Sfxn5 Regulation of Actin Polymerization for Neutrophil Spreading Depends on a Citrate-Cholesterol-PI(4,5)P2 Pathway.

Cell spreading is an initial and critical step in neutrophil adhesion and migration, leading to neutrophil recruitment to inflammatory tissues. Sideroflexin (Sfxn) family proteins are metabolite transporters located in the mitochondrial membrane. Recombinant SFXN5 protein is a citrate transporter in vitro; however, whether Sfxn5 regulates any cellular behavior or function remains unknown. In this study, we found that small interfering RNA transfection or morpholino injection achieving Sfxn5 deficiency in neutrophils significantly decreased neutrophil recruitment in mice and zebrafish, respectively. Sfxn5 deficiency impaired neutrophil spreading and spreading-associated cellular phenotypes, such as cell adhesion, chemotaxis, and ROS production. Actin polymerization is critical for neutrophil spreading, and we found that actin polymerization in spreading neutrophils was partially inhibited by Sfxn5 deficiency. Mechanistically, we observed that the levels of cytosolic citrate and its downstream metabolic products, acetyl-CoA and cholesterol, were decreased in Sfxn5-deficient neutrophils. The levels of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), a mediator for the regulation of actin polymerization by cholesterol, were reduced in the plasma membrane of Sfxn5-deficient neutrophils. Exogenous supplementation with citrate or cholesterol partially reversed the reduction in PI(4,5)P2 levels, defective neutrophil actin polymerization, and cell spreading. Altogether, we demonstrated that Sfxn5 maintains cytosolic citrate levels and ensures the synthesis of sufficient cholesterol to promote actin polymerization in a PI(4,5)P2-dependent manner during neutrophil spreading, which is essential for the eventual inflammatory recruitment of neutrophils. Our study revealed the importance of Sfxn5 in neutrophil spreading and migration, thus identifying, to our knowledge, for the first time, the physiological cellular functions of the Sfxn5 gene.

KGF-2 ameliorates UVB-triggered skin photodamage in mice by attenuating DNA damage and inflammatory response and mitochondrial dysfunction.

BACKGROUND: Long-term exposure to UVB induces DNA damage, inflammatory response, mitochondrial dysfunction, and apoptosis in skin cells, thus causing skin photodamage. Research has demonstrated the noteworthy antioxidant, anti-inflammatory, DNA repair, and mitochondrial protective properties of keratinocyte growth factor-2 (KGF-2). METHODS: To examine the impact of KGF-2 on UVB-triggered skin photodamage in mice, hair-removed mice were initially exposed under UVB radiation and subsequently treated with KGF-2 hydrogel and repeated for 6 days. On day 7, the assessment of histopathological alterations, inflammation, DNA damage, mitochondrial function, and apoptosis in mouse skin was assessed. RESULTS: It was found that KGF-2 could effectively relieve cutaneous photodamage symptoms and inhibit epidermal proliferation in mice. Meanwhile, KGF-2 was found to significantly reduce DNA damage, attenuate the inflammatory response, and inhibit the mitochondria-mediated intrinsic apoptotic pathway in the UVB-exposed mouse skin photodamage model. CONCLUSION: To summarize, our results indicated that KGF-2 reduces the severity of mouse skin photodamage caused by UVB rays by attenuating DNA damage and the inflammatory response, besides inhibiting the mitochondria-mediated intrinsic apoptosis pathway.

Ab initio study revealing remarkable oscillatory effects and negative differential resistance in the molecular device of silicon carbide chains.

Inspired by the requirements of miniaturization and multifunction of molecular devices, we investigate the quantum transport properties of three unique molecular devices with silicon carbide chains bridging gold electrodes by an ab initio approach. The pronounced quantum effects, including the oscillation of charge, conductance, and current, together with the negative differential resistance (NDR), have been observed simultaneously over a wide region in the double-chain device. It changes the regular situation that these two effects usually emerge in single-chain systems at the same time. Inspections of the visible differences in the transport behaviors relevant to length and bias between the three devices further evidence that the interchain interaction and molecule-electrode coupling are decisive factors for achieving the quantum effects of oscillation and NDR. These two factors can improve electronic transport capability through enhancing transmission, strengthening the delocalization of frontier molecular orbitals, and reducing potential barriers. Our results not only lay a solid foundation for the application of silicon carbide chains in the miniaturized and multifunctional molecular devices with good performance, but also provide an efficient way to the continuing search for materials with multiple controllable quantum effects in nanoelectronics.

