Allelic variation in the autotetraploid potato: genes involved in starch and steroidal glycoalkaloid metabolism as a case study.

BACKGROUND: Tuber starch and steroidal glycoalkaloid (SGA)-related traits have been consistently prioritized in potato breeding, while allelic variation pattern of genes that underlie these traits is less explored. RESULTS: Here, we focused on the genes involved in two important metabolic pathways in the potato: starch metabolism and SGA biosynthesis. We identified 119 genes consisting of 81 involved in starch metabolism and 38 in the biosynthesis of steroidal glycoalkaloids, and discovered 96,166 allelic variants among 2,169 gene haplotypes in six autotetraploid potato genomes. Comparative analyses revealed an uneven distribution of allelic variants among gene haplotypes and that the vast majority of deleterious mutations in these genes are retained in heterozygous state in the autotetraploid potato genomes. Leveraging full-length cDNA sequencing data, we find that approximately 70% of haplotypes of the 119 genes are transcribable. Population genetic analyses identify starch and SGA biosynthetic genes that are potentially conserved or diverged between potato varieties with varying starch or SGA content. CONCLUSIONS: These results deepen the understanding of haplotypic diversity within functionally important genes in autotetraploid genomes and may facilitate functional characterization of genes or haplotypes contributing to traits related to starch and SGA in potato.

Prevention of Dialysis Catheter Malfunction with Urokinase and Heparin: A Randomized, Controlled Trial.

Objective: To evaluate the effectiveness of urokinase and heparin in preventing catheter infection and dysfunction in permanent hemodialysis tunneled cuffed catheters. Methods: We randomized 153 cases of maintenance hemodialysis patients with newly implanted permanent hemodialysis tunneled cannula catheters from November 2018 to November 2021 for this single-center prospective randomized controlled trial The eligible patients were given one of two treatment plans: Patients in the control group (73 patients) were given heparin (6260 U/mL)three times a week after hemodialysis. The intervention group (80 cases) was administered urokinase(25000 U/mL) on the basis of heparin. After six months of maintenance hemodialysis with the above sealing protocols, the primary result was the frequency of catheter malfunction, and the secondary outcome was the frequency of catheter-associated infection. Results: In the final analysis of 153 patients, catheter malfunctions occurred in 29 of the 80 patients assigned to heparin alone, with an incidence of 36.3%, and 16 of the 73 subjects assigned to urokinase combined with heparin, with a rate of 21.9%. This represents an almost 2-fold increase in the risk of catheter malfunction among patients treated with heparin alone as compared to those treated with urokinase once weekly (hazard ratio, 1.85; 13 patients (16.3%) allocated to heparin alone experienced catheter-related bacteremia, compared to 4 patients (5.5%) assigned to urokinase (hazard ratio, 2.79; 95%CI, 1.08 to 7.22; P = .03). Baseline levels, and adverse events, including bleeding incidents, did not statistically differ between the two groups. Conclusion: Urokinase can be used as a secondary prevention drug for long-term catheter malfunction and infection based on its cheapness, efficacy, and safety, which can effectively save medical costs, and its sealing protocol is simple and suitable for promotion.

Foliar spraying of lanthanum activates endocytosis in lettuce (Lactuca sativa L.) root cells, increasing Cd and Pb accumulation and their bioaccessibility.

Cadmium (Cd) and lead (Pb) accumulate easily in leafy vegetables and can harm human health. Lanthanum (La) have been used to improve agricultural yield and quality, but the effect of La application on Cd/Pb enrichment in leafy vegetables remains incomplete currently. A previous study reported that the endocytosis in lettuce leaf cells can be activated by La, leading to an increase in Pb accumulation in lettuce leaves. However, it has not been investigated whether foliar application of La enhances root cellular endocytosis and promotes its uptake of Cd and Pb. In this study, the influence of La on the uptake of Cd and Pb, Cd bioaccessibility, and the safety risks of cultivating lettuce under Cd and Pb stress were explored. It was found that La increased Cd (16-30 % in shoot, 16-34 % in root) and Pb (25-29 % in shoot, 17-23 % in root) accumulation in lettuce. The increased accumulation of Cd and Pb could be attributed to La-enhanced endocytosis. Meanwhile, La enhanced the toxicity of both Cd and Pb, inhibited lettuce growth, and aggravated the damage to the photosynthetic and antioxidant systems. Finally, gastrointestinal simulation experiments showed that La increased the Cd bioaccessibility in both gastric and intestinal phase by 7-108 % and 9-87 %, respectively. These results offer valuable insights into the safety of REEs for agricultural applications.

