Structural insights into the substrate binding sites of O-carbamoyltransferase VtdB from Streptomyces sp. NO1W98.

The O-carbamoyltransferase VtdB catalyzes the carbamoylation of venturicidin B, which is essential for the biosynthesis of the antibiotic venturicidin A. Here, the crystal structures of VtdB and VtdB in complex with the intermediate carbamoyladenylate (VtdBCAO) were determined at resolutions of 2.99 Å and 2.90 Å, respectively. The structures resemble the conserved YrdC-like and specific Kae1-like domains. A magnesium ion and the intermediate carbamoyladenylate were also observed in the Kae1-like domain of VtdB. The structure of VtdBCAO in complex with the substrate venturicidin B was modeled by a molecular docking method to better understand the substrate binding mode, revealing a novel venturicidin B binding pocket.

JMJD6 protects against isoproterenol-induced cardiac hypertrophy via inhibition of NF-κB activation by demethylating R149 of the p65 subunit.

Histone modification plays an important role in pathological cardiac hypertrophy and heart failure. In this study we investigated the role of a histone arginine demethylase, Jumonji C domain-containing protein 6 (JMJD6) in pathological cardiac hypertrophy. Cardiac hypertrophy was induced in rats by subcutaneous injection of isoproterenol (ISO, 1.2 mg·kg-1·d-1) for a week. At the end of the experiment, the rats underwent echocardiography, followed by euthanasia and heart collection. We found that JMJD6 levels were compensatorily increased in ISO-induced hypertrophic cardiac tissues, but reduced in patients with heart failure with reduced ejection fraction (HFrEF). Furthermore, we demonstrated that JMJD6 overexpression significantly attenuated ISO-induced hypertrophy in neonatal rat cardiomyocytes (NRCMs) evidenced by the decreased cardiomyocyte surface area and hypertrophic genes expression. Cardiac-specific JMJD6 overexpression in rats protected the hearts against ISO-induced cardiac hypertrophy and fibrosis, and rescued cardiac function. Conversely, depletion of JMJD6 by single-guide RNA (sgRNA) exacerbated ISO-induced hypertrophic responses in NRCMs. We revealed that JMJD6 interacted with NF-κB p65 in cytoplasm and reduced nuclear levels of p65 under hypertrophic stimulation in vivo and in vitro. Mechanistically, JMJD6 bound to p65 and demethylated p65 at the R149 residue to inhibit the nuclear translocation of p65, thus inactivating NF-κB signaling and protecting against pathological cardiac hypertrophy. In addition, we found that JMJD6 demethylated histone H3R8, which might be a new histone substrate of JMJD6. These results suggest that JMJD6 may be a potential target for therapeutic interventions in cardiac hypertrophy and heart failure.

A case of congenital left ventricular diverticulum in an adult patient.

Congenital left ventricular diverticulum (CL.koVD) refers to a localized cystic protrusion of the ventricular wall that interacts with the heart cavities through a narrow channel and is a rare heart malformation. In recent years, many cases of this disease involving infants and children have been reported, while few cases involving adults have been described. The case of an adult with CLVD who underwent successful surgery was retrospectively evaluated. The echocardiography examination indicated that the apical myocardium of the left ventricle was thin and bulging outward and that the contractile movement was significantly reduced. During the surgery, it was observed that the left ventricle was enlarged, and a left ventricular diverticulum structure was observed on the left side of the apex. A bovine pericardial patch of the corresponding size was used to continuously suture and repair the internal orifice of the diverticulum. The postoperative pathology revealed that the resected sample was composed of full myocardial tissue. This report focused on the imaging characteristics of left ventricular diverticula to improve the understanding of CLVD. With its simple, economical, and noninvasive characteristics, echocardiography presents the best option for diagnosing a ventricular diverticulum.

Tanshinone IIA protects human coronary artery endothelial cells from ferroptosis by activating the NRF2 pathway.

