Targeting New Functions and Applications of Bacterial Two-component Systems.

Two-component signal transduction systems (TCSs) are regulatory systems widely distributed in eubacteria, archaea, and a few eukaryotic organisms, but not in mammalian cells. A typical TCS consists of a histidine kinase and a response regulator protein. Functional and mechanistic studies on different TCSs have greatly advanced the understanding of cellular phosphotransfer signal transduction mechanisms. In this concept paper, we focus on the His-Asp phosphotransfer mechanism, the ATP synthesis function, antimicrobial drug design, cellular biosensors design, and protein allostery mechanisms based on recent TCS investigations to inspire new applications and future research perspectives.

Identification and Pathogenicity of Pestalotioid Species on Alpinia oxyphylla in Hainan Province, China.

Alpinia oxyphylla is a traditional Chinese medicinal plant with a medicinal history of more than 1700 years. Ring leaf blight (RLB) disease, caused by pestalotioid species, is an important disease of A. oxyphylla, seriously affecting the yield and quality of its fruits. The causal agent of RLB disease has not been systematically identified or characterized yet. In this study, thirty-six pestalotioid strains were isolated from the leaves and stems of A. oxyphylla that was collected from six cities of Hainan province, China. Based on the multi-locus phylogeny (ITS, tef-1α and tub2) and morphological characteristic analyses, seventeen species belonging to three genera (Neopestalotiopsis, Pestalotiopsis and Pseudopestalotiopsis) were identified, and six new species (N. baotingensis, N. oblatespora, N. olivaceous, N. oxyphylla, N. wuzhishanensis and N. yongxunensis) were described. Pathogenicity tests revealed that strains of Neopestalotiopsis species caused more severe ring leaf blight on A. oxyphylla than strains of Pestalotiopsis and Pseudopestalotiopsis under wounded inoculation conditions.

Home Heart Hospital Associated With Reduced Hospitalizations and Costs Among High-Cost Patients With Cardiovascular Disease.

BACKGROUND: There is no widely accepted care model for managing high-need, high-cost (HNHC) patients. We hypothesized that a Home Heart Hospital (H3), which provides longitudinal, hospital-level at-home care, would improve care quality and reduce costs for HNHC patients with cardiovascular disease (CVD). OBJECTIVE: To evaluate associations between enrollment in H3, which provides longitudinal, hospital-level at-home care, care quality, and costs for HNHC patients with CVD. METHODS: This retrospective within-subject cohort study used insurance claims and electronic health records data to evaluate unadjusted and adjusted annualized hospitalization rates, total costs of care, part A costs, and mortality rates before, during, and following H3. RESULTS: Ninety-four patients were enrolled in H3 between February 2019 and October 2021. Patients' mean age was 75 years and 50% were female. Common comorbidities included congestive heart failure (50%), atrial fibrillation (37%), coronary artery disease (44%). Relative to pre-enrollment, enrollment in H3 was associated with significant reductions in annualized hospitalization rates (absolute reduction (AR): 2.4 hospitalizations/year, 95% confidence interval [95% CI]: -0.8, -4.0; p < 0.001; total costs of care (AR: -$56 990, 95% CI: -$105 170, -$8810; p < 0.05; and part A costs (AR: -$78 210, 95% CI: -$114 770, -$41 640; p < 0.001). Annualized post-H3 total costs and part A costs were significantly lower than pre-enrollment costs (total costs of care: -$113 510, 95% CI: -$151 340, -$65 320; p < 0.001; part A costs: -$84 480, 95% CI: -$121 040, -$47 920; p < 0.001). CONCLUSIONS: Longitudinal home-based care models hold promise for improving quality and reducing healthcare spending for HNHC patients with CVD.

Construction of fatty acid-ovalbumin binary complexes to improve the water dispersibility, thermal/digestive stability and bioaccessibility of lutein: A comparative study of different fatty acids.

Lipids are increasingly being incorporated into delivery systems due to their ability to facilitate intestinal absorption of lipid-soluble nutrients through molecular solubilization and micellization. In this work, self-assembled complexes of ovalbumin (OVA) and nine dietary fatty acids (FAs) were constructed to improve the processability and absorbability of lutein (LUT). Results showed that all FAs could form stable hydrophilic particles with OVA under the optimized ultrasound-coupled pH conditions. Fourier infrared spectroscopy and transmission electron microscopy analysis showed that these binary complexes effectively encapsulated LUT with an encapsulation rate > 90.0 %. Stability experiments showed that these complexes protected LUT well, which could improve thermal stability and in vitro digestive stability by 1.66-3.58-fold and 1.27-2.74-fold, respectively. Besides, the bioaccessibility of LUT was also enhanced by 7.16-24.99-fold. The chain length and saturation of FAs affected the stability and absorption of LUT. Therefore, these results provided some reference for the selection of FAs for efficient delivery of lipid-soluble nutrients.