Conformers, properties, and docking mechanism of the anticancer drug docetaxel: DFT and molecular dynamics studies.

The conformational structures and properties of the anticancer drug docetaxel (DTX) are studied theoretically. A total of 3888 trial structures were initially generated by all combinations of internal single-bond rotamers and screened with the B3LYP/3-21G* method. A total of 31 unique conformers were further optimized at the B3LYP/6-311G* method. Their relative energies, dipole moments, rotational constants, and harmonic vibrational frequencies were predicted. Single-point relative energies were then determined at the M06-L/6-311G(2df,p) level. The UV spectrum of the lowest-lying DTX conformer in methanol was investigated with the TD-CAM-B3LYP/6-311 + G(2df,p) method. The 31 unique DTX structures are mainly docked at three different sites within ß-tubulin. Based on the results of molecular docking and double-float MD simulations, the lowest-lying DTX conformer consistently exhibits good docking performance with ß-tubulin. We identified the residues LYS299, ARG215, GLN294, LEU275, THR216, GLU290, PRO274, and THR276 on ß-tubulin as active sites forming a binding pocket responsible for locking DTX within ß-tubulin to make the combination more stable. The RMSD values show that the predicted complexes are favorable, and the SASA analysis shows that the hydrophilic properties of DTX are better than paclitaxel. © 2018 Wiley Periodicals, Inc.

Treatment Outcomes and Prognostic Factors of Adult Sinonasal Sarcomas: A Single-Institution Case Series.

BACKGROUND The purpose of this study was to investigate the treatment outcomes and evaluate the prognostic factors of adult sinonasal sarcomas. MATERIAL AND METHODS A retrospective review was performed on consecutive patients with adult sinonasal sarcomas treated in our institution from 2005 to 2016. The Kaplan-Meier method was used to evaluate local recurrence-free survival (LRFS), distant metastases-free survival (DMFS), and overall survival (OS). Univariate and multivariate analyses using Cox proportional hazard models were performed to determine the prognostic factors associated with survival outcomes. RESULTS A total of 49 patients were followed up for 6-122 months, with a median time of 36 months. The 5-year LRFS, DMFS, and OS rates of all patients were 68.3%, 62.8%, and 43.2%, respectively. The results of univariate analysis revealed that patients with an advanced stage of primary tumor and those who received incomplete surgical resection had worse LRFS (p=0.013; p=0.026). Patients with the histological type rhabdomyosarcoma (RMS) and existing regional lymph node metastasis had worse DMFS (p=0.000; p=0.001). The histological type RMS, advanced stage of primary tumor, existing regional lymph node metastasis, and receiving incomplete surgical resection had an unfavorable effect on OS (p=0.001; p=0.002; p=0.008; p=0.011). The results of multivariate analysis showed that histological type and degree of surgical resection were the independent prognostic factors for OS. CONCLUSIONS Our results suggest that the histological type RMS and receiving incomplete surgical resection are independent prognostic factors for worse OS.

Activation of Chiral (Salen)AlCl Complex by Phosphorane for Highly Enantioselective Cyanosilylation of Ketones and Enones.

Phosphoranes 2 are identified as a class of effective Lewis bases to activate chiral (salen)AlCl complex 1 to enhance its electrophilicity. Accordingly, a three-component catalyst system consisting of complex 1, phosphorane 2e, and Ph3PO is developed as a powerful tool for asymmetric ketone cyanosilylation. In particular, an unprecedented highly enantioselective cyanosilylation of linear aliphatic ketones is achieved. A tandem Wittig-cyanosilylation sequence starting from phosphorane 2a and enals 10 is further achieved, which internally utilizes the Ph3PO byproduct and remaining phosphorane 2a as cocatalysts for cyanosilylation of α,ß,γ,δ-unsaturated enones, providing atom-efficient access to valuable chiral conjugated dienes and enynes. The high efficiency of the cyanosilylation originates from orthogonal activation of both (salen)AlCl complex 1 and cyanotrimethylsilane by the phosphorane and Ph3PO, respectively. This mechanistic insight is supported by NMR, MS, and ReactIR analyses and DFT calculations. Furthermore, the formation of charged complexes through the activation of chiral complex 1 by phosphorane 2a is confirmed by electrical conductivity experiments.

