[Discovery of cytochrome P450 enzymes-inhibiting components in traditional Chinese medicine].

With the widespread use of traditional Chinese medicine(TCM) and the integration of TCM and western medicine, drug-drug interaction(DDI) is considered as a major cause of therapeutic failures and side effects. Cytochrome P450 enzymes(CYPs) are responsible for large number of drug metabolism. CYP3 A4 and CYP2 D6, two important CYP isoforms, are responsible for about 80% drug metabolism of CYPs super family. The inhibition of CYPs is likely to be the most common factor leading to adverse DDI. Therefore, it is of great significance to predict potential CYP3 A4 and CYP2 D6 inhibitors to prevent the DDI. A fast and low-cost me-thod for calculating and predicting CYP inhibiting components was established in this paper, namely support vector machine(SVM) and molecular docking technology which are used to predict and screen drugs. Firstly, 12 qualitative models of two targets were established by using SVM, and the optimal model was selected to predict the compounds in traditional Chinese medicine database(TCMD). Then, molecular docking technology was used to establish docking model. By analyzing the key amino acids involved in drug-target interactions and combining with SVM model, potential inhibitors of CYP3 A4 and CYP2 D6 were found. From the computational results, astin D and epiberberine exhibited inhibition effect on CYP3 A4 and CYP2 D6, respectively. Astin D was only found in astins family from Aster tataricus, while epiberberine was considered to be the active constituent of Coptidis Rhizoma. Therefore, for the risk of DDI, extra attention should be paid to the source of these potential inhibitors, Asteris Radix et Rhizoma and Coptidis Rhizoma. This computational method provides technical support for discovering potential natural inhibitors of CYPs from Chinese herbs by using SVM and molecular docking model, and it is also helpful to recognize the CYPs-mediated DDI existing in TCM, providing research ideas for further pharmacovigilance of integrated therapy.

Remarkable Roles of Cu To Synergistically Optimize Phonon and Carrier Transport in n-Type PbTe-Cu2Te.

High thermoelectric performance of n-type PbTe is urgently needed to match its p-type counterpart. Here, we show a peak ZT ∼ 1.5 at 723 K and a record high average ZT > 1.0 at 300-873 K realized in n-type PbTe by synergistically suppressing lattice thermal conductivity and enhancing carrier mobility by introducing Cu2Te inclusions. Cu performs several outstanding roles: Cu atoms fill the Pb vacancies and improve carrier mobility, contributing to an unexpectedly high power factor of ∼37 µW cm-1 K-2 at 423 K; Cu atoms filling Pb vacancies and Cu interstitials both induce local disorder and, together with nano- and microscale Cu-rich precipitates and their related strain fields, lead to a very low lattice thermal conductivity of ∼0.38 Wm-1 K-1 in PbTe-5.5%Cu2Te, approaching the theoretical minimum value of ∼0.36 Wm-1 K-1. This work provides an effective strategy to enhance thermoelectric performance by simultaneously improving electrical and thermal transport properties.

Multiple Converged Conduction Bands in K2Bi8Se13: A Promising Thermoelectric Material with Extremely Low Thermal Conductivity.

We report that K2Bi8Se13 exhibits multiple conduction bands that lie close in energy and can be activated through doping, leading to a highly enhanced Seebeck coefficient and a high power factor with elevated temperature. Meanwhile, the large unit cell, complex low symmetry crystal structure, and nondirectional bonding lead to the very low lattice thermal conductivity of K2Bi8Se13, ranging between 0.42 and 0.20 W m-1 K-1 in the temperature interval 300-873 K. Experimentally, we further support the low thermal conductivity of K2Bi8Se13 using phonon velocity measurements; the results show a low average phonon velocity (1605 ms-1), small Young's modulus (37.1 GPa), large Grüneisen parameter (1.71), and low Debye temperature (154 K). A detailed investigation of the microstructure and defects was carried out using electron diffraction and transmission microscopy which reveal the presence of a K2.5Bi8.5Se14 minor phase intergrown along the side of the K2Bi8Se13 phase. The combination of enhanced power factor and low thermal conductivity results in a high ZT value of ∼1.3 at 873 K in electron doped K2Bi8Se13 material.