Reaction interferometry with ultracold molecules.

We propose to coherently control the ultracold 2KRb → K2 + Rb2 reaction product state distribution via quantum interference. By leveraging that the nuclear spin degrees of freedom in the reaction maintain coherence, which was demonstrated in Liu, Zhu et al., arXiv, 2023, arXiv:2310.07620, https://doi.org/10.48550/arXiv.2310.07620, we explore the concept of a "reaction interferometer". Such an interferometer involves splitting one KRb molecular cloud into two, imprinting a well-defined relative phase between them, recombining the clouds for reactions, and measuring the product state distribution. We show that the interference patterns provide a mechanism to coherently control the product states, and specific product channels also serve as an entanglement witness of the atoms in the reactant KRb molecule.

Parental exposure to Cypermethrin causes intergenerational toxicity in zebrafish offspring.

Cypermethrin (CYP), a synthetic pyrethroid pesticide, has been detected in agriculture and aquaculture. However, there is limited knowledge about the transgenerational impacts. This study aimed to investigate the developmental toxicity of CYP on F1 larvae offspring of adult zebrafish exposed to various CYP concentrations (5, 10, and 20 µg/L) for 28 days. The results indicated that CYP accumulated in parental zebrafish, and CYP was below the limit of quantification in offspring. Paternal exposure impacted the hatching rate and heart rate of the F1 generation. Furthermore, CYP significantly impacted the development of swim bladders in progeny and dysregulated the genes relevant to swim bladder development. The neutrophil migrated to the swim bladder. The mRNA levels of the inflammatory factors were also significantly elevated. According to network toxicology, PI3-AKT may be the signaling pathway for CYP-influenced bladder development. Subsequent molecular docking and Western blot analysis showed CYP affected the PI3-AKT signaling pathway. Notably, MK-2206, a specific Akt inhibitor, rescued the CYP-induced damage of swim bladder development in offspring. The present study highlights the potential risks of CYP on the development of offspring and lasting impact in aquatic environments.

Quantum interference in atom-exchange reactions.

Chemical reactions, in which bonds break and form, are highly dynamic quantum processes. A fundamental question is whether coherence can be preserved in chemical reactions and then harnessed to generate entangled products. Here we investigated this question by studying the 2KRb [Formula: see text][Formula: see text] + Rb2 reaction at 500 nanokelvins, focusing on the nuclear spin degrees of freedom. We prepared the initial nuclear spins in KRb (potassium-rubidium) in an entangled state by lowering the magnetic field to where the spin-spin interaction dominates and characterized the preserved coherence in nuclear spin wave function after the reaction. We observed an interference pattern that is consistent with full coherence at the end of the reaction, suggesting that entanglement prepared within the reactants could be redistributed through the atom-exchange process.

Allergenicity and Linear Epitope Analysis of Scy p 8, an Allergen from Mud Crab.

Scy p 8 (triosephosphate isomerase) as a crab allergen in inducing distinct T-helper (Th) cell differentiation and a linear epitope associated with allergenicity remain elusive. In this study, mice sensitized with Scy p 8 exhibited significantly upregulated levels of IgE, IgG1, and IL-4 release, inducing a Th2 immune response. Moreover, the release of IFN-γ (Th1) and the levels of Treg cells were downregulated, while IL-17A (Th17) was upregulated, indicating that Scy p 8 disrupted the Th1/Th2 balance and Th17/Treg balance in mice. Furthermore, bioinformatics prediction and serum samples from crab-allergic patients and mice enabled the discovery of 8 linear epitopes of Scy p 8. Meanwhile, the analysis of peptide similarity and tertiary superposition revealed that 8 epitopes of Scy p 8 exhibited conservation across various species, potentially resulting in cross-reactivity. These findings possess the potential to enhance the comprehension of crab allergens, thereby establishing a foundation for investigating cross-reactivity.

An in-depth analysis of wound incidence and injury status among professional athletes: A comprehensive review.

