Fibroblast growth factor 7 protects osteoblasts against oxidative damage through targeting mitochondria.

The pathophysiology of osteoporosis is significantly influenced by the impaired functioning of osteoblasts, which is particularly caused by oxidative stress. Nevertheless, the underlying mechanisms responsible for this phenomenon are still not well understood. The objective of this study was to elucidate the impact of fibroblast growth factor 7 (FGF7) on the behavior of osteoblasts under conditions of oxidative stress. The osteoblast-like MC3T3 cells were pretreated with recombinant FGF7 in the presence of oxidative stress induced by hydrogen peroxide (H2 O2 ). We first provided the evidence that the endogenous FGF7 was significantly increased in osteoblasts in response to the increased H2 O2 levels. Recombined FGF7 demonstrated a remarkable capacity to resist the detrimental effects of H2 O2 -induced oxidative stress, including the increase in cell apoptosis, decrease in osteoblast viability, and impairment in osteogenic differentiation capacity, on osteoblasts. Furthermore, we extensively explored the mechanism underlying these protective effects and discovered a remarkable modulation of reactive oxygen species (ROS) homeostasis in H2 O2 -treated cells following the pronounced expression of FGF7, which significantly differed from the control group. Additionally, we observed that FGF7 exerted partial preservation on both the morphology and function of mitochondria when exposed to oxidative stress conditions. Furthermore, FGF7 exhibited the ability to enhance the activation of the p38/MAPK signaling pathway while concurrently suppressing the JNK/MAPK signaling pathway in response to oxidative stress. These results underscore the promising role and underlying mechanisms of FGF7 in preserving osteoblast homeostasis in the face of oxidative stress.

Genome-wide analysis of acid tolerance genes of Enterococcus faecalis with RNA-seq and Tn-seq.

Enterococcus faecalis, a formidable nosocomial and community-acquired opportunistic pathogen, can persist a wide range of extreme environments, including low pH and nutrient deficiency. Clarifying the survival mechanism of E. faecalis in low-pH conditions is the key to combating the infectious diseases caused by E. faecalis. In this study, we combined transcriptome profiling (RNA-seq) and transposon insertion sequencing (TIS) to comprehensively understand the genes that confer these features on E. faecalis. The metadata showed that genes whose products are involved in cation transportation and amino acid biosynthesis were predominantly differentially expressed under acid conditions. The products of genes such as opp1C and copY reduced the hydrion concentration in the cell, whereas those of gldA2, gnd2, ubiD, and ubiD2 mainly participated in amino metabolism, increasing matters to neutralize excess acid. These, together with the folE and hexB genes, which are involved in mismatch repair, form a network of E. faecalis genes necessary for its survival under acid conditions.

IMPORTANCE: As a serious nosocomial pathogen, Enterococcus faecalis was considered responsible for large numbers of infections. Its ability to survive under stress conditions, such as acid condition and nutrient deficiency was indispensable for its growth and infection. Therefore, understanding how E. faecalis survives acid stress is necessary for the prevention and treatment of related diseases. RNA-seq and TIS provide us a way to analyze the changes in gene expression under such conditions.

Overcoming the Low-Stability Bottleneck in the Clinical Translation of Liposomal Pressurized Metered-Dose Inhalers: A Shell Stabilization Strategy Inspired by Biomineralization.

Currently, several types of inhalable liposomes have been developed. Among them, liposomal pressurized metered-dose inhalers (pMDIs) have gained much attention due to their cost-effectiveness, patient compliance, and accurate dosages. However, the clinical application of liposomal pMDIs has been hindered by the low stability, i.e., the tendency of the aggregation of the liposome lipid bilayer in hydrophobic propellant medium and brittleness under high mechanical forces. Biomineralization is an evolutionary mechanism that organisms use to resist harsh external environments in nature, providing mechanical support and protection effects. Inspired by such a concept, this paper proposes a shell stabilization strategy (SSS) to solve the problem of the low stability of liposomal pMDIs. Depending on the shell material used, the SSS can be classified into biomineralization (biomineralized using calcium, silicon, manganese, titanium, gadolinium, etc.) biomineralization-like (composite with protein), and layer-by-layer (LbL) assembly (multiple shells structured with diverse materials). This work evaluated the potential of this strategy by reviewing studies on the formation of shells deposited on liposomes or similar structures. It also covered useful synthesis strategies and active molecules/functional groups for modification. We aimed to put forward new insights to promote the stability of liposomal pMDIs and shed some light on the clinical translation of relevant products.