Enhanced Thermoelectric Properties in the Counter-Doped SnTe System with Strained Endotaxial SrTe.

We report enhanced thermoelectric performance in SnTe, where significantly improved electrical transport properties and reduced thermal conductivity were achieved simultaneously. The former was obtained from a larger hole Seebeck coefficient through Fermi level tuning by optimizing the carrier concentration with Ga, In, Bi, and Sb dopants, resulting in a power factor of 21 µW cm(-1) K(-2) and ZT of 0.9 at 823 K in Sn(0.97)Bi(0.03)Te. To reduce the lattice thermal conductivity without deteriorating the hole carrier mobility in Sn(0.97)Bi(0.03)Te, SrTe was chosen as the second phase to create strained endotaxial nanostructures as phonon scattering centers. As a result, the lattice thermal conductivity decreases strongly from ∼2.0 Wm(-1) K(-1) for Sn(0.97)Bi(0.03)Te to ∼1.2 Wm(-1) K(-1) as the SrTe content is increased from 0 to 5.0% at room temperature and from ∼1.1 to ∼0.70 Wm(-1) K(-1) at 823 K. For the Sn(0.97)Bi(0.03)Te-3% SrTe sample, this leads to a ZT of 1.2 at 823 K and a high average ZT (for SnTe) of 0.7 in the temperature range of 300-823 K, suggesting that SnTe is a robust candidate for medium-temperature thermoelectric applications.

[NIR Assignment of Magnolol by 2D-COS Technology and Model Application Huoxiangzhengqi Oral Liduid].

Near infrared (NIR) spectroscopy assignment of Magnolol was performed using deuterated chloroform solvent and two-dimensional correlation spectroscopy (2D-COS) technology. According to the synchronous spectra of deuterated chloroform solvent and Magnolol, 1365~1455, 1600~1720, 2000~2181 and 2275~2465 nm were the characteristic absorption of Magnolol. Connected with the structure of Magnolol, 1440 nm was the stretching vibration of phenolic group O-H, 1679 nm was the stretching vibration of aryl and methyl which connected with aryl, 2117, 2304, 2339 and 2370 nm were the combination of the stretching vibration, bending vibration and deformation vibration for aryl C-H, 2445 nm were the bending vibration of methyl which linked with aryl group, these bands attribut to the characteristics of Magnolol. Huoxiangzhengqi Oral Liduid was adopted to study the Magnolol, the characteristic band by spectral assignment and the band by interval Partial Least Squares (iPLS) and Synergy interval Partial Least Squares (SiPLS) were used to establish Partial Least Squares (PLS) quantitative model, the coefficient of determination Rcal(2) and Rpre(2) were greater than 0.99, the Root Mean of Square Error of Calibration (RM-SEC), Root Mean of Square Error of Cross Validation (RMSECV) and Root Mean of Square Error of Prediction (RMSEP) were very small. It indicated that the characteristic band by spectral assignment has the same results with the Chemometrics in PLS model. It provided a reference for NIR spectral assignment of chemical compositions in Chinese Materia Medica, and the band filters of NIR were interpreted.

High thermoelectric performance realized in a BiCuSeO system by improving carrier mobility through 3D modulation doping.

We report a greatly enhanced thermoelectric performance in a BiCuSeO system, realized by improving carrier mobility through modulation doping. The heterostructures of the modulation doped sample make charge carriers transport preferentially in the low carrier concentration area, which increases carrier mobility by a factor of 2 while maintaining the carrier concentration similar to that in the uniformly doped sample. The improved electrical conductivity and retained Seebeck coefficient synergistically lead to a broad, high power factor ranging from 5 to 10 µW cm(-1) K(-2). Coupling the extraordinarily high power factor with the extremely low thermal conductivity of ∼0.25 W m(-1) K(-1) at 923 K, a high ZT ≈ 1.4 is achieved in a BiCuSeO system.

[Rapid assessment of critical quality attributes of Chinese materia medica (II): strategy of NIR assignment].