Mechanistic Insights into Effects of Different Dietary Polyphenol Supplements on Arsenic Bioavailability, Biotransformation, and Toxicity Based on a Mouse Model.

Arsenic (As) exposure has been related to many diseases, including cancers. Given the antioxidant and anti-inflammatory properties, the dietary supplementation of polyphenols may alleviate As toxicity. Based on a mouse bioassay, this study investigated the effects of chlorogenic acid (CA), quercetin (QC), tannic acid (TA), resveratrol (Res), and epigallocatechin gallate (EGCG) on As bioavailability, biotransformation, and toxicity. Intake of CA, QC, and EGCG significantly (p < 0.05) increased total As concentrations in liver (0.48-0.58 vs 0.27 mg kg-1) and kidneys (0.72-0.93 vs 0.59 mg kg-1) compared to control mice. Upregulated intestinal expression of phosphate transporters with QC and EGCG and proliferation of Lactobacillus in the gut of mice treated with CA and QC were observed, facilitating iAsV absorption via phosphate transporters and intestinal As solubility via organic acid metabolites. Although As bioavailability was elevated, serum levels of alpha fetoprotein and carcinoembryonic antigen of mice treated with all five polyphenols were reduced by 13.1-16.1% and 9.83-17.5%, suggesting reduced cancer risk. This was mainly due to higher DMAV (52.1-67.6% vs 31.4%) and lower iAsV contribution (4.95-10.7% vs 27.9%) in liver of mice treated with polyphenols. This study helps us develop dietary strategies to lower As toxicity.

Xuebijing Injection Attenuates Heat Stroke-Induced Brain Injury through Oxidative Stress Blockage and Parthanatos Modulation via PARP-1/AIF Signaling.

Heat stroke (HS) is a potentially fatal acute condition caused by an interplay of complex events including inflammation, endothelial injury, and coagulation abnormalities that make its pharmacological treatment a challenging problem. The traditional Chinese medicine Xuebijing injection (XBJ) has been shown to reduce inflammatory responses and prevent organ injuries in HS-induced mice. However, the underlying mechanism of XBJ in HS-induced brain injury remains unclear. In this study, HS-induced rat models and cell models were established to elucidate the effects and underlying mechanisms of XBJ injection on HS-induced brain injury in vivo and in vitro. The results revealed that XBJ injection improved the survival outcome of HS rats and attenuated HS-induced brain injury in a concentration-dependent manner. Subsequently, the reduction in viability and proliferation of neurons induced by HS were reversed by XBJ treatment, while the HS-induced increased ROS levels and neuron death were also inhibited by XBJ injection. Mechanistically, HS activated PARP-1/AIF signaling in vitro and in vivo, inducing the translocation of AIF from the cytoplasm to the nucleus, leading to PARP-1-dependent cell death of neurons. Additionally, we compared XBJ injection effects in young and old age rats. Results showed that XBJ also provided protective effects in HS-induced brain injury in aging rats; however, the treatment efficacy of XBJ injection at the same concentration was more significant in the young age rats. In conclusion, XBJ injection attenuates HS-induced brain injury by inhibiting oxidative stress and Parthanatos via the PARP-1/AIF signaling, which might provide a novel therapeutic strategy for HS treatment.

Unveiling the Therapeutic Potentials of Mushroom Bioactive Compounds in Alzheimer's Disease.

Alzheimer's disease (AD) stands as a prevailing neurodegenerative condition (NDs), leading to the gradual deterioration of brain cells and subsequent declines in memory, thinking, behavior, and emotion. Despite the intensive research efforts and advances, an effective curative treatment for the disease has not yet been found. Mushrooms, esteemed globally for their exquisite flavors and abundant nutritional benefits, also hold a wealth of health-promoting compounds that contribute to improving AD health. These compounds encompass polysaccharides, proteins, lipids, terpenoids, phenols, and various other bioactive substances. Particularly noteworthy are the potent neuroprotective small molecules found in mushrooms, such as ergothioneine, erinacine, flavonoids, alkaloids, ergosterol, and melanin, which warrant dedicated scrutiny for their therapeutic potential in combating AD. This review summarizes such positive effects of mushroom bioactive compounds on AD, with a hope to contribute to the development of functional foods as an early dietary intervention for this neurodegenerative disease.

Foliar application of selenium nanoparticles alleviates cadmium toxicity in maize (Zea mays L.) seedlings: Evidence on antioxidant, gene expression, and metabolomics analysis.

