Bloom dynamics under the effects of periodic driving forces.

Phytoplankton bloom received considerable attention for many decades. Different approaches have been used to explain the bloom phenomena. In this paper, we study a Nutrient-Phytoplankton-Zooplankton (NPZ) model consisting of a periodic driving force in the growth rate of phytoplankton due to solar radiation and analyse the dynamics of the corresponding autonomous and non-autonomous systems in different parametric regions. Then we introduce a novel aspect to extend the model by incorporating another periodic driving force into the growth term of the phytoplankton due to sea surface temperature (SST), a key point of innovation. Temperature dependency of the maximum growth rate (µmax) of the phytoplankton is modelled by the well-known Q10 formulation: [Formula: see text] , where µ0 is maximum growth at 0oC. Stability conditions for all three equilibrium points are expressed in terms of the new parameter ρ2, which appears due to the incorporation of periodic driving forces. System dynamics is explored through a detailed bifurcation analysis, both mathematically and numerically, with respect to the light and temperature dependent phytoplankton growth response. Bloom phenomenon is explained by the saddle point bloom mechanism even when the co-existing equilibrium point does not exist for some values of ρ2. Solar radiation and SST are modelled using sinusoidal functions constructed from satellite data. Our results of the proposed model describe the initiation of the phytoplankton bloom better than an existing model for the region 25-35° W, 40-45° N of the North Atlantic Ocean. An improvement of 14 days (approximately) is observed in the bloom initiation time. The rate of change method (ROC) is applied to predict the bloom initiation.

Evolution of Cooperation in Spatio-Temporal Evolutionary Games with Public Goods Feedback.

In biology, evolutionary game-theoretical models often arise in which players' strategies impact the state of the environment, driving feedback between strategy and the surroundings. In this case, cooperative interactions can be applied to studying ecological systems, animal or microorganism populations, and cells producing or actively extracting a growth resource from their environment. We consider the framework of eco-evolutionary game theory with replicator dynamics and growth-limiting public goods extracted by population members from some external source. It is known that the two sub-populations of cooperators and defectors can develop spatio-temporal patterns that enable long-term coexistence in the shared environment. To investigate this phenomenon and unveil the mechanisms that sustain cooperation, we analyze two eco-evolutionary models: a well-mixed environment and a heterogeneous model with spatial diffusion. In the latter, we integrate spatial diffusion into replicator dynamics. Our findings reveal rich strategy dynamics, including bistability and bifurcations, in the temporal system and spatial stability, as well as Turing instability, Turing-Hopf bifurcations, and chaos in the diffusion system. The results indicate that effective mechanisms to promote cooperation include increasing the player density, decreasing the relative timescale, controlling the density of initial cooperators, improving the diffusion rate of the public goods, lowering the diffusion rate of the cooperators, and enhancing the payoffs to the cooperators. We provide the conditions for the existence, stability, and occurrence of bifurcations in both systems. Our analysis can be applied to dynamic phenomena in fields as diverse as human decision-making, microorganism growth factors secretion, and group hunting.

Atractylenolide-I Alleviates Hyperglycemia-Induced Heart Developmental Malformations through Direct and Indirect Modulation of the STAT3 Pathway.

