperture Radar (SAR) imagery is a preferred alternative for monitoring coastal wetlands because it is unaffected by weather conditions. Polarimetric SAR (PolSAR) enables the detection of different backscattering mechanisms and thus has potential applications in land cover classification. Gaofen-3 (GF-3) is the first Chinese civilian satellite with multi-polarized C-band SAR imaging capability. Coastal wetland classification with GF-3 polarimetric SAR imagery has attracted increased attention in recent years, but it remains challenging. The aim of this study was to classify land cover in coastal wetlands using an object-oriented random forest algorithm on the basis of GF-3 polarimetric SAR imagery. First, a set of 16 commonly used SAR features was extracted. Second, the importance of each SAR feature was calculated, and the optimal polarimetric features were selected for wetland classification by combining random forest (RF) with sequential backward selection (SBS). Finally, the proposed algorithm was utilized to classify different land cover types in the Yancheng Coastal Wetlands. The results show that the most important parameters for wetland classification in this study were Shannon entropy, Span and orientation randomness, combined with features derived from Yamaguchi decomposition, namely, volume scattering, double scattering, surface scattering and helix scattering. When the object-oriented RF classification approach was used with the optimal feature combination, different land cover types in the study area were classified, with an overall accuracy of up to 92%.

Ningxiang pigs, a fat-type pig, are native to Ningxiang County in Hunan Province, with thousands of years of breeding history. This study aims to explore the expression profiles and functional networks on messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) in the liver. Liver tissue of Ningxiang piglets was collected at 30, 90, 150, and 210 days after birth (four development stages), and the mRNA and lncRNA expression was profiled. Compared to mRNA and lncRNA expression profiles, most differentially expressed mRNAs (DEmRNAs) were upregulated at 30 days; however, most DElncRNAs were downregulated at 210 days. Via Short Time-series Expression Miner (STEM) analysis and weighted gene co-expression network analysis (WGCNA), a complex interaction between mRNAs and lncRNAs was identified, indicating that lncRNAs may be a critical regulatory element for mRNAs. One module of genes in particular (module profile 4) was related to fibril organization, vasculogenesis, GTPase activator activity, and regulation of kinase activity. The mRNAs and lncRNAs in module profile 4 had a similar pattern of expression, indicating that they have functional and regulatory relationships. Only CAV1, PACSIN2, and CDC42 in the particular mRNA profile 4 were the target genes of lncRNAs in that profile, which shows the possible regulatory relationship between lncRNAs and mRNAs. The expression of these genes and lncRNAs in profile 4 was the highest at 30 days, and it is believed that these RNAs may play a critical role during the suckling period in order to meet the dietary requirements of piglets. In the lncRNA–mRNA co-expression network, the identified gene hubs and associated lncRNAs were shown to be involved in saccharide, lipid, and glucose metabolism, which may play an important role in the development and health of the liver. This result will lead to further investigation of liver lncRNA functions at various stages of development in Ningxiang pigs.

Controllable electric transport of topological particles in solid state systems hold the key towards novel electronic applications. Here, Wang et al. demonstrate gate-tunable negative longitudinal magnetoresistance in WTe2, featuring controllable transport of Type-II Weyl fermions.

Peanut hull residues were considered for the manufacturing of particleboards. Various concentrations of two types of adhesive—polymeric diphenylmethane diisocyanate (MDI) and urea-formaldehyde (UF)—were separately combined with four types of peanut hull particles (fine, mixed, coarse particles, and peanut hull powder) to manufacture particleboards with a certain target density. The confidence level of the effect of the selected production parameters on the physical and mechanical properties of the panels was evaluated. The results showed that increasing the adhesive mass percentage significantly improved the dimensional stability of the boards. A better mechanical performance was achieved for the MDI-bonded boards compared with the UF-bonded boards. Superior bonding between the MDI adhesive and the peanut hulls with different particle geometries was also observed; the peanut hull powder and coarse particles were unsuitable for the manufacturing of panels, due to the risk of an internal blowout. The water resistance of the panels was poor, whereas the mechanical strength of the peanut hull particleboard met the class M-1 requirement of the ANSI A208.1 (2009) standard for wood particleboard.

The outbreak of coronavirus disease 2019 (COVID-19) has become a global public health crisis due to its high contagious characteristics. In this article, we propose a new epidemic-dynamics model combining the transmission characteristics of COVID-19 and then use the reported epidemic data from 15 February to 30 June to simulate the spread of the Italian epidemic. Numerical simulations showed that (1) there was a remarkable amount of asymptomatic individuals; (2) the lockdown measures implemented by Italy effectively controlled the spread of the outbreak; (3) the Italian epidemic has been effectively controlled, but SARS-CoV-2 will still exist for a long time; and (4) the intervention of the government is an important factor that affects the spread of the epidemic.