This review aims to synthesize current knowledge on the incidence, characteristics and management of wounds and injuries among professional ice hockey athletes, with the specific focus on the emerging population of Chinese female players. An extensive literature search was conducted across several databases to gather data on injury patterns and wounds, causes, severity and prevention strategies in ice hockey. Special attention was given to studies involving female athletes and unique challenges faced by players in developing regions like China. The review also examined the impact of training modalities, protective equipment and medical interventions on injury rates. The findings reveal a significant seasonal fluctuation in wound incidence, with marked reduction following the preseason period. This trend underscores the effectiveness of adjusted training programmes and essential role of medical teams in injury prevention and rehabilitation. Analysis did not show significant difference in wound rates between technical and physical training sessions, suggesting that injuries are pervasive risk across all training activities. Skating, collisions and inadequate warm-ups were identified as the leading causes of wounds, highlighting areas for targeted preventive measures. The distribution of wounds across various body regions pointed to knee, lower back and wrist as the most vulnerable sites, necessitating focused protection and training adjustments. Ice hockey, particularly among female athletes in China, presents complex injury landscape characterized by the wide range of wounds. The study emphasizes the necessity of comprehensive, multidisciplinary approach to injury prevention that includes training modifications, enhanced protective gear and strategic medical oversight. By addressing the specific causes and patterns of injuries identified, stakeholders can better protect athletes from the inherent risks of the sport, promote safer play and extend career longevity.

Diallyl Trisulfide Acts as a Soil Disinfestation Against the Ilyonectria destructans through Inducing the Burst of Reactive Oxygen Species.

Soil-borne diseases represent an impediment to the sustainable development of agriculture. A soil-borne disease caused by Ilyonectria destructans severely impacts Panax species, and soil disinfestation has proven to be an effective management approach. Here, diallyl trisulfide (DATS), derived from garlic, exhibited pronounced inhibitory effects on the growth of I. destructans in vitro tests and contributed to the alleviation of soil-borne diseases in the field. A comprehensive analysis demonstrated that DATS inhibits the growth of I. destructans by activating detoxifying enzymes, such as GSTs, disrupting the equilibrium of redox reactions. A series of antioxidant amino acids were suppressed by DATS. Particularly noteworthy is the substantial depletion of glutathione by DATS, resulting in the accumulation of ROS, ultimately culminating in the inhibition of I. destructans growth. Briefly, DATS could effectively suppress soil-borne diseases by inhibiting pathogen growth through the activation of ROS, and it holds promise as a potential environmentally friendly soil disinfestation.

Correlation between the serum FABP4, ANGPTL3, and ANGPTL4 levels and coronary artery disease.

BACKGROUND: Lipid metabolism related factors, such as angiopoietin-like protein 3 (ANGPTL3), angiopoietin-like 4 (ANGPTL4), fatty acid-binding protein 4 (FABP4) are newly discovered factors that can affect coronary artery disease (CAD). In this study, we aimed to investigate the relationship between CAD and these lipid metabolism factors. HYPOTHESIS: ANGPTL3, ANGPTL4, and FABP4 may provide a new method for the control of CAD risk factors and the prevention and treatment of CAD. METHODS: We enrolled 284 consecutive inpatients with suspected CAD and divided them into CAD and non-CAD groups based on the coronary angiography results. Serum ANGPTL3, ANGPTL4, FABP4, and tumor necrosis factor-α (TNF-α) levels were estimated using the enzyme-linked immunosorbent assay. Multivariate logistic regression was used to assess the risk factors for CAD. The receiver operating characteristic curve was used to determine the cutoff and diagnostic values. RESULTS: The serum TNF-α, FABP4, ANGPTL3, and ANGPTL4 values showed a significant difference between the CAD and non-CAD groups (p < .05). After adjusting for confounding factors, the FABP4, ANGPTL3, and ANGPTL4 levels were independently associated with CAD (p < .05). The ANGPTL3 expression level was an independent risk factor for CAD in patients with hypertension, but not in those without hypertension. The ANGPTL3 > 67.53 ng/mL, ANGPTL4 > 29.95 ng/mL, and FABP4 > 1421.25 ng/L combination had the highest diagnostic value for CAD. CONCLUSION: ANGPTL3, ANGPTL4, and FABP4 were identified as independent risk factors for CAD and have valuable clinical implications for the diagnosis and treatment of CAD.

The pro-absorptive effect of glycosylated zein-fatty acid complexes on fucoxanthin via the lipid transporter protein delivery pathway.

