Robust antibacterial activity of rare-earth ions on planktonic and biofilm bacteria.

Bacterial infections pose a serious threat to human health, with emerging antibiotic resistance, necessitating the development of new antibacterial agents. Cu2+and Ag+are widely recognized antibacterial agents with a low propensity for inducing bacterial resistance; however, their considerable cytotoxicity constrains their clinical applications. Rare-earth ions, owing to their unique electronic layer structure, hold promise as promising alternatives. However, their antibacterial efficacy and biocompatibility relative to conventional antibacterial agents remain underexplored, and the variations in activity across different rare-earth ions remain unclear. Here, we systematically evaluate the antibacterial activity of five rare-earth ions (Yb3+, Gd3+, Sm3+, Tb3+, and La3+) againstStaphylococcus aureusandPseudomonas aeruginosa, benchmarked against well-established antibacterial agents (Cu2+, Ag+) and the antibiotic norfloxacin. Cytotoxicity is also assessed via live/dead staining of fibroblasts after 24 h rare-earth ion exposure. Our findings reveal that rare-earth ions require higher concentrations to match the antibacterial effects of traditional agents but offer the advantage of significantly lower cytotoxicity. In particular, Gd3+demonstrates potent bactericidal efficacy against both planktonic and biofilm bacteria, while maintaining the lowest cytotoxicity toward mammalian cells. Moreover, the tested rare-earth ions also exhibited excellent antifungal activity againstCandida albicans. This study provides a critical empirical framework to guide the selection of rare-earth ions for biomedical applications, offering a strategic direction for the development of novel antimicrobial agents.

Insight into the probability of ethoxy(pentafluoro)cyclotriphosphazene (PFPN) as the functional electrolyte additive in lithium-sulfur batteries.

Enhancing the flame retardancy of electrolytes and the stability of lithium anodes is of great significance to improve the safety performance of lithium-sulfur (Li-S) batteries. It is well known that the most commonly used ether based electrolyte solvents in Li-S batteries have a lower flash point and higher volatility than the ester electrolyte solvents in Li-ion batteries. Hence, lithium-sulfur batteries have greater safety risks than lithium-ion batteries. Herein, ethoxy(pentafluoro)cyclotriphosphazene (PFPN), which is commonly used as a flame retardant for ester electrolytes in lithium-ion batteries, is utilized as both a film-forming electrolyte additive and a flame retardant additive for the ether electrolyte to investigated its applicability in Li-S batteries. It is found that the ether electrolyte containing PFPN not only has good flame retardant properties and a wide potential window of about 5 V, but also can form a stable SEI film on the surface of a lithium anode. As a result, with the ether-based electrolyte containing 10 wt% PFPN, Li-Cu and Li-S batteries all delivered a stable cycling performance with a high coulombic Efficiency and a long-lifespan performance, which were all superior to the batteries using the ether-based electrolyte without PFPN. This study demonstrates an effective solution to solve the problems of flammable ether-based electrolytes and reactive lithium anodes, and it may contribute to the development of safe Li-S batteries.

Hierarchical antibiotic delivery system based on calcium phosphate cement/montmorillonite-gentamicin sulfate with drug release pathways.

Antibiotic-loaded calcium phosphate cement (CPC) has emerged as a promising biomaterial for drug delivery in orthopedics. However, there are problems such as the burst release of antibiotics, low cumulative release ratio, inappropriate release cycle, inferior mechanical strength, and poor anti-collapse properties. In this research, montmorillonite-gentamicin (MMT-GS) was fabricated by solution intercalation method and served as the drug release pathways in CPC to avoid burst release of GS, achieving promoted cumulative release ratios and a release cycle matched the time of inflammatory response. The results indicated that the highest cumulative release ratio and release concentration of GS in CPC/MMT-GS was 94.1 ± 2.8 % and 1183.05 µg/mL, and the release cycle was up to 504 h. In addition, the hierarchical GS delivery system was divided into three stages, and the kinetics followed the Korsmeyer-Peppas model, the zero-order model, and the diffusion-dissolution model, respectively. Meanwhile, the compressive strength of CPC/MMT-GS was up to 51.33 ± 3.62 MPa. Antibacterial results demonstrated that CPC/MMT-GS exhibited excellent in vitro long-lasting antibacterial properties to E. coli and S. aureus. Furthermore, CPC/MMT-GS promoted osteoblast proliferation and exhibited excellent in vivo histocompatibility. Therefore, CPC/MMT-GS has favorable application prospects in the treatment of bone defects with bacterial infections and inflammatory reactions.

