Trained immunity: A link between risk factors and cardiovascular disease.

Cardiovascular diseases are significant contributors to human mortality, closely associated with inflammation. With the changing living conditions and the extension of human lifespan, greater attention has been directed towards understanding the impact of early, long-term events on the development of cardiovascular events. Lifestyle factors such as stress, unhealthy diet and physical inactivity can increase the risk of cardiovascular diseases. Interestingly, even if the risk factors are addressed later, their influence may persist. Recently, the concept of trained innate immunity (TRIM), defined as sustained alterations in the function of innate immunocyte that promote a more robust response to downstream stimuli, has been proposed to be involved in cardiovascular diseases. It is hypothesized that TRIM may serve as a mediator bridging the impacts of aforementioned risk factors. This review aims to elucidate the role of TRIM in cardiovascular diseases and highlight its significance in uncovering new mechanisms and therapeutic targets.

Evaluating the efficacy of combined flap coverage, antibiotic-loaded bone cement and negative pressure irrigation in traumatic osteomyelitis management.

Traumatic osteomyelitis with accompanying soft tissue defects presents a significant therapeutic challenge. This prospective, randomised controlled trial aims to evaluate the efficacy of antibiotic-impregnated bone cement, flap coverage and negative pressure sealed irrigation in the management of traumatic osteomyelitis complicated by soft tissue defects. A total of 46 patients with clinically diagnosed traumatic osteomyelitis and soft tissue defects were randomised into a control group (n = 23) and an observation group (n = 23). The control group underwent standard flap coverage and negative-pressure lavage, while the observation group received an additional treatment with antibiotic-loaded bone cement. Efficacy was measured based on clinical criteria, surgical metrics and morphometric assessment of bone and soft tissue defects. Statistical analyses were performed using SPSS version 27.0. The observation group, treated with an integrated approach of flap coverage, negative pressure wound therapy (NPWT) and antibiotic-impregnated bone cement, demonstrated significantly higher overall treatment efficacy (91.3%) compared to the control group, which received only flap coverage and NPWT (65.2%) (p < 0.01). This enhanced efficacy was evidenced through various outcomes: the observation group experienced reduced surgical times, shorter hospital stays, fewer dressing changes and accelerated wound healing, all statistically significant (p < 0.001). Additionally, a quantitative analysis at 6-month post-treatment revealed that the observation group showed more substantial reductions in both bone and soft tissue defect sizes compared to the control group (p < 0.001). The multi-modal treatment strategy, combining skin flap coverage, antibiotic bone cement and negative-pressure irrigation, showed marked efficacy in treating traumatic osteomyelitis and associated soft tissue defects. This approach accelerated postoperative recovery and lowered costs.

Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway.

OBJECTIVE: To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments. METHODS: A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed. RESULTS: FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05). CONCLUSION: FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.

Multilocus Distance-Regulated Sensor Array for Recognition of Polyphenols via Machine Learning and Indicator Displacement Assay.

Developing new strategies to construct sensor arrays that can effectively distinguish multiple natural components with similar structures in mixtures is an exceptionally challenging task. Here, we propose a new multilocus distance-modulated indicator displacement assay (IDA) strategy for constructing a sensor array, incorporating machine learning optimization to identify polyphenols. An 8-element array, comprising two fluorophores and their six dynamic covalent complexes (C1-C6) formed by pairing two fluorophores with three distinct distance-regulated quenchers, has been constructed. Polyphenols with diverse spatial arrangements and combinatorial forms compete with the fluorophores by forming pseudocycles with quenchers within the complexes, leading to varying degrees of fluorescence recovery. The array accurately and effectively distinguished four tea polyphenols and 16 tea varieties, thereby demonstrating the broad applicability of the multilocus distance-modulated IDA array in detecting polyhydroxy foods and natural medicines.

Biomimetic inducer enabled dual ferroptosis of tumor and M2-type macrophages for enhanced tumor immunotherapy.