BACKGROUND: Gestational diabetes could elevate the risk of congenital heart defects (CHD) in infants, and effective preventive and therapeutic medications are currently lacking. Atractylenolide-I (AT-I) is the active ingredient of Atractylodes Macrocephala Koidz (known as Baizhu in China), which is a traditional pregnancy-supporting Chinese herb. PURPOSE: In this study, we investigated the protective effect of AT-I on the development of CHD in embryos exposed to high glucose (HG). STUDY DESIGN AND METHODS: First, systematic review search results revealed associations between gestational diabetes mellitus (GDM) and cardiovascular malformations. Subsequently, a second systematic review indicated that heart malformations were consistently associated with oxidative stress and cell apoptosis. We assessed the cytotoxic impacts of Atractylenolide compounds (AT-I, AT-II, and AT-III) on H9c2 cells and chick embryos, determining an optimal concentration of AT-I for further investigation. Second, immunofluorescence, western blot, Polymerase Chain Reaction (PCR), and flow cytometry were utilized to delve into the mechanisms through which AT-I mitigates oxidative stress and apoptosis in cardiac cells. Molecular docking was employed to investigate whether AT-I exerts cardioprotective effects via the STAT3 pathway. Then, we developed a streptozotocin-induced diabetes mellitus (PGDM) mouse model to evaluate AT-I's protective efficacy in mammals. Finally, we explored how AT-I protects hyperglycemia-induced abnormal fetal heart development through microbiota analysis and untargeted metabolomics analysis. RESULTS: The study showed the protective effect of AT-I on embryonic development using a chick embryo model which rescued the increase in the reactive oxygen species (ROS) and decrease in cell survival induced by HG. We also provided evidence suggesting that AT-I might directly interact with STAT3, inhibiting its phosphorylation. Further, in the PGDM mouse model, we observed that AT-I not only partially alleviated PGDM-related blood glucose issues and complications but also mitigated hyperglycemia-induced abnormal fetal heart development in pregnant mice. This effect is hypothesized to be mediated through alterations in gut microbiota composition. We proposed that dysregulation in microbiota metabolism could influence the downstream STAT3 signaling pathway via EGFR, consequently impacting cardiac development and formation. CONCLUSIONS: This study marks the first documented instance of AT-I's effectiveness in reducing the risk of early cardiac developmental anomalies in fetuses affected by gestational diabetes. AT-I achieves this by inhibiting the STAT3 pathway activated by ROS during gestational diabetes, significantly reducing the risk of fetal cardiac abnormalities. Notably, AT-I also indirectly safeguards normal fetal cardiac development by influencing the maternal gut microbiota and suppressing the EGFR/STAT3 pathway.

Characterization of the Active Ingredient and Prediction of the Potential Mechanism of Dahuoluo Pill via Mass Spectrometry with the Network Pharmacology Method.

The Dahuoluo pill (DHLP) is a classic Chinese patent medicine used to treat rheumatoid arthritis and other conditions. However, there has been no research on the chemical components of DHLP and the mechanisms by which it ameliorates rheumatoid arthritis. Hence, we analysed the chemical components of DHLP and the DHLP components absorbed in blood by using ultraperformance liquid chromatography-Q-exactive-orbitrap-mass spectrometry. We then used network pharmacology to predict the underlying mechanisms by which DHLP ameliorates rheumatoid arthritis. We identified 153 chemical compounds from DHLP, together with 27 prototype components absorbed in blood. We selected 48 of these compounds as potential active ingredients to explore the mechanism. These compounds are related to 88 significant pathways, which are linked to 18 core targets. This study preliminarily reveals the potential mechanisms by which DHLP ameliorates rheumatoid arthritis and provides a basis for further evaluation of the drug's efficacy.

Systems biology strategy through integrating metabolomics and network pharmacology to reveal the mechanisms of Xiaopi Hewei Capsule improves functional dyspepsia.

Functional dyspepsia (FD) is one of the more common functional disorders, with a prevalence of 20-25 %. It seriously affects the quality life of patients. Xiaopi Hewei Capsule (XPHC) is a classic formula originated from the Chinese Miao minority. Clinical studies have demonstrated that XPHC can effectively alleviate the symptoms of FD, but the molecular mechanism has not been elucidated. The purpose of this work is to investigate the mechanism of XPHC on FD by integrating metabolomics and network pharmacology. The mice models of FD were established, and gastric emptying rate, small intestine propulsion rate, serum level of motilin and gastrin were evaluate to study the interventional effect of XPHC on FD. Next, a metabolomics strategy has been developed to screen differential metabolites and related metabolic pathways induced by XPHC. Then, prediction of active compounds, targets and pathways of XPHC in treating FD were carried out by commonly used network pharmacological method. Finally, two parts of the results were integrated to investigate therapeutic mechanism of XPHC on FD, which were preliminary validated based on molecular docking. Thus, twenty representative different metabolites and thirteen related pathways of XPHC in treating FD were identified. Most of these metabolites were restored using modulation after XPHC treatment. The results of the network pharmacology analysis showed ten crucial compounds and nine hub genes related to the treatment of FD with XPHC. The further integrated analysis focused on four key targets, such as albumin (ALB), epidermal growth factor receptor (EGFR), tumor necrosis factor (TNF) and roto-oncogene tyrosine-protein kinase Src (SRC), and three representative biomarkers such as citric acid, L-leucine and eicosapentaenoic acid. Furthermore, molecular docking results showed that ten bioactive compounds from XPHC have good binding interactions with the four key genes. The functional enrichment analysis indicated that the potential mechanism of XPHC in treating FD was mainly associated with energy metabolism, amino acid metabolism, lipid metabolism, inflammatory reactions and mucosal repair. Our work confirms that network pharmacology-integrated metabolomics strategyis a powerful means to reveal the therapeutic mechanisms of XPHC improves FD, which contribute its further scientific research.