Properties, theoretical study and crystal structure of 3-benzothiazole-9-ethyl carbazole.

The title compound of 3-benzothiazole-9-ethyl carbazole was synthesized by the reaction of 3-aldehyde-9-ethyl carbazole and 2-aminothiophenol. The compound was characterized by (1) H nuclear magnetic resonance (NMR) and mass spectrometry (MS). Its crystal structure was obtained and determined by single crystal X-ray diffraction. The results showed that the crystal belongs to the orthorhombic crystal system and the cell parameters of space group P2(1)2(1)2(1) were a = 5.6626 (12) Å, b = 12.606 (3) Å, c = 22.639 (5) Å, α = 90°, ß = 90°, γ = 90°, V = 1616.0 (6) Å(3) , Z = 4, Dc = 1.350 mg/m(3) . The UV-vis and fluorescence spectra were also studied preliminarily. The fluorescence spectra of the title compound with bovine serum albumin (BSA) showed that BSA could be marked with the compound and the stability constant between them was 0.82 × 10(7)  M(-1) . Meanwhile, the crystal and molecule were theoretically surveyed by density functional tight-binding (DFTB). The results showed that there was an orbital overlap for lowest unoccupied molecular orbital (LUMO) between the neighbouring molecules for the crystal, which is different from the molecule structure. It was also showed that the crystal structure is a non-conductor. Copyright © 2016 John Wiley & Sons, Ltd.

A benzindole substituted carbazole cyanine dye: a novel targeting fluorescent probe for parallel c-myc G-quadruplexes.

Many organic ligands were synthesized to recognize G-quadruplexes. However, different kinds of G-quadruplexes (G4s) possess different structures and functions. Therefore, selective recognition of certain types of G4s is important for the study of G4s. In this paper, a novel cyanine dye, 3-(2-(4-vinylpyridine))-6-(2-((1-(4-sulfobutyl))-3,3-dimethyl-2-vinylbenz[e]indole)-9-ethyl-carbazole (9E PBIC), composed of benzindole and carbazole was designed and synthesised. The studies on UV-vis and fluorescence properties of the dye with different DNA forms showed that the dye exhibits almost no fluorescence under aqueous buffer conditions, but it increased over 100 fold in the presence of c-myc G4 and 10-30 fold in the presence of other G4s, while little in the presence of single/double-stranded DNA, indicating that it has excellent selectivity to c-myc 2345 G4. For the binding studies the dye is interacted with the c-myc 2345 G-quadruplex by using the end-stack binding model. It can be said that the dye is an excellent targeting fluorescent probe for c-myc G-quadruplexes.

The predictive value and potential mechanisms of miRNA-328 and miRNA-378 for brain metastases in operable and advanced non-small-cell lung cancer.

OBJECTIVE: The incidence of brain metastases greatly varies in patients with non-small-cell lung cancer, and molecular markers are considered to predict brain metastases. Therefore, this study sought to identify the predictive value and potential mechanisms of miRNA-328 and miRNA-378 for brain metastases in non-small-cell lung cancer. METHODS: Patients who received a curable surgery for their lung cancer were screened according to our criteria. Formalin-fixed paraffin-embedded samples from the patients were examined for the expression of miRNA-328 and miRNA-378 using real-time polymerase chain reaction and the expression of N-cadherin, E-cadherin, vascular endothelial growth factor, protein kinase Cα and S100B were investigated using immunohistochemical staining. RESULTS: In total, 86 patients were screened for this study and 23 patients were diagnosed with brain metastases during the follow-up period. Comparing patients with and without brain metastases, the expression of miRNA-328 and miRNA-378 in tumor tissues were significantly different (P = 6.2 × 10(-5) and P = 2.8 × 10(-5), respectively). For the patients with brain metastases, the expression of miRNA-328 and miRNA-378 in tumor tissues compared with para-carcinoma tissues were also significantly different (P = 2.2 × 10(-5) and P = 1.6 × 10(-5), respectively). For patients with brain metastases, the association between miRNA-328 and protein kinase Cα was significant (r = 0.591, P = 0.003), but that between miRNA-378 and protein kinase Cα was not significant (r = 0.259, P = 0.232). CONCLUSIONS: The expression of miRNA-328 and miRNA-378 in tumor tissues can be used to predict brain metastases in patients with non-small-cell lung cancer. miRNA-328 might promote brain metastases by regulating the expression of protein kinase Cα. However, the mechanisms of miRNA-378 to promote brain metastases should be studied in the future.

