Analysis of chloroplast genome characteristics and codon usage bias in 14 species of Annonaceae.

For the study of species evolution, chloroplast gene expression, and transformation, the chloroplast genome is an invaluable resource. Codon usage bias (CUB) analysis is a tool that is utilized to improve gene expression and investigate evolutionary connections in genetic transformation. In this study, we analysed chloroplast genome differences, codon usage patterns and the sources of variation on CUB in 14 Annonaceae species using bioinformatics tools. The study showed that there was a significant variation in both gene sizes and numbers between the 14 species, but conservation was still maintained. It's worth noting that there were noticeable differences in the IR/SC sector boundary and the types of SSRs among the 14 species. The mono-nucleotide repeat type was the most common, with A/T repeats being more prevalent than G/C repeats. Among the different types of repeats, forward and palindromic repeats were the most abundant, followed by reverse repeats, and complement repeats were relatively rare. Codon composition analysis revealed that all 14 species had a frequency of GC lower than 50%. Additionally, it was observed that the proteins in-coding sequences of chloroplast genes tend to end with A/T at the third codon position. Among these species, 21 codons exhibited bias (RSCU > 1), and there were 8 high-frequency (HF) codons and 5 optimal codons that were identical across the species. According to the ENC-plot and Neutrality plot analysis, natural selection had less impact on the CUB of A. muricate and A. reticulata. Based on the PR2-plot, it was evident that base G had a higher frequency than C, and T had a higher frequency A. The correspondence analysis (COA) revealed that codon usage patterns different in Annonaceae.

New Cocrystals of Ligustrazine: Enhancing Hygroscopicity and Stability.

Ligustrazine (TMP) is the main active ingredient extracted from Rhizoma Chuanxiong, which is used in the treatment of cardiovascular and cerebrovascular diseases, with the drawback of being unstable and readily sublimated. Cocrystal technology is an effective method to improve the stability of TMP. Three benzoic acid compounds including P-aminobenzoic acid (PABA), 3-Aminobenzoic acid (MABA), and 3,5-Dinitrobenzoic acid (DNBA) were chosen for co-crystallization with TMP. Three novel cocrystals were obtained, including TMP-PABA (1:2), TMP-MABA (1.5:1), and TMP-DNBA (0.5:1). Hygroscopicity was characterized by the dynamic vapor sorption (DVS) method. Three cocrystals significantly improved the hygroscopicity stability, and the mass change in TMP decreased from 25% to 1.64% (TMP-PABA), 0.12% (TMP-MABA), and 0.03% (TMP-DNBA) at 90% relative humidity. The melting points of the three cocrystals were all higher than TMP, among which the TMP-DNBA cocrystal had the highest melting point and showed the best stability in reducing hygroscopicity. Crystal structure analysis shows that the mesh-like structure formed by the O-H⋯N hydrogen bond in the TMP-DNBA cocrystal was the reason for improving the stability of TMP.

A Novel Cocrystal of Daidzein with Piperazine to Optimize the Solubility, Permeability and Bioavailability of Daidzein.

It is well known that daidzein has various significant medicinal values and health benefits, such as anti-oxidant, anti-inflammatory, anti-cancer, anti-diabetic, cholesterol lowering, neuroprotective, cardioprotective and so on. To our disappointment, poor solubility, low permeability and inferior bioavailability seriously limit its clinical application and market development. To optimize the solubility, permeability and bioavailability of daidzein, the cocrystal of daidzein and piperazine was prepared through a scientific and reasonable design, which was thoroughly characterized by single-crystal X-ray diffraction, powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry and thermogravimetric analysis. Combining single-crystal X-ray diffraction analysis with theoretical calculation, detailed structural information on the cocrystal was clarified and validated. In addition, a series of evaluations on the pharmacogenetic properties of the cocrystal were investigated. The results indicated that the cocrystal of daidzein and piperazine possessed the favorable stability, increased solubility, improved permeability and optimized bioavailability of daidzein. Compared with the parent drug, the formation of cocrystal, respectively, resulted in 3.9-, 3.1-, 4.9- and 60.8-fold enhancement in the solubility in four different media, 4.8-fold elevation in the permeability and 3.2-fold in the bioavailability of daidzein. Targeting the pharmaceutical defects of daidzein, the surprising elevation in the solubility, permeability and bioavailability of daidzein was realized by a clever cocrystal strategy, which not only devoted assistance to the market development and clinical application of daidzein but also paved a new path to address the drug-forming defects of insoluble drugs.

