Search

(20 S)-Ginsenoside Rh2 is a natural saponin derived from Panax ginseng Meyer (P. ginseng), which showed significantly potent anticancer properties. However, its low water solubility and bioavailability strongly restrict its pharmaceutical applications. The aim of current research is to develop a modified (20 S)-Ginsenoside Rh2 formulation with high solubility, dissolution rate and bioavailability by combined computational and experimental methodology. The "PharmSD" model was employed to predict the optimal polymer for (20 S)-Ginsenoside Rh2 solid dispersion formulations. The solubility of (20 S)-Ginsenoside Rh2 in various polymers was assessed, and the optimal ternary solid dispersion was evaluated across different dissolution mediums. Characterization techniques included the Powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FTIR). Molecular dynamics simulations were employed to elucidate the formation mechanism of the solid dispersion and the interactions among active pharmaceutical ingredient (API) and excipient molecules. Cell and animal experiments were conducted to evaluate the in vivo performance of the modified formulation. The "PharmSD" solid dispersion model identified Gelucire 44/14 as the most effective polymer for enhancing the dissolution rate of Rh2. Subsequent experiment also confirmed that Gelucire 44/14 outperformed the other selected polymers. Moreover, the addition of the third component, sodium dodecyl sulfate (SDS), in the ternary solid dispersion formulation significantly amplified dissolution rates than the binary systems. Characterization experiments revealed that the API existed in an amorphous state and interacted via hydrogen bonding with SDS and Gelucire. Moreover, molecular modeling results provided additional evidence of hydrogen bonding interactions between the API and excipient molecules within the optimal ternary solid dispersion. Cell experiments demonstrated efflux ratio (EfR) of Rh2 ternary solid dispersion was lower than that of pure Rh2. In vivo experiments revealed that the modified formulation substantially improved the absorption of Rh2 in rats. Our research successfully developed an optimal ternary solid dispersion for Rh2 with high solubility, dissolution rate and bioavailability by integrated computational and experimental tools. The combination of Artificial Intelligence (AI) technology and molecular dynamics simulation is a wise way to support the future formulation development., Competing Interests: Declarations. Ethics approval and consent to participate: No ethical approval is required for this study. Consent to publish: All the authors read and approved the final version of the manuscript. Competing interests: The authors report no conflicts of interest., (© 2024. Controlled Release Society.)

Although biopharmaceuticals constitute around 10% of the drug landscape, eight of the ten top-selling products were biopharmaceuticals in 2023. This study did a comprehensive analysis of the FDA's Purple Book database. Firstly, our research uncovered market trends and provided insights into biologics distributions. According to the investigation, although biotechnology has advanced and legislative shifts have made the approval process faster, there are still challenges to overcome, such as molecular instability and formulation design. Moreover, our research comprehensively analyzed biological formulations, pointing out significant strategies regarding administration routes, dosage forms, product packaging, and excipients. In conjunction with biologics, the widespread integration of innovative delivery strategies will be implemented to confront the evolving challenges in healthcare and meet an expanding array of treatment needs., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Low aqueous solubility is a common and serious challenge for most drug substances not only in development but also in the market, and it may cause low absorption and bioavailability as a result. Amorphization is an intermolecular modification strategy to address the issue by breaking the crystal lattice and enhancing the energy state. However, due to the physicochemical properties of the amorphous state, drugs are thermodynamically unstable and tend to recrystallize over time. Glass-forming ability (GFA) is an experimental method to evaluate the forming and stability of glass formed by crystallization tendency. Machine learning (ML) is an emerging technique widely applied in pharmaceutical sciences. In this study, we successfully developed multiple ML models (i.e., random forest (RF), XGBoost, and support vector machine (SVM)) to predict GFA from 171 drug molecules. Two different molecular representation methods (i.e., 2D descriptor and Extended-connectivity fingerprints (ECFP)) were implemented to process the drug molecules. Among all ML algorithms, 2D-RF performed best with the highest accuracy, AUC, and F1 of 0.857, 0.850, and 0.828, respectively, in the testing set. In addition, we conducted a feature importance analysis, and the results mostly agreed with the literature, which demonstrated the interpretability of the model. Most importantly, our study showed great potential for developing amorphous drugs by in silico screening of stable glass formers., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Microspheres have gained much attention from pharmaceutical and medical industry due to the excellent biodegradable and long controlled-release characteristics. However, the drug release behavior of microspheres is influenced by complicated formulation and manufacturing factors. The traditional formulation development of microspheres is intractable and inefficient by the experimentally trial-and-error methods. This research aims to build a prediction model to accelerate microspheres product development for small-molecule drugs by machine learning (ML) techniques. Two hundred eighty-six microsphere formulations with small-molecule drugs were collected from the publications and pharmaceutical company, including the dissolution temperature at both 37 ℃ and 45 ℃. After the comparison of fourteen ML approaches, the consensus model achieved accurate predictions for the validation set at 37 ℃ and 45 ℃ (R 2  = 0.880 vs. R 2  = 0.958), indicating the good performance to predict the in vitro drug release profiles at both 37 ℃ and 45 ℃. Meanwhile, the models revealed the feature importance of formulations, which offered meaningful insights to the microspheres development. Experiments of microsphere formulations further validated the accuracy of the consensus model. Furthermore, molecular dynamics (MD) simulation provided a microscopic view of the preparation process of microspheres. In conclusion, the prediction model of microsphere formulations for small-molecule drugs was successfully built with high accuracy, which is able to accelerate microspheres product development and promote the quality control of microspheres for the pharmaceutical industry., (© 2022. Controlled Release Society.)