Catalytic functionalization of tertiary alcohols to fully substituted carbon centres.

The catalytic nucleophilic substitution of tertiary alcohols using carbon or heteroatom based nucleophiles is a versatile methodology for the efficient, diverse and atom economical construction of fully substituted carbon centres, including both quaternary carbons and heteroatom substituted tetrasubstituted carbons, which only produces water as the by-product. This review summarizes the recent progress in this field, including the catalytic asymmetric studies and their application in the natural product synthesis, briefly discusses the reaction mechanism and challenges, and outlines synthetic opportunities that are still open.

Selective adsorption of L-serine functional groups on the anatase TiO2(101) surface in benthic microbial fuel cells.

To help design bacteria-friendly anodes for unmediated benthic microbial fuel cells (MFCs), we explore the role of anatase TiO2(101) surface biocompatibility in selecting the functional groups of the levo-isomer serine (L-Ser), which contains carboxyl, hydroxyl, and amino groups in a single molecule. By performing total energy calculations and molecular dynamics simulations based on a density-functional tight-binding method, we find that at room temperature, the surface should be active for biomolecules with carboxyl/carboxylic and hydroxyl groups, but it is not sensitive to those with amino groups. The hydrogen bonding between the hydroxyl H and surface O facilitates electron transfer from the pili or the bacterial matrix to the anode surface, which improves the output power density. Thus, in combination with conductive polymers, the anatase TiO2(101) surface can be an effective biocompatible substrate in benthic MFCs by enabling the surface O to form more hydrogen bonds with the hydroxyl H of the biomolecule.

Serum CIAPIN1 is lower in septic patients with cardiac dysfunction.

The study aimed to investigate the clinical significance of serum cytokine-induced apoptosis inhibitor 1 (CIAPIN1) and its potential impact on cardiac dysfunction and inflammatory response induced by sepsis. A cross-sectional study was conducted in an intensive care unit (ICU) involving 80 healthy individuals and 95 severe sepsis patients. The data were analyzed to establish the correlation between CIAPIN1 levels and the onset of cardiac dysfunction in patients with sepsis. The associations have been established by the Pearson correlation test, one-way ANOVA, Bonferroni post hoc test, and plotting the receiver operating characteristic (ROC). H9c2 cells were treated with LPS (1 µg/mL) for 24 h to establish an in vitro model of septic cardiomyopathy. Meanwhile, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) were detected by enzyme-linked immunosorbent assay (ELISA). Serum CIAPIN1 levels were considerably lower in sepsis patients with cardiac dysfunction. CIAPIN1 expression levels were negatively correlated with TNF-α (r = -0.476, P<0.001), IL-1ß (r = -0.584, P<0.001), IL-6 (r = -0.618, P<0.001), creatine kinase- MB (CK-MB) (r = -0.454, P<0.001), and high-sensitive cardiac troponin T (hs-cTnT) (r = -0.586, P<0.001). The ROC curve showed that CIAPIN1 significantly identify sepsis patients from healthy individuals. CIAPIN1 knockdown decreases cardiomyocyte proliferation and increases apoptosis induced by LPS. In addition, CIAPIN1 knockdown reduced cardiac dysfunction and increased inflammatory response in H9c2 rat cardiomyocytes. CIAPIN1 could be a potential biomarker for detecting sepsis patients and suppressing CIAPIN1 expression in H9c2 rat cardiomyocytes, attenuating sepsis-induced cardiac dysfunction.

Evaluation of inhibition effect and interaction mechanism of antiviral drugs on main protease of novel coronavirus: Molecular docking and molecular dynamics studies.