Tumor-associated macrophages (TAMs) are abundant in the tumor microenvironment which promotes the formation of the immunosuppressive tumor microenvironment (ITME) through multiple mechanisms, severely counteracting the therapeutic efficacy of immunotherapy. In this study, a novel biomimetic ferroptosis inducer (D@FMN-M) capable of ITME regulation for enhanced cancer ferroptosis immunotherapy is reported. Upon tumor accumulation of D@FMN-M, the intratumoral mild acidity triggers the biodegradation of Fe-enriched nanocarriers and the concurrent co-releases of dihydroartemisinin (DHA) and Fe3+. The released Fe3+ is reduced to Fe2+ by consuming intratumoral glutathione (GSH), which promotes abundant free radical generation via triggering Fenton and Fe2+-DHA reactions, thus inducing ferroptosis of both cancer cells and M2-type TAMs. Resultantly, the anticancer immune response is strongly activated by the massive tumor-associated antigens released by ferroptositic cancer cells. Also importantly, the ferroptosis-sensitive M2-type TAMs will be either damaged or gradually domesticated to ferroptosis-resistant M1 TAMs under the ferroptosis stress, favoring the normalization of ITME and finally amplifying cancer ferroptosis immunotherapeutic efficacy. This work provides a novel strategy for ferroptosis immunotherapy of solid tumors featuring TAMs infiltration and immunosuppression by inducing dual ferroptosis of tumor cells and M2-type TAMs.

Current and Novel Therapeutics for Articular Cartilage Repair and Regeneration.

Articular cartilage repair is a sophisticated process that has is being recently investigated. There are several different approaches that are currently reported to promote cartilage repair, like cell-based therapies, biologics, and physical therapy. Cell-based therapies involve the using stem cells or chondrocytes, which make up cartilage, to promote the growth of new cartilage. Biologics, like growth factors, are also being applied to enhance cartilage repair. Physical therapy, like exercise and weight-bearing activities, can also be used to promote cartilage repair by inducing new cartilage growth and improving joint function. Additionally, surgical options like osteochondral autograft, autologous chondrocyte implantation, microfracture, and others are also reported for cartilage regeneration. In the current literature review, we aim to provide an up-to-date discussion about these approaches and discuss the current research status.

Structural optimization of tetrahydroisoquinoline-hydroxamate hybrids as potent dual ERα degraders and HDAC inhibitors.

Both estrogen receptor α (ERα) and histone deacetylases (HDACs) are valid therapeutic targets for anticancer drug development. Combination therapies using diverse ERα antagonists or degraders and HDAC inhibitors have been proven effective in endocrine-resistant ER + breast cancers based on the crosstalk between ERα and HDAC pathway. In this study, we reported the optimization of a series of methoxyphenyl- or pyridinyl- substituted tetrahydroisoquinoline-hydroxamates, which were optimized from 31, a dual ERα degrader/HDAC inhibitor previously reported by our group. Most of the synthesized compounds displayed potent ERα degradation efficacy and antiproliferative activity. Among them, A04 demonstrated the best anti-proliferation activity (MCF-7 IC50 = 1.96 µM) and HDAC6 inhibitory activity (HDAC6 IC50 = 25.96 nM), which is slightly more potent than the lead compound 31 (MCF-7 IC50 = 4.38 µM, HDAC6 IC50 = 63.03 nM). In addition, compound A04 exerted ERα-independent HDAC6-inhibiting effect without agonistic activity in endometrial cells. These results demonstrated that A04 is a novel and promising dual ERα degrader/HDAC inhibitor worthy of further development.

Two new alkaloids from a strain of endophytic fungus Aspergillus sp.

19-Hydroxybrevianamide M (1) and 6 R-methoxybrevianamide V (2), two new alkaloids, were isolated from an extract of the endophytic fungus Aspergillus sp. JNU18HC0517J, together with six known analogues (3- 8). Their structures were elucidated by extensive spectroscopic analyses, NMR calculations, and ECD calculations. 6 R-methoxybrevianamide V (2) was the first L-proline indole DKP alkaloid with substitution at C-6 on the proline ring. Furthermore, the cytotoxities and antimicrobial activities of these isolated compounds were also evaluated. Compound 8 exhibited moderate antibacterial activity against Staphylococcus aureus 209 P with a minimal inhibitory concentration (MIC) value of 16 µg/ml.[Figure: see text].