Lead-zinc tailings are complex heavy metal solid wastes produced in the mining process. In this study, two kinds of organic-inorganic mixed improvers mushroom residue + calcium carbonate (M + C) and peat soil + calcium carbonate (N + C) were selected. Then, the effect of two improvers and a woody plant, Nerium oleander L., on the combined remediation of lead-zinc tailings was compared, respectively. The results showed that two combined improvers can slightly improve the pH of tailing, significantly increase the activity of phosphatase and catalase, effectively reduce the contents of DTPA-extractable Pb and Zn, and significantly improve the structure of tailing. However, the improvement effect of M + C was better than that of N + C on tailings' physical and chemical properties. Two improvers can reduce the enrichment and the stress degree of Pb and Zn on the N. oleander and increase the accumulation of Pb and Zn while promoting the growth of the N. oleander. The content of Pb and Zn showed the trend of root > stem > leaf under the two improvers, and the content of Zn was basically higher than that of Pb. To sum up, the combination of two modifiers and N. oleander has a good effect on the remediation of lead-zinc tailings, and the remediation effect of M + C was better than N + C., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In this paper, we study the problem of ( p , q )-biclique counting and enumeration for large sparse bipartite graphs. Given a bipartite graph G = ( U , V , E ) and two integer parameters p and q , we aim to efficiently count and enumerate all ( p , q )-bicliques in G , where a ( p , q )-biclique B ( L ,  R ) is a complete subgraph of G with L ⊆ U , R ⊆ V , | L | = p , and | R | = q . The problem of ( p , q )-biclique counting and enumeration has many applications, such as graph neural network information aggregation, densest subgraph detection, and cohesive subgroup analysis. Despite the wide range of applications, to the best of our knowledge, we note that there is no efficient and scalable solution to this problem in the literature . This problem is computationally challenging, due to the worst-case exponential number of ( p , q )-bicliques. In this paper, we propose a competitive branch-and-bound baseline method, namely BCList, which explores the search space in a depth-first manner, together with a variety of pruning techniques. Although BCList offers a useful computation framework to our problem, its worst-case time complexity is exponential to p + q . To alleviate this, we propose an advanced approach, called BCList++. Particularly, BCList++ applies a layer-based exploring strategy to enumerate ( p , q )-bicliques by anchoring the search on either U or V only, which has a worst-case time complexity exponential to either p or q only. Consequently, a vital task is to choose a layer with the least computation cost. To this end, we develop a cost model, which is built upon an unbiased estimator for the density of 2-hop graph induced by U or V . To improve computation efficiency, BCList++ exploits pre-allocated arrays and vertex labeling techniques such that the frequent subgraph creating operations can be substituted by array element switching operations. We conduct extensive experiments on 16 real-life datasets, and the experimental results demonstrate that BCList++ significantly outperforms the baseline methods by up to 3 orders of magnitude. We show via a case study that ( p , q )-bicliques optimizes the efficiency of graph neural networks. In this paper, we extend our techniques to count and enumerate ( p , q )-bicliques on uncertain bipartite graphs. An efficient method IUBCList is developed on the top of BCList++, together with a couple of pruning techniques, including common neighbor refinement and search branch early termination, to discard unpromising uncertain ( p , q )-bicliques early. The experimental results demonstrate that IUBCList significantly outperforms the baseline method by up to 2 orders of magnitude., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The heart-liver axis is of growing importance. Previous studies have identified independent association of liver dysfunction and fibrosis with adverse cardiac outcomes, but mechanistic pathways remain uncertain. We sought to understand the relations between the degree of hepatic fibrosis identified by the Fibrosis-4 (Fib-4) risk score and comprehensive cardiac MRI (CMR) measures of subclinical cardiac disease. We conducted a retrospective single-center cohort study of patients between 2011 and 2021. We identified consecutive patients who underwent a comprehensive CMR imaging protocol including contrast enhanced with stress/rest perfusion, and lacked pre-existing cardiovascular disease or perfusion abnormalities on CMR. We examined the association of hepatic fibrosis, using the Fib-4 score, with subclinical cardiac disease on CMR while adjusting for cardiometabolic traits. Given known associations of hepatic disease and coronary microvascular dysfunction, we prioritized analyses with the myocardial perfusion reserve index (MPRI), a marker of coronary microvascular function. Of the 66 patients in our study cohort, 54 were female (81%) and the mean age was 53.7 ± 15.3 years. We found that higher Fib-4 was associated with reduction in the MPRI (β [SE] - 1.12 [0.46], P = 0.02), after adjusting for cardiometabolic risk factors. Importantly, Fib-4 was not significantly associated with any other CMR phenotypes including measures of cardiac remodeling, inflammation, fibrosis, or dysfunction. We found evidence that hepatic fibrosis associated with coronary microvascular dysfunction, in the absence of overt associations with any other subclinical cardiac disease measures. These findings highlight a potentially important precursor pathway leading to development of subsequent heart-liver disease., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