ATP-binding cassette protein ABCA7 deficiency impairs sphingomyelin synthesis, cognitive discrimination, and synaptic plasticity in the entorhinal cortex.

Sphingomyelin (SM) is an abundant plasma membrane and plasma lipoprotein sphingolipid. We previously reported that ATP-binding cassette family A protein 1 (ABCA1) deficiency in humans and mice decreases plasma SM levels. However, overexpression, induction, downregulation, inhibition, and knockdown of ABCA1 in human hepatoma Huh7 cells did not decrease SM efflux. Using unbiased siRNA screening, here, we identified that ABCA7 plays a role in the biosynthesis and efflux of SM without affecting cellular uptake and metabolism. Since loss of function mutations in the ABCA7 gene exhibit strong associations with late-onset Alzheimer's disease across racial groups, we also studied the effects of ABCA7 deficiency in the mouse brain. Brains of ABCA7-deficient (KO) mice, compared with WT, had significantly lower levels of several SM species with long chain fatty acids. In addition, we observed that older KO mice exhibited behavioral deficits in cognitive discrimination in the active place avoidance task. Next, we performed synaptic transmission studies in brain slices obtained from older mice. We found anomalies in synaptic plasticity at the intracortical synapse in layer II/III of the lateral entorhinal cortex but not in the hippocampal CA3-CA1 synapses in KO mice. These synaptic abnormalities in KO brain slices were rescued with extracellular SM supplementation but not by supplementation with phosphatidylcholine. Taken together, these studies identify a role of ABCA7 in brain SM metabolism and the importance of SM in synaptic plasticity and cognition, as well as provide a possible explanation for the association between ABCA7 and late-onset Alzheimer's disease.

Dual peptides-modified cationic liposomes for enhanced Lung cancer gene therapy by a gap junction regulating strategy.

BACKGROUND: Gene therapy for lung cancer has emerged as a novel tumor-combating strategy for its superior tumor specificity, low systematical toxicity and huge clinical translation potential. Especially, the applications of microRNA shed led on effective tumor ablation by directly interfering with the crucial gene expression, making it one of the most promising gene therapy agents. However, for lung cancer therapy, the microRNA treatment confronted three bottlenecks, the poor tumor tissue penetration effect, the insufficient lung drug accumulation and unsatisfied gene transfection efficiency. To address these issues, an inhalable RGD-TAT dual peptides-modified cationic liposomes loaded with microRNA miR-34a and gap junction (GJ) regulation agent all-trans retinoic acid (ATRA) was proposed, which was further engineered into dry powder inhalers (DPIs). RESULTS: Equipped with a rough particle surface and appropriate aerodynamic size, the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs were expected to deposit into the deep lung and reach lung tumor lesions guided by targeting peptide RGD. Assisted by cellular transmembrane peptides TAT, the RGD-TAT-CLPs/ARTA@miR-34a was proven to be effectively internalized by cancer cells, enhancing gene transfection efficiency. Then, the GJ between tumor cells was upregulated by ARTA, facilitating the intercellular transport of miR-34a and boosting the gene expression in the deep tumor. CONCLUSION: Overall, the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs could enhance tumor tissue penetration, elevate lung drug accumulation and boost gene transfection efficiency, breaking the three bottlenecks to enhancing tumor elimination in vitro and in vivo. We believe that the proposed RGD-TAT-CLPs/ARTA@miR-34a DPIs could serve as a promising pulmonary gene delivery platform for multiple lung local disease treatments.

