Thiotepa-busulfan-fludarabine-based conditioning as a promising approach prior to allogeneic hematopoietic stem cell transplantation in patients with blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive myeloid malignancy associated with a poor prognosis. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) has emerged as a potential treatment strategy for BPDCN, standardized conditioning regimens remain lacking. In this manuscript, we present two cases of BPDCN that were treated with a thiotepa-busulfan-fludarabine (TBF)-based conditioning regimen prior to allo-HSCT. Both cases demonstrated complete remission post-transplantation, sustained donor chimerism, and remission maintenance, suggesting the potential efficacy of the TBF conditioning regimen for BPDCN transplantation. Given the small sample size in our study, we emphasize caution and advocate for larger studies to confirm the efficacy of TBF in the treatment of BPDCN.

Structure-Based Rational and General Strategy for Stabilizing Single-Chain T-Cell Receptors to Enhance Affinity.

The T-cell receptor (TCR) is a crucial molecule in cellular immunity. The single-chain T-cell receptor (scTCR) is a potential format in TCR therapeutics because it eliminates the possibility of αß-TCR mispairing. However, its poor stability and solubility impede the in vitro study and manufacturing of therapeutic applications. In this study, some conserved structural motifs are identified in variable domains regardless of germlines and species. Theoretical analysis helps to identify those unfavored factors and leads to a general strategy for stabilizing scTCRs by substituting residues at exact IMGT positions with beneficial propensities on the consensus sequence of germlines. Several representative scTCRs are displayed to achieve stability optimization and retain comparable binding affinities with the corresponding αß-TCRs in the range of µM to pM. These results demonstrate that our strategies for scTCR engineering are capable of providing the affinity-enhanced and specificity-retained format, which are of great value in facilitating the development of TCR-related therapeutics.

An effective cross-scenario remote heart rate estimation network based on global-local information and video transformer.

Remote photoplethysmography (rPPG) technology is a non-contact physiological signal measurement method, characterized by non-invasiveness and ease of use. It has broad application potential in medical health, human factors engineering, and other fields. However, current rPPG technology is highly susceptible to variations in lighting conditions, head pose changes, and partial occlusions, posing significant challenges for its widespread application. In order to improve the accuracy of remote heart rate estimation and enhance model generalization, we propose PulseFormer, a dual-path network based on transformer. By integrating local and global information and utilizing fast and slow paths, PulseFormer effectively captures the temporal variations of key regions and spatial variations of the global area, facilitating the extraction of rPPG feature information while mitigating the impact of background noise variations. Heart rate estimation results on the popular rPPG dataset show that PulseFormer achieves state-of-the-art performance on public datasets. Additionally, we establish a dataset containing facial expressions and synchronized physiological signals in driving scenarios and test the pre-trained model from the public dataset on this collected dataset. The results indicate that PulseFormer exhibits strong generalization capabilities across different data distributions in cross-scenario settings. Therefore, this model is applicable for heart rate estimation of individuals in various scenarios.

Effective management of a rare case of primary renal intravascular large B-cell lymphoma with modified R-CHOP regimen: A case report.

Intravascular large B-cell lymphoma, known for its diverse organ involvement, presents significant diagnostic challenges, particularly when it affects the kidneys. This report highlights a rare case of primary renal intravascular large B-cell lymphoma in a 60-year-old male patient, who presented with persistent fever and renal dysfunction. The case underscores the intricacy of diagnosis and the efficacy of personalized treatment. Following the identification of primary renal intravascular large B-cell lymphoma, a modified R-CHOP regimen was administered, resulting in notable amelioration of symptoms and renal function following the initial treatment cycle. The patient achieved sustained complete remission without any complications after completing five subsequent R-CHOP cycles and two additional cycles of rituximab monotherapy, as confirmed by recent assessments. He is currently under regular follow-up for ongoing monitoring and improvement. This case adds to the limited yet expanding pool of knowledge concerning intravascular large B-cell lymphoma, emphasizing the necessity for personalized therapeutic strategies in atypical presentations. It also highlights the importance of early detection and customized intervention in managing rare lymphoma subtypes with unique organ involvement.

Impact of Fulvic Acid and Acidithiobacillus ferrooxidan Inoculum Amount on the Formation of Secondary Iron Minerals.