To cure the illness in the brain glioblastoma, the Gliadel wafer, as the first FDA-approved chemotherapy, was available on the market since 1997. Due to the complex studies in vivo, more and more researchers have paid their attention to investigate the dynamic process in the brain by numerical methods. This study aimed to simulate the drug concentration in the cavity after drug releases from Gliadel wafers into the brain tumor by a two-dimensional simulation. The government equations, the parameters, and corresponding initial and boundary conditions are specified. Then the models are discretized and solved by finite element method (FEM) and finite difference method (FDM) based on C++ library Adaptive Finite Element Package (AFEPack) and MATLAB, respectively. First of all, the numerical convergence of the method is studied by numerical results represented in several successively refined meshes, which shows the reliability of our method. In the results from FEM, a steady state of the pressure in the normal tissue can be simulated. As for FDM, the changes of drug concentration are displayed at six different times. The numerical method in this paper is an effective tool for the numerical study on drug release from polymers. Additionally, convection is a critical factor in drug transportation. Moreover, the simulation approach can be used as the guild for remedy optimization and dynamic analysis of other drugs (paclitaxel) for tumor treatment in the clinic. This mathematical model has wide applications about drug release in multiple dosage forms, such as long sustained release microspheres, oral extended release hydrophilic matrix tablets, hydrogel, and sustained release topical rings., (© 2021. Controlled Release Society.)