Differences in medical costs between TCM users and TCM nonusers in inpatients with thalassemia.

BACKGROUND: Thalassemia has brought serious health threats and economic burdens to patients worldwide. There is no sovereign remedy for thalassemia, both conventional and Traditional Medicine (TM) methods have certain effects on this disease. As typical of TM, Traditional Chinese Medicine (TCM) has been widely used in the treatment of thalassemia. Previous studies mainly focused on conventional treatments for thalassemia and patients' medical burden, but no research has examined the effects of TCM use on the economic burdens for thalassemia inpatients in mainland China. The main objective of this study is to compare the medical cost differences between TCM users and TCM nonusers, furtherly, we will discuss the role of TCM use in the treatment of thalassemia. METHODS: We employed the 2010-2016 Medicare claims database provided by the China Health Insurance Research Association (CHIRA). Chi-square and Mann-Whitney tests were used to analyze the differences between TCM users and TCM nonusers. Multiple regression analysis was performed using the ordinary least squares method to compare the TCM users' inpatient medical cost with TCM nonusers', and to further examine the correlation between TCM cost, conventional medication cost and nonpharmacy cost for TCM users. RESULTS: A total of 588 urban thalassemia inpatients were identified, including 222 TCM users and 366 TCM nonusers. The inpatient medical cost of TCM users was RMB10,048 (USD1,513), which was significantly higher than TCM nonusers (RMB1,816 (USD273)). Total inpatient cost for TCM users was 67.4% higher than those of TCM nonusers (P < 0.001). With confounding factors fixed, we found that the conventional medication cost and nonpharmacy cost were positively correlated with TCM cost. CONCLUSION: Total hospitalization expenses for TCM users were higher than TCM nonusers. Both the conventional medication cost and nonpharmacy cost of TCM users were all higher than TCM nonusers. We infer TCM plays a complementary role, rather than an alternative, in the treatment of thalassemia due to the lack of cooperative treatment guidelines. It is recommended that a cooperative diagnosis and treatment guidelines should be generated to balance the use of TCM and conventional medicine for treating thalassemia, so as to reduce the economic burdens on patients.

Evaluation of developmental toxicity of safinamide in zebrafish larvae (Danio rerio).

Monoamine oxidase-B (MAO-B), as a principal metabolizing enzyme, plays important roles in the metabolism of catecholamines and xenobiotics in the central nervous system and peripheral tissues. Safinamide, the third-generation reversible MAO-B inhibitor, has potential to alleviate many neurological diseases such as Parkinson's disease (PD) and depression. Exposure to clinical psychotropic drugs often has adverse effects on fetuses. Currently, a variety of studies of safinamide focus on its curative effect and pharmacological effect, while its side effect of embryonic development is barely studied. In this study, we used zebrafish as a model to evaluate the embryonic developmental toxicity of safinamide. Our results revealed that higher concentrations (30 µM) of safinamide treatment caused a decrease in hatching rate and an increase in malformation and mortality in zebrafish larvae. Meanwhile, we observed that lower safinamide exposure (10 µM) increased the body length of zebrafish larvae and resulted in hyperactivity-like behaviors. In addition, an increased trend in dopamine (DA) level was found in 3.3 µM and 10 µM safinamide-exposed groups. Transcriptome analysis identified that safinamide exposure may disturb a variety of physiological processes such as neuroactive ligand-receptor interaction signaling pathway. In summary, our study reveals that safinamide may cause developmental defects in zebrafish larvae and provides insights into its toxic reactions in early develoment.

Developmental and behavioral toxicity assessment of opicapone in zebrafish embryos.