The molecular and metabolic mechanisms of foliar selenium (Se) nanoparticles (SeNPs) application in mitigating cadmium (Cd) toxicity in crops have not been well studied. Herein, hydroponically cultured maize seedlings were exposed to Cd (20 µM) and treated without and with foliar SeNPs application. Effects of SeNPs on Cd transporter genes and plant metabolism were also explored. Results showed that compared to control plants without Cd exposure, Cd exposure decreased shoot height (16.8 %), root length (17.7 %), and fresh weight of root (24.2 %), stem (28.8 %), and foliar-applied leaves (Se-leaves) (15.0 %) via oxidative damage. Compared to Cd exposure alone, foliar SeNPs application at 20 mg/L (0.25 mg/plant) significantly alleviated the Cd toxicity by promoting photosynthesis and antioxidant capacity and fixing Cd in cell wall. Meanwhile, the mineral concentration of Ca (26.0 %), Fe (55.4 %), Mg (27.0 %), Na (28.6 %), and Zn (10.1 %) in Se-leaves was improved via foliar SeNPs application at 20 mg/L. QRT-PCR analysis further revealed that down- and up-regulation of the expression of ZmHMA2 and ZmHMA3 gene in Se-leaves contributed to reduced translocation of Cd in plants and enhanced Cd sequestration in the vacuole, respectively. Metabolomic results further indicated that metabolic pathways including carbohydrate metabolism, membrane transport, translation, amino acid metabolism, and energy metabolism were significantly affected by foliar SeNPs application. In conclusion, foliar SeNPs application at 20 mg/L could be a prospective strategy to mitigate Cd toxicity in maize.

Phylogenomic discovery of deleterious mutations facilitates hybrid potato breeding.

Hybrid potato breeding will transform the crop from a clonally propagated tetraploid to a seed-reproducing diploid. Historical accumulation of deleterious mutations in potato genomes has hindered the development of elite inbred lines and hybrids. Utilizing a whole-genome phylogeny of 92 Solanaceae and its sister clade species, we employ an evolutionary strategy to identify deleterious mutations. The deep phylogeny reveals the genome-wide landscape of highly constrained sites, comprising ∼2.4% of the genome. Based on a diploid potato diversity panel, we infer 367,499 deleterious variants, of which 50% occur at non-coding and 15% at synonymous sites. Counterintuitively, diploid lines with relatively high homozygous deleterious burden can be better starting material for inbred-line development, despite showing less vigorous growth. Inclusion of inferred deleterious mutations increases genomic-prediction accuracy for yield by 24.7%. Our study generates insights into the genome-wide incidence and properties of deleterious mutations and their far-reaching consequences for breeding.

Application of tea polyphenols as additives in brown fermented milk: Potential analysis of mitigating Maillard reaction products.

Brown fermented milk (BFM) is favored by consumers in the dairy market for its unique burnt flavor and brown color. However, Maillard reaction products (MRP) from high-temperature baking are also noteworthy. In this study, tea polyphenols (TP) were initially developed as potential inhibitors of MRP formation in BFM. The results showed that the flavor profile of BFM did not change after adding 0.08% (wt/wt) of TP, and its inhibition rates on 5-hydroxymethyl-2-furaldehyde (5-HMF), glyoxal (GO), methylglyoxal (MGO), Nε-carboxymethyl lysine (CML), and Nε-carboxyethyl lysine (CEL) were 60.8%, 27.12%, 23.44%, 57.7%, and 31.28%, respectively. After 21 d of storage, the levels of 5-HMF, GO, MGO, CML, and CEL in BFM with TP were 46.3%, 9.7%, 20.6%, 5.2%, and 24.7% lower than the control group, respectively. Moreover, a smaller change occurred in their color and the browning index was lower than that of the control group. The significance of this study was to develop TP as additives to inhibit the production of MRP in brown fermented yogurt without changing color and flavors, thereby making dairy products safer for consumers.

The effect of vegetable oil pre-emulsified with whey protein and pectin on physicochemical properties and microstructure of low-fat yogurt.