Growing research confirms that lipid transport proteins play a key role in the trans-intestinal epithelial transport of carotenoids. In this study, to simultaneously improve the digestive stability and intestinal absorption of fucoxanthin (FX), functionalized vectors with a capability of up-regulating the expression of FX-specific lipid transporter proteins was fabricated. The results showed that myristic acid, palmitic acid, and stearic acid effectively promoted FX-specific lipid transporter protein expression and formed stable self-assembly complexes with Millard-modified zein (MZ). The FX was sufficiently encapsulated in the MZ-fatty acid (FA) particles, forming spherical nanoparticles with a "core-shell" structure. Simulated gastrointestinal digestion showed that FA introduction significantly increased the FX bioaccessibility. In vivo results further verified that adding FAs dramatically increased the FX serum response concentration. These findings suggest that incorporating nutrients that can promote lipid transporter protein expression into delivery vehicles should be an effective strategy for improving oral carotenoid absorption.

Ultrasound-mediated host-guest self-assembly between different dietary fatty acids and sodium caseinate and their complexes improving the water dispersibility, stability, and bioaccessibility of quercetin.

Quercetin (QUE) sufferred from poor processing adaptability and absorbability, hindering its application as a dietary supplement in the food industry. In this study, fatty acids (FAs)-sodium caseinate (NaCas) ligand complexes carriers were fabricated to improve the aqueous dispersibility, storage/thermal stability, and bioaccessibility of QUE using an ultrasound method. The results indicated that all six selected common dietary FAs formed stable hydrophilic complexes with NaCas and the FAs-NaCas complexes achieved an encapsulation efficiency greater than 90 % for QUE. Furthermore, the introduction of FAs enhanced the binding affinity between NaCas and QUE, but did not change the binding mode (static bursting) and types of intermolecular forces (mainly hydrogen bonding). In addition, a distinct improvement was discovered in the storage stability (>2.37-fold), thermal processing stability (>32.54 %), and bioaccessibility (>2.37-fold) of QUE. Therefore, the FAs-NaCas ligand complexes could effectively protect QUE to minimize degradation as fat-soluble polyphenol delivery vehicles.

Albumin combined with neutrophil-to-lymphocyte ratio score and outcomes in patients with acute coronary syndrome treated with percutaneous coronary intervention.

BACKGROUND: Evidence about the association between albumin combined with neutrophil-to-lymphocyte ratio score (ANS) and survival outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) is rare. This study aimed to evaluate the prognostic value of ANS in patients with ACS undergoing PCI by propensity score matching (PSM) analysis. PATIENTS AND METHODS: Patients with ACS undergoing PCI were consecutively enrolled in this prospective cohort study from January 2016 to December 2018. The albumin and neutrophil-to-lymphocyte ratio cutoff values for predicting major adverse cardiovascular events (MACEs) were calculated using receiver operating characteristic curves. Survival analysis was performed using Kaplan-Meier estimates, the Cox proportional hazard regression models and PSM. The study endpoint was the occurrence of a MACE, which included all-cause mortality and rehospitalization for severe heart failure during follow-up. RESULTS: Overall, 1549 patients with adequate specimens were identified and assigned into different groups for comparison. Before and after PSM, the Kaplan-Meier curves showed that a higher ANS value was associated with a higher risk of MACEs (all P  < 0.001). The multivariate Cox proportional hazard regression model showed that the ANS (per 1 score increase) [hazard ratio (HR), 2.016; 95% confidence interval (CI), 1.329-3.057; P  = 0.001 vs. HR, 2.166; 95% CI, 1.344-3.492; P  = 0.002] was an independent predictor for MACEs. CONCLUSION: This study tentatively confirms that ANS may be a valuable clinical indicator to identify high-risk ACS patients after PCI. More high-quality prospective studies are needed in the future.

An ATP "Synthase" Derived from a Single Structural Domain of Bacterial Histidine Kinase.

ATP (adenosine triphosphate) is a vital energy source for living organisms, and its biosynthesis and precise concentration regulation often depend on macromolecular machinery composed of protein complexes or complicated multidomain proteins. We have identified a single-domain protein HK853CA derived from bacterial histidine kinases (HK) that can catalyze ATP synthesis efficiently. Here, we explored the reaction mechanism and multiple factors that influence this catalysis through a combination of experimental techniques and molecular simulations. Moreover, we optimized its enzymatic activity and applied it as an ATP replenishment machinery to other ATP-dependent systems. Our results broaden the understanding of ATP biosynthesis and show that the single CA domain can be applied as a new biomolecular catalyst used for ATP supply.