Current advances on the therapeutic potential of scutellarin: an updated review.

Scutellarin is widely distributed in Scutellaria baicalensis, family Labiatae, and Calendula officinalis, family Asteraceae, and belongs to flavonoids. Scutellarin has a wide range of pharmacological activities, it is widely used in the treatment of cerebral infarction, angina pectoris, cerebral thrombosis, coronary heart disease, and other diseases. It is a natural product with great research and development prospects. In recent years, with in-depth research, researchers have found that wild scutellarin also has good therapeutic effects in anti-tumor, anti-inflammatory, anti-oxidation, anti-virus, treatment of metabolic diseases, and protection of kidney. The cancer treatment involves glioma, breast cancer, lung cancer, renal cancer, colon cancer, and so on. In this paper, the sources, pharmacological effects, in vivo and in vitro models of scutellarin were summarized in recent years, and the current research status and future direction of scutellarin were analyzed.

Metformin-Mediated Improvement in Solubility, Stability, and Permeability of Nonsteroidal Anti-Inflammatory Drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are class II biopharmaceutics classification system drugs. The poor aqueous solubility of NSAIDs can lead to limited bioavailability after oral administration. Metformin (MET), a small-molecule compound, can be used in crystal engineering to modulate the physicochemical properties of drugs and to improve the bioavailability of orally administered drugs, according to the literature research and preliminary studies. We synthesized two drug-drug molecular salts (ketoprofen-metformin and phenylbutazone-metformin) with NSAIDs and thoroughly characterized them using SCXRD, PXRD, DSC, and IR analysis to improve the poor solubility of NSAIDs. In vitro evaluation studies revealed that the thermal stability and solubility of NSAIDs-MET were substantially enhanced compared with those of NSAIDs alone. Unexpectedly, an additional increase in permeability was observed. Since the structure determines the properties, the structure was analyzed using theoretical calculations to reveal the intermolecular interactions and to explain the reason for the change in properties. The salt formation of NSAIDs with MET could substantially increase the bio-absorption rate of NSAIDs, according to the in vivo pharmacokinetic findings, which provides an experimental basis for developing new antipyretic and analgesic drugs with rapid onset of action.

Impact of Bullying Victimization on Chinese College Students' Suicidal Tendency: The Moderating Effect of Teachers' Emotional Support and Family Support.

Objective: To explore the influence of bully victims on the suicidal tendencies of college students, and the moderating role of teacher emotional support and family support in the relationship between bully victims and college students' suicidal tendencies, in order to provide a reference for the effective intervention of college students' suicide behavior. Methods: Based on a survey of 15,560 college students. Multiple stepwise regression and Interaction analysis explore the impact of the bully victimization on college students' suicidal tendencies and the moderating role of family support and teacher emotional support in the relationship between the bully victim and college students' suicidal tendencies. Results: This study found that the Suicidal Tendencies score of college students was 19.79 points, indicating that some college students have a risk of suicidal tendencies; secondly, verbal bullying (ß = 0.084, P <0.001), physical bullying (ß = 0.222, P <0.001) and social relationship bullying (ß = 0.122, P <0.001) have a positive and significant impact on the suicidal tendencies of college students; in addition, family support and teacher emotional support have a significant regulatory effect on the bully victim and college students Suicidal Tendencies and family support. The regulating effect was significantly higher than that of teacher emotional support. Conclusion: Chinese college students have the risk of suicidal tendencies; peer bullying victimization is an important reason for affecting college students' suicidal tendencies, teacher emotional support is a protective factor for bully victims to affect college students' suicidal tendencies, and family support has a significant moderating effect on the bully victim and college students' suicidal tendencies. Therefore, it is necessary to actively adopt home-school linkage and home-school communication to reduce campus violence and increase the psychological resilience of college students.

Optimized solubility and bioavailability of genistein based on cocrystal engineering.

With various potential health-promoting bioactivities, genistein has great prospects in treatment of a series of complex diseases and metabolic syndromes such as cancer, diabetes, cardiovascular diseases, menopausal symptoms and so on. However, poor solubility and unsatisfactory bioavailability seriously limits its clinical application and market development. To optimize the solubility and bioavailability of genistein, the cocrystal of genistein and piperazine was prepared by grinding assisted with solvent based on the concept of cocrystal engineering. Using a series of analytical techniques including single-crystal X-ray diffraction, powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry and thermogravimetric analysis, the cocrystal was characterized and confirmed. Then, structure analysis on the basis of theoretical calculation and a series of evaluation on the stability, dissolution and bioavailability were carried out. The results indicated that the cocrystal of genistein and piperazine improved the solubility and bioavailability of genistein. Compared with the previous studies on the cocrystal of genistein, this is a systematic and comprehensive investigation from the aspects of preparation, characterization, structural analysis, stability, solubility and bioavailability evaluation. As a simple, efficient and green approach, cocrystal engineering can pave a new path to optimize the pharmaceutical properties of natural products for successful drug formulation and delivery.