The use of clinical psychoactive drugs often poses unpredictable threats to fetal development. Catechol-O-methyltransferase (COMT) is a key enzyme that regulates dopamine metabolism and a promising target for modulation of cognitive functions. Opicapone, a newly effective third-generation peripheral COMT inhibitor, is used for the treatment of Parkinson's disease (PD) and possibly to improve other dopamine-related disorders such as alcohol use disorder (AUD) and obsessive-compulsive disorder (OCD). The widespread use of opicapone will inevitably lead to biological exposure and damage to the human body, such as affecting fetal development. However, the effect of opicapone on embryonic development remains unknown. Here, zebrafish larvae were used as an animal model and demonstrated that a high concentration (30 µM) of opicapone exposure was teratogenic and lethal, while a low concentration also caused developmental delay such as a shortened body size, a smaller head, and reduced locomotor behaviors in zebrafish larvae. Meanwhile, opicapone treatment specifically increased the level of dopamine (DA) in zebrafish larvae. The depletion response of the total glutathione level (including oxidized and reduced forms of glutathione) and changed antioxidant enzymes activities in zebrafish larvae suggest oxidative damage caused by opicapone. In addition, enhanced glutathione metabolism and cytokine-cytokine receptor interaction were found in zebrafish larvae treated with opicapone, indicating that opicapone treatment caused an oxidation process and immune responses. Our results provide a new insight into the significant developmental toxicity of opicapone in zebrafish larvae.

Medical costs and hospital utilization for hemophilia A and B urban inpatients in China: a national cross-sectional study.

BACKGROUND: Hemophilia care in mainland China has been greatly improved since the establishment of the Hemophilia Treatment Center Collaborative Network of China (HTCCNC), and most of drugs for hemophilia have been covered by basic medical insurance schemes. This study assesses whether medical costs and hospital utilization disparities exist between hemophilia A and hemophilia B urban inpatients in China and, second, whether the prescription of coagulation factor concentrates for hemophilia A and hemophilia B inpatients was optimal, from the third payer perspective. METHODS: We conducted a retrospective nationwide analysis based on a 5% random sample from claims data of China Urban Employees' Basic Medical Insurance (UEBMI) and Urban Residents' Basic Medical Insurance (URBMI) schemes from 2010 to 2016. Univariate analysis and multiple regression analysis based on a generalized linear model were conducted. RESULT: A total of 487 urban inpatients who had hemophilia were identified, including 407 inpatients with hemophilia A and 80 inpatients with hemophilia B. Total medical cost for hemophilia B inpatients was significantly higher than for hemophilia A inpatients (USD 2912.81 versus USD 1225.60, P < 0.05), and hemophilia B inpatients had a significantly longer length of hospital stay than hemophilia A inpatients (9.00 versus 7.00, P < 0.05). Total medical costs were mostly allocated to coagulation factor products (76.86-86.68%), with coagulation factor cost of hemophilia B significantly higher than hemophilia A (P < 0.05). Both hemophilia cohorts utilized greatest amount of plasma-derived Factor VIII, followed by recombinant Factor VIII and prothrombin complex concentrates. CONCLUSIONS: Patients with hemophilia B experienced significantly higher inpatient cost, coagulation factor cost and longer length of hospital stay than patients with hemophilia A. Our findings revealed the suboptimal use of coagulation factor concentrate drugs and a higher drug cost burden incurred by hemophilia B than hemophilia A inpatients. Our results call for efforts to strengthen drug regulatory management for hemophilia and to optimize medical insurance schemes according to hemophilia types.

Online selection of a physician by patients: the impression formation perspective.