Novel 6-amino-1,3,5-triazine derivatives as potent BTK inhibitors: structure-activity relationship (SAR) analysis and preliminary mechanism investigation.

Bruton's tyrosine kinase (BTK) is a promising drug target for the treatment of B-cell related malignancies. Irreversible inhibition of BTK by a covalent inhibitor has been proved to be a clinically effective therapy. However, most irreversible BTK inhibitors also inhibit other kinases including JAK3 and EGFR, leading to some adverse events. Herein, we reported the structure-based design and optimization of a series of irreversible BTK inhibitors bearing the 6-amino-1,3,5-triazine scaffold. Most of the synthesized compounds demonstrated considerable BTK inhibition and improved anti-proliferative activity against Raji and Ramos cells. Among them, compound C11 exhibited potent BTK inhibition (BTK IC50 = 17.0 nM) and a desirable selectivity profile especially over EGFR. Moreover, C11 effectively blocked activation of BTK and downstream signaling, arrested the cell cycle in G0/G1 phase and induced apoptosis in Raji cells. Its irreversible binding mode was further investigated by both molecular modeling and a washout experiment. Collectively, C11 is a novel selective irreversible BTK inhibitor worthy of further in-depth research.

Machine Learning-Assisted Sensor Array Based on Poly(amidoamine) (PAMAM) Dendrimers for Diagnosing Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, and the early diagnosis of AD remains challenging. Here we have developed a fluorescent sensor array composed of three modified polyamidoamine dendrimers. Proteins of various properties were differentiated via this array with 100% accuracy, proving the rationality of the array's design. The mechanism of the fluorescence response was discussed. Furthermore, the robust three-element array enables parallel detection of multiple Aß40/Aß42 aggregates (0.5 µM) in diverse interferents, serum media, and cerebrospinal fluid (CSF) with high accuracy, through machine learning algorithms, demonstrating the tremendous potential of the sensor array in Alzheimer's disease diagnosis.

Recent Advances and Perspective of Nanotechnology-Based Implants for Orthopedic Applications.

Bioimplant engineering strives to provide biological replacements for regenerating, retaining, or modifying injured tissues and/or organ function. Modern advanced material technology breakthroughs have aided in diversifying ingredients used in orthopaedic implant applications. As such, nanoparticles may mimic the surface features of real tissues, particularly in terms of wettability, topography, chemistry, and energy. Additionally, the new features of nanoparticles support their usage in enhancing the development of various tissues. The current study establishes the groundwork for nanotechnology-driven biomaterials by elucidating key design issues that affect the success or failure of an orthopaedic implant, its antibacterial/antimicrobial activity, response to cell attachment propagation, and differentiation. The possible use of nanoparticles (in the form of nanosized surface or a usable nanocoating applied to the implant's surface) can solve a number of problems (i.e., bacterial adhesion and corrosion resilience) associated with conventional metallic or non-metallic implants, particularly when implant techniques are optimised. Orthopaedic biomaterials' prospects (i.e., pores architectures, 3D implants, and smart biomaterials) are intriguing in achieving desired implant characteristics and structure exhibiting stimuli-responsive attitude. The primary barriers to commercialization of nanotechnology-based composites are ultimately discussed, therefore assisting in overcoming the constraints in relation to certain pre-existing orthopaedic biomaterials, critical factors such as quality, implant life, treatment cost, and pain alleviation.

Optical Sensor Array for the Early Diagnosis of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder and has complicated pathobiology, leading to irreversible memory loss and severe cognitive dysfunction. For patients with AD, the advent of the disease usually occurs after years of pathological changes. The early diagnosis and monitoring of AD are of great significance as the early-stage intervention and treatment may be the most effective. Biomarkers, such as beta-amyloid and tau levels in cerebrospinal fluid (CSF) and brain, offer one of the most promising paths and are combined with neuroimaging and immunological detection for AD diagnosis. However, high expense and radiation of neuroimaging and low sensitivity of immunosorbent assay limited their applications. Meanwhile, the relevance of Aß peptides and tau proteins to the development of AD remains highly debatable, meaning that detecting one specific biomarker holds limited prospects in achieving early and accurate detection of AD. Optical sensor arrays based on pattern recognition enable the discrimination of multiple analytes in complicated environments and are thus highly advantageous for the detection of AD with multi-biomarkers. In this review, we survey the recent advances of optical sensor arrays for the diagnosis of AD, as well as the remaining challenges.