Stochastic sensitivity analysis and feedback control of noise-induced transitions in a predator-prey model with anti-predator behavior.

In this study, we investigate a stochastic predator-prey model with anti-predator behavior. We first analyze the noise-induced transition from a coexistence state to the prey-only equilibrium by using the stochastic sensitive function technique. The critical noise intensity for the occurrence of state switching is estimated by constructing confidence ellipses and confidence bands, respectively, for the coexistence the equilibrium and limit cycle. We then study how to suppress the noise-induced transition by using two different feedback control methods to stabilize the biomass at the attraction region of the coexistence equilibrium and the coexistence limit cycle, respectively. Our research indicates that compared with the prey population, the predators appear more vulnerable and prone to extinction in the presence of environmental noise, but it can be prevented by taking some appropriate feedback control strategies.

OsHLS1 regulates plant height and development by controlling active gibberellin accumulation in rice (Oryza sativa L.).

In this study, we identified a gene related to plant height, leaf, and premature senescence in rice, and named it OsHLS1. Through bioinformatics analysis, it was found that this gene belongs to a new gene family-HLS family, and this gene family exists widely in higher plants. Expression of OsHLS1 was significantly brought about by gibberellin (GA). Subcellular localization showed that OsHLS1 was located in the nucleus. oshls1-3 displayed a GA-deficient phenotype, with dwarf plants. In addition, oshls1-3 also showed premature senescence, shorter and narrower leaves, and pollen abortion. Exogenous GA3 can restore the plant height of oshls1-3. Histomorphological analysis showed that the gene affected the progress of internode cells in the first and third nodes under the rice panicle. Through the verification of the homologous gene AT4G25690 in Arabidopsis, it was found that the mutant at4g25690 lines also showed plant dwarfing, premature senescence, and shortening and narrowing of leaves and pollen abortion. OsHLS1 affected the expression levels of genes involved in the GA metabolic pathway and affected the content of active GA, thereby regulating plant height development in rice. In conclusion, we suggest that OsHLS1 regulates plant height and development by controlling the accumulation of active gibberellins in rice.

Controlling Biological Invasions: A Stochastic Host-Generalist Parasitoid Model.

On a global scale, biological invasions are seriously destroying the stability of ecosystem, sharply decreasing biodiversity and even endangering human health and causing huge economic losses. However, there exist few effective measures controlling biological invasions. To more accurately examine the prevention and control effects of biological control on biological invasions in real environments of random fluctuations, we construct a stochastic host-generalist parasitoid model. We first establish, respectively, the sufficient conditions for the persistence and extinction of invasive hosts and generalist parasitoids, including (1) only the intrusive hosts go extinct; (2) only the generalist parasitoids are extinct, and (3) the intrusive hosts and generalist parasitoids are both extinct or persistent. Then, we perform a series of numerical simulations to verify the validity of the theoretical results obtained, based on which we further discuss the impacts of stochastic environmental fluctuations on the control of intrusive hosts, especially the possible changes of qualitative behavior caused by environmental noises in the bistable scenario. Our theoretical and numerical results indicate that compared with the invasive hosts, the generalist parasitoids are more vulnerable to environmental noises, and the prevention and control effects of biological control on invasive hosts are closely dependent to the initial population sizes. Thus, improving the ability of early detection of ecosystems, including the initial densities of biological populations and their dynamic characteristics, will provide effective predictive guidance for the prevention and control of alien host invasions.

Investigating the Active Substance and Mechanism of San-Jiu-Wei-Tai Granules via UPLC-QE-Orbitrap-MS and Network Pharmacology.