The effects of whey protein isolate (WPI)-pectin pre-emulsified vegetable oil on the physicochemical properties and microstructure of low-fat yogurt (LFY) were investigated by particle size distribution, water-holding capacity (WHC), texture, rheology, electron microscopy, storage stability, and sensory analysis. The vegetable oil was pre-emulsified into two types of emulsions, a mixed emulsion (ME: WPI-pectin complexes were adsorbed directly at the interface) and a bilayer emulsion (BE: Pectin was added to a previously established WPI-stabilized interface). The results showed that yogurts added with pre-emulsified vegetable oil (ME-Y, BE-Y) had significantly better quality than LFY, with better WHC, textural properties, rheological properties, and storage stability. The average particle size of ME (11.96 µm) was larger than that of BE (10.23 µm). The consistency of yogurt added with ME (ME-Y) was significantly higher than that of yogurt added with BE (BE-Y), at 2359.10 and 2181.12 g s, respectively. Meanwhile, ME-Y exhibited storage stability similar to full-fat control (FFY) and higher sensory scores. Interestingly, the WHC of BE-Y (49.03%) was higher than that of ME-Y (45.63%). In addition, WPI + Pectin-Y exhibited higher WHC (53.81%) and consistency (2518.73 g s) compared to ME-Y and BE-Y, but the particle size distribution was not uniform, and the direct addition of WPI, pectin, and oil had no positive effect on improving the rheological properties of yogurt. Overall, the addition of WPI-pectin pre-emulsified vegetable oil improved the quality of LFY. These findings are particularly relevant for the production of higher quality LFY.

Super-pangenome analyses highlight genomic diversity and structural variation across wild and cultivated tomato species.

Effective utilization of wild relatives is key to overcoming challenges in genetic improvement of cultivated tomato, which has a narrow genetic basis; however, current efforts to decipher high-quality genomes for tomato wild species are insufficient. Here, we report chromosome-scale tomato genomes from nine wild species and two cultivated accessions, representative of Solanum section Lycopersicon, the tomato clade. Together with two previously released genomes, we elucidate the phylogeny of Lycopersicon and construct a section-wide gene repertoire. We reveal the landscape of structural variants and provide entry to the genomic diversity among tomato wild relatives, enabling the discovery of a wild tomato gene with the potential to increase yields of modern cultivated tomatoes. Construction of a graph-based genome enables structural-variant-based genome-wide association studies, identifying numerous signals associated with tomato flavor-related traits and fruit metabolites. The tomato super-pangenome resources will expedite biological studies and breeding of this globally important crop.

Using Fe biofortification strategies to reduce both Ni concentration and oral bioavailability for rice with high Ni.

Due to naturally high Ni or soil Ni contamination, high Ni concentrations are reported in rice, raising a need to reduce rice Ni exposure risk. Here, reduction in rice Ni concentration and Ni oral bioavailability with rice Fe biofortification and dietary Fe supplementation was assessed using rice cultivation and mouse bioassays. Results showed that for rice grown in a high geogenic Ni soil, increases in rice Fe concentration from ∼10.0 to ∼30.0 µg g-1 with foliar EDTA-FeNa application led to decreases in Ni concentration from ∼4.0 to ∼1.0 µg g-1 due to inhibited Ni transport from shoot to grains via down-regulated Fe transporters. When fed to mice, Fe-biofortified rice was significantly (p < 0.01) lower in Ni oral bioavailability (59.9 ± 11.9% vs. 77.8 ± 15.1%; 42.4 ± 9.81% vs. 70.4 ± 6.81%). Dietary amendment of exogenous Fe supplements to two Ni-contaminated rice samples at 10-40 µg Fe g-1 also significantly (p < 0.05) reduced Ni RBA from 91.7% to 61.0-69.5% and from 77.4% to 29.2-55.2% due to down-regulation of duodenal Fe transporter expression. Results suggest that the Fe-based strategies not only reduced rice Ni concentration but also lowered rice Ni oral bioavailability, playing dual roles in reducing rice-Ni exposure.

Incorporation of probiotics into 3D printed Pickering emulsion gel stabilized by tea protein/xanthan gum.

Different xanthan gum (XG) concentrations on the rheological/texture properties of Pickering emulsion (PE) gel stabilized by tea protein/xanthan gum (TP/XG) were studied to achieve an ink feasible for 3D printing. Afterwards, the effects of 3D printing and digestion process on the viability of probiotics were studied when encapsulated in the PE gel. Results indicated that gel strength, stability, storage modulus (G') and loss modulus (G″) increased as XG concentration increased. Nozzle diameter and printing temperature of 45 and 55℃ had no significant effect on probiotic's viability, but printing temperature of 65℃ reduced viable probiotics from 8.07 to 6.59 log CFU/g. No significant change of probiotics viability in 3D printed samples was observed during 11-day storage at 4℃. PE gel encapsulated probiotic's viability was significantly improved under heat treatment and simulated gastrointestinal environment. This study gives insights on the production of 3D printed foods using PE gel incorporating probiotics.