The pathogenesis of atherosclerosis is closely related to endothelial cell injury caused by lipid peroxidation-induced ferroptosis. Tanshinone IIA (TSA) protects endothelial tissues from damage. In this study, we investigated whether TSA exerts its protective effect on endothelial cells by inhibiting ferroptosis. Ferroptosis was induced in human coronary artery endothelial cells (HCAECs), and cells were treated with TSA. Morphological examination indicated that TSA exerted a significant protective effect on the HCAECs. This was further confirmed by LDH release and cell death detection assays. Flow cytometry revealed that TSA significantly reduced the excessive accumulation of total cellular ROS and lipid ROS caused by ferroptosis inducers. TSA also restored the reduction of glutathione (GSH), a potent and abundant reductant in cells. In addition, we found that TSA promoted the expression of NRF2, an essential player in response to oxidative stress, and its downstream genes. Immunofluorescent staining revealed that TSA promoted the nuclear translocation of NRF2. Increased nuclear translocation of NRF2 was validated by Western blot evaluation of cytoplasmic and nuclear protein extracts. Furthermore, NRF2 inhibition abolished the protective effects of TSA on HCAECs. These data demonstrate that TSA represses ferroptosis via activation of NRF2 in HCAECs.

Amentoflavone prevents ox-LDL-induced lipid accumulation by suppressing the PPARγ/CD36 signal pathway.

The formation of fat-laden foam cells plays an important role in the initiation and progression of atherosclerosis (AS). Amentoflavone (AF) is found in various traditional Chinese medicines, such as ginkgo biloba, which are used to treat cardiovascular diseases (CVDs). We aimed to explore the potential effects and mechanisms of AF on lipid accumulation, and its possible application in atherosclerotic cardiovascular disease (ASCVD). Cellular models of lipid accumulation were established by treatment of HUASMCs and THP-1 cells with oxidized low-density lipoprotein (ox-LDL). Cell viability, lipid accumulation, and ox-LDL uptake were assessed. Small interfering RNAs (siRNAs) and overexpression plasmids were used to reveal the hierarchical correlations of regulatory pathways. AF reduced the lipid accumulation and ox-LDL uptake induced by ox-LDL, and reduced the expression levels of cluster of differentiation 36 (CD36) and peroxisome proliferator-activated receptor gamma (PPARγ) proteins, while the expression level of ATP binding cassette subfamily A member 1 (ABCA1) increased. Knockdown of PPARγ or CD36 with siRNAs prevented ox-LDL-induced lipid accumulation. Overexpression of CD36 or PPARγ promoted the lipid accumulation induced by ox-LDL and eliminated the effect of AF on ox-LDL-induced lipid accumulation. Overall, AF prevents ox-LDL-induced lipid accumulation by suppressing the PPARγ/CD36 signaling pathway.

Comparative Performance of Four Nucleic Acid Amplification Tests for SARS-CoV-2 Virus.

BACKGROUND: COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was discovered in 2019 and spread around the world in a short time. SARS-CoV-2 nucleic acid amplification tests (NAATs) have been rapidly developed and quickly applied to clinical testing of COVID-19. Aim of this study was to evaluate the performance of four NAAT assays. METHODS: Limit of detection (LOD), precision, accuracy, analytical specificity and analytical interference studies on four NAATs (Daan, Sansure, Hybribio, and Bioperfectus) were performed according to Clinical Laboratory Standards Institute protocols and guidelines. The four NAATs were compared using 46 clinical samples. RESULTS: The LOD of the N gene for Daan, Sansure, and Hybribio was 500 copies/mL, and that for Bioperfectus was 1,000 copies/mL. The LOD of the ORF1ab gene for Daan, Bioperfectus, and Hybribio was 3,000 copies/mL, and that for Sansure was 2,000 copies/mL. A good precision was shown at the concentration above 20% of the LOD for all four NAATs, with all individual coefficients of variation below 3.6%. Satisfactory results were also observed in the accuracy, analytical specificity, and analytical interference tests. The results of the comparison test showed that Daan, Sansure, and Hybribio NAATs could detect the samples with a specificity of 100% (30/30) and a sensitivity of 100% (16/16), whereas Bioperfectus NAAT detected the samples with a specificity of 100% (30/30) and a sensitivity of 81.25% (13/16). However, no significant difference in sensitivity was found between Bioperfectus NAAT and the three other NAATs (p > 0.05). CONCLUSIONS: The four SARS-CoV-2 NAATs showed comparable performance, with the LOD of the N gene lower than the LOD of the ORF1ab gene.

Establishing Classifiers With Clinical Laboratory Indicators to Distinguish COVID-19 From Community-Acquired Pneumonia: Retrospective Cohort Study.