San-Jiu-Wei-Tai granules (SJWTG) are a significant Chinese patent medicine for the treatment of chronic gastritis (CG), having outstanding advantages in long-term treatment; however, the chemical composition and potential mechanism have not been investigated until now. In this study, a rapid separation and identification method based on UPLC-QE-Orbitrap-MS was established, and 95 chemical components from SJWTGs were identified, including 6 chemical components of an unknown source that are not derived from the 8 herbs included in SJWTGs. The identified chemical components were subsequently analysed by network pharmacology, suggesting that the core targets for the treatment of CG with SJWTGs were EGFR, SRC, AKT1, HSP90AA1, MAPK1, and MAPK3 and thus indicating that SJWTGs could reduce the inflammatory response of gastric epithelial cells and prevent persistent chronic inflammation that induces cancerization by regulating the MAPK signalling pathway and the C-type lectin receptor signalling pathway as well as their upstream and downstream pathways in the treatment of CG. The key bioactive components in SJWTGs were identified as 2,6-bis(4-ethylphenyl)perhydro-1,3,5,7-tetraoxanaphth-4-ylethane-1,2-diol, a chemical component of an unknown source, murrangatin, meranzin hydrate, paeoniflorin, and albiflorin. The results of molecular docking showed the strong binding interaction between the key bioactive components and the core targets, demonstrating that the key bioactive components deserve to be further studied and considered as Q-markers. By acting on multiple targets, SJWTG is less susceptible to drug resistance during the long-term treatment of CG, indicating the advantage of Chinese patent medicines. Furthermore, the preventive effect of SJWTGs on gastric cancer also demonstrates the superiority of preventive treatment of disease with traditional Chinese medicine.

Bistability and noise-induced transient behaviour of steady states in a cancer network with the regulation of microRNA.

MicroRNAs (miRs) regulatory network models are highly non-linear due to the negative regulation of gene expression at the post-transcriptional level by miRs and can produce interesting dynamics of the system such as bistability for miR-transcriptional factors interactions. In this article, we focus on the miR-17-92 cluster and its interaction with transcriptional factors (proteins) E2F and Myc. Environmental fluctuations (noise) and randomness in the bio-chemical reactions can be very important and change the dynamical role of miR-17-92 in the regulatory network. We have formulated a stochastically forced miR-17-92 and E2F-Myc interaction model and study the phenomena of intrinsic and extrinsic noise which can induce random switching between steady states or the destruction of the bistability. Using a method that employs stochastic sensitivity functions we have constructed confidence ellipses to determine the configurational arrangements of equilibrium and spatial arrangements of random states near stable equilibria. Simulations are carried out to numerically show the flow of the solution trajectories under noise. Finally, we summarize the simulation results and the impact of noise on the dual non-linear role of miR-17-92 cluster to act as an oncogene or as a tumour suppressor gene.

Study on the synergistic and attenuating mechanism of the combination of Epimedium and Ligustri lucidi fructus based on pharmacokinetics.

Epimedium has a wide range of clinical applications; however, there have been numerous reports of adverse reactions in recent years, which has resulted in it being changed from a widely recognized "nontoxic" to a "potentially toxic" traditional Chinese medicine. The combination of Epimedium and Ligustri lucidi fructus is commonly used in the clinic. The purpose of this study was to investigate the pharmacokinetic characteristics of Epimedium and Ligustri lucidi fructus to explore the possible synergism and reduction in toxicity. Based on liquid chromatography tandem mass spectrometry, a method was established for the determination of icariin, epimedin A, epimedin B, epimedin C, baohuoside Ⅰ, and specnuezhenide in biological samples and was successfully applied to study the pharmacokinetics of the drug pair. The results showed that the five flavonoids (specnuezhenide could not be detected) could be rapidly absorbed into the blood, and the second peak time in vivo was earlier after the combination, indicating that the metabolic pathway may be changed. In addition, combination with Ligustri lucidi fructus could significantly reduce the concentration of 5 flavonoids in vivo and increase their elimination rate, which may attenuate their virulence, thus providing a reference for the rational clinical use of Epimedium.

Impact of low vaccine coverage on the resurgence of COVID-19 in Central and Eastern Europe.

The coronavirus disease 2019 (COVID-19) pandemic has caused a tremendous global impact both socially and economically. The mechanisms behind the disparity in the severity, vaccine coverage, and variant replacement patterns across European countries are unclear. In this work, we aim to reveal the possible reasons via data visualization and model fitting. We developed a model with a vaccination component to simulate the mortality waves in these countries. Deaths averted by the vaccination campaign were estimated. Finally, we discuss the potential reasons behind the differences in vaccine coverage across European countries. Contemporary transportation and global trade bring significant convenience to our daily life but also facilitate the spread of the novel virus COVID-19 to anywhere globally within a short time. The observations and results in this work highlight the importance of the global campaign to mitigate the COVID-19 pandemic and future pandemics under the One Health approach.

Slurryability and Influencing Mechanism of Hydrophobic Structures in Additive-Coal-Water Ternary System.