BACKGROUND: With the rapid development of online health communities (OHCs), an increasing number of physicians provide services in OHCs that enable patients to consult online in China. However, it is difficult for patients to figure out the professional level of doctors before consultation and diagnosis because of information asymmetry. A wealth of information about physicians is displayed in their profiles as a new way to help patients evaluate and select quickly and accurately. OBJECTIVE: This research explores how the profile information (PI) presented in OHCs influences patients' impression formation, especially the perception of professional capital (i.e., status capital and decisional capital). The impression influences their intention to consult further, which is partially mediated by the initial trust. The Toulmin's model of argumentation is used to decide the strength of the argument presented in physicians' homepage information and divide it into claim, data, and backing. METHODS: This study conducts an internet experiment and recruits 386 subjects through the internet to investigate the effect of impression formation on online selection behavior by a patient. RESULTS: The results show that the strength of argument has a significant positive association with the perception of professional capital. Perceptions of professional capital are highest when a fully composed argument (claim/data/backing) is included in a profile, with claim/data being the next highest and claim only the lowest. Recommendations from connections have the strongest impact. In turn, patients' selection decisions are influenced by their perception of professional capital, which is partially mediated by initial trust. CONCLUSIONS: This study is significant in terms of its implications for theory and practice. On the one hand, this research contributes to the online health community literature and suggests that the perception of professional capital on physicians should be pre-presumed and built based on the information before in-person interaction online. On the other hand, this study is helpful in understanding the effect of various components included in PI on perceiving physicians' abilities, and not all information is equally important.

Three Different Interaction Patterns between MCM-41 and Proteins.

As one of the most studied mesoporous silica nanoparticles (MSNs) in drug delivery systems, Mobil Composition of Matter No. 41 (MCM-41) possesses unique properties including perfect channel architecture, excellent load capacity, and good biocompatibility. However, the applications of MCM-41 nanoparticles in drug delivery have not yet been industrialized, due to the interaction between MCM-41 and biomolecules (especially proteins) that affect their in vivo behaviors after dosing. To investigate the interactions between MCM-41 and proteins, this study selected bovine serum albumin (BSA), lysozyme (Lyso), and bovine hemoglobin (BHb) as model proteins and characterized the ultraviolet-visible, fluorescence, circular dichroism spectra and the protein adsorption of MCM-41-protein complex. The UV-Vis spectra exhibited the different absorption increment degrees of three proteins. The fluorescence spectra showed that the fluorescence intensity of proteins changed by different trends. The CD spectra indicated that the secondary structure changes were ranked as BSA > Lyso > BHb, which is consistent with the protein's adsorption capability on MCM-41. It was shown that there were three different patterns of MCM-41-proteins interactions. The hydrophilic and low-charged BSA followed the strong interaction pattern, the hydrophilic but heavily charged Lyso followed the moderate interaction pattern, and the hydrophobic BHb followed the weak interaction pattern. Different interaction patterns would lead to different effects on the structural properties of proteins, the surface chemistry of MCM-41, and the absorption capability of proteins on MCM-41. We believe our study will provide a better insight into the application of MCM-41 nanoparticles in drug delivery systems.

Dry Powder Inhalers Based on Chitosan-Mannitol Binary Carriers: Effect of the Powder Properties on the Aerosolization Performance.

Carriers play an important role in improving the aerosolization performance of dry powder inhalers (DPIs). Despite that intensive attention had been paid to the establishment of the advanced carriers with controllable physicochemical properties in recent years, the design and optimization of carrier-based DPIs remain an empiricism-based process. DPIs are a powder system of complex multiphase, and thus their physicochemical properties cannot fully explain the powder behavior. A comprehensive exposition of powder properties is demanded to build a bridge between the physicochemical properties of carriers and the aerosolization performance of DPIs. In this study, an FT-4 powder rheometer was employed to explore the powder properties, including dynamic flow energy, aeration, and permeability of the chitosan-mannitol binary carriers (CMBCs). CMBCs were self-designed as an advanced carrier with controllable surface roughness to obtain enhanced aerosolization performance. The specific mechanism of CMBCs to enhance the aerosolization performance of DPIs was elaborated based on the theory of pulmonary delivery processes by introducing powder properties. The results exhibited that CMBCs with appropriate surface roughness had lower special energy, lower aeration energy, and higher permeability. It could be predicted that CMBC-based DPIs had greater tendency to fluidize and disperse in airflow, and the lower adhesion force between particles enabled drugs to be detached from the carrier to achieve higher fine particle fractions. The specific mechanism on how physicochemical properties influenced the aerosolization performance during the pulmonary delivery processes could be figured out with the introduction of powder properties.