BACKGROUND: The initial symptoms of patients with COVID-19 are very much like those of patients with community-acquired pneumonia (CAP); it is difficult to distinguish COVID-19 from CAP with clinical symptoms and imaging examination. OBJECTIVE: The objective of our study was to construct an effective model for the early identification of COVID-19 that would also distinguish it from CAP. METHODS: The clinical laboratory indicators (CLIs) of 61 COVID-19 patients and 60 CAP patients were analyzed retrospectively. Random combinations of various CLIs (ie, CLI combinations) were utilized to establish COVID-19 versus CAP classifiers with machine learning algorithms, including random forest classifier (RFC), logistic regression classifier, and gradient boosting classifier (GBC). The performance of the classifiers was assessed by calculating the area under the receiver operating characteristic curve (AUROC) and recall rate in COVID-19 prediction using the test data set. RESULTS: The classifiers that were constructed with three algorithms from 43 CLI combinations showed high performance (recall rate >0.9 and AUROC >0.85) in COVID-19 prediction for the test data set. Among the high-performance classifiers, several CLIs showed a high usage rate; these included procalcitonin (PCT), mean corpuscular hemoglobin concentration (MCHC), uric acid, albumin, albumin to globulin ratio (AGR), neutrophil count, red blood cell (RBC) count, monocyte count, basophil count, and white blood cell (WBC) count. They also had high feature importance except for basophil count. The feature combination (FC) of PCT, AGR, uric acid, WBC count, neutrophil count, basophil count, RBC count, and MCHC was the representative one among the nine FCs used to construct the classifiers with an AUROC equal to 1.0 when using the RFC or GBC algorithms. Replacing any CLI in these FCs would lead to a significant reduction in the performance of the classifiers that were built with them. CONCLUSIONS: The classifiers constructed with only a few specific CLIs could efficiently distinguish COVID-19 from CAP, which could help clinicians perform early isolation and centralized management of COVID-19 patients.

LncRNA IGFL2-AS1 functions as a ceRNA in regulating ARPP19 through competitive binding to miR-802 in gastric cancer.

Gastric cancer (GC) is one of the most common malignancies of the digestive system worldwide. Multiple long noncoding RNAs (lncRNAs) participate in the regulation of GC development and metastasis. In this study, we aimed to elucidate the expression and function of lncRNA IGFL2-AS1 in GC. We found that IGFL2-AS1 was highly expressed in GC tissues and cell lines. Knockdown of IGFL2-AS1 suppressed GC cell proliferation, migration, and invasion in vitro. Furthermore, we identified that IGFL2-AS1 exerted its function as a molecular sponge of miR-802. MiR-802 was demonstrated to be a tumor suppressor, and overexpression of miR-802 suppressed GC cell growth, migration, and invasion. Mechanistically, we revealed that the cAMP-regulated phosphoprotein 19 (ARPP19) was a direct target of miR-802 and could reverse the inhibitory function of miR-802. Moreover, our results confirmed that knockdown of IGFL2-AS1 inhibited GC tumor development in an in vivo GC tumor xenograft model. In summary, our data suggest that the IGFL2-AS1/miR-802/ARPP19 axis plays a critical role in the progression and metastasis of GC. Therapies targeting the IGFL2-AS1/miR-802/ARPP19 axis can potentially improve GC treatment.

Reference intervals for thyroid-stimulating hormone and thyroid hormones using the access TSH 3rd IS method in China.

BACKGROUND: To calculate the reference intervals for thyroid-stimulating hormone (TSH) and thyroid hormones using the Access TSH 3rd IS method and evaluate the differences between age and genders in Chinese populations. METHODS: This study collected 349 serum samples of healthy subjects were from Shengli Oilfield Central Hospital in China. Subjects who tested positive for thyroid peroxidase antibody or thyroglobulin antibody were excluded. Accordingly, 313 subjects were included for establishing reference intervals for the thyroid hormones. The serum concentrations of TSH, total and free thyroxine (TT4 and FT4), and total and free triiodothyronine (TT3 and FT3) were measured using the Access TSH 3rd IS method. The 2.5th and 97.5th percentiles or mean with standard deviation were calculated as the reference interval as appropriate. RESULTS: The reference intervals for TSH, FT4, FT3, TT4, and TT3 calculated in present study were 0.61-4.16 mIU/L, 0.67-1.11 ng/dL, 2.63-4.33 pg/mL, 5.56-11.33 µg/dL, and 0.72-1.32 ng/mL, respectively. The FT3, TT4, and TT3 levels in males were significantly higher than in females (P < .05), while TSH levels in males were significantly lower than in females (P < .05). The levels of FT3 in subjects with the age of less than 30 years were significantly higher than other groups (P < .05). CONCLUSION: The present study provided a valid basis for the reference intervals for TSH, FT4, FT3, TT4, and TT3 in Chinese populations. In addition, this present study indicated that age and gender should be considered in diagnostic evaluation of thyroid diseases.