The present paper firstly reviewed the research progress and main methods of NIR spectral assignment coupled with our research results. Principal component analysis was focused on characteristic signal extraction to reflect spectral differences. Partial least squares method was concerned with variable selection to discover characteristic absorption band. Two-dimensional correlation spectroscopy was mainly adopted for spectral assignment. Autocorrelation peaks were obtained from spectral changes, which were disturbed by external factors, such as concentration, temperature and pressure. Density functional theory was used to calculate energy from substance structure to establish the relationship between molecular energy and spectra change. Based on the above reviewed method, taking a NIR spectral assignment of chlorogenic acid as example, a reliable spectral assignment for critical quality attributes of Chinese materia medica (CMM) was established using deuterium technology and spectral variable selection. The result demonstrated the assignment consistency according to spectral features of different concentrations of chlorogenic acid and variable selection region of online NIR model in extract process. Although spectral assignment was initial using an active pharmaceutical ingredient, it is meaningful to look forward to the futurity of the complex components in CMM. Therefore, it provided methodology for NIR spectral assignment of critical quality attributes in CMM.

Rapid identification and determination of adulteration in medicinal Arnebiae Radix by combining near infrared spectroscopy with chemometrics.

The medicinal Arnebia Radix (AR) is one of widely-used Chinese herbal medicines (CHMs), usually adulterated with non-medicinal species that seriously compromise the quality of AR and affect patients' health. Detection of these adulterants is usually performed by using expensive and time-consuming analytical instruments. In this study, a rapid, non-destructive, and effective method was proposed to identify and determine the adulteration in the medicinal AR by near-infrared (NIR) spectroscopy coupled with chemometrics. 37 batches of medicinal AR samples originated from Arnebia euchroma (Royle) Johnst., 11 batches of non-medicinal AR samples including Onosma paniculatum Bur. et Franch and Arnebia benthamii (Wall. ex G. Don) Johnston, and 72 batches of adulterated AR samples were characterized by NIR spectroscopy. The data driven-soft independent modeling by class analogy (DD-SIMCA) and partial least squares-discriminant analysis (PLS-DA) were separately used to differentiate the authentic from adulterated AR samples. Then the PLS and support vector machine (SVM) were applied to predict the concentration of the adulteration in the adulterated AR samples, respectively. As a result, the classification accuracies of DD-SIMCA and PLS-DA models were 100% for the calibration set, and 96.7% vs. 100% for the prediction set. Moreover, the relative prediction deviation (RPD) values of PLS models reached 11.38 and 7.75 for quantifying two adulterants species, which were obviously superior to the SVM models. It can be concluded that the NIR spectroscopy coupled with chemometrics is feasible to identify the authentic from adulterated AR samples and quantify the adulteration in adulterated AR samples.

Synthesis and characterization of one-dimensional bifunctional carbon nanotubes/Fe3O4@SiO2 (FITC) nanohybrids.

A new type of one-dimensional bifunctional CNTs/Fe3O4 @ SiO2 (FITC) nanohybrids with both magnetic and fluorescent properties were fabricated by a polyol method combined with stöber method. The CNTs/Fe3O4 @ SiO2 (FITC) nanohybrids exhibit strong and stable photoluminescence emission at about 520 nm, display superparamagenetic behavior with high saturation magnetization and possess MRI function at room temperature. All these properties make the CNTs/Fe3O4 @ SiO2 (FITC) nanohybrids a potential candidate for biomedical agent such as MRI contrast agent, cells labelling, in-vivo image and drug deliver for cancer diagnosis and treatment.

[Multivariate detection limits of baicalin in qingkailing injection based on four NIR spectrometer types].