[Correlational Study of Thyroid-Stimulating Hormone and Salivary Microecology].

Objective: To investigate the relationship between the composition of salivary microecology and thyroid-stimulating hormone (TSH) levels in healthy adults. Methods: Healthy subjects were included in the high-TSH group (n=22, 3.00-4.20 mIU/L) and the low-TSH group (n=24, 0.60-1.80 mIU/L) according to their TSH level. Clinical and laboratory examinations were conducted to measure and analyze the relevant clinical and biochemical indicators. Saliva samples were collected in the two groups and microbial genetic profiles were acquired by 16S rDNA sequencing and bioinformatics analysis. Results: There was no significant difference in the relevant clinical and biochemical indicators between the high-TSH group and the low-TSH group (P>0.05). Individuals with higher TSH levels had higher abundance and species diversity of salivary microbiome. Partial least squares discriminant analysis (PLS-DA) found that the microecology of the the high-TSH group and the low-TSH group (Adonis, P=0.0460) showed obvious differences in ß diversity. Wilcoxon rank-sum test and LEFSe analysis showed significant difference in the abundance of Fusobacteriumbetween the high-TSH group and the low-TSH group. Conclusion: Differences in the composition of microecology were observed in the saliva of healthy subjects with high TSH levels and those with low TSH levels, and the abundance of Fusobacteriumshowed the most significant difference between the high and low TSH groups.

Health care utilization for patients with stroke: a 3-year cross-sectional study of China's two urban health insurance schemes across four cities.

BACKGROUND: Stroke is a devastating disease and a major cause of death and disability in China. While existing studies focused mainly on differences in stroke patients' health care utilization by insurance type, this study assesses whether health utilization and medical costs differed by insurance type across four cities in China. METHODS: A 5% random sample from the 2014-2016 China Urban Employees' Basic Medical Insurance (UEBMI) and Urban Residents' Basic Medical Insurance (URBMI) claims data were collected across four cities, Beijing, Shanghai, Tianjin, and Chongqing. Descriptive statistics and ordinary least squares regression were employed to analyze the data. RESULTS: We found that differences in healthcare utilization and inpatient and outpatient medical expenses varied more by city-specific insurance type than they did between the UEBMI and URBMI schemes. For example, the median UEBMI medical outpatient costs in Beijing (RMB500.2) were significantly higher than UEBMI patients in Shanghai (RMB260.8), Tianjin (RMB240.8), and Chongqing (RMB293.0), and Beijing URBMI patients had significantly higher outpatient medical costs (RMB356.9) than URBMI patients in Shanghai (RMB233.4) and Chongqing (RMB211.0), which were significantly higher than Tianjin (RMB156.2). Patients in Chongqing had 66.4% (95% CI: - 0.672, - 0.649) fewer outpatient visits, 13.0% (95% CI: - 0.144, - 0.115) fewer inpatient visits, and 34.2% (95% CI: - 0.366, - 0.318) shorter length of stay than patients in Beijing. The divergence of average length of stay and out-of-pocket (OOP) expenses by insurance type was also greater between cities than the UEMBI-URBMI mean difference. CONCLUSIONS: Significant city-specific differences in stroke patients' healthcare utilization and medical costs reflected inequalities in health care access. The fragmented social health insurance schemes in China should be consolidated to provide patients in different cities equal financial protection and benefit packages and to improve the equity of stroke patient access to health care.

An equity evaluation in stroke inpatients in regard to medical costs in China: a nationwide study.