Chronic restraint stress promotes hepatocellular carcinoma growth by mobilizing splenic myeloid cells through activating ß-adrenergic signaling.

Psychological stress promotes tumor progression and has a large impact on the immune system, particularly the spleen. The spleen plays an important role in tumor behavior. However, the role and mechanism of the spleen in hepatocellular carcinoma progression induced by stress is unclear. Here, we showed that the spleen plays a critical role in hepatocellular carcinoma growth induced by restraint stress. Our results demonstrated that restraint stress promoted hepatocellular carcinoma growth, changed the spleen structure, and redistributed splenic myeloid cells to tumor tissues. Interestingly, we found that splenectomy could inhibit hepatocellular carcinoma growth and prevent increases in myeloid cells and macrophages in tumor tissues in stressed mice. Restraint stress significantly elevated the concentration of norepinephrine in the spleen, serum and tumor tissues. Meanwhile, propranolol, an inhibitor of ß-adrenergic signaling, could inhibit hepatocellular carcinoma growth and prevent the redistribution of splenic myeloid cells induced by restraint stress, suggesting that restraint stress promotes hepatocellular carcinoma growth and redistributes splenic myeloid cells through ß-adrenergic signaling. Mechanistic studies revealed that restraint stress upregulated the expressions of CXCL2/CXCL3 in tumor tissues and changed the expression of CXCR2 in myeloid cells. SB225002, an inhibitor of CXCR2, could prevent the recruitment of myeloid cells in tumor tissues and inhibit tumor growth in stressed mice. Together, these data indicate that chronic restraint stress promotes hepatocellular carcinoma growth by mobilizing splenic myeloid cells to tumor tissues via activating ß-adrenergic signaling. The CXCR2-CXCL2/CXCL3 axis contributed to the recruitment of myeloid cells in tumor tissues induced by restraint stress.

[Discussion on safety evaluation and risk control measures of Epimedii Folium].

Epimedii Folium,a commonly used traditional Chinese medicine,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism. However,in recent years,the number of reports on adverse reactions of Epimedii Folium and its Chinese patent medicines such as Xianling Gubao Capsules and Zhuanggu Guanjie Pills has been gradually increased,and the toxicity of Epimedii Folium has attracted more and more attention. In this article,the ancient and modern literature on Epimedii Folium was traced through a comprehensive and systematic literature analysis method. According to the 2015 edition of the Chinese Pharmacopoeia,Epimedii Folium refers to the dried leaves of Epimedii Folium brevicomu,E. sugittutum,E. pubescens or E. koreuuum. The Chinese Pharmacopoeia also includes E. wushanense of Wushan Epimedium,which is the same plant variety as Epimedium. The study showed that there were differences in the geographical distribution,composition and toxicity among five species of Epimedium. This paper also explained the toxicity mechanism as well as efficacy enhancing and toxicity reducing effects of Epimedii Folium,and reported its related adverse reaction cases. Through a retrospective comparative study on the toxicity of the modern Chinese patent medicines Xianling Gubao Capsules and Zhuanggu Guanjie Pills containing Epimedii Folium,it was believed that Epimedii Folium had cardiovascular system toxicity,neurotoxicity,hepatotoxicity,long-term toxicity,acute toxicity,genotoxicity and special toxicity; its safe medication factors included patient syndrome,doctor factors,drug factors,processing and compatibility factors. Meanwhile,strategies were proposed to improve patient safety medication awareness,standardize Epimedii Folium varieties and quality supervision,and the toxicity of Epimedii Folium was studied,hoping to draw attention from scholars to the safety of Epimedii Folium,improve the safe use of Epimedii Folium,and prevent adverse reactions.

Repetitive restraint stress changes spleen immune cell subsets through glucocorticoid receptor or ß-adrenergic receptor in a stage dependent manner.