The catalytic oxidation of Fe2+ by Acidithiobacillus ferrooxidan (A. ferrooxidans) and the synthesis of iron sulfate-based secondary minerals is considered to be of great significance to the treatment of acid mine drainage (AMD). Along these lines, in this work, the shaker experiment was carried out to study the underlying mechanism of the inoculation amount of fulvic acid (FA) and A. ferrooxidans on the synthesis process of secondary minerals. From the acquired results, it was demonstrated that the oxidation rate of Fe2+ increased with the increase in the concentration of fulvic acid in the range of 0.1-0.2 g/L. On top of that, the concentration of fulvic acid in the range of 0.3-0.5 g/L inhibited the activity of A. ferrooxidans. However, A. ferrooxidans retained its activity, and the complete oxidation time of Fe2+ was delayed. When the concentration of fulvic acid was 0.3 g/L, the TFe (total iron) precipitation efficiency was 30.2%. Interestingly, when 0.2 g/L fulvic acid was added to different inoculum systems, the incorporation of a higher inoculum amount of A. ferrooxidans led to an increased oxidation rate. On the contrary, the lower inoculum amount yielded a more obvious effect of the fulvic acid. From the mineralogical characteristics, it was also revealed that a fulvic acid concentration of 0.2 g/L and different inoculation amounts of A. ferrooxidans did not change the mineral facies, whereas pure schwertmannite was obtained.

Developing explicit customer preference models using fuzzy regression with nonlinear structure.

In online sales platforms, product design attributes influence consumer preferences, and consumer preferences also have a significant impact on future product design optimization and iteration. Online review data are the most intuitive feedback from consumers on products. Using the value of online review information to explore consumer preferences is the key to optimize the products, improve consumer satisfaction and meet consumer requirements. Therefore, the study of consumer preferences based on online reviews is of great importance. However, in previous research on consumer preferences based on online reviews, few studies have modeled consumer preferences. The models often suffer from the nonlinear structure and the fuzzy coefficients, making it challenging to build explicit models. Therefore, this study adopts a fuzzy regression approach with a nonlinear structure to model consumer preferences based on online reviews to provide reference and insight for subsequent studies. First, smartwatches were selected as the research object, and the sentiment scores of product reviews under different topics were obtained by text mining on the product online data. Second, a polynomial structure between product attributes and consumer preferences was generated to investigate the association between them further. Afterward, based on the existing polynomial structure, the fuzzy coefficients of each item in the structure were determined by the fuzzy regression approach. Finally, the mean relative error and mean systematic confidence of the fuzzy regression with nonlinear structure method were numerically calculated and compared with fuzzy least squares regression, fuzzy regression, adaptive neuro fuzzy inference system (ANFIS) and K-means-based ANFIS, and it was found that the proposed method was relatively more effective in modeling consumer preferences.

Association between serum vitamin D and refractive status in United States adolescents: A cross-sectional study.

Purpose: We performed this study to determine the relationship between serum vitamin D levels and refractive status in adolescents aged 12-19 years. Methods: Cross-sectional study using the National Health and Nutrition Examination Survey (NHANES) database from 2001 to 2006. We used weighted multivariate linear regression models to assess the association between serum vitamin levels and adolescent refractive status and then built a smooth curve fitting to investigate their internal non-linear relationships. Finally, subgroup analysis was performed according to gender, and the threshold effect of serum vitamin D levels on spherical equivalent degree was analyzed using a two-piecewise linear regression model. Result: A total of 5,901 adolescents aged 12 to 19 years were included in this study. After adjusting for all confounding factors, the multiple linear regression model showed no significant correlation between adolescent spherical equivalent degree and serum vitamin D [0.0019 (-0.0018, 0.0046)]. However, smooth curve fitting analysis showed an inverted U-shaped curve relationship between spherical equivalent degree and serum vitamin D levels in adolescents (turning point: 58.1 nmol/L). In analyses by gender subgroup, this inverted U-shaped relationship was found to be more pronounced in female adolescents (turning point: 61.6 nmol/L). Conclusion: Our results suggest that the correlation between refractive status and serum vitamin D in adolescents differs by gender. When serum vitamin D concentrations were <61.6 nmol/L in female adolescents and <53.2 nmol/L in male adolescents, the spherical equivalent degree showed a positive correlation with serum vitamin D levels. However, there was no significant correlation when adolescent vitamin levels exceeded this threshold.

Autonomous driving testing scenario generation based on in-depth vehicle-to-powered two-wheeler crash data in China.