Multivariate detection limits (MDLs) of different types of near-infrared instruments were investigated to guide the selection of device type for TCM NIR analysis. In this paper, near-infrared spectroscopy of Qingkailing injection was performed in transmission mode on four near-infrared spectrometers named a, b, c and d, respectively. High performance liquid chromatography (HPLC) was used as the reference method to determine the content of baicalin in Qingkailing injection. Partial least squares (PLS) and interval partial least squares (iPLS) quantitative models of baicalin in Qingkailing injection were established and MDLs of quantitative models based on different types of instruments were calculated. The determination coefficient of prediction (R2(pre))and the root mean square errors of prediction (SEP) of PLS models of four different near-infrared spectrometers are 0.9762 and 230.4 microg x mL(-1) (a), 0.9561 and 246.4 microg x mL(-1) (b), 0.9662 and 264.4 microg x mL*-1) (c), 0.9985 and 71.5 microg x mL(-1) (d). And the model of instrument d shows a better prediction performance than the other three types. There are no remarkable superiorities in predictability in iPLS models of instruments a and b after variable selection, since the R2(pre) and SEP values for instruments a and b are 0.9771 and 218.4 microg x mL(-1), and 0.9754 and 219.4 microg x mL(-1), respectively. Models c and d show no results of variable selection. MDLs (delta(0.05, 0.05) of different instruments are all less than 250 microg x mL(-1), and the MDLs of instruments c and d reach to 58 and 2.9 microg x mL(-1) respectively. The results reveal that the predictability of models and corresponding MDLs are different for different detection equipments. This paper innovatively used the theory of MDL to investigate the detection performance of different types of NIR instruments. The results demonstrated the feasibility of the approach. And it is expected that in actual applications, choosing the right type of instrument should be based on the characteristics of the study carrier to ensure quantitative accuracy.

Identifying absorbable bioactive constituents of Yupingfeng Powder acting on COVID-19 through integration of UPLC-Q/TOF-MS and network pharmacology analysis.

Objective: Yupingfeng Powder (YPF), a kind of preventative patent medicine, is chosen for treatment of coronavirus disease 2019 (COVID-19) due to its high frequency application in respiratory tract diseases, such as chronic obstructive pulmonary disease, asthma, respiratory tract infections, and pneumonia, with the advantage of reducing the relapse rate and the severity. However, the active components of YPF and the mechanisms of components affecting COVID-19 are unclear. This study aimed to determine active constituents and elucidate its potential mechanisms. Methods: Ultra performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q/TOF-MS) and liquid chromatography-triple quadrupole mass spectrometry (LC-QQQ-MS) were used to determine the components and absorbable constituents of YPF. Secondly, TCMSP, Drugbank, Swiss and PharmMapper were used to search the targets of absorbable bioactive constituents of YPF, and the targets of COVID-19 were identified based on GeneCards and OMIM databases. STRING database was used to filter the possible inter-protein interactions. Thirdly, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were performed to identify molecular function and systemic involvement of target genes. Results: A total of 61 components of YPF and 36 absorbable constituents were identified through UPLC-Q/TOF-MS. Wogonin, prim-O-glucosylcimifugin, 5-O-methylvisamminol, astragaloside IV and 5-O-methylvisamminol (hydroxylation) were vital constituents for the treatment of COVID-19, and RELA, TNF, IL-6, MAPK14 and MAPK8ere recognized as key targets of YPF. The major metabolic reactions of the absorbed constituents of YPF were demethylation, hydroxylation, sulfation and glucuronidation. GO and KEGG pathway analysis further showed that the most important functions of YPF were T cell activation, response to molecule of bacterial origin, cytokine receptor binding, receptor ligand activity, cytokine activity, IL-17 signaling pathway, Chagas disease, lipid and atherosclerosis, etc. Conclusion: The approach of combining UPLC-Q/TOF-MS with network pharmacology is an effective tool to identify potentially bioactive constituents of YPF and its key targets on treatment of COVID-19.

Effects of Different Surface Native Pre-Oxides on the Hot Corrosion Properties of Nickel-Based Single Crystal Superalloys.

A study is carried out on the effect of different surface native pre-oxides on hot corrosion of single crystal nickel-based superalloy at 900 °C. The effect of different oxides formed by different superalloys through pre-oxidation on hot corrosion is verified by normal hot corrosion and tube sealing experiments. The relationship between different surface oxides and the effect of different surface oxides layer on the hot corrosion properties of alloys are studied. In summary, the stable and dense surface pre-Al2O3 layer which can be obtained by pre-oxidation has an obvious positive effect on the improvement of superalloy hot corrosion resistance in reaction. In addition, the internal sulfides are analyzed in depth, and the relationship between Cr, Mo, O and S is discussed in detail.