HOXB3 promotes trophoblast cell proliferation, invasion, and migration to alleviate preeclampsia via mediating the Notch/Wnt/ß-catenin pathway.

Preeclampsia (PE) harms a significant number of pregnant women and fetuses. However, because of its complex pathological mechanisms, there is no cure except for delivery. This study identified the impact and mechanisms of action of HOXB3 in PE. The behaviors of HTR-8/SVneo cells were analyzed using a cell counting kit-8, EdU, and transwell assays. The interaction between HOXB3 and Notch1 was assessed using a luciferase reporter and chromatin immunoprecipitation assays. Expression was measured by quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence assays. Additionally, the function of HOXB3 was evaluated in an established rat model of PE. We found that HOXB3 was upregulated in PE. HOXB3 overexpression facilitated trophoblast cell proliferation, migration, and invasion. HOXB3 transcriptionally regulated Notch1 by binding to its promoter. Notch1 knockdown abrogated the functions of HOXB3 and the-catenin pathway in trophoblasts. Suppression of the Wnt/ß-catenin pathway abrogated the effects of HOXB3. Additionally, HOXB3 alleviated the symptoms in PE rats. In conclusion, HOXB3 transcriptionally activated Notch1 expression and the-catenin pathway, promoting trophoblast cell proliferation, invasion, and migration, thereby alleviating PE progression. This study provides a novel approach for PE therapy.

Reconstitution of double-negative T cells after cord blood transplantation and its predictive value for acute graft-versus-host disease.

BACKGROUND: With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation (UCBT), the correlation between immune reconstitution (IR) after UCBT and graft-versus-host disease (GVHD) has been reported successively, but reports on double-negative T (DNT) cell reconstitution and its association with acute GVHD (aGVHD) after UCBT are lacking. METHODS: A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology, the First Affiliated Hospital of USTC, between August 2018 and June 2021. IR differences were compared between the patients with and without aGVHD. RESULTS: The absolute number of DNT cells in the healthy Chinese population was 109 (70-157)/µL, accounting for 5.82 (3.98-8.19)% of lymphocytes. DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation. Importantly, the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year (F = 4.684, P = 0.039 and F = 5.583, P = 0.026, respectively). In addition, the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased, and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD (HR = 0.46, 95% confidence interval [CI]: 0.23-0.93; P = 0.031). CONCLUSIONS: Compared to the number of DNT cells in Chinese healthy people, the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow. In addition, the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

A systematic review and meta-analysis of factors related to non-suicidal self-injury among Chinese adolescents.

BACKGROUND: Over the past several decades the prevalence of adolescent non-suicidal self-injury (NSSI) has been rising steadily. Understanding the factors associated with NSSI is a critical public health concern. The current study aims to explore the critical factors related to NSSI among Chinese adolescents. METHODS: A systematic literature search was conducted to identify the studies meeting our eligibility criteria (published until June 2022) in PubMed, Web of Science, Science Direct, Springer Link, CNKI, VIP, and Wanfang data. The meta-package of R language was used to perform a meta-analysis to compute the pooled effect (r). RESULTS: A total of 59 studies were included in this analysis, with a sample size of 192,546. Twenty-four democratic, personal, and social factors were examined in current study. The pooled effect value (r) has revealed that 23 factors are associated with NSSI behaviors among Chinese adolescents. The factor, Internet addiction, has demonstrated the greatest association with NSSI compared to other factors. CONCLUSION: Consistent with previous studies on adolescent NSSI, findings have demonstrated that a number of demographic, personal, and social factors significantly contribute to NSSI behaviors among Chinese adolescents. Future research on prevention and intervention for adolescent NSSI may benefit from targeting these factors.

Versatile Solid Modifications of Multicomponent Pharmaceutical Salts: Novel Metformin-Rhein Salts Based on Advantage Complementary Strategy Design.