General synthesis of ultrafine metal oxide/reduced graphene oxide nanocomposites for ultrahigh-flux nanofiltration membrane.

Graphene-based membranes have great potential to revolutionize nanofiltration technology, but achieving high solute rejections at high water flux remains extremely challenging. Herein, a family of ultrafine metal oxide/reduced graphene oxide (rGO) nanocomposites are synthesized through a heterogenous nucleation and diffusion-controlled growth process for dye nanofiltration. The synthesis is based on the utilization of oxygen functional groups on GO surface as preferential active sites for heterogeneous nucleation, leading to the formation of sub-3 nm size, monodispersing as well as high-density loading of metal oxide nanoparticles. The anchored ultrafine nanoparticles could inhibit the wrinkling of the rGO nanosheet, forming highly stable colloidal solutions for the solution processing fabrication of nanofiltration membranes. By functioning as pillars, the nanoparticles remarkably increase both vertical interlayer spacing and lateral tortuous paths of the rGO membranes, offering a water permeability of 225 L m-2 h-1 bar-1 and selectivity up to 98% in the size-exclusion separation of methyl blue.

Machine Learning-Assisted Pattern Recognition of Amyloid Beta Aggregates with Fluorescent Conjugated Polymers and Graphite Oxide Electrostatic Complexes.

Five fluorescent positively charged poly(para-aryleneethynylene) (P1-P5) were designed to construct electrostatic complexes C1-C5 with negatively charged graphene oxide (GO). The fluorescence of conjugated polymers was quenched by the quencher GO. Three electrostatic complexes were enough to distinguish between 12 proteins with 100% accuracy. Furthermore, using these sensor arrays, we could identify the levels of Aß40 and Aß42 aggregates (monomers, oligomers, and fibrils) via employing machine learning algorithms, making it an attractive strategy for early diagnosis of Alzheimer's disease.

In Situ Formed Lithiophilic LixNbyO in a Carbon Nanofiber Network for Dendrite-Free Li-Metal Anodes.

Lithium metal is considered as a strongly attractive anode candidate for the high-energy-storage field, but its dreadful dendrite growth has haunted its commercialization progress. Herein, we develop a lithiophilic Nb2O5-embedded three-dimensional (3D) carbon nanofiber network (Nb2O5-CNF) as a scaffold to preload molten Li for the fabrication of dendrite-free composite anode. The in situ lithiation reaction between molten Li and Nb2O5 nanocrystals results in the formation of nanosize LixNbyO nanoparticles, which can serve as preferred sites that regulate nucleation/growth behavior of Li during the plating process. Besides, due to its high structural stability and abundant internal inner space, the 3D CNF network can function as a reservoir to confine the dimensional expansion of "hostless Li". The resulting Li composite anodes exhibit enlarged active areas and reduced interfacial energy barriers, delivering a prolonged cycling of 1000 h with an ultralow hysteresis of 52 mV and dendrite-free morphology in a symmetric cell (1.0 mA cm-2). Coupled with the LiFePO4 cathode, the Li@Nb2O5-CNF anode sustains a reversible capacity of 163 mAh g-1 with an excellent capacity retention of 93.0% after 370 cycles at 0.5C. This all-around strategy of lithiophilic sites coupled with a 3D conductive nanofiber matrix may shed light on promising applications of high-capacity and dendrite-free Li-metal batteries.

Pt-NbC Composite as a Bifunctional Catalyst for Redox Transformation of Polysulfides in High-Rate-Performing Lithium-Sulfur Batteries.