Peptide NCTX15 derived from spider toxin gland effectively relieves hyperuricemia in mice.

Hyperuricemia is a clinical disease characterized by a continuous increase in uric acid (UA) due to purine metabolism disorder. As current drug treatments are limited, it is imperative to explore new drugs that offer better safety and efficacy. In this study, Nephila clavata toxin gland homogenates were isolated and purified by exclusion chromatography and high-performance liquid chromatography, resulting in the identification and isolation of a short peptide (NCTX15) with the sequence 'QSGHTFK'. Analysis showed that NCTX15 exhibited no cytotoxicity in mouse macrophages or toxic and hemolytic activity in mice. Notably, NCTX15 inhibited UA production by down-regulating urate transporter 1 and glucose transporter 9 and up-regulating organic anion transporter 1, thus promoting UA excretion. In addition, NCTX15 alleviated the inflammatory response and renal injury by inhibiting the expression of inflammatory factors interleukin-6, interleukin-1ß, tumor necrosis factor alpha, NLR family, pyrin domain-containing 3, and pyroptosis-related factor gasdermin D. These results indicate that NCTX15 displayed urate-lowering, anti-inflammatory, and analgesic effects. As the first urate-reducing short peptide isolated from a spider toxin gland homogenate, NCTX15 exhibits considerable potential as a novel drug molecule for anti-gout and hyperuricemia treatment.

Integrated analysis of transcriptome, metabolome, and histochemistry reveals the response mechanisms of different ages Panax notoginseng to root-knot nematode infection.

Panax notoginseng (P. notoginseng) is an invaluable perennial medicinal herb. However, the roots of P. notoginseng are frequently subjected to severe damage caused by root-knot nematode (RKN) infestation. Although we have observed that P. notoginseng possessed adult-plant resistance (APR) against RKN disease, the defense response mechanisms against RKN disease in different age groups of P. notoginseng remain unexplored. We aimed to elucidate the response mechanisms of P. notoginseng at different stages of development to RKN infection by employing transcriptome, metabolome, and histochemistry analyses. Our findings indicated that distinct age groups of P. notoginseng may activate the phenylpropanoid and flavonoid biosynthesis pathways in varying ways, leading to the synthesis of phenolics, flavonoids, lignin, and anthocyanin pigments as both the response and defense mechanism against RKN attacks. Specifically, one-year-old P. notoginseng exhibited resistance to RKN through the upregulation of 5-O-p-coumaroylquinic acid and key genes involved in monolignol biosynthesis, such as PAL, CCR, CYP73A, CYP98A, POD, and CAD. Moreover, two-year-old P. notoginseng enhanced the resistance by depleting chlorogenic acid and downregulating most genes associated with monolignol biosynthesis, while concurrently increasing cyanidin and ANR in flavonoid biosynthesis. Three-year-old P. notoginseng reinforced its resistance by significantly increasing five phenolic acids related to monolignol biosynthesis, namely p-coumaric acid, chlorogenic acid, 1-O-sinapoyl-D-glucose, coniferyl alcohol, and ferulic acid. Notably, P. notoginseng can establish a lignin barrier that restricted RKN to the infection site. In summary, P. notoginseng exhibited a potential ability to impede the further propagation of RKN through the accumulation or depletion of the compounds relevant to resistance within the phenylpropanoid and flavonoid pathways, as well as the induction of lignification in tissue cells.

Peptide OA-VI12 restrains melanogenesis in B16 cells and C57B/6 mouse ear skin via the miR-122-5p/Mitf/Tyr axis.