The outbreak of pneumonia caused by the novel coronavirus (SARS-CoV-2) has presented a challenge to public health. The identification and development of effective antiviral drugs is essential. The main protease (3CLpro) plays an important role in the viral replication of SARS-CoV-2 and is considered to be an effective therapeutic target. In this study, according to the principle of drug repurposing, a variety of antiviral drugs commonly used were studied by molecular docking and molecular dynamics (MD) simulations to obtain potential inhibitors of main proteases. 24 antiviral drugs were docked with 5 potential action sites of 3CLpro, and the drugs with high binding strength were further simulated by MD and the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy calculations. The results showed that the drugs with high flexibility could bind to 3CLpro better than those with low flexibility. The interaction mechanism between antiviral drugs and main protease was analyzed in detail by calculating the root mean square displacement (RMSD), root mean square fluctuation (RMSF) and interaction residues properties. The results showed that the six drugs with high flexibility (Remdesivir, Simnotrelvir, Sofosbuvir, Ledipasvir, Indinavir and Raltegravir) had strong binding strength with 3CLpro, and the last four antiviral drugs can be used as potential candidates for main protease inhibitors.

Nanocarriers Loaded with Danshensu for Treating Ischemic Stroke by Reducing Oxidative Stress and Glial Overactivation.

Ischemic stroke is a complex health condition that can cause ischemia and necrosis of brain tissue. Subsequently, the excessive activation of glial cells can result in various inflammatory and oxidative stress reactions that exacerbate ischemic brain injury. In this paper, we propose the targeted self-assembly of a three-dimensional nanoparticle network containing Danshensu to rescue ischemic penumbra by reducing oxidative stress and glial overactivation. The network comprises nanoparticles composed of chitosan, thiol ketone, and carboxymethyl-ß-cyclodextrin as the core wrapped by the Pro-His-Ser-Arg-Asn (PHSRN) peptide sequence as the outer layer and loaded with Danshensu. The PHSRN-peptide-modified nanoparticles bind to integrin α5ß1 overexpressed on the damaged blood-brain barrier and accumulate in the damaged brain in a rat model of ischemia/reperfusion. When stimulated by reactive oxygen species, thiol ketone bonded to the nanoparticles was hydrolyzed, facilitating responsive drug release while consuming the reactive oxygen species. Subsequently, the released Danshensu scavenged the reactive oxygen species to prevent oxidative stress and inhibited the activation of astrocytes, thereby suppressing proinflammatory cytokine secretion, improving the inflammatory brain microenvironment and reducing neuronal apoptosis.

MR radiomics unveils neoadjuvant chemo-responsiveness with insights into selective treatment de-intensification in HPV-positive oropharyngeal carcinoma.

BACKGROUND: Accurate prediction of neoadjuvant chemotherapy (NAC) response allows for NAC-guided personalized treatment de-intensification in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). In this study, we aimed to apply baseline MR radiomic features to predict NAC response to help select NAC-guided de-intensification candidates, and to explore biological underpinnings of response-oriented radiomics. METHODS: Pre-treatment MR images and clinical data of 131 patients with HPV-positive OPSCC were retrieved from Fudan University Shanghai Cancer Center. Patients were divided into training cohort (n = 47), validation cohort 1 (n = 49) from NAC response-adapted de-intensification trial (IChoice-01, NCT04012502) and real-world validation cohort 2 (n = 35). NAC prediction model using linear support vector machine (SVM) was built and validated. Subsequent nomograms combined radiomics and clinical characteristics were established to predict survival outcomes. RNA-seq and proteomic data were compared to interpret the molecular features underlying radiomic signatures with differential NAC response. FINDINGS: For NAC response prediction, the fusion model with both oropharyngeal and nodal signatures achieved encouraging performance to predict good responders in the training cohort (AUC 0·89, 95% CI, 0·79-0·95) and validation cohort 1 (AUC 0·71, 95% CI, 0·59-0·83). For prognosis prediction, radiomics-based nomograms exhibited satisfactory discriminative ability between low-risk and high-risk patients (PFS, C-index 0·85, 0·76 and 0·83; OS, C-index 0·79, 0·76 and 0·87, respectively) in three cohorts. Expression analysis unveiled NAC poor responders had predominantly enhanced keratinization while good responders were featured by upregulated immune response and oxidative stress. INTERPRETATION: The MR-based radiomic models and prognostic models efficiently discriminate among patients with different NAC response and survival risk, which help candidate selection in HPV-positive OPSCC with regard to personalized treatment de-intensification.

One-pot tandem approach to spirocyclic oxindoles featuring adjacent spiro-stereocenters.

All in a sequence: An organocatalyzed Morita-Baylis-Hillman (MBH)/bromination/[3+2] annulation sequence for highly stereoselective syntheses of bis(spirooxindole)s featuring adjacent spiro-stereocenters is described. The key step is an unprecedented catalytic asymmetric [3+2] annulation of isatin-derived MBH adducts, containing a tetrasubstituted alkene moiety, with isatins.