This study aimed to develop an effective treatment for diabetes and diabetic complications, based on the advantage complementary strategy of drug-drug salt, by designing and synthesizing the multicomponent molecular salts containing metformin (MET) and rhein (RHE). Finally, the salts of MET-RHE (1:1), MET-RHE-H2O (1:1:1), MET-RHE-ethanol-H2O (1:1:1:1), and MET-RHE-acetonitrile (2:2:1) were obtained, indicating the polymorphism of salts formed by MET and RHE. The structures were analyzed by the combination of characterization experiments and theoretical calculation, and the formation mechanism of polymorphism was discussed. The obtained results of in vitro evaluation showed that MET-RHE had a similar hygroscopicity with metformin hydrochloride (MET·HCl), and the solubility of the component of RHE increased by approximately 93 times, which laid a foundation for improving the bioavailability of MET and RHE in vivo. The evaluation of hypoglycemic activity in mice (C57BL/6N) indicated that MET-RHE exhibited better hypoglycemic activity than the parent drugs and the physical mixtures of MET and RHE. The above findings demonstrate that this study achieved the complementary advantages of MET and RHE through the multicomponent pharmaceutical salification technique, and provides new possibilities for the treatment of diabetic complications.

Application potential of zero-valent aluminum in nitrophenols wastewater decontamination: Enhanced reactivity, electron selectivity and anti-passivation capability.

Nitrophenols (NPs) are highly toxic and easy to accumulate to high concentrations (> 500 mg/L) in real wastewater. The nitro group contained in NPs is an electron-absorbing group that is easy to reduce and difficult to oxidize, so there is an urgent need to develop reduction removal technology. Zero-valent aluminum (ZVAl) is an excellent electron donor that can reductively transform various refractory pollutants. However, ZVAl is prone to rapid deactivation due to non-selective reactions with water, ions, etc. To overcome this critical limitation, we prepared a new type of carbon nanotubes (CNTs) modified microscale ZVAl, CNTs@mZVAl, through a facile mechanochemical ball milling method. CNTs@mZVAl had outstanding high reactivity in degrading p-nitrophenol even 1000 mg/L and showed up to 95.50% electron utilization efficiency. Moreover, CNTs@mZVAl was highly resistant to the passivation by dissolved oxygen, ions and natural organic matters coexisting in water matrix, and remained highly reactive after aging in the air for 10 days. Furthermore, CNTs@mZVAl could effectively remove dinitrodiazophenol from real explosive wastewater. The excellent performance of CNTs@mZVAl is due to the combination of selective adsorption of NPs and CNTs-mediated e-transfer. CNTs@mZVAl looks promising for the efficient and selective degradation of NPs, with broader prospects for real wastewater treatment.

Design, Preparation, Characterization and Evaluation of Five Cocrystal Hydrates of Fluconazole with Hydroxybenzoic Acids.

To modulate the physicochemical properties of fluconazole (FLZ), a multifunctional antifungal drug, the crystal engineering technique was employed. In this paper, five novel cocrystal hydrates of FLZ with a range of phenolic acids from the GRAS list, namely, 2,4-dihydroxybenzoic acid (24DHB), 3,4-dihydroxybenzoic acid (34DHB, form I and form II), 3,5-dihydroxybenzoic acid (35DHB), and 3,4,5-trihydroxybenzoic acid (345THB) were disclosed and reported for the first time. Crystals of these five hydrates were all obtained for single-crystal X-ray diffraction (SCXRD) analysis. Robust (hydroxyl/carboxyl) O-H. . . Narom hydrogen bonds between acids and FLZ triazolyl moiety were observed to be dominant in guiding these crystal forms. The water molecule plays the role of supramolecular "linkage" in the strengthening and stabilization of these hydrates by interacting with FLZ and acids through O-H. . . O hydrogen bonds. In particular, the formation of FLZ-34DHB-H2O (1:1:1) significantly reduces hygroscopicity and hence improves the stability of FLZ, the latter of which is unstable and easily transforms into its monohydrate form. Increased initial dissolution rates were observed in the obtained cocrystal forms, and an enhanced intrinsic dissolution rate was obtained in FLZ-35DHB-H2O (1:1:1) in comparison with commercialized FLZ form II.

Recent Advances on the Biological Study of Pharmaceutical Cocrystals.