GRAS gene family in rye (Secale cereale L.): genome-wide identification, phylogeny, evolutionary expansion and expression analyses.

BACKGROUND: The GRAS transcription factor family plays a crucial role in various biological processes in different plants, such as tissue development, fruit maturation, and environmental stress. However, the GRAS family in rye has not been systematically analyzed yet. RESULTS: In this study, 67 GRAS genes in S. cereale were identified and named based on the chromosomal location. The gene structures, conserved motifs, cis-acting elements, gene replications, and expression patterns were further analyzed. These 67 ScGRAS members are divided into 13 subfamilies. All members include the LHR I, VHIID, LHR II, PFYRE, and SAW domains, and some nonpolar hydrophobic amino acid residues may undergo cross-substitution in the VHIID region. Interested, tandem duplications may have a more important contribution, which distinguishes them from other monocotyledonous plants. To further investigate the evolutionary relationship of the GRAS family, we constructed six comparative genomic maps of homologous genes between rye and different representative monocotyledonous and dicotyledonous plants. The response characteristics of 19 ScGRAS members from different subfamilies to different tissues, grains at filling stages, and different abiotic stresses of rye were systematically analyzed. Paclobutrazol, a triazole-based plant growth regulator, controls plant tissue and grain development by inhibiting gibberellic acid (GA) biosynthesis through the regulation of DELLA proteins. Exogenous spraying of paclobutrazol significantly reduced the plant height but was beneficial for increasing the weight of 1000 grains of rye. Treatment with paclobutrazol, significantly reduced gibberellin levels in grain in the filling period, caused significant alteration in the expression of the DELLA subfamily gene members. Furthermore, our findings with respect to genes, ScGRAS46 and ScGRAS60, suggest that these two family members could be further used for functional characterization studies in basic research and in breeding programmes for crop improvement. CONCLUSIONS: We identified 67 ScGRAS genes in rye and further analysed the evolution and expression patterns of the encoded proteins. This study will be helpful for further analysing the functional characteristics of ScGRAS genes.

A review of nanomaterials for biosensing applications.

A biosensor is a device that reacts with the analyte to be analyzed, detects its concentration, and generates readable information, which plays an important role in medical diagnosis, detection of physiological indicators, and disease prevention. Nanomaterials have received increasing attention in the fabrication and improvement of biosensors due to their unique physicochemical and optical properties. In this paper, the properties of nanomaterials such as the size effect, optical and electrical properties, and their advantages in the field of biosensing are briefly summarized, and the application of nanomaterials can effectively improve the sensitivity and reduce the detection limit of biosensors. The advantages of commonly used nanomaterials such as gold nanoparticles (AuNPs), carbon nanotubes (CNTs), quantum dots (QDs), graphene, and magnetic nanobeads for biosensor applications are also reviewed. Besides, the two main types of biosensors using nanomaterials involved in their construction and their working principles are described, and the toxicity and biocompatibility of nanomaterials and the future direction of nanomaterial biosensors are discussed.

Gene cloning, protein expression, and enzymatic characterization of a double-stranded RNA degrading enzyme in Apolygus lucorum.