Dynamic Analysis and Optimal Control of Fractional Order African Swine Fever Models with Media Coverage.

African swine fever is a highly contagious virus that causes pig disease. Its onset process is short, but the mortality rate is as high as 100%. There are still no effective drugs that have been developed to treat African swine fever, and prevention and control measures are currently the best means to avoid infection in pig herds. In this paper, two fractional order mathematical models with media coverage are constructed to describe the transmission of African swine fever. The first model is a basic model with media coverage, and no control measures are considered. For this model, the reproduction number is obtained by using the next generation matrix method. Then, the sufficient conditions for the existence and stability of two equilibriums are obtained. Based on the first model, the second model is established incorporating two control measures. By using Pontryagin's maximal principle, the optimal control solution is derived. After that, some numerical simulations are performed for the two models to verify the theoretical results. Both the qualitative analysis and numerical results indicate that timely media coverage combined with disinfection control measures is crucial to preventing the spread of disease.

Computational assessment of herbal medicine-derived compounds as potential inhibitors of SARS-CoV-2 main protease.

Since the main protease (Mpro) is crucial for the COVID-19 virus replication and transcription, searching for Mpro inhibitors is one possible treatment option. In our study, 258 small molecules were collected from lung-related herbal medicines, and their structures were optimized with the B3LYP-D3/6-31G* method. After the molecular docking with Mpro, we selected the top 20 compounds for the further geometry optimization with the larger basis sets. After the further molecular docking, the top eight compounds were screened out. Then we performed molecular dynamics simulations and binding free energy calculations to determine stability of the complexes. Our results show that mulberrofuran G, Xambioona, and kuwanon D can bind Mpro well. In quantum chemistry studies, such as ESP and CDFT analyses, the compounds properties are predicted. Additionally, the drug-likeness analyses and ADME studies on these three candidate compounds verified that all of them conform to Libinski's rule and may be drug-like compounds.

Case report: Enhancing prognosis in severe COVID-19 through human herpes virus coinfection treatment strategies.

Background: In the context of increasing reports of co-infection with coronavirus disease 2019 (COVID-19), particularly with human herpes viruses (HHVs), it is important to consider the appropriate treatment options for HHVs that have been reactivated by COVID-19. Case presentation: This study presents two cases of severe COVID-19 with HHV co-infection. The first case involved a critically ill patient with COVID-19 co-infected with herpes simplex virus type 1, confirmed using metagenomic next-generation sequencing, and another patient with severe COVID-19 experiencing Epstein-Barr virus (EBV) reactivation, as evidenced by elevated EBV-DNA levels in the serum. Treatment included high-dose glucocorticoids and sivelestat sodium, with notable improvements observed after initiating ganciclovir anti-herpesvirus therapy. Conclusion: This study underscores the significance of recognizing HHV co-infections in severe COVID-19 cases and highlights the potential of combining anti-HHV treatment, increased glucocorticoid dosages, and anti-cytokine storm therapy to enhance prognosis.

Study of folate-based carbon nanotube drug delivery systems targeted to folate receptor α by molecular dynamic simulations.

We designed targeted drug delivery systems containing folate (FOL), the functionalized carbon nanotube (f-CNT) and doxorubicin (DOX), and studied the targeting properties of folate, f-CNT-FOL and DOX/f-CNT-FOL to folate receptor α (FRα). Folate was actively targeted to FRα in molecular dynamics simulations, and the dynamic process, effect of folate receptor evolution, and characteristics were analyzed. On this basis, the f-CNT-FOL and DOX/f-CNT-FOL nano-drug-carrier systems were designed, and the drug delivery process targeted to FRα was studied by 4 times MD simulations. The system evolution and detailed interactions of f-CNT-FOL and DOX/f-CNT-FOL with FRα residues were examined. We found that though the connection of CNT with the FOL could decrease the insertion depth of the pterin of FOL into the pocket of FRα, the loading of drug molecules could reduce this effect. Representative snapshots from the MD simulations were analyzed, showing that the location of DOX on the surface of CNT was constantly changed during the MD simulation, but the surface of the four rings of DOX were almost always parallel to the surface of CNT. The RMSD and RMSF were used to further analyze. The results may provide new insights for the design of novel targeted nano-drug-delivery systems.