Immune system is sensitive to stress. Spleen is the largest peripheral immune organ innervated with sympathetic nerves and controlled by adrenomedullary system in the body. However, the alterations and mechanism of spleen immune cell subsets caused by repetitive restraint stress (RRS) is poorly understood. In this study, we found that RRS reduced spleen index in mice, and induced an expansion of white pulp and involution of the red pulp. Meanwhile, the percentage of CD3+CD8+ T lymphocytes, CD11b+F4/80+ macrophages, CD11b+Ly-6G-Ly-6Chi monocytic myeloid derived suppressor cells (mMDSCs) and CD11b+Ly-6G+Ly-6Cint granulocytic myeloid derived suppressor cells (gMDSCs) in spleen were significantly changed by RRS. Mechanistically, we found that the expression of norepinephrine (NE) and ß-adrenergic receptor (ß-AR) in spleen were up-regulated after 21 days of RRS, but not 7 days. The expression of corticosterone (CORT) and glucocorticoid receptor (GR) in spleen were up-regulated after 7 days of RRS but were lower after 21 days of RRS, even though they were still higher than that in mice without stress. By treating the stressed mice with RU486 (antagonist of GR) or propranolol (antagonist of ß-AR), we demonstrated that GR was responsible for the changes of spleen induced by 7 days of RRS and ß-AR was for 21 days of RRS. Our data suggest that RRS changes spleen immune cell subsets through GR or ß-AR in a stage dependent manner.

Azoalkyl ether imidazo[2,1-b]benzothiazoles as potentially antimicrobial agents with novel structural skeleton.

A series of new azoalkyl ether imidazo[2,1-b]benzothiazoles were developed via a convenient synthetic procedure. The antimicrobial assays showed that a good number of the prepared derivatives exhibited significant inhibitory properties against most of the tested strains. Especially 2-methyl-5-nitroimidazole derivative 5a presented superior inhibit activity against MRSA and B. typhi with MIC = 4 µg/mL and MIC = 1 µg/mL, respectively. The highly active compound 5a showed low toxicity against mammalian cells without obvious triggering of the development of bacterial resistance, and it also possessed rapid bactericidal efficacy. Molecular docking study exposed that the active molecule 5a could interact with the active site of S. aureus gyrase through hydrogen bond. Quantum chemical studies were also performed to explain the high antibacterial activity. Further investigation revealed that compound 5a could significantly associate with gyrase-DNA complex by mean of hydrogen bonds and could efficiently intercalate into MRSA DNA to form 5a-DNA supramolecular complex, which impart potent bioactivity.

A new carbon allotrope with orthorhombic symmetry formed via graphitic sheet buckling.

We identified by ab initio calculations a new simple orthorhombic carbon allotrope with Pmc21 (C2v2) symmetry that has a 32-atom unit cell in all-sp3 hybridized covalent bonds. This new carbon phase can be formed from graphite via a one-layer by three-layer slip and buckling mechanism along the [210] direction above 7.16 GPa and is more favorable than previously proposed cold-compressed graphite phases such as Z-carbon and M-carbon in terms of both kinetics and energetics. Its dynamic stability has been confirmed by phonon mode analysis. Electronic band structure calculations reveal that it has a large indirect band gap of 5.91 eV, wider than that of diamond, which is expected to be optically transparent. The calculated hardness of 95.1 GPa is comparable to 97.5 GPa for diamond. These results offer insights into understanding the complex structural landscape of compressed graphite.

Structural stability and electronic properties of alkaline-earth metal induced Si(111)-(3 × 2) surfaces.

Alkaline-earth metal (Ca, Sr, and Ba) induced Si(111)-(3 × 2) honeycomb chain-channel (HCC) surfaces have been systematically studied by means of ab initio calculations. The large adsorption energy and anisotropic diffusion energy barriers ensure the high structural stability of the one-dimensional HCC structure. Electronic band structures and band-decomposed charge density distributions reveal that the first conduction band and the third valence band level are contributed by the surface Si and metal atoms, while the top first and second valence bands are caused by the bulk silicon atoms. These results identify a larger surface band gap of 1.65-1.68 eV and provide an excellent explanation for the recent experimental observations of a band gap of 1.7 eV for the Sr/Si(111)-(3 × 2) HCC surface.

[Safety evaluation and risk control measures for Aconiti Kusnezoffii Radix].