A reliable critical-scenario-based safety assessment of autonomous vehicles in China requires a thorough understanding of complex crash scenarios in Chinese background traffic. Based on actual crashes between a vehicle and a powered two-wheeler (PTW) in China, this study generated the autonomous driving testing scenarios from functional, logical and concrete levels. First, 239 video-recorded crash cases were selected from the China In-depth mobility Safety Study - Traffic Accident (CIMSS-TA) database. Using the k-medoids clustering method, six functional scenarios were generalized according to seven crash characteristics (time of day, road type, road surface, obstruction, motion of vehicle, motion of PTW, relative moving direction and position of PTW with respect to vehicle), which contained two straight road scenarios, two T-junction scenarios and two intersection scenarios. Then, using a trajectory analysis program written by Python, the dangerous time instant of each crash was extracted based on the relative trajectory. According to five dynamic parameters of dangerous time instant, namely vehicle velocity (Vehicle_V), PTW X'-coordinate velocity (PTW_VX'), PTW Y'-coordinate velocity (PTW_VY'), PTW X'-coordinate relative position (PTW_LocX') and PTW Y'-coordinate relative position (PTW_LocY'), a crash trigger scheme was built to remain a case challenging when the involved vehicle is replaced by an autonomous vehicle with completely different maneuvers. Using the kernel density estimation (KDE), the logical scenarios were evolved by calculating the distribution of these dynamic parameters in each cluster. The results showed that there were differences in the distribution of dynamic parameters between six functional scenarios. For instance, the Vehicle_V in the scenario where a vehicle turning right impacts with a right/right rear PTW traveling straight ahead was higher than that in the scenario where a vehicle changing to the left lane impacts with a left/left rear PTW traveling straight ahead, with ranges of (10 km/h, 30 km/h) and (5 km/h, 15 km/h), respectively. Finally, considering the correlation of dynamic parameters, a virtual crash generation approach based on the independent component analysis (ICA) representing the original crashes with independent parameters was proposed to obtain sufficient concrete testing scenarios. The results showed that the statistical characteristics of virtual crashes were consistent with those of original crashes. Therefore, the virtual crash generation approach was effective. And a concrete crossing testing scenario with the crash trigger conditions of Vehicle_V = 26.272 km/h, PTW_VX' = 15.567 km/h, PTW_VY' = -1.670 km/h, PTW_LocX' = -27.265 m and PTW_LocY' = 52. 149 m was especially demonstrated. This study provides a theoretical basis for generating autonomous driving testing scenarios and data support for establishing relevant testing schemes tailored to the traffic environment in China.

The Real-World Effects of Route Familiarity on Drivers' Eye Fixations at Urban Intersections in Changsha, China.

A crucial factor, route familiarity, can affect traffic safety. Nevertheless, focus on the influence of route familiarity on drivers' eye fixations at urban intersections has received less attention. Identifying the real-world effect of route familiarity on drivers' eye fixations at urban intersections in Changsha, China, was the objective of this study. Their visual fixation indicators were recorded while unfamiliar drivers and familiar drivers drove a 9 km-long route with nine intersections in an urban environment, but their effectiveness was indicated by the data collected 150 m before the lane stop and 50 m after the lane stop at these intersections. From the analysis of the extracted data, the results indicated that route familiarity could influence drivers' processing times in the left window (LW) and other areas (OT). Compared with familiar drivers, unfamiliar drivers had longer processing times and higher mental workloads for the right front (RF). For the vehicle's front (RF, FL, FR), the sampling rates and mental workloads of unfamiliar drivers were higher than those of familiar drivers, but it was the opposite for the driver's sides (LW, RW) and rear (LM, RM, ReM). It was also indicated that the phenomenon said to increase familiarity with the route and make drivers more likely to be distracted in urban intersections had not been found. From the present findings, the effect of route familiarity on drivers' eye fixations at urban intersections was confirmed. The high accident risk of familiar drivers could be partly explained by the decrement in drivers' eye fixation strategies. However, the strategies could not account for the phenomenon that more familiar drivers are involved in rear-end accidents. Therefore, the reason can be investigated based on drivers' visual scanning strategies, their physiological signals and driving behavior in the future.

Investigating the severity of non-urban road traffic accidents in typical regions of Sichuan and Guizhou, China.