Purpose of Review: Anatomical segmentation has played a major role within clinical cardiology. Novel techniques through artificial intelligence-based computer vision have revolutionized this process through both automation and novel applications. This review discusses the history and clinical context of cardiac segmentation to provide a framework for a survey of recent manuscripts in artificial intelligence and cardiac segmentation. We aim to clarify for the reader the clinical question of "Why do we segment?" in order to understand the question of "Where is current research and where should be?"., Recent Findings: There has been increasing research in cardiac segmentation in recent years. Segmentation models are most frequently based on a U-Net structure. Multiple innovations have been added in terms of pre-processing or connection to analysis pipelines. Cardiac MRI is the most frequently segmented modality, which is due in part to the presence of publically-available, moderately sized, computer vision competition datasets. Further progress in data availability, model explanation, and clinical integration are being pursued., Summary: The task of cardiac anatomical segmentation has experienced massive strides forward within the past five years due to convolutional neural networks. These advances provide a basis for streamlining image analysis, and a foundation for further analysis both by computer and human systems. While technical advances are clear, clinical benefit remains nascent. Novel approaches may improve measurement precision by decreasing inter-reader variability and appear to also have the potential for larger-reaching effects in the future within integrated analysis pipelines., Competing Interests: Compliance with Ethical Standards Conflict of Interest: Alan C Kwan, Gerran Salto, Susan Cheng, and David Ouyang report no relevant conflicts of interest.

Previous studies showed that the onset age of second language acquisition (AoA-L2) can modulate brain structure of bilinguals. However, the underlying mechanism of anatomical plasticity induced by AoA-L2 is still a question in debate. In order to explore the issue, we recruited two groups of native Cantonese-Mandarin speakers, the early group began to speak in Mandarin at about 3.5 and the late group at about 6.5 years old. In addition, the early group had earlier experience in reading Chinese characters than the late group did. Through estimating the cortical thickness (CT), we found that (1) compared with the late group, the early group had thicker CT in the lateral occipital region, left middle temporal gyrus, and left parahippocampal region, which are all involved in visuospatial processing, probably reflecting the effect induced by the earlier or later experiences in processing the characters of Chinese for the two groups; and (2) compared with the late group, the early group had thicker CT in left superior parietal region, which is believed to be involved in language switching, maybe for the early group had the earlier experience in switching back and forth between Cantonese and Mandarin and therefore recruited the executive control network earlier. Our findings revealed the effects of the AoA-L2 in oral language acquisition as well as in written language acquisition as the main determinants of bilingual language structural representation in human brain., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Chronic kidney disease (CKD) is characterized by decreased glomerular filtration rate (GFR) due to a variety of causes. Most patients remain undiagnosed at early stage of CKD and proceed to end stage CKD due to unawareness and lacking of efficient biomarkers. Trimethylamine-N-oxide (TMAO) and its predecessor products: choline, L-carnitine and betaine are associated with reduced renal function. However, whether the combined variation of the four metabolites could contribute in prediction and stratification of impaired glomerular function in Chinese CKD patients is unknown. Our aim is to investigate the associations of plasma TMAO, choline, L-carnitine and betaine with glomerular filtration in CKD patients., Materials and Methods: A total of 65 CKD patients and 64 healthy controls were enrolled in this study. Fasting plasma metabolites were detected using liquid chromatography-based method., Results: Plasma TMAO, choline, betaine and L-carnitine levels were differentially correlated with eGFR. The four metabolites were independently associated with CKD after adjustment for multiple traditional risk factors. The combination of the four metabolites had good performance at discriminating CKD from healthy controls (AUC = 0.96) as well as discriminating low eGFR from high eGFR in CKD (AUC = 0.96)., Conclusion: Combinations of TMAO and its precursors were associated with glomerular function and might be utilized in evaluation of CKD.