As a low-risk, low-cost, but high-reward route, cocrystallization of drugs with appropriate coformers is applied to improve the physiochemical and biopharmaceutical properties of drugs. Currently, most researchers concentrate their efforts on the preparation, characterization, and improvement of physicochemical properties of pharmaceutical cocrystals. On the contrary, the biological study of pharmaceutical cocrystals has not attracted wide attention of researchers. In this review, we have focused on recent advances reporting the biological studies of pharmaceutical cocrystals. The covered areas consist of the solubility and permeability, the pharmacokinetics study, metabolism and distribution, pharmacodynamics research, and the toxicological evaluation of pharmaceutical cocrystals. Besides, discussions have been made on the in vivo-in vitro correlations for pharmaceutical cocrystals, the enhancement of efficiency and reduction of toxicity for pharmaceutical cocrystals, and the interaction between APIs and coformers in pharmaceutical cocrystals and marketed pharmaceutical cocrystals as well as their biological studies. At the same time, some problems such as the amount of animal samples, the number and distribution of blood sampling points, investigation on the pharmacokinetics of physical mixtures containing APIs and coformers, and the consideration of species differences should be taken into account. Although pharmaceutical cocrystals face some challenges in clarifying the characteristics of metabolism and distribution, revealing potential pharmacological mechanism, and evaluating safety, cocrystal engineering is still considered a green and promising approach to developing valuable new drugs.

The influence of alkali-modified biochar on the removal and release of Zn in bioretention systems: Adsorption and immobilization mechanism.

Generally, Zn in stormwater runoff is considered as low toxicity, but in the senarios of roads and zinc-based materials roof runoff, the concentration of Zn becomes extremely high and cannot be ignored. Bioretention systems are used to remove heavy metals from stormwater runoff, while Zn adsorption is insufficient by conventional filler and is prone to secondary release when exposed to acid rain or high salinity runoff. This study integrated batch experiments and density functional theory calculation to investigate the mechanisms of how KOH-modified biochar (KBC) influences the removal and release of Zn in bioretention systems. The results revealed that KBC adsorbed 89.0-97.5% Zn in the influent, the main adsorption mechanism were complexation and precipitation, and precipitation is more important. In addition, 67% of Zn was immoblized as the residual form by KBC. In acidic and saline runoff, KBC reduced Zn secondary release by 43.6% and 37.08% compared to the results in the absence of KBC, which was attributed to the convertion of most dissolved Zn in acidic and saline runoff into residual Zn. Therefore, KBC has a considerable application potential not only to decontaminate the runoff of roads and Zn-containing roofs, but also to deal with secondary Zn release in acid rain or under the treatment of snow-melting agents.

Systems Pharmacology-Based Strategy to Investigate Pharmacological Mechanisms of Total Flavonoids in Dracocephalum moldavica on Chronic Heart Failure.

Heart failure (HF) is a clinical syndrome of cardiac insufficiency caused by abnormalities in cardiac structure and function that arise for various reasons, and it is the final stage of most cardiovascular diseases' progression. Total flavonoid extract from Dracocephalum moldavica L. (TFDM) has many pharmacological and biological roles, such as cardioprotective, neuroprotective, anti-atherogenic, antihypertensive, anti-diabetic, anti-inflammatory, antioxidant, etc. However, its effect on HF and its molecular mechanism are still unclear. In this study, we used systems pharmacology and an animal model of HF to investigate the cardioprotective effect of TFDM and its molecular mechanism. Eleven compounds in TFDM were obtained from the literature, and 114 overlapping genes related to TFDM and HF were collected from several databases. A PPI network and C-T network were established, and GO enrichment analysis and KEGG pathway analysis were performed. The top targets from the PPI network and C-T network were validated using molecular docking. The pharmacological activity was investigated in an HFpEF (heart failure with preserved ejection fraction) mouse model. This study shows that TFDM has a protective effect on HFpEF, and its protective mechanism may be related to the regulation of proinflammatory cytokines, apoptosis-related genes, fibrosis-related genes, etc. Collectively, this study offers new insights for researchers to understand the protective effect and mechanism of TFDM against HFpEF using a network pharmacology method and a murine model of HFpEF, which suggest that TFDM is a promising therapy for HFpEF in the clinic.

Potential of Establishing the Corresponding Human Microbial Community in Pseudo Germ-Free Mice through Fecal Microbe Transfer from Three Urolithin Metabotypes.