RNA interference (RNAi) is a powerful tool that post-transcriptionally silences target genes in eukaryotic cells. However, silencing efficacy varies greatly among different insect species. Recently, we met with little success when attempting to knock down genes in the mirid bug Apolygus lucorum via dsRNA injection. The disappearance of double-stranded RNA (dsRNA) could be a potential factor that restricts RNAi efficiency. Here, we found that dsRNA can be degraded in midgut fluids, and a dsRNase of A. lucorum (AldsRNase) was identified and characterized. Sequence alignment indicated that its 6 key amino acid residues and the Mg2+ -binding site were similar to those of other insects' dsRNases. The signal peptide and endonuclease non-specific domain shared high sequence identity with the brown-winged green stinkbug Plautia stali dsRNase. AldsRNase showed high salivary gland and midgut expression and was continuously expressed through the whole life cycle, with peaks at the 4th instar ecdysis in the whole body. The purified AldsRNase protein obtained by heterologously expressed can rapidly degrade dsRNA. When comparing the substrate specificity of AldsRNase, 3 specific substrates (dsRNA, small interfering RNA, and dsDNA) were all degraded, and the most efficient degradation is dsRNA. Subsequently, immunofluorescence revealed that AldsRNase was expressed in the cytoplasm of midgut cells. Through cloning and functional study of AldsRNase, the enzyme activity and substrate specificity of the recombinant protein, as well as the subcellular localization of nuclease, the reason for the disappearance of dsRNA was explained, which was useful in improving RNAi efficiency in A. lucorum and related species.

Assessment of relationships between bullous pemphigoid and neurological diseases: A bidirectional two-sample Mendelian randomization study.

Bullous pemphigoid (BP) is the most prevalent autoimmune vesiculobullous skin illness that tends to affect the elderly. Growing evidence has hinted a correlation between BP and neurological diseases. However, existing observational studies contained inconsistent results, and the causality and direction of their relationship remain poorly understood. To assess the causal relationship between BP and neurological disorders, including Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD), and stroke. A bidirectional two-sample Mendelian randomization (MR) adopted independent top genetic variants as instruments from the largest accessible genome-wide association studies (GWASs), with BP (n = 218 348), PD (n = 482 730), AD (n = 63 926), stroke (n = 446 696), and MS (n = 115 803). Inverse variance weighted (IVW), MR-Egger, weighted mode methods, weighted median, and simple mode were performed to explore the causal association. Multiple sensitivity analyses, MR-Pleiotropy Residual Sum and Outlier (PRESSO) was used to evaluate horizontal pleiotropy and remove outliers. With close-to-zero effect estimates, no causal impact of BP on the risk of the four neurological diseases was discovered. However, we found that MS was positively correlated with higher odds of BP (OR = 1.220, 95% CI: 1.058-1.408, p = 0.006), while no causal associations were observed between PD (OR = 0.821, 95% CI: 0.616-1.093, p = 0.176), AD (OR = 1.066, 95% CI: 0.873-1.358, p = 0.603), stroke (OR = 0.911, 95% CI: 0.485-1.713, p = 0.773) and odds of BP. In summary, no causal impact of BP on the risk of PD, AD, MS and stroke was detected in our MR analysis. However, reverse MR analysis identified that only MS was positively correlated with higher odds of BP, but not PD, AD and stroke.

Fully integrated wearable microneedle biosensing platform for wide-range and real-time continuous glucose monitoring.

Wearable microneedle sensors for continuous glucose monitoring (CGM) have great potential for clinical impact by allowing access to large data sets to provide individualized treatment plans. To date, their development has been challenged by the accurate wide linear range tracking of interstitial fluid (ISF) glucose (Glu) levels. Here, we present a CGM platform consisting of a three-electrode microneedle electrochemical biosensor and a fully integrated radio-chemical analysis system. The long-term performance of the robust CGM on diabetic rats was achieved by electrodepositing Prussian blue (PB), and crosslinking glucose oxidase (GOx) and chitosan to form a 3D network using glutaraldehyde (GA). After redox by GOx, PB rapidly decomposes hydrogen peroxide and mediates charge transfer, while the 3D network and graphite powder provide enrichment and release sites for Glu and catalytic products, enabling a sensing range of 0.25-35 mM. Microneedle CGM has high sensitivity, good stability, and anti-interference ability. In diabetic rats, CGM can accurately monitor Glu levels in the ISF in real-time, which are highly consistent with levels measured by commercial Glu meters. These results indicate the feasibility and application prospects of the PB-based CGM for the clinical management of diabetes. STATEMENT OF SIGNIFICANCE: This study addresses the challenge of continuous glucose monitoring system design where the narrow linear range of sensing due to the miniaturization of sensors fails to meet the monitoring needs of clinical diabetic patients. This was achieved by utilizing a three-dimensional network of glutaraldehyde cross-linked glucose oxidase and chitosan. The unique topology of the 3D network provides a large number of sites for glucose enrichment and anchors the enzyme to the sensing medium and the conductive substrate through covalent bonding, successfully blocking the escape of the enzyme and the sensing medium and shortening the electron transfer and transmission path.