Lycopene, the aliphatic hydrocarbon carotenoid with abundant bioactivities, has instability, extremely poor water solubility, and low oral bioavailability. The study aimed to develop a highly water-soluble and practical lycopene formulation to improve the oral bioavailability and efficiency of lycopene. Environment-friendly hot-melt extrusion (HME) technique was applied to fabricate lycopene-cyclodextrin-polyethylene glycol 6000 (PEG 6000) ternary systems, which possessed highly aqueous solubility (897.665 μg mL -1 ), almost 32-fold higher than that of the reported lycopene binary inclusion (27.1 ± 3.2 μg mL -1 ). The dissolution rate was significantly accelerated compared to pure lycopene. The molecular mechanism was further investigated by the integrated experimental and modeling tools. Molecular dynamics (MD) simulation revealed lycopene molecule was wrapped within the aggregates of hydroxypropyl-beta-cyclodextrin (HP-β-CD) and PEG 6000 through extensive hydrogen bond interactions, which was experimentally validated by DSC, XRD, and FTIR spectrum analysis. The third component PEG 6000 facilitated the process of HME and augmented hydrogen bond interactions with HP-β-CD. Moreover, lycopene inclusions exhibited significant antitumor activity via inhibiting cell proliferation and inducing apoptosis. The pharmacokinetic studies showed the relative bioavailability of lycopene ternary preparation was up to 313.08% and the C max was 4.9-fold higher than that of the marketed tablet. In conclusion, the lycopene cyclodextrin ternary formulation developed by the modified HME techniques is suitable for industrial production, while PEG 6000 plays a vital part in the multicomponent systems to increase solubility, dissolution rate, and oral bioavailability of lycopene. The combination of experimental and computational tools is able to benefit the development of multicomponent formulations accurately and effectively.

With the increase concern of solubilization for insoluble drug, ternary solid dispersion (SD) formulations developed more rapidly than binary systems. However, rational formulation design of ternary systems and their dissolution molecular mechanism were still under development. Current research aimed to develop the effective ternary formulations and investigate their molecular mechanism by integrated experimental and modeling techniques. Glipizide (GLI) was selected as the model drug and PEG was used as the solubilizing polymer, while surfactants (e.g., SDS or Tween80) were the third components. SD samples were prepared at different weight ratio by melting method. In the dissolution tests, the solubilization effect of ternary system with very small amount of surfactant (drug/PEG/surfactant 1/1/0.02) was similar with that of binary systems with high polymer ratios (drug/PEG 1/3 and 1/9). The molecular structure of ternary systems was characterized by differential scanning calorimetry (DSC), infrared absorption spectroscopy (IR), X-ray diffraction (XRD), and scanning electron microscope (SEM). Moreover, molecular dynamic (MD) simulations mimicked the preparation process of SDs, and molecular motion in solvent revealed the dissolution mechanism of SD. As the Gordon-Taylor equation described, the experimental and calculated values of Tg were compared for ternary and binary systems, which confirmed good miscibility of GLI with other components. In summary, ternary SD systems could significantly decrease the usage of polymers than binary system. Molecular mechanism of dissolution for both binary and ternary solid dispersions was revealed by combined experiments and molecular modeling techniques. Our research provides a novel pathway for the further research of ternary solid dispersion formulations.

In this study, we proposed and experimentally demonstrated a high breakdown voltage (BV) and low dynamic ON-resistance (R ON, D ) AlGaN/GaN high electron mobility transistor (HEMT) by implanting fluorine ions in the thick SiN x passivation layer between the gate and drain electrodes. Instead of the fluorine ion implantation in the thin AlGaN barrier layer, the peak position and vacancy distributions are far from the two-dimensional electron gas (2DEG) channel in the case of fluorine ion implantation in the thick passivation layer, which effectively suppresses the direct current (DC) static and pulsed dynamic characteristic degradation. The fluorine ions in the passivation layer also extend the depletion region and increase the average electric field (E-field) strength between the gate and drain, leading to an enhanced BV. The BV of the proposed HEMT increases to 803 V from 680 V of the conventional AlGaN/GaN HEMT (Conv. HEMT) with the same dimensional parameters. The measured R ON, D of the proposed HEMT is only increased by 23% at a high drain quiescent bias of 100 V, while the R ON, D of the HEMT with fluorine ion implantation in the thin AlGaN barrier layer is increased by 98%.

Two-dimensional (2D) mesoporous VO 2 microarrays have been prepared using an organic-inorganic liquid interface. The units of microarrays consist of needle-like VO 2 particles with a mesoporous structure, in which crack-like pores with a pore size of about 2 nm and depth of 20-100 nm are distributed on the particle surface. The liquid interface acts as a template for the formation of the 2D microarrays, as identified from the kinetic observation. Due to the mesoporous structure of the units and high conductivity of the microarray, such 2D VO 2 microarrays exhibit a high specific capacitance of 265 F/g at 1 A/g and excellent rate capability (182 F/g at 10 A/g) and cycling stability, suggesting the effect of unique microstructure for improving the electrochemical performance.