This study investigates the effects of additive adsorption onto coal particles on surface properties, hydrophobic groups on the slurryability, and the moisture occurrence form on the performance of coal water slurry (CWS). Mechanisms related to the different hydrophobic structures of the additives are proposed. The adsorption method of sulfonated acetone formaldehyde enhances the adsorption capacity of coal surfaces but is not conducive to slurrying. Sodium lignin sulfonate has hydrophobic ends with nonpolar aromatic groups, three-dimensional macromolecular structures, and complex branched chains, which provide CWS with good stability and slurryability. Naphthalenesulfonate formaldehyde has a double benzene ring structure and provides the thick but nonuniform adsorption layers on coal surfaces. The many amorphous structures and low molecular weights of sodium humic sulfonate lead to nonuniform hydration films and poor slurryability. The results of this paper provide guidance for improving synergism in coal-water-additive systems and enhancing slurry performance.

Stochastic switches of eutrophication and oligotrophication: Modeling extreme weather via non-Gaussian Lévy noise.

Disturbances related to extreme weather events, such as hurricanes, heavy precipitation events, and droughts, are important drivers of evolution processes of a shallow lake ecosystem. A non-Gaussian α-stable Lévy process is esteemed to be the most suitable model to describe such extreme events. This paper incorporates extreme weather via α-stable Lévy noise into a parameterized lake model for phosphorus dynamics. We obtain the stationary probability density function of phosphorus concentration and examine the pivotal roles of α-stable Lévy noise on phosphorus dynamics. The switches between the oligotrophic state and the eutrophic state can be induced by the noise intensity σ, skewness parameter ß, or stability index α. We calculate the mean first passage time, also referred to as the mean switching time, from the oligotrophic state to the eutrophic state. We observe that the increased noise intensity, skewness parameter, or stability index makes the mean switching time shorter and thus accelerates the switching process and facilitates lake eutrophication. When the frequency of extreme weather events exceeds a critical value, the intensity of extreme events becomes the most key factor for promoting lake eutrophication. As an application, we analyze the available data of Lake Taihu (2014-2018) for monthly precipitation, phosphorus, and chlorophyll-a concentrations and quantify the linkage among them using the Lévy-stable distribution. This study provides a fundamental framework to uncover the impact of any extreme climate event on aquatic nutrient status.

Threshold dynamics of a stochastic SIHR epidemic model of COVID-19 with general population-size dependent contact rate.

In this paper, we propose a stochastic SIHR epidemic model of COVID-19. A basic reproduction number $ R_{0}^{s} $ is defined to determine the extinction or persistence of the disease. If $ R_{0}^{s} < 1 $, the disease will be extinct. If $ R_{0}^{s} > 1 $, the disease will be strongly stochastically permanent. Based on realistic parameters of COVID-19, we numerically analyze the effect of key parameters such as transmission rate, confirmation rate and noise intensity on the dynamics of disease transmission and obtain sensitivity indices of some parameters on $ R_{0}^{s} $ by sensitivity analysis. It is found that: 1) The threshold level of deterministic model is overestimated in case of neglecting the effect of environmental noise; 2) The decrease of transmission rate and the increase of confirmed rate are beneficial to control the spread of COVID-19. Moreover, our sensitivity analysis indicates that the parameters $ \beta $, $ \sigma $ and $ \delta $ have significantly effects on $ R_0/ $.

Stability and Bifurcation Analysis of a Diffusive miR-9/Hes1 Network With Time Delay.

In this paper, a model of miR-9/Hes1 interaction network involving one time delay and diffusion effect under the Neumann boundary conditions is studied. First of all, the stability of the positive equilibrium and the existence of local Hopf bifurcation and Turing-Hopf bifurcation are investigated by analyzing the associated characteristic equation. Second, a algorithm for determining the direction, stability and period of the corresponding bifurcating periodic solutions is presented. The obtained results suggest that the quiescent progenitors (high steady-state Hes1) can be easily excited into oscillation by time delay whereas the differentiated state (low steady-state Hes1) is basically unaffected, and the integrated effect of delay and diffusion can induce the occurrence of spatially inhomogeneous patterns. More importantly, spatially homogeneous/inhomogeneous periodic solutions can exist simultaneously when the diffusion coefficients of Hes1 mRNA and Hes1 protein are appropriately small, conversely, there is only spatially homogeneous periodic solutions. Intriguingly, both temporal patterns and spatial-temporal patterns show that time delay can prompt Hes1 protein to shift from the high concentration state to the low concentration one ("ON" → "OFF"), where Hes1 protein shows low level whereas miR-9 shows high level. Finally, some numerical examples are presented to verify and visualize theoretical results.