New strategies to address world food security and elimination of malnutrition: future role of coarse cereals in human health.

As we face increasing challenges of world food security and malnutrition, coarse cereals are coming into favor as an important supplement to human staple foods due to their high nutritional value. In addition, their functional components, such as flavonoids and polyphenols, make them an important food source for healthy diets. However, we lack a systematic understanding of the importance of coarse cereals for world food security and nutritional goals. This review summarizes the worldwide cultivation and distribution of coarse cereals, indicating that the global area for coarse cereal cultivation is steadily increasing. This paper also focuses on the special adaptive mechanisms of coarse cereals to drought and discusses the strategies to improve coarse cereal crop yields from the perspective of agricultural production systems. The future possibilities, challenges, and opportunities for coarse cereal production are summarized in the face of food security challenges, and new ideas for world coarse cereal production are suggested.

Biomass-derived 2D carbon materials: structure, fabrication, and application in electrochemical sensors.

Biomass, a renewable hydrocarbon, is one of the favorable sources of advanced carbon materials owing to its abundant resources and diverse molecular structures. Biomass-based two-dimensional carbon nanomaterials (2D-BC) have attracted extensive attention due to their tunable structures and properties, and have been widely used in the design and fabrication of electrochemical sensing platforms. This review embarks on the thermal conversion process of biomass from different sources and the synthesis strategy of 2D-BC materials. The affinity between 2D-BC structure and properties is emphasized. The recent progress in 2D-BC-based electrochemical sensors for health and environmental monitoring is also presented. Finally, the challenges and future development directions related to such materials are proposed in order to promote their further application in the field of electrochemical sensing.

[Quality evaluation of Compound Cheqian Tablets based on UPLC-Q-TOF-MS/MS, network pharmacology and "double external standards" QAMS].

The Compound Cheqian Tablets are derived from Cheqian Power in Comprehensive Recording of Divine Assistance, and they are made by modern technology with the combination of Plantago asiatica and Coptis chinensis. To investigate the material basis of Compound Cheqian Tablets in the treatment of diabetic nephropathy, in this study, the chemical components of Compound Cheqian Tablets were characterized and analyzed by UPLC-Q-TOF-MS/MS, and a total of 48 chemical components were identified. The identified chemical compounds were analyzed by network pharmacology. By validating with previous literature, six bioactive compounds including acteoside, isoacteoside, coptisine, magnoflorine, palmatine, and berberine were confirmed as the index components for qua-lity evaluation. Furthermore, the content of the six components in the Compound Cheqian Tablets was determined by the "double external standards" quantitative analysis of multi-components by single marker(QAMS), and the relative correction factor of isoacteoside was calculated as 1.118 by using acteoside as the control; the relative correction factors of magnoflorine, palmatine, and berberine were calculated as 0.729, 1.065, and 1.126, respectively, by using coptisine as the control, indicating that the established method had excellent stability under different conditions. The results obtained by the "double external standards" QAMS approximated those obtained by the external standard method. This study qualitatively characterized the chemical components in the Compound Cheqian Tablets by applying UPLC-Q-TOF-MS/MS and screened the pharmacodynamic substance basis for the treatment of diabetic nephropathy via network pharmacology, and primary pharmacodynamic substance groups were quantitatively analyzed by the "double external stan-dards" QAMS method, which provided a scientific basis for clarifying the pharmacodynamic substance basis and quality control of Compound Cheqian Tablets.