OBJECTIVE: The traffic characteristics of Sichuan and Guizhou differ from those of other regions due to its unique geographical features. In addition, accident studies in China mainly focus on urban roads in the eastern and central regions. However, studies on western regions, especially non-urban roads, are scarce. Thus, this study aims to explore the factors that influence the severity of accidents on non-urban roads in typical regions of Sichuan and Guizhou. METHODS: A total of 541 cases from 2014 to 2020 were selected from the database of the China In-Depth Accident Study, where 18 variables, which may exert an impact on accident severity, were extracted after screening. First, heterogeneity of data was eliminated through latent class analysis (LCA). The ordered probit (OP) model was then conducted for each class to obtain significant variables that exert an impact on accident severity. The study quantified the degree of influence of the significant variables using marginal effect analysis. RESULTS: The LCA results demonstrate that data were categorized into the following classes, namely, (a) two-vehicle accidents involving trucks, (b) pedestrian and multiple-vehicle accidents, (c) two-wheeler accidents, and (d) single-vehicle accidents. The OP results show that most variables could exert impact on accident severity, and some of them exerted varying levels of influence on the severity of different classes, whereas others only influence a specific class. CONCLUSION: According to this study, we obtained the accident characteristics of these regions and put forward some targeted suggestions to further improve the level of road traffic safety. The findings can provide support for the construction of transportation in line with the regional characteristics in China.

Effectiveness and Efficiency of Externally Bonded CFRP Sheets for Shear Strengthening of RC Beam-Column Joints.

To develop feasible carbon fiber reinforced polymer (CFRP) retrofit schemes for the shear strengthening of real three-dimensional reinforced concrete (RC) beam-column joints, a series of parameters in relation to the contributions of the CFRP sheets externally bonded to joint panels was numerically investigated in this study. The parameters include CFRP reinforcement ratio, CFRP layout, transverse beam-to-joint panel width ratio, transverse beam-to-joint panel height ratio, location of transverse beam, and number of transverse beams. Strengthening efficiency, a new dimensionless index, was introduced to evaluate the residual effect of a CFRP-strengthening system weakened by the presence of transverse beams in comparison with the increase in joint shear capacity in relation to the one-way counterpart. The results obtained from 44 nonlinear finite element models, which were calibrated against experimental observations, confirmed the effectiveness of the CFRP strengthening technique with regard to the relatively wide ranges of the parameters. The significant differences among the roles of the parameters were revealed, and the reasons behind the differences were analyzed. Furthermore, the shear mechanism of the CFRP-retrofitted joint panels was discussed with the proposed strut-and-tie model.

Visual differences in topography-guided versus wavefront-optimized LASIK in the treatment of myopia: a Meta-analysis.

AIM: To investigate the potential differences between topography-guided (TG) and wavefront-optimized (WFO) laser in situ keratomileusis (LASIK) for the treatment of myopia. METHODS: A systematic literature search was performed to determine relevant trials comparing LASIK with TG and WFO from the time of library construction to August 2020, and The PubMed, Cochrane, Web of Science, EMBASE and Chinese databases (i.e. CNKI, CBM, WAN FANG and VIP) were accessed. The data on visual acuity, refractive status and wavefront aberration were retrieved and evaluated from three to six months after surgery. STATA (version 14.0) software was used for statistical analysis. A cumulative Meta-analysis was simultaneously performed. RESULTS: Eleven studies with a total of 1425 eyes were incorporated. No statistically significant differences were evident between TG and WFO ablation in the proportion of eyes achieving an uncorrected distance visual acuity (UCVA) of 20/20 or better (P=0.377), gaining one line or more (P=0.05), postoperative cylinder (P=0.40), vertical coma (P=0.593) and horizontal coma (P=0.957). After TG ablation, the proportion of the patients' eyes of which postoperative refraction is within ±0.5 diopter of the target refraction was significantly higher than that undergoes WFO (P=0.003). As opposed to the WFO group, manifest refraction spherical equivalent (MRSE; P=0.000) was lower, and UCVA (P=0.005) was better in the TG group. The higher-order aberrations (HOAs; P=0.000), spherical aberration (P=0.000) and coma (P=0.000) were significantly lower in TG group. The cumulative Meta-analysis illustrated that the proportion of eyes achieving UCVA of 20/20 or better, postoperative refraction within ±0.5 diopter, and MRSE has steady between the two groups. CONCLUSION: Both TG-LASIK and WFO-LASIK are safe, effective, and predictable for correcting myopia. TG-LASIK may produce fewer aberration and is more precise than WFO-LASIK.