Through the comprehensive and systematic research of domestic and overseas literature and information, we studied ancient original records on Aconiti Kusnezoffii Radix and its toxicity, analyzed related adverse cases and the animal toxicity experiments in recent years, then systematically analyzed the safety of Aconitum and its preparations, and finally we summarized the clinical characteristics and potential risk factors related to the safety of Aconitum. A report on adverse events of Aconitum in 76 patients with myocardial damage and renal damage accounting for 53.9% and 42.1% respectively, indicated that the safety problems of Aconitum may be related to heart toxicity and liver-kidney toxicity. Aconitum had complex compositions, and based on the animal experiments, Aconitum decoction had the highest toxicity at 2 h, and it reduced significantly at 4 h, which showed that the toxic components mainly depend on the hydrolysis or the decomposition degree of diester diterpenoid alkaloids. According to the toxicity study, Aconitum toxicity might occur in cardiovascular system, nervous system, kidney, embryo, reproductive system, and it was contraindicated in pregnant women. So far, specific antidote for aconitine poisoning is still a blank. The key for treatment is to correct arrhythmia timely and effectively, maintain stable vital signs, and meanwhile, give gastric lavage, intravenous fluid infusion and other therapies. So we suggest that the basic study for Aconitum toxicology should be strengthened, and the pharmacology and mechanism of toxicity, as well as the mechanism of processing for raising efficiency and reducing toxicity, should be further clarified to determine the quantity-effect relationship and eliminate safety hazards in using Aconitum.

Surface expression of anti-CD3scfv stimulates locoregional immunotherapy against hepatocellular carcinoma depending on the E1A-engineered human umbilical cord mesenchymal stem cells.

Tumor antigens is at the core of cancer immunotherapy, however, the ideal antigen selection is difficult especially in poorly immunogenic tumors. In this study, we designed a strategy to modify hepatocellular carcinoma (HCC) cells by surface expressing anti-CD3scfv within the tumor site strictly, which depended on the E1A-engineered human umbilical cord mesenchymal stem cells (HUMSC.E1A) delivery system. Subsequently, membrane-bound anti-CD3scfv actived the lymphocytes which lysed HCC cells bypassing the expression of antigens or MHC restriction. First, we constructed the anti-CD3scfv gene driven by human α-fetoprotein (AFP) promoter into an adenoviral vector and the E1A gene into the lentiviral vector. Our results showed that anti-CD3scfv could specifically express on the surface of HCC cells and activate the lymphocytes to kill target cells effectively in vitro. HUMSC infected by AdCD3scfv followed by LentiR.E1A could support the adenoviral replication and packaging in vitro 36 h after LentiR.E1A infection. Using a subcutaneous HepG2 xenograft model, we confirmed that AdCD3scfv and LentiR.E1A co-transfected HUMSC could migrate selectively to the tumor site and produce considerable adenoviruses. The new generated AdCD3scfv infected and modified tumor cells successfully. Mice injected with the MSC.E1A.AdCD3scfv and lymphocytes significantly inhibited the tumor growth compared with control groups. Furthermore, 5-fluorouracil (5-FU) could sensitize adenovirus infection at low MOI resulting in improved lymphocytes cytotoxicity in vitro and in vivo. In summary, this study provides a promising strategy for solid tumor immunotherapy.

Discovery of novel nitroimidazole enols as Pseudomonas aeruginosa DNA cleavage agents.

A series of nitroimidazole enols as new bacterial DNA-targeting agents were for the first time designed, synthesized and characterized by NMR, IR and HRMS spectra. The antimicrobial screening revealed that 2-methoxyphenyl nitroimidazole enol 3i possessed stronger anti-P. aeruginosa efficacy (MIC = 0.10 µmol/mL) than reference drugs Norfloxacin and Metronidazole. Time-kill kinetic assay manifested that the active molecule 3i could rapidly kill the tested strains. Molecular docking indicated that the interactions between compound 3i and topoisomerase II were driven by hydrogen bonds. Quantum chemical study was also performed on 3i to understand the structural features essential for activity. Further research found that compound 3i was not able to effectively intercalate into bacterial DNA but could cleave DNA isolated from the standard P. aeruginosa strain, which might block DNA replication to exert the efficient bioactivities, and this active molecule was also able to be stored and carried by human serum albumin via hydrophobic interactions and hydrogen bonds.

Computational prediction of a simple cubic carbon allotrope consisting of C12 clusters.

We identify by ab initio calculations a new simple cubic carbon phase in Pa3¯ symmetry, which has a 48-atom unit cell in all-sp3 bonding networks, thus termed SC48 carbon. It can be viewed as a crystalline form of C12 clusters or a combined structure of SC24 and BC12 carbon, but it is energetically more stable than the recently reported cubic carbon phases such as BC8, SC24, BC12, and fcc-C12. The structural stability is verified by phonon mode analysis. Electronic band and density of state calculations reveal that SC48 carbon is an insulator with a large direct band gap of 4.40 eV. Moreover, simulated x-ray diffraction patterns provide an excellent match to the distinct diffraction peaks found in milled fullerene soot. These results provide a solid foundation for further exploration of this new carbon allotrope.