Recycling of discarded face masks for modification and use in SBS-modified bitumen.

Since the outbreak of the COVID-19 pandemic, the discarded face masks have attracted widespread attention in society. In line with sustainable development, a physicochemical treatment method was used to recycle discarded face masks into styrene-butadiene-styrene (SBS) modified bitumen. Utilizing the highly adhesive polydopamine-polyethyleneimine (PDA-PEI) coating, it has improved the surface damage of the discarded face mask fibers (DFMF) caused by natural aging and mechanical fragmentation, simultaneously strengthening the connection between the fibers and bitumen. At 46 °C, the 2% embellish-face mask fiber (E-FMF)/SBS modified bitumen, compared to the 2%DFMF/SBS modified bitumen, exhibited improvements in complex modulus (G*), elastic modulus (G'), and loss modulus (G″) by 12.27%, 16.39%, and 13.35%, respectively. Furthermore, at 0.1 kPa and 3.2 kPa, the creep recovery rate (R) increased by 23.3% and 32%, and the average creep compliance (Jnr) decreased by 54.7% and 64%. It was demonstrated that DFMF adhered with the coating, were more effective in improving the mechanical properties, deformation resistance, and shear resistance of the bitumen. This approach enriches the application scenarios of discarded single-use face masks and supports environmental protection and road construction.

Public's preferences for health science popularization short videos in China: a discrete choice experiment.

Background: Health science popularization short video disseminates health information to the public in an understandable way about health information. Objective: To investigate the preferences of Chinese residents for health science popularization short videos and provide suggestions for optimizing the production of short videos. Methods: An online survey of Chinese people was conducted using a self-administered questionnaire, and a discrete choice experiment (DCE) was used to explore the public's preferences for health science popularization short videos. Results: A total of 618 respondents were included, of which 306 (45.51%) were male and 312 (50.49%) were female, 271 (43.85%) were aged 18-25, 239 (38.67%) were aged 26-60, and 108 (17.48%) were aged 60 and above. Whether the video is charged or not (46.891%) and the account subject (28.806%) were both considered important. The results of the DCE revealed that the participants considered video free of charge as the most significant attribute of health science popularization short videos (OR 3.433, 95% CI 3.243-3.633). Overall, participants preferred and were more willing to pay for health science popularization short videos with a hospital account subject (OR 1.192, 95% CI 1.116-1.274), with the form of graphic narration (OR 1.062, 95% CI 1.003-1.126), free of charge (OR 3.433, 95% CI 3.243-3.633), with the content that satisfies their needs (very much needed: OR 1.253, 95% CI 95% CI 1.197-1.311; generally needed: OR 1.078, 95% CI 1.029-1.129), with platform certification (OR 1.041, 95% CI 1.011-1.073), without commercial advertisements (OR 1.048, 95% CI 1.018-1.080), with simple-to-understand content (OR 1.071, 95% CI 1.040-1.104), and with video content that evokes fear or dread of illness in the viewer (OR 1.046, 95% CI 1.015-1.078). Conclusion: Participants favor free health popularization short videos, which are hospital accounts, with content that is illustrated, understandable, meets their needs, and can serve as a warning. In the future, the production of health popularization short videos should focus on improving the diversity and relevance of video content, making it as easy to understand to achieve good science popularization effects.

Antibacterial black phosphorus nanosheets for biomedical applications.

Bacterial infections pose a significant threat to human health and a heavy burden on the global healthcare system. Antibiotics are the primary treatment, but they can lead to bacterial resistance and adverse side effects. Two-dimensional (2D) nanomaterials such as graphene, MoS2, and MXene have emerged as novel antibacterial agents due to their potential to circumvent bacterial resistance. Among the 2D nanomaterials, black phosphorus nanosheets (BPNs) have attracted great research interest due to their excellent biocompatibility. BPNs possess unique properties, such as a high specific surface area, tunable bandgap, and easy surface functionalization, enabling them to combat bacteria through physical disruption of bacterial membranes, photothermal and photodynamic therapies. However, the low preparation efficiency and inevitable oxidative degradation of BPNs have limited their wide application. This review provides a comprehensive overview of recent advances in antibacterial research on BPNs, encompassing their preparation methods, structural and physicochemical properties, antibacterial mechanisms, and potential applications. By addressing the challenges and prospects of using BPNs as an alternative to antibiotics, this review provides valuable insights and guidance for utilizing BPNs in shaping the future of antibacterial therapy.