The Application of Nanobody in CAR-T Therapy.

Chimeric antigen receptor (CAR) T therapy represents a form of immune cellular therapy with clinical efficacy and a specific target. A typical chimeric antigen receptor (CAR) construct consists of an antigen binding domain, a transmembrane domain, and a cytoplasmic domain. Nanobodies have been widely applied as the antigen binding domain of CAR-T due to their small size, optimal stability, high affinity, and manufacturing feasibility. The nanobody-based CAR structure has shown a proven function in more than ten different tumor-specific targets. After being transduced in Jurkat cells, natural killer cells, or primary T cells, the resulting nanobody-based CAR-T or CAR-NK cells demonstrate anti-tumor effects both in vitro and in vivo. Interestingly, anti-BCMA CAR-T modulated by a single nanobody or bi-valent nanobody displays comparable clinical effects with that of single-chain variable fragment (scFv)-modulated CAR-T. The application of nanobodies in CAR-T therapy has been well demonstrated from bench to bedside and displays great potential in forming advanced CAR-T for more challenging tasks.

The Antiresection Activity of the X Protein Encoded by Hepatitis Virus B.

Chronic infection of hepatitis B virus (HBV) is associated with an increased incidence of hepatocellular carcinoma (HCC). HBV encodes an oncoprotein, hepatitis B x protein (HBx), that is crucial for viral replication and interferes with multiple cellular activities including gene expression, histone modifications, and genomic stability. To date, it remains unclear how disruption of these activities contributes to hepatocarcinogenesis. Here, we report that HBV exhibits antiresection activity by disrupting DNA end resection, thus impairing the initial steps of homologous recombination (HR). This antiresection activity occurs in primary human hepatocytes undergoing a natural viral infection-replication cycle as well as in cells with integrated HBV genomes. Among the seven HBV-encoded proteins, we identified HBx as the sole viral factor that inhibits resection. By disrupting an evolutionarily conserved Cullin4A-damage-specific DNA binding protein 1-RING type of E3 ligase, CRL4WDR70 , through its H-box, we show that HBx inhibits H2B monoubiquitylation at lysine 120 at double-strand breaks, thus reducing the efficiency of long-range resection. We further show that directly impairing H2B monoubiquitylation elicited tumorigenesis upon engraftment of deficient cells in athymic mice, confirming that the impairment of CRL4WDR70 function by HBx is sufficient to promote carcinogenesis. Finally, we demonstrate that lack of H2B monoubiquitylation is manifest in human HBV-associated HCC when compared with HBV-free HCC, implying corresponding defects of epigenetic regulation and end resection. Conclusion: The antiresection activity of HBx induces an HR defect and genomic instability and contributes to tumorigenesis of host hepatocytes.

Biophysical and structural characterization of the thermostable WD40 domain of a prokaryotic protein, Thermomonospora curvata PkwA.

WD40 proteins belong to a big protein family with members identified in every eukaryotic proteome. However, WD40 proteins were only reported in a few prokaryotic proteomes. Using WDSP ( http://wu.scbb.pkusz.edu.cn/wdsp/ ), a prediction tool, we identified thousands of prokaryotic WD40 proteins, among which few proteins have been biochemically characterized. As shown in our previous bioinformatics study, a large proportion of prokaryotic WD40 proteins have higher intramolecular sequence identity among repeats and more hydrogen networks, which may indicate better stability than eukaryotic WD40s. Here we report our biophysical and structural study on the WD40 domain of PkwA from Thermomonospora curvata (referred as tPkwA-C). We demonstrated that the stability of thermophilic tPkwA-C correlated to ionic strength and tPkwA-C exhibited fully reversible unfolding under different denaturing conditions. Therefore, the folding kinetics was also studied through stopped-flow circular dichroism spectra. The crystal structure of tPkwA-C was further resolved and shed light on the key factors that stabilize its beta-propeller structure. Like other WD40 proteins, DHSW tetrad has a significant impact on the stability of tPkwA-C. Considering its unique features, we proposed that tPkwA-C should be a great structural template for protein engineering to study key residues involved in protein-protein interaction of a WD40 protein.

PSN-PC: A Novel Antimicrobial and Anti-Biofilm Peptide from the Skin Secretion of Phyllomedusa-camba with Cytotoxicity on Human Lung Cancer Cell.