The objective of this study was to develop an authentic ionic-driven osmotic pump system and investigate the release mechanism, simultaneously exploring the in vitro and in vivo correlation of the ionic-driven osmotic pump tablet. A comparison of the ionic-driven and conventional theophylline osmotic pump, the influence of pH and the amount of sodium chloride on drug release, the relationship between the ionic osmotic pressure and the drug release, and the pharmacokinetics experiment in beagle dogs were investigated. Consequently, the similarity factor (f 2 ) between the novel and conventional theophylline osmotic pump tablet was 60.18, which indicated a similar drug-release behavior. Also, the release profile fitted a zero-order kinetic model. The relative bioavailability of the ionic-driven osmotic pump to the conventional osmotic pump calculated from the AUC (0-∞) was 93.6% and the coefficient (R = 0.9945) confirmed that the ionic-driven osmotic pump exhibited excellent IVIVC. The driving power of the ionic-driven osmotic pump was produced only by ions, which was strongly dependent on the ion strength, and a novel formula for the ionic-driven osmotic pump was derived which indicated that the drug-release rate was proportional to the ionic osmotic pressure and the sodium chloride concentration. Significantly, the formula can predict the drug-release rate and release characteristics of theophylline ionic-driven osmotic pumps, guiding future modification of the ionic osmotic pump.

The aim of this study was to design a polyethylene oxide (PEO) binary hydrophilic matrix controlled system and investigate the most important influence(s) on the in vitro water-insoluble drug release behavior of this controlled system. Direct-compressed PEO binary matrix tablets were obtained from a variety of low viscosity hydrophilic materials as a sustained agent, using anhydrous drugs as a model drug. Water uptake rate, swelling rate, and erosion rate of matrices were investigated for the evaluation of the PEO hydrophilic matrix systems. The effect of the dose, the solubility of water-insoluble drug, and the rheology of polymers on in vitro release were also discussed. Based on the in vitro release kinetics study, three optimized PEO binary matrices were selected for further research. And, these PEO binary matrices had shown the similar release behavior that had been evaluated by the similarity factor f 2 . Further study indicated that they had identical hydration, swelling, and erosion rate. Moreover, rheology study exhibited the similar rheological equation of Herschel-Bulkley and their viscosity was also within the same magnitude. Therefore, viscosity plays the most important role to control drug release compared to other factors in PEO binary matrix system. This research provides fundamental understanding of in vitro drug release of PEO binary hydrophilic matrix tablets and helps pharmaceutical workers to develop a hydrophilic controlled system, which will effectively shorten the process of formulation development by reducing trial-and-error.

While student-run clinics are often important healthcare safety nets for underserved populations, their efficacy for improving patient health knowledge has not been thoroughly explored. From September 2011 to April 2012, we assessed patients' retention of hepatitis B virus (HBV) knowledge after receiving student-led education at two student-run HBV screening and vaccination clinics. Patient education was provided by trained first and second-year medical, nursing, and pharmacy students, aided by a script and interpreters. Patient knowledge of HBV was evaluated at three points: before education, after the initial visit, and at one-month follow-up. Student-led education produced improved knowledge of HBV transmission, prevention, and management, which was retained 1 month after education for 52 patients tracked through time. Mean scores on an HBV knowledge survey improved from 56.4 % (SD = 15.2 %) at baseline to 66.6 % (SD = 15.1 %) after education, and 68.3 % (SD = 15.2 %) after one month. There was a statistically significant difference between the first and second (paired T test, p < 0.001) and the first and third tests (paired T test, p < 0.001), but no difference between the second and third tests (paired T test, p = 0.45). Multivariate analysis demonstrated that retention was correlated with patient educational background but independent of patient age, gender, income, primary language and number of years lived in the United States. Our study suggests that trained health professional students can effectively impart health knowledge that is retained by patients for at least 1 month. These results warrant consideration of student-led educational sessions at SRCs as a promising community health education model.