Adenosine Monophosphate-Activated Protein Kinase (AMPK) Phosphorylation Is Required for 20-Hydroxyecdysone Regulates Ecdysis in Apolygus lucorum.

The plant mirid bug Apolygus lucorum is an omnivorous pest that can cause considerable economic damage. The steroid hormone 20-hydroxyecdysone (20E) is mainly responsible for molting and metamorphosis. The adenosine monophosphate-activated protein kinase (AMPK) is an intracellular energy sensor regulated by 20E, and its activity is regulated allosterically through phosphorylation. It is unknown whether the 20E-regulated insect's molting and gene expression depends on the AMPK phosphorylation. Herein, we cloned the full-length cDNA of the AlAMPK gene in A. lucorum. AlAMPK mRNA was detected at all developmental stages, whereas the dominant expression was in the midgut and, to a lesser extent, in the epidermis and fat body. Treatment with 20E and AMPK activator 5-aminoimidazole-4-carboxamide-1-ß-d-ribofuranoside (AlCAR) or only AlCAR resulted in activation of AlAMPK phosphorylation levels in the fat body, probed with an antibody directed against AMPK phosphorylated at Thr172, enhancing AlAMPK expression, whereas no phosphorylation occurred with compound C. Compared to compound C, 20E and/or AlCAR increased the molting rate, the fifth instar nymphal weight and shortened the development time of A. lucorum in vitro by inducing the expression of EcR-A, EcR-B, USP, and E75-A. Similarly, the knockdown of AlAMPK by RNAi reduced the molting rate of nymphs, the weight of fifth-instar nymphs and blocked the developmental time and the expression of 20E-related genes. Moreover, as observed by TEM, the thickness of the epidermis of the mirid was significantly increased in 20E and/or AlCAR treatments, molting spaces began to form between the cuticle and epidermal cells, and the molting progress of the mirid was significantly improved. These composite data indicated that AlAMPK, as a phosphorylated form in the 20E pathway, plays an important role in hormonal signaling and, in short, regulating insect molting and metamorphosis by switching its phosphorylation status.

CD36-SREBP1 Axis Mediates TSLP Production in Obesity-Exacerbated Atopic Dermatitis.

Obesity is associated with an increased risk of atopic dermatitis (AD) and may accelerate its development. Keratinocyte dysfunction has been observed in obesity-related skin diseases, including psoriasis and acanthosis nigricans, but is not fully understood in AD. In this study, we found that high-fat diet-induced obesity exacerbated AD-like dermatitis in mice, with elevated inflammatory molecules and increased CD36-SREBP1-related fatty acid accumulation in the lesional skin. Blocking CD36 or SREBP1 with chemical inhibitors effectively alleviated AD-like inflammation, decreased fatty acid accumulation, and downregulated TSLP expression in obese calcipotriol (MC903)-treated mice. Moreover, palmitic acid treatment induced TSLP overexpression in keratinocytes through the activation of the CD36-SREBP1 signaling pathway. The chromatin immunoprecipitation assay further revealed increased binding of SREBP1 to the TSLP promoter region. Our findings provide compelling evidence that obesity triggers the activation of the CD36-SREBP1-TSLP axis in keratinocytes, leading to epidermal lipid disorders and the aggravation of AD-like inflammation. By targeting CD36 or SREBP1, future combination therapies or modified treatment strategies could be developed to help manage patients with both obesity and AD.

Physiological and pathological roles of locally expressed kisspeptin and KISS1R in the endometrium.