Metabolic profiling on the analysis of different parts of Schisandra chinensis based on UPLC-QTOF-MS with comparative bioactivity assays.

The Schisandra chinensis is an important edible plant, and previous phytochemical research focused on the S. chinensis fruit (SF) due to its long history as traditional Chinese medicine. Schisandra chinensis fruit was used as an astringent tonic to astringe the lungs and the kidneys, replenish energy, promote the production of body fluids, tonify the kidney, and induce sedation. The components of S. chinensis, such as its stems (SS), leaves (SL), and roots (SR), have drawn little attention regarding their metabolites and bioactivities. In this study, a strategy of combining a chemical database with the Progenesis QI informatics platform was applied to characterize the metabolites. A total of 332 compounds were tentatively identified, including lignans, triterpenoids, flavonoids, tannins, and other compound classes. Heatmap and principal component analysis (PCA) showed remarkable differences in different parts of the plants. By multiple orthogonal partial least-squares discriminant analyses (OPLS-DA), 76 compounds were identified as potential marker compounds that differentiate these different plant parts. Based on the variable influence on the projection score from OPLS-DA, the active substances including gomisin D, schisandrol B, schisantherin C, kadsuranin, and kadlongilactone F supported the fact that the biological activity of the roots was higher than that of the fruit. These substances can be used as marker compounds in the plant roots, which likely contribute to their antioxidant and anti-inflammatory activities. The plant roots could be a new medicinal source that exhibits better activity than that of traditional medicinal parts, which makes them worth exploring.

Effects of various Fe compounds on the bioavailability of Pb contained in orally ingested soils in mice: Mechanistic insights and health implications.

Reducing lead (Pb) exposure via oral ingestion of contaminated soils is highly relevant for child health. Elevating dietary micronutrient iron (Fe) intake can reduce Pb oral bioavailability while being beneficial for child nutritional health. However, the practical performance of various Fe compounds was not assessed. Here, based on mouse bioassays, ten Fe compounds applied to diets (100-800 mg Fe kg-1) reduced Pb oral relative bioavailability (RBA) in two soils variedly depending on Fe forms. EDTA-FeNa was most efficient, which reduced Pb-RBA in a soil from 79.5 ± 14.7 % to 23.1 ± 2.72 % (71 % lower) at 100 mg Fe kg-1 in diet, more effective than other 9 compounds at equivalent or higher doses (3.6-68 % lower). When EDTA-FeNa, ferrous gluconate, ferric citrate, and ferrous bisglycinate were supplemented, Fe-Pb co-precipitation was not observed in the intestinal tract. EDTA-FeNa, ferrous gluconate, ferric citrate, and ferrous sulfate suppressed duodenal divalent metal transporter 1 (DMT1)mRNA relative expression similarly (27-68 % lower). In comparison, among ten compounds, EDTA-FeNa elevated Fe concentrations in mouse liver, kidney, and blood (1.50-2.69-fold higher) most efficiently, suggesting the most efficient Fe absorption that competed with Pb. In addition, EDTA was unique from other organic ligands, ingestion of which caused 12.0-fold higher Pb urinary excretion, decreasing Pb concentrations in mouse liver, kidney, and blood by 68-88 %. The two processes (Fe-Pb absorption competition and Pb urinary excretion with EDTA) interacted synergistically, leading to the lowest Pb absorption with EDTA-FeNa. The results provide evidence of a better inhibition of Pb absorption by EDTA-FeNa, highlighting that EDTA-FeNa may be the most appropriate supplement for intervention on human Pb exposure. Future researches are needed to assess the effectiveness of EDTA-FeNa for intervention on human Pb exposure.

Application of whey protein emulsion gel microparticles as fat replacers in low-fat yogurt: Applicability of vegetable oil as the oil phase.