Accelerating the redox reaction of polysulfides via catalysis is an effective way to suppress the shuttling effect in lithium-sulfur (Li-S) cells. However, recent studies have mainly focused on the singular function of the catalyst, i.e., either oxidation or reduction of polysulfides. As such, the goal of rapid cycling of sulfur species remains to be highly desired. Herein, a Pt-carbide composite as a bifunctional catalyst was developed to simultaneously accelerate both the reduction of soluble polysulfides and the oxidation of insoluble Li2S/Li2S2. Typically, a Pt-NbC composite was synthesized by growing Pt nanoparticles on the surface of NbC, and the resultant intimate interface in the hybrid is a key component for the bifunctional catalysis. During the reduction process, polysulfides could be grabbed on the surface of NbC via strong adsorption, and then these trapped polysulfides could be catalytically converted by Pt nanoparticles. During the oxidation process, both NbC and Pt exhibited catalytic activities for the dissolution of Li2S. This process could lead to the renewal of the surface of the catalyst. By combining the sulfur cathode with a Pt-NbC-CNT (Pt-NbC anchored on a carbon nanotube)-coated separator, the cell was able to demonstrate a high initial capacity of 1382 mAh g-1 at a current density of 0.2C. Furthermore, the cell was able to achieve an exceptional rate capability of 795 mAh g-1 at 5C, and it was also able to show significantly inhibited self-discharge behavior. Thus, this work explores the catalyst design and the mechanism of a bifunctional catalyst for the performance enhancement in Li-S cells.

Efficacy and safety of non-vitamin K antagonist oral anticoagulants for venous thromboembolism: a meta-analysis.

OBJECTIVE: Several trials had compared the efficacy and safety between non-vitamin K antagonist oral anticoagulants and warfarin for acute venous thromboembolism, but the results were incomplete. This updated review comprehensively assessed the efficacy and safety of non-vitamin K antagonist oral anticoagulants for venous thromboembolism. DESIGN: Meta-analysis of randomised control trials. Six databases were searched from January 2000 to December 2018. SETTING: Adult patients had got non-vitamin K antagonist oral anticoagulants or warfarin for venous thromboembolism. PARTICIPANTS: Randomised control trials that compared the efficacy and safety between non-vitamin K antagonist oral anticoagulants and warfarin. MAIN OUTCOME MEASURES: The efficacy and safety of non-vitamin K antagonist oral anticoagulants . RESULTS: Seven studies involving 29,879 cases were included, among which 14,943 cases were assigned to non-vitamin K antagonist oral anticoagulants group and 14,936 cases to warfarin group. Meta-analysis showed that compared with warfarin, recurrent venous thromboembolism (odds ratio 0.94 [95% confidence interval 0.81 to 1.11]), death related to venous thromboembolism or fatal pulmonary embolism (odds ratio 1.00 [95% confidence interval 0.63 to 1.60]), symptomatic deep-vein thrombosis (odds ratio 0.88 [95% confidence interval 0.72 to 1.09]), symptomatic nonfatal pulmonary embolism (odds ratio 1.03 [(95% confidence interval 0.82 to 1.30]) and all deaths (odds ratio 0.92 [95% confidence interval 0.76 to 1.12]) are similar in non-vitamin K antagonist oral anticoagulants group, but major bleeding event (odds ratio 0.61 [95% confidence interval 0.50 to 0.75]) and clinically relevant non-major bleeding event (odds ratio [95% confidence interval 0.53 to 0.85]) are less in non-vitamin K antagonist oral anticoagulants group. . CONCLUSIONS: For the treatment of venous thromboembolism, non-vitamin K antagonist oral anticoagulants is as effective as warfarin, and has a better safety profile than warfarin.

Research on Laser Illumination Based on Phosphor in Metal (PiM) by Utilizing the Boron Nitride-Coated Copper Foams.