Systematic discovery about NIR spectral assignment from chemical structural property to natural chemical compounds.

Spectra-structure interrelationship is still the weakness of NIR spectral assignment. In this paper, a comprehensive investigation from chemical structural property to natural chemical compounds was carried out for NIR spectral assignment. Surprisingly, we discovered that NIR absorption frequency of the skeleton structure with sp2 hybridization is higher than one with sp3 hybridization. Specifically, substituent was another vital factor to be explored, the first theory discovery demonstrated that the absorption intensity of methyl substituted benzene at 2330 nm has a linear relationship with the number of substituted methyl C-H. The greater the number of electrons given to the substituents, the larger the displacement distance of absorption bands is. In addition, the steric hindrance caused by the substituent could regularly reduce the intensity of NIR absorption bands. Furthermore, the characteristic bands and group attribution of 29 natural chemical compounds from 4 types have been systematic assigned. These meaningful discoveries provide guidance for NIR spectral assignment from chemical structural property to natural chemical compounds.

3D charge and 2D phonon transports leading to high out-of-plane ZT in n-type SnSe crystals.

Thermoelectric technology enables the harvest of waste heat and its direct conversion into electricity. The conversion efficiency is determined by the materials figure of merit ZT Here we show a maximum ZT of ~2.8 ± 0.5 at 773 kelvin in n-type tin selenide (SnSe) crystals out of plane. The thermal conductivity in layered SnSe crystals is the lowest in the out-of-plane direction [two-dimensional (2D) phonon transport]. We doped SnSe with bromine to make n-type SnSe crystals with the overlapping interlayer charge density (3D charge transport). A continuous phase transition increases the symmetry and diverges two converged conduction bands. These two factors improve carrier mobility, while preserving a large Seebeck coefficient. Our findings can be applied in 2D layered materials and provide a new strategy to enhance out-of-plane electrical transport properties without degrading thermal properties.

Active lower limb orthosis with one degree of freedom for people with paraplegia.

The main challenges of designing devices for paraplegic walking can be summarized into three groups, stability and comfort, high efficiency or low energy consumption, dimensions and weight. A new economical device for people with paraplegia which tackles all problems of the three groups is introduced in this paper. The main idea of this device is based on HALO mechanism. HALO is compact passive medial hip joint orthosis with contralateral hip and ankle linkage, which keeps the feet always parallel to the ground and assists swinging the leg. The medial hip joint is equipped with one actuator in the new design and the new orthosis is called @halo. Due to this update, we can achieve more stable and smoother walking patterns with decreased energy consumption of the users, yet maintain its compact and lightweight features. It is proven by the results from preliminary experiments with able-bodied subjects during which the same device with and without actuator was evaluated. Waddling and excessive vertical elevation of the center of gravity were decreased by 40% with significantly smaller standard deviations in case of the active orthosis. There was 52% less energy spent by the user wearing @halo which was calculated from the vertical excursion difference. There was measured 38.5% bigger impulse in crutches while using passive orthosis. The new @halo device is the first active orthosis for lower limbs with just one actuated degree of freedom for users with paraplegia.

Dislocation network with pair-coupling structure in {111} γ/γ' interface of Ni-based single crystal superalloy.

The γ/γ' interface dislocation network is reported to improve the high temperature creep resistance of single crystal superalloys and is usually found to deposit in {001} interface. In this work, a new type of dislocation network was found in {111} γ/γ' interface at a single crystal model superalloy crept at 1100 °C/100 MPa. The dislocations in the network are screw with Burgers vectors of 1/2 a<110> and most interestingly, they exhibit a pair-coupling structure. Further investigation indicates that the formation of {111} interface dislocation network occurs when the γ' raft structure begins to degrade by the dislocations cutting into the rafted γ' through the interface. In this condition, the pair-coupling structure is established by the dislocations gliding in a single {111} plane of γ', in order to remove the anti-phase boundary in γ'; these dislocations also act as diffusion channels for dissolving of the γ' particle that is unstable under the interfacial stress from lattice misfit, which leads to the formation of {111}-type zigzag interface. The formation of this network arises as a consequence of more negative misfit, low-alloying γ' particle and proper test conditions of temperature and stress.