Kisspeptins, encoded by the KISS1 gene, are a family of polypeptides that bind the kisspeptin receptor (KISS1R) to perform biological functions. Produced mainly in the hypothalamus, these neuropeptides regulate the pulsatile secretion of GnRH and trigger the hypothalamus-pituitary-gonadal axis. Other peripheral organs also express kisspeptin, which inhibits metastasis. Kisspeptin and KISS1R are reportedly present in the endometrium and may play roles in limiting the migration and invasion of trophoblasts into the endometrium during pregnancy (decidua) to maintain endometrial homeostasis. A deficiency of kisspeptin and KISS1R in the endometrium can lead to pathological conditions such as endometriosis and endometrial carcinoma. Kisspeptin and KISS1R in the endometrium can also promote endometrial receptivity and decidualization. Overall, kisspeptin and KISS1R are important for maintaining the normal physiological functions of the endometrium. By summarizing the roles of kisspeptin and KISS1R in the endometrium, our review explores the regulatory roles in the peripheral reproductive system of this peptide family that plays broad and profound roles in many physiological processes.

Injectable polyaniline nanorods/alginate hydrogel with AAV9-mediated VEGF overexpression for myocardial infarction treatment.

Intramyocardial injection of hydrogels possesses great potential in the minimally invasive treatment of myocardial infarction (MI), but the current injectable hydrogels lack conductivity, long-term angiogenesis inductive ability, and reactive oxygen species (ROS)-scavenging ability, which are essential for myocardium repair. In this study, lignosulfonate-doped polyaniline (PANI/LS) nanorods and adeno-associated virus encoding vascular endothelial growth factor (AAV9-VEGF) are incorporated in the calcium-crosslinked alginate hydrogel to develop an injectable conductive hydrogel with excellent antioxidative and angiogenic ability (Alg-P-AAV hydrogel). Due to the special nanorod morphology, a conductive network is constructed in the hydrogel with the conductivity matching the native myocardium for excitation conduction. The PANI/LS nanorod network may also have large specific surfaces and effectively scavenges ROS to protect cardiomyocytes from oxidative stress damage. AAV9-VEGF transfects the surrounding cardiomyocytes for continuously expressing VEGF, which significantly promotes the proliferation, migration and tube formation of endothelial cells. After injecting the Alg-P-AAV hydrogel around the MI area in rats, the generation of gap junctions and angiogenesis are greatly improved with reduced infarct area and recovered cardiac function. The remarkable therapeutic effect indicates the promising potential of this multi-functional hydrogel for MI treatment.

Study on herb-herb interaction between active components of Plantago asiatica L. seed and Coptis chinensis Franch. rhizoma based on transporters using UHPLC-MS/MS.

The combined efficacy in lowering serum lipid levels and increasing kidney protection of Plantago asiatica L. seed (Plantago) and Coptis chinensis Franch. rhizoma (Coptis) is far better than the effects of either herb alone. This finding suggests that there must be some degree of herb-herb interactions (HHI) affect potency. Here, we chose geniposidic acid (GPA), acteoside (ACT), and plantagoamidinic acid A (PLA) as active components in Plantago, and berberine (BBR) as the active component in Coptis, and, using transporter gene-transfected Madin-Darby canine kidney (MDCK) cells in combination with specific substrates and inhibitors, investigated Plantago- Coptis HHIs. We also established a UPLC-MS/MS analytical method to determine substrate content. Results showed that PLA in Plantago was a substrate of rOCT1/2 and rMATE1, and had inhibitory effects on rOCT2 and rMATE1. We also found that ACT is a substrate of rMATE1, but GPA was not a substrate of any transporter that we investigated. When BBR was used as the substrate, the inhibition rate of 10 µM PLA was 53.6% on rOCT2 and 31.5% on rMATE1. The inhibition rates of 30 µM ACT and 30 µM GPA on rMATE1 were 47.0% and 31.0%, respectively. Thus, our findings suggest that GPA, ACT, PLA, and BBR have competitive interactions that are driven by the rOCT2 and rMATE1 transporters. These interactions affect the transport and excretion of compounds and result in efficacy changes after co-administration.