Peptides derived from amphibian skin secretion are promising drug prototypes for combating widespread infection. In this study, a novel peptide belonging to the phylloseptin family of antimicrobial peptides was isolated from the skin secretion of the Phyllomedusa camba, namely phylloseptin-PC (PSN-PC). The biosynthetic precursor was obtained by molecular cloning and the mature peptide sequence was confirmed through tandem mass spectrometry (MS/MS) fragmentation sequencing in the skin secretion. The synthetic replicate exhibited a broad spectrum antimicrobial activity against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus,Escherichia coli, Pseudomonas aeruginosa, Candida albicans at concentrations of 2, 2, 8, 32 and 2 µM, respectively. It also showed the capability of eliminating S. aureus biofilm with a minimal biofilm eradication concentration of 8 µM. The haemolysis of this peptide was not significant at low concentrations but had a considerable increase at high concentrations. Additionally, this peptide showed an anti-proliferation effect on the non-small cell lung cancer cell line (NCI-H157), with low cytotoxicity on the human microvascular endothelial cell line (HMEC-1). The discovery of the novel peptide may provide useful clues for new drug discoveries.

[Screen absorption enhancer for intranasal administration preparations of paeoniflorin based on nasal perfusion method in rats].

This experiment was aimed to screen the absorption enhancer for intranasal administration preparations of paeoniflorin. In this study, HPLC method for determination of paeoniflorin in perfusion liquid was established and the improved model of nasal perfusion in rats was used to screen out the species and amounts of absorption enhancer. In order to avoid the influence of the secretion and absorption of nasal cavity on the volume of perfusion fluid, the residual dose was calculated by using the volume correction method. Linear regression was carried out between the logarithm to the percentage of the residual dose and the corresponding time, and the slope of the regression line was exactly the absorption rate constant. Experimental results showed that hydroxypropyl-ß-cyclodextrin and water-soluble azone can significantly improve the nasal absorption of paeoniflorin. Furthermore, water-soluble azone had the highest absorption rate constant and the best promoting penetration effect on intranasal administration preparations of paeoniflorin. It was also found that when the mass concentration of water-soluble azone in the perfusion liquid increased from 5 g•L⁻¹ to 20 g•L⁻¹, the absorption rate constant was gradually increased and peaked at 20 g•L⁻¹. When the mass concentration was increased to 30 g•L⁻¹, the absorption rate constant was decreased, indicating that the best mass concentration of water-soluble azone was 20 g•L⁻¹.

Prokaryotic and Highly-Repetitive WD40 Proteins: A Systematic Study.

As an ancient protein family, the WD40 repeat proteins often play essential roles in fundamental cellular processes in eukaryotes. Although investigations of eukaryotic WD40 proteins have been frequently reported, prokaryotic ones remain largely uncharacterized. In this paper, we report a systematic analysis of prokaryotic WD40 proteins and detailed comparisons with eukaryotic ones. About 4,000 prokaryotic WD40 proteins have been identified, accounting for 6.5% of all WD40s. While their abundances are less than 0.1% in most prokaryotes, they are enriched in certain species from Cyanobacteria and Planctomycetes, and participate in various functions such as prokaryotic signal transduction and nutrient synthesis. Comparisons show that a higher proportion of prokaryotic WD40s tend to contain multiple WD40 domains and a large number of hydrogen bond networks. The observation that prokaryotic WD40 proteins tend to show high internal sequence identity suggests that a substantial proportion of them (~20%) should be formed by recent or young repeat duplication events. Further studies demonstrate that the very young WD40 proteins, i.e., Highly-Repetitive WD40s, should be of higher stability. Our results have presented a catalogue of prokaryotic WD40 proteins, and have shed light on their evolutionary origins.

In-silico ADME Studies for New Drug Discovery: From Chemical Compounds to Chinese Herbal Medicines.

Nowadays, in silico tools are widely used to provide the potential structure of the metabolites formed depending on the site of metabolism. These methods can also highlight the molecular moieties that help to direct the molecule into the cytochrome cavity so that the site of metabolism is in proximity to the catalytic center. In this minireview, we summarized three aspects of the in silico methods in the application of prediction of ADME (absorption, distribution, metabolism and excretion) properties of compounds: structure-based approaches for predicting molecular modeling of drug metabolizing enzymes; in silico metabolite prediction; and pharmacophore models for analysis substrate specificity. Moreover, we also extended the in silico studies in Chinese herbal medicines (CHM) research.