Misdiagnosis Analysis of Cervical Minimal Deviation Adenocarcinoma: a Report of Three Rare Cases and Literature Review.

Cervical minimal deviation adenocarcinoma (MDA) is a rare variant of cervical adenocarcinoma that is difficult to diagnose due to the deep location, endogenous growth pattern, deceptively benign appearance of tumor cells, and lack of connection to human papillomavirus (HPV). Cytological evaluation and biopsies offer suboptimal detection and transvaginal sonography or Magnetic Resonance Imaging (MRI) only reveal multiple lesions that mimic multiple benign nabothian cysts. Besides, standard screening, diagnostic tools, and treatments are not established. Thus, MDA tends to be misdiagnosed with other gynecological diseases. In this study, we examine three cases with extensive abdominal metastasis and adhesions, which are not initially associated clinically with HPV and cervical malignancies. All cases were misdiagnosed as nabothian cysts, endometrial adenocarcinoma or ovarian cancer, though finally diagnosed as MDA by postoperative pathology. Delay in diagnosis and treatment can result in irreversible outcomes. Misdiagnoses are analyzed and suggestions for improving early detection are discussed with a brief review of the literature.

Ultrahigh power factor and thermoelectric performance in hole-doped single-crystal SnSe.

Thermoelectric technology, harvesting electric power directly from heat, is a promising environmentally friendly means of energy savings and power generation. The thermoelectric efficiency is determined by the device dimensionless figure of merit ZT(dev), and optimizing this efficiency requires maximizing ZT values over a broad temperature range. Here, we report a record high ZT(dev) ∼1.34, with ZT ranging from 0.7 to 2.0 at 300 to 773 kelvin, realized in hole-doped tin selenide (SnSe) crystals. The exceptional performance arises from the ultrahigh power factor, which comes from a high electrical conductivity and a strongly enhanced Seebeck coefficient enabled by the contribution of multiple electronic valence bands present in SnSe. SnSe is a robust thermoelectric candidate for energy conversion applications in the low and moderate temperature range.

Enhanced thermoelectric performance of a BiCuSeO system via band gap tuning.

Upon 20% Te substitution, the band gap decreases from 0.8 eV to 0.65 eV. Rising temperature promotes minority carrier jumps across the band gap, thereby improving electrical conductivity. With low thermal conductivity and large Seebeck coefficients, a remarkable ZT of 0.71 at 873 K is achieved for BiCuSe0.94Te0.06O.

Adding vancomycin to bone cement: research on its influence on mechanical and fixation strength using rabbit femoral prostheses.

OBJECTIVE: To compare the influence of different methods of adding vancomycin on the strength of bone cement used for fixing rabbits' femoral prostheses. METHODS: Eighteen New Zealand white rabbits (36 femora) were allocated to three groups of six rabbits (12 femora) each: a control group, an experimental group 1 and experimental group 2. The bone cement used in the control group was mixed manually without vancomycin; in experimental group 1 it was mixed manually with 5% (2 g/40 g) vancomycin; and in experimental group 2 it was mixed in a vacuum with 5% (2 g/40 g) vancomycin. The cement combinations were then used to fill the marrow cavity of rabbit femurs to fix prostheses. An electronic universal testing machine (EUTM) was used to test the pullout force of the prostheses with bone cement 48 hours later. Student's paired t-test was used for statistical analysis. RESULTS: It was found that the maximum load of pullout force was 559.3 ± 82.3 N in the control group; 523.6 ± 86.5 N in experimental group 1; and 645.1 ± 105.9 N in experimental group 2. Statistical analysis showed there was no significant difference between the control group and experimental group 1 (P > 0.05). However, there were significant differences between the control group and experimental group 2 (P < 0.05); and between experimental group 1 and experimental group 2 (P < 0.05). CONCLUSION: When bone cement and vancomycin were mixed manually in a low concentration (<5%) vancomycin had no influence on the strength of the bone cement. However, bone cement and vancomycin mixed at the same concentrations in a vacuum did have a statistically significant effect on the strength of the bone cement.