A Diffusive Sveir Epidemic Model with Time Delay and General Incidence.

In this paper, we consider a delayed diffusive SVEIR model with general incidence. We first establish the threshold dynamics of this model. Using a Nonstandard Finite Difference (NSFD) scheme, we then give the discretization of the continuous model. Applying Lyapunov functions, global stability of the equilibria are established. Numerical simulations are presented to validate the obtained results. The prolonged time delay can lead to the elimination of the infectiousness. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at 10.1007/s10473-021-0421-9.

Efficient development of silk fibroin membranes on liquid surface for potential use in biomedical materials.

Silk fibroin (SF) protein is versatile for the application of biomaterials due to its excellent mechanical properties, biocompatibility and biodegradability. However, the efficient way to fabricate SF membranes with special structure is still challenging. Here, we develop an efficient and simple way to create SF membranes on the liquid (i.e. subphase) surface. It is essential to prepare highly concentrated SF solution with low surface tension by dissolving the degummed SF powders in 6% (w/v) LiBr/methanol solution by one step. 95 wt% polyethylene glycol (PEG) 200 and 30 wt% (NH4)2SO4 are the subphases, on which the SF solution spreads quickly, generating nonporous and microporous SF membranes (SFM-1 and SFM-2), respectively. PEG 200 causes more ordered molecular packing (ß-sheets) in SFM-1. While Fast diffusion and denaturation of SF on (NH4)2SO4 solution lead to the formation of microporous, water-unstable membrane SFM-2. Both membranes have good transparency, hydrophilicty, and mechanical properties. To fabricate antibacterial biomaterials, we design a composite membrane by SFM-1 and SFM-2 sandwiching a layer of hydroxypropyl trimethylammonium chloride chitosan (HACC) to provide antibacterial functions. The sandwich membrane has good cell viability and antibacterial properties, showing potential use for biomedical materials.

Competitive Exclusion in a General Multi-species Chemostat Model with Stochastic Perturbations.

Based on the fact that the continuous culture of microorganisms in a chemostat is subject to environmental noises, we present and analyze a stochastic competition chemostat model with general monotonic response functions and differential removal rates. The existence and boundedness of the unique positive solution are first obtained. By defining a stochastic break-even concentration for every species, we prove that at most one competitor survives in the chemostat and the winner has the smallest stochastic break-even concentration, provided its response function satisfies a technical assumption. That is to say, the competitive exclusion principle holds for the stochastic competition chemostat model. Furthermore, we find that the noise experienced by one species is adverse to its growth while may be favorable for the growth of other one species. Namely, the destinies can be exchanged between two microorganism species in the chemostat due to the environmental noise.

Discovery of the Potential Novel Pharmacodynamic Substances From Zhi-Zi-Hou-Po Decoction Based on the Concept of Co-Decoction Reaction and Analysis Strategy.

Background: Zhi-Zi-Hou-Po Decoction (ZZHPD), a classic traditional Chinese medicine (TCM) formula, is clinically used to treat insomnia and depression. The analysis strategy based on the concept of co-decoction of TCM is helpful to analyse the effective substances of TCM formula in depth. Aim of the study: This manuscript intends to take ZZHPD as a model sample to explore the phenomenon of co-decoction of complex formula in the combination of liquid chromatography-mass spectrometry (LC-MS) technology, data analysis, and molecular docking. Materials and methods: In the current research, an innovative LC-MS method has been established to study the active ingredients in ZZHPD, and to identify the ingredients absorbed into the blood and brain tissues of mice. And molecular docking was used to study the binding pattern and affinities of known compounds of the brain tissue toward insomnia related proteins. Results: Based on new processing methods and analysis strategies, 106 chemical components were identified in ZZHPD, including 28 blood components and 18 brain components. Then, by comparing the different compounds in the co-decoction and single decoction, it was surprisingly found that 125 new ingredients were produced during the co-decoction, 2 of which were absorbed into the blood and 1 of which was absorbed into brain tissue. Ultimately, molecular docking studies showed that 18 brain components of ZZHPD had favourable binding conformation and affinity with GABA, serotonin and melatonin receptors. The docking results of GABRA1 with naringenin and hesperidin, HCRTR1 with naringenin-7-O-glucoside, poncirenin and genipin 1-gentiobioside, and luteolin with SLC6A4, GLO1, MAOB and MTNR1A may clarify the mechanism of action of ZZHPD in treating insomnia and depression. Conclusion: Our study may provide new ideas for further exploring the effective substances in ZZHPD.