A series of crown ethers containing the azobenzene moiety incorporated into crowns of various sizes [Cr(O(6))(,) Cr(O(7)) and Cr(O(8))] and their corresponding alkali metal cation (Li(+), Na(+), K(+), Rb(+)) complexes have been studied theoretically. The density functional theory (DFT) method was employed to elucidate the stereochemical structural natures and thermodynamic properties of all of the target molecules at the B3LYP/6-31 G(d) and LANL2DZ level for the cation Rb(+). The fully optimized geometries had real frequencies, thus indicating their minimum-energy status. In addition, the bond lengths between the metal cation and oxygen atoms, atomic torsion angles and thermodynamic energies for complexes were studied. Natural bond orbital (NBO) analysis was used to explore the origin of the internal forces and the intermolecular interactions for the metal complexes. The calculated results show that the most significant interaction is that between the lone pair electrons of electron-donating oxygens in the cis-forms of azobenzene crown ethers (cis-ACEs) and the LP (1-center valence antibond lone pair) orbitals of the alkali-metal cations (Li(+), Na(+), K(+) and Rb(+)). The electronic spectra for the cis-ACEs [cis-Cr(O(6)), cis-Cr(O(7)) and cis-Cr(O(8))] are obtained by the time-dependent density functional theory (TDDFT) at the B3LYP/6-31 G(d) level. The spectra of the cis-isomers show broad π → π (S(0) → S(2)) absorption bands at 310-340 nm but weaker n → π (S(0) → S(1)) bands at 480-490 nm. The calculated results are in good agreement with the experimental results.

Theoretical studies of an unsymmetrical calix[4]-crown-5-N-azacrown-5 (1) in a fixed 1,3-alternate conformation and the complexes 1·K(+)(a), 1·K(+)(b), 1·K(+)(c) and 1·K(+)K(+) were performed using density functional theory (DFT) at the B3LYP/6-31G level. The fully optimized geometric structures of the free macroligand and its 1:1 and 1:2 complexes, as obtained from DFT calculations, were used to perform natural bond orbital (NBO) analysis. The two main types of driving force metal-ligand and cation-π interactions were investigated. NBO analysis indicated that the stabilization interaction energies (E (2)) for O…K(+) and N…K(+) are larger than the other intermolecular interactions in each complex. The significant increase in electron density in the RY or LP orbitals of K(+) results in strong host-guest interactions. In addition, the intermolecular interaction thermal energies (ΔE, ΔH, ΔG) were calculated by frequency analysis at the B3LYP/6-31G level. For all structures, the most pronounced changes in the geometric parameters upon interaction are observed in the calix[4]arene molecule. The results indicate that both the intermolecular electrostatic interactions and the cation-π interactions between the metal ion and π orbitals of the two pairs that face the inverted benzene rings play a significant role.

A new bacterial blight recessive resistance gene xa34(t) was identified from the descendant of somatic hybridization between an aus rice cultivar (cv.) BG1222 and susceptible cv. IR24 against Chinese race V (isolate 5226). The isolate was used to test the resistance or susceptibility of F(1) progenies and reciprocal crosses of the parents. The results showed that F(1) progenies appeared susceptibility there were 128R (resistant):378S (susceptible) and 119R:375S plants in F(2) populations derived from two crosses of BG1222/IR24 and IR24/BG1222, respectively, which both calculates into a 1R:3S ratio. 320 pairs of stochastically selected SSR primers were used for genes' initial mapping. The screened results showed that two SSR markers, RM493 and RM446, found on rice chromosome 1 linked to xa34(t). Linkage analysis showed that these two markers were on both sides of xa34(t) with the genetic distances 4.29 and 3.05 cM, respectively. The other 50 SSR markers in this region were used for genes' fine mapping. The further results indicated that xa34(t) was mapped to a 1.42 cM genetic region between RM10927 and RM10591. In order to further narrow down the genomic region of xa34(t), 43 of insertion/deletion (Indel) markers (BGID1-43) were designed according to the sequences comparison between japonica and indica rice. Parents' polymorphic detection and linkage assay showed that the Indel marker BGID25 came closer to the target gene with a 0.4 cM genetic distance. A contig map corresponding to the locus was constructed based on the reference sequences aligned by the xa34(t) linked markers. Consequently, the locus of xa34(t) was defined to a 204 kb interval flanked by markers RM10929 and BGID25.