Excessive melanogenesis leads to hyperpigmentation, which is one of the common skin conditions in humans. Existing whitening cosmetics cannot meet market needs due to their inherent limitations. Thus, the development of novel skin-whitening agents continues to be a challenge. The peptide OA-VI12 from the skin of amphibians at high altitude has attracted attention due to its remarkable anti light damage activity. However, whether OA-VI12 has the skin-whitening effect of inhibiting melanogenesis is still. Mouse melanoma cells (B16) were used to study the effect of OA-VI12 on cell viability and melanin content. The pigmentation model of C57B/6 mouse ear skin was induced by UVB and treated with OA-VI12. Melanin staining was used to observe the degree of pigmentation. MicroRNA sequencing, quantitative real-time PCR (qRT-PCR), immunofluorescence analysis and Western blot were used to detect the change of factor expression. Double luciferase gene report experiment was used to prove the regulatory relationship between miRNA and target genes. OA-VI12 has no effect on the viability of B16 cells in the concentration range of 1-100 µM and significantly inhibits the melanin content of B16 cells. Topical application of OA-VI12, which exerted transdermal potency, prevented UVB-induced pigmentation of ear skin. MicroRNA sequencing and double luciferase reporter analysis results showed that miR-122-5p, which directly regulated microphthalmia-associated transcription factor (Mitf), had significantly different expression before and after treatment with OA-VI12. Mitf is a simple helix loop and leucine zipper transcription factor that regulates tyrosinase (Tyr) expression by binding to the M-box promoter element of Tyr. qRT-PCR, immunofluorescence analysis and Western blot showed that OA-VI12 up-regulated the expression of miR-122-5p and inhibited the expression of Mitf and Tyr. The effects of OA-VI12 on melanogenesis inhibition in vitro and in vivo may involve the miR-122-5p/Mitf/tyr axis. OA-VI12 represents the first report on a natural amphibian-derived peptide with skin-whitening capacity and the first report of miR-122-5p as a target for regulating melanogenesis, thereby demonstrating its potential as a novel skin-whitening agent and highlighting amphibian-derived peptides as an underdeveloped resource.

Effects of allyl isothiocyanate fumigation on medicinal plant root knot disease control, plant survival, and the soil bacterial community.

BACKGROUND: Allyl isothiocyanate (AITC) is a natural product with high volatility that is used as a biofumigant to alleviate soil-borne plant diseases, and problems such as root knot nematodes (RKNs) that necessitate continuous cropping. However, little research has assessed the effects of AITC fumigation on medicinal plants. RESULTS: AITC significantly reduced the population of RKNs in soil (p < 0.0001) and showed an excellent RKN disease control effect within 6 months after sowing Panax notoginseng (p < 0.0001). The seedling survival rate of 2-year-old P. notoginseng was approximately 1.7-fold higher after soil treatment with AITC (p = 0.1008). 16S rRNA sequencing indicated that the AITC treatment affected bacterial richness rather than diversity in consecutively cultivated (CC) soil. Furthermore, biomarkers with statistical differences between AITC-treated and untreated CC soil showed that Pirellulales (order), Pirellulaceae (family), Pseudomonadaceae (family), and Pseudomonas (genus) played important roles in the AITC-treated group. In addition, the microbiome functional phenotypes predicted using the BugBase tool suggested that AITC treatment is more conducive to improving CC soil through changes in the bacterial community structure. Crucially, our research also suggested that AITC soil treatment significantly increases soil organic matter (p = 0.0055), total nitrogen (p = 0.0054), and available potassium (p = 0.0373), which promotes the survival of a succeeding medicinal plant (Polygonatum kingianum). CONCLUSION: AITC is an ecologically friendly soil treatment that affects the top 10 bacterial richness but not diversity. It could also provide a basis for a useful agricultural soil management measure to alleviate soil sickness.

miR-186-5p targets TGFßR2 to inhibit RAW264.7 cell migration and proliferation during mouse skin wound healing.

BACKGROUND: Active peptides play a vital role in the development of new drugs and the identification and discovery of drug targets. As the first reported native peptide homodimer with pro-regenerative potency, OA-GP11d could potentially be used as a novel molecular probe to help elucidate the molecular mechanism of skin wound repair and provide new drug targets. METHODS: Bioinformatics analysis and luciferase assay were adopted to determine microRNAs (miRNAs) and its target. The prohealing potency of the miRNA was determined by MTS and a Transwell experiment against mouse macrophages. Enzyme-linked immunosorbent assay, realtime polymerase chain reaction, and western blotting were performed to explore the molecular mechanisms. RESULTS: In this study, OA-GP11d was shown to induce Mus musculus microRNA-186-5p (mmu-miR-186-5p) down-regulation. Results showed that miR-186-5p had a negative effect on macrophage migration and proliferation as well as a targeted and negative effect on TGF-ß type II receptor (TGFßR2) expression and an inhibitory effect on activation of the downstream SMAD family member 2 (Smad2) and protein-p38 kinase signaling pathways. Importantly, delivery of a miR-186-5p mimic delayed skin wound healing in mice. CONCLUSION: miR-186-5p regulated macrophage migration and proliferation to delay wound healing through the TGFßR2/Smad2/p38 molecular axes, thus providing a promising new pro-repair drug target.