Low-fat, healthy yogurt is becoming increasingly favored by consumers. In the present study, whey protein emulsion gel microparticles were used to improve the quality of low-fat yogurt, and the effects of vegetable oil emulsion gel as a fat substitute on the qualities of low-fat yogurt were investigated, expecting to obtain healthier and even more excellent quality low-fat yogurt by applying a new method. First, emulsion gel microparticles were prepared, and then particle size distribution of emulsion gel and water holding capacity (WHC), textural properties, rheological properties, microstructure, storage stability, and sensory evaluation of yogurt were carried out. The results showed that yogurt with emulsion gel had significantly superior qualities than yogurt made with skim milk powder, with better WHC, textural properties, rheological properties, and storage stability. The average particle size of whey protein-vegetable oil emulsion gel microparticles was significantly larger than that of whey protein-milk fat emulsion gel microparticles, and the larger particle size affected the structural stability of yogurt. The WHC of yogurt made with whey protein-vegetable oil emulsion gel microparticles (V-EY) was lower (40.41%) than that of yogurt made with whey protein-milk fat emulsion gel microparticles (M-EY; 42.81%), and the texture results also showed that the hardness, consistency, and viscosity index of V-EY were inferior to these of M-EY, whereas no significant differences were found in the cohesiveness. Interestingly, the microstructure of V-EY was relatively flatter, with more and finer network branching. The whey separation between V-EY and M-EY also did not show significant differences during the 14 d of storage. Compared with yogurt made with whey protein, vegetable oil, and skim milk powder, the structure of V-EY remained relatively stable and had no cracks after 14 d of storage. The sensory evaluation results found that the total score of V-EY (62) was only lower than M-EY (65) and significantly higher than that of yogurt made with skim milk powder. The emulsion gel addition improved the sensory qualities of yogurt. Whey protein emulsion gel microparticles prepared from vegetable oil can be applied to low-fat yogurt to replace fat and improve texture and sensory defects associated with fat reduction.

Soil multifunctionality of paddy field is explained by soil pH rather than microbial diversity after 8-years of repeated applications of biochar and nitrogen fertilizer.

Biochar and nitrogen (N) fertilizer application can increase soil carbon sequestration and enhance soil nutrient cycling. However, few studies have systematically explored the effects of the long-term application of biochar and N fertilizer on soil multifunctionality and characterized its driving factors. Based on an 8-year biochar paddy-field experiment in anthropogenic alluvial alkaline soil in northwest China, we measured eleven soil functions associated with soil carbon sequestration and nutrient cycling and four potential factors (soil bacterial and fungal richness, pH, and aggregates) governing soil functions to investigate the effects of three biochar rates (C0, no biochar; C1, 4.5 t ha-1 year-1; C2, 13.5 t ha-1 year-1) and two N fertilizer rates (N0, no N fertilizer; N1, 300 kg N ha-1 year-1) on individual soil ecosystem functions and soil multifunctionality. Our results showed that biochar and N fertilizer application increased soil organic carbon (SOC) by 20-58 % and total N content by 9.3-15 % and had a varied effect (but mainly positive) on the activity of enzymes associated with soil carbon, N, and phosphorus cycling. Different application rates of biochar and N fertilizer had no influence on soil DNA concentrations, but did change soil microbial diversity, soil aggregation, and pH. The carbon storage function (SOC content) of soils is an important predictor of multifunctionality. Long-term biochar and N fertilizer application indirectly explained soil multifunctionality by altering soil pH, whereas bacterial and fungal diversity and soil aggregates did not play significant roles in explaining soil multifunctionality. These findings suggest that the application of biochar and N fertilizer can enhance soil multifunctionality by directly improving the individual functions [soil carbon sequestration (SOC content)] and decreasing soil pH in alkaline paddy fields.

Universal and Sensitive Drug Assessment Biosensing Platform Using Optimal Mechanical Beating Detection of Single Cardiomyocyte.

The preclinical assessment of efficacy and safety is essential for cardiovascular drug development in order to guarantee effective prevention and treatment of cardiovascular disease and avoid human health endangerment and a huge waste of resources. Rhythmic mechanical beating as one of the crucial cardiomyocyte properties has been exploited to establish a drug assessment biosensing platform. However, the conventional label-free biosensing platforms are difficult to perform high-throughput and high-resolution mechanical beating detection for a single cardiomyocyte, while label-based strategies are limited by pharmacologically adverse effects and phototoxicity. Herein, we propose a biosensing platform involving the multichannel electrode array device and the universal mechanical beating detection system. The platform can determine the optimal characteristic working frequency of different devices and dynamically interrogate the viability of multisite single cardiomyocytes to establish the optimized cell-based model for sensitive drug assessment. The subtle changes of mechanical beating signals induced by cardiovascular drugs can be detected by the platform, thereby demonstrating its high performance in pharmacological assessment. The universal and sensitive drug assessment biosensing platform is believed to be widely applied in cardiology investigating and preclinical drug screening.