Laser-driven illumination has unique advantages in high-power applications. Taking advantage of the valuable experience of light-emitting diodes (LED) development, phosphor in silicone (PiS) is considered to be one of the most potential commercial phosphor converter solutions for laser-driven illumination. However, the thermal quenching of the PiS converter is a bottleneck problem. Herein, a boron nitride (BN)-coated copper foam strategy is introduced for the laser-driven illumination system. The phosphor/silicone is embedded in the designed BN/copper foam to form a phosphor in metal (PiM) converter. Copper foam serves as an internal connected heat transfer channel; the BN coating solves the light absorption problem of the copper foam effectively. Based on this PiM(BN/copper foam) design, the heat dissipation is effectively improved. Under high-power laser excitation (8.13 W), the PiS converter cannot reach thermal equilibrium, and therefore the temperature increases sharply up to 660 °C. In comparison, the thermal performance of an optimized PiM(BN/copper foam) converter is able to maintain excellent stability, where the maximum temperature is only 166.5 °C. The proposed PiM strategy has a maximum temperature that is 493.5 °C lower than that of the reference PiS solution. Due to the superior thermal management, the luminous efficiency of the illumination system is constantly stable at 254 lm/W, though with less phosphor mass; and the related color temperature is about 6000 K all the time. This provides a practical and feasible heat-dissipation solution for high-power laser-driven illumination.

Efficacy and safety of methylprednisolone against acute respiratory distress syndrome: A systematic review and meta-analysis.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is caused by an inflammatory injury to the lung. Dysregulated inflammation is the cardinal feature of ARDS. Methylprednisolone is an option for treating ARDS. However, the benefits and adverse effects of methylprednisolone have not been well assessed in patients with ARDS. This study aimed to evaluate the efficacy and safety of methylprednisolone against ARDS. MATERIAL AND METHODS: The electronic database of Embase, PubMed, the Cochrane Library, CNKI, and Wanfang were searched, and randomized controlled trials (RCTs) reporting the efficacy and safety of methylprednisolone for ARDS were included. Revman 5.3 and Stata 15.0 were used to conduct the analysis. The fixed-effects model was used to calculate summary odds ratios (ORs) and 95% confidence interval (CIs). RESULTS: Ten RCTs studies involving 692 patients with ARDS. The summary results demonstrated that, compared with placebo, methylprednisolone had a statistically significant effect on mortality (OR = 0.64; 95% CI: 0.43-0.95, I2 = 42%); the time of mechanical ventilation (MD) = -2.70, 95% CI: -3.31 to -2.10; I2 = 0%) in patients with ARDS, but it was not associated with increased rates of adverse events (OR = 0.80; 95% CI: 0.34-1.86; I2 = 58%). CONCLUSIONS: This systematic review and meta-analysis demonstrated that Methylprednisolone is safe against ARDS. It may reduce mortality and shorten the time of mechanical ventilation. However, well-designed and large-sample studies were required to fully characterize the efficacy and safety of methylprednisolone against ARDS.

Network Pharmacology and Molecular Docking Analyses of Mechanisms Underlying Effects of the Cyperi Rhizoma-Chuanxiong Rhizoma Herb Pair on Depression.

OBJECTIVE: We aimed to investigate the mechanisms underlying the effects of the Cyperi Rhizoma-Chuanxiong Rhizoma herb pair (CCHP) against depression using a network pharmacology approach. METHODS: A network pharmacology approach, including screening of active compounds, target prediction, construction of a protein-protein interaction (PPI) network, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and molecular docking, molecular dynamics (MD) simulations, and molecular mechanics Poisson-Boltzmann surface area (MMPBSA), were used to explore the mechanisms of CCHP against depression. RESULTS: Twenty-six active compounds and 315 and 207 targets of CCHP and depression, respectively, were identified. The PPI network suggested that AKT1, IL-6, TP53, DRD2, MAPK1, NR3C1, TNF, etc., were core targets. GO enrichment analyses showed that positive regulation of transcription from RNA polymerase II promoter, plasma membrane, and protein binding were of great significance. Neuroactive ligand-receptor interaction, PI3K-Akt signaling pathway, dopaminergic synapse, and mTOR signaling pathway were important pathways. Molecular docking results revealed good binding affinities for the core compounds and core targets. MD simulations and MMPBSA validated that quercetin can stably bind to 6hhi. CONCLUSIONS: The effects of CCHP against depression involve multiple components, targets, and pathways, and these findings will promote further research on and clinical application of CCHP.