Sirtuin 6 (SIRT6), as a NAD + -dependent deacetylase, plays an indispensable role in the regulation of health and physiology. Loss of SIRT6 causes spontaneous colitis in mice and makes intestinal epithelial cells prone to stress. However, whether SIRT6 overexpression increases resistance to colitis remains unknown. Here, in vivo results demonstrated that SIRT6 overexpression attenuates DSS-induced colitis in terms of clinical manifestations, histopathological damage, loss of tight junction function and imbalanced intestinal microenvironment. Additionally, we also found that the activation of NF-κB and c-Jun induced by DSS is diminished by SIRT6 overexpression. Furthermore, SIRT6 may regulate TAK1 to inhibit NF-κB and c-Jun signaling. Thus, our findings highlight the protective effect of SIRT6 on colon, further supporting the perspective that SIRT6 may be a therapeutic target for intestine injury under stress.

Aortic valve calcification is a common clinical disease, caused by valve interstitial cells (VICs), which initiate the thickening and then calcification of valve leaflets. Classical valve-derived cells can be seen in different cell populations according to their different morphologies, but it is not clear whether different types of mesenchymal cells exist. In this study, culture conditions for mesenchymal stromal cells were used to selectively isolate valve-derived stromal cells (VDSCs). After subculturing, the morphology, proliferation, multidifferentiation, immunophenotype, and gene expression profiling in isolated VDSCs were compared with those in conventional cultured VICs. VDSCs isolated from human aortic valves were uniform spindle-shaped fibroblasts, had mutilineage differentiation abilities, and proliferated faster than VICs. Classic mesenchymal markers including cluster of differentiation 90 (CD90), CD44, and CD29 were positively expressed. In addition, the stem cell markers CD163, CD133, and CD106 were all expressed in VDSCs. RNA-sequencing identified 1595 differentially expressed genes between VDSCs and VICs of which 301 were upregulated and 1294 were downregulated. Valvular extracellular matrix genes of VDSCs such as collagen type 1, alpha 1 (COL1A1), COL1A2, and fibronectin 1 were abundantly expressed. In addition, runt-related transcription factor 2 and Ki-67 proteins were also markedly upregulated in VDSCs, whereas there was less expression of the focal adhesion genes integrin alpha and laminin alpha in VDSCs compared to VICs. In conclusion, novel rapidly proliferating VDSCs with fibroblast morphology, which were found to express mesenchymal and osteogenic markers, may contribute to aortic valve calcification.

This paper presents a new strategy for the control of large displacements in structures under earthquake excitation. Firstly, an improved fractional order proportional-derivative (FOPD) controller is proposed. Secondly, a decentralized strategy is designed by adding a regulator and fault self-regulation to a standard decentralized controller. A new control architecture is obtained by combining the improved FOPD and the decentralized strategy. The parameters of the control system are tuned using an intelligent optimization algorithm. Simulation results demonstrate the performance and reliability of the proposed method.

Exploring effective therapies for delaying calcific heart valve disease (CHVD) is the focus of current cardiovascular clinical and scientific research. In this study, human aortic valve interstitial cells (hVICs) were isolated from patients with CHVD. After expansion, cultured hVICs were induced with the tumor necrosis factor-alpha (TNF-α) with or without anthraquinone emodin (EMD) treatments. Cytotoxicity and flow cytometric analysis were used to assess cell growth, while Alizarin Red S staining was used to detect hVICs calcification. Furthermore, RNA-sequencing analysis was utilized to investigate changes in mRNA profiles of cells cultured in TNF-α conditioned medium with or without EMD. Western blotting and qRT-PCR analyses were used for the verification of key selected genes. Our results indicated that EMD had limited influence on hVIC morphology, whereas in a dose-dependent fashion, EMD interfered with hVIC growth under TNF-α conditioned cell culture. Additionally, hVICs treated with TNF-α plus EMD, presented a gradual decrease of positive Alizarin Red S staining, when compared with cells treated with TNF-α only. Notably, cells treated with TNF-α plus EMD showed 1874 differential expression genes (DEGs), among them, 1131 were upregulated and 743 were downregulated. These DEGs displayed an enrichment of biological functions and signaling pathways, among them, BMP2, RELA, TNF, and TRAF1, were found to be significantly suppressed by EMD and selected given their role in mediating hVIC calcification. In conclusion, our study shows that EMD inhibits TNF-α-induced calcification and phenotypical transformation of hVICs via the NF-κB signaling pathway, thereby preventing calcification events stimulated during acute inflammatory responses.