Three urolithin metabotypes (UMs) have been defined in the population according to final urolithins converted by gut microbiota. Currently, it is difficult to establish the cause-and-effect relationship between urolithins and microbiota in human studies. Studies on the health effects of ellagic acid (EA) in animal models rarely consider the differences in the urolithin production. Therefore, the objective of this study is to establish human microbiota-associated (HMA) mice, imitating the microbiota composition of the three UMs. Antibiotic-induced pseudo germ-free mice were gavaged with fecal bacteria of the three UM donors for four weeks. The results showed that the ability to produce corresponding urolithins was successfully transferred from the donor of the three UMs to HMA mice. The three UM HMA mice adopted a humanized microbiota profile similar to their corresponding donor. The family Eggerthellaceae and genera Eggerthella and Gordonibacter were successfully transferred and colonized from UM-A/B donors to HMA mice. Overall, the three UM HMA mouse models were successfully established, which provide a basis for exploring the health effects of EA.

Toward rapid reduction of carbon tetrachloride in water by zero-valent aluminum/persulfate system.

The oxidation performance of the zero-valent aluminum (ZVAl)/persulfate (PS) combined system had been studied by researchers in the past, which relied on the activation of PS by ZVAl to generate potent oxidizing radicals (•OH and SO4•-) to degrade pollutants. However, ZVAl is a strong reductant and its reduction effect cannot be ignored. The reductive performance of the ZVAl/PS combined system is still unknown. Therefore, carbon tetrachloride (CT), an antioxidant organic pollutant, was selected as the target pollutant to test the reductive performance of the ZVAl/PS system in this study. We found a significant synergistic effect between ZVAl and PS, and the ZVAl/PS combined system could rapidly degrade CT in a wide pH range of 3-11 after an induction period. By SEM-EDS, TEM, XPS, and XRD analysis, it was found that PS could promote the corrosion of the oxide film on the ZVAl surface. The quenching experiment proved that PS could accept the electrons released from ZVAl to produce superoxide radical anion (O2•-), which led to the degradation of CT rather than the oxidative process by •OH and SO4•-. The hydrogen evolution experiment indicated that electronic reduction might play a secondary role in CT degradation. In conclusion, our study further explored the reductive performance of the ZVAl/PS combined system and expanded the pathway of CT degradation without any organic solvent addition, which provides a new strategy for the efficient degradation of refractory halogenated organic pollutants.

Insights Into the Properties of Amygdalin Solvatomorphs: X-ray Structures, Intermolecular Interactions, and Transformations.

Amygdalin is an effective component of the traditional Chinese medicine bitter almond, peach kernel, and plum kernel. It has pharmacological effects, such as relieving cough and asthma. In a study of the crystallization process, we found a series of solvatomorphs of amygdalin (including hydrate). Interestingly, in the structures of these solvatomorphs, the same characteristic structural fragment is present, that is, amygdalin dihydrate. Multiple analytical techniques were used to characterize the solvatomorphs, such as X-ray diffraction and thermogravimetry-mass spectrometry. Void calculations of water and solvent were used to analyze the occupied volume in the unit cell of the corresponding solvatomorphs to explain the formation mechanism of the solvatomorphs from the perspective of space. To elucidate the formation mechanism of the solvatomorphs with this kind of characteristic structure from the perspective of energy, theoretical calculations based on density functional theory were applied, such as energy decomposition and molecular electrostatic potential surfaces. In addition, the transformation phenomenon between these solvatomorphs and amygdalin was identified, and the transformation pathways are described in detail.

Cocrystals of Praziquantel with Phenolic Acids: Discovery, Characterization, and Evaluation.

Solvent-assisted grinding (SAG) and solution slow evaporation (SSE) methods are generally used for the preparation of cocrystals. However, even by using the same solvent, active pharmaceutical ingredient (API), and cocrystal coformer (CCF), the cocrystals prepared using the two methods above are sometimes inconsistent. In the present study, in the cocrystal synthesis of praziquantel (PRA) with polyhydroxy phenolic acid, including protocatechuic acid (PA), gallic acid (GA), and ferulic acid (FA), five different cocrystals were prepared using SAG and SSE. Three of the cocrystals prepared using the SAG method have the structural characteristics of carboxylic acid dimer, and two cocrystals prepared using the SSE method formed cocrystal solvates with the structural characteristics of carboxylic acid monomer. For phenolic acids containing only one phenolic hydroxyl group (ferulic acid), when preparing cocrystals with PRA by using SAG and SSE, the same product was obtained. In addition, the weak molecular interactions that were observed in the cocrystal are explained at the molecular level by using theoretical calculation methods. Finally, the in vitro solubility of cocrystals without crystal solvents and in vivo bioavailability of PRA-FA were evaluated to further understand the influence on the physicochemical properties of API for the introduction of CCF.