BACKGROUND: Stroke has always been a severe disease and imposed heavy financial burden on the health system. Equity in patients in regard to healthcare utilization and medical costs are recognized as a significant factor influencing medical quality and health system responsiveness. The aim of this study is to understand the equity in stroke patients concerning medical costs and healthcare utilization, as well as identify potential factors contributing to geographic variation in stroke patients' healthcare utilization and costs. METHODS: Covering 31 provinces in mainland China, our main data were a 5% random sample of stroke claims from Urban Employees Basic Medical Insurance (UEBMI) and Urban Residents Basic Medical Insurance (URBMI) from 2013 to 2016. The Theil index was employed to evaluate the equity in stroke patients in regard to healthcare utilization and medical costs, and the random-effect panel model was used to explore the impact of province-level factors (health resource factors, enabling factors, and economic factors) on medical costs and health care utilization. RESULTS: Stroke patients' healthcare utilization and medical costs showed significant differences both within and between regions. The UEBMI scheme had an overall lower Theil index value than the URBMI scheme. The intra-region Theil index value was higher than the inter-region Theil index, with the Theil index highest within eastern China, China's richest and most developed region. Health resource factors and enabling factors (represented by reimbursement rate and education attainment years) were identified significantly associated with medical costs (P < 0.05), but have no impact on average length of stay. CONCLUSIONS: China's fragmented urban health insurance schemes require further reform to ensure better equity in healthcare utilization and medical costs for stroke patients. Improving education attainment, offering equal access to healthcare, allocating health resources reasonably and balancing health services prices in different regions also count.

Genome-Wide Identification and Expression Analysis of JAZ Family Involved in Hormone and Abiotic Stress in Sweet Potato and Its Two Diploid Relatives.

Jasmonate ZIM-domain (JAZ) proteins are key repressors of a jasmonic acid signaling pathway. They play essential roles in the regulation of plant growth and development, as well as environmental stress responses. However, this gene family has not been explored in sweet potato. In this study, we identified 14, 15, and 14 JAZs in cultivated hexaploid sweet potato (Ipomoea batatas, 2n = 6x = 90), and its two diploid relatives Ipomoea trifida (2n = 2x = 30) and Ipomoea triloba (2n = 2x = 30), respectively. These JAZs were divided into five subgroups according to their phylogenetic relationships with Arabidopsis. The protein physiological properties, chromosome localization, phylogenetic relationship, gene structure, promoter cis-elements, protein interaction network, and expression pattern of these 43 JAZs were systematically investigated. The results suggested that there was a differentiation between homologous JAZs, and each JAZ gene played different vital roles in growth and development, hormone crosstalk, and abiotic stress response between sweet potato and its two diploid relatives. Our work provided comprehensive comparison and understanding of the JAZ genes in sweet potato and its two diploid relatives, supplied a theoretical foundation for their functional study, and further facilitated the molecular breeding of sweet potato.

Major difference in particle size, minor difference in release profile: a case study of solid lipid nanoparticles.

Solid lipid nanoparticles (SLN) have been widely used in a variety of drug delivery routes, which have the outstanding advantage of controlled drug release. The release of SLN is dominated by many factors, among which the particle size of SLN is a critical one. The aim of this project was to explore the relationship between drug release profile and particle size of SLN. SLN were synthesized via the hot high-pressure homogenization (HPH) method, budesonide (BUD) was used as the model drug, and BUD-SLN1-BUD-SLN4 with increasing particle size was obtained, i.e. 120, 240, 360, and 480 nm. The prepared SLN has good encapsulation efficiency, drug loading capacity, and stability. In vitro release behavior studies showed that the cumulative release of BUD-SLN in Tris-Maleate (Tris-M) media was negligible, while that in Tris-M plus pancreatin media or Tris-M-ethanol media obeyed Ritger-Peppas model or first-order kinetic model, respectively. Noticeably, the release behavior of SLN was to some extent related to the average particle size of SLN, but the correlation was insignificant when the intersection degree of particle size distribution was great. This study provides a new idea for the understanding of in vitro release of SLN and has a certain referencing value for the research and development of novel nanomedicines.

Stability Evaluation of Lyotropic Liquid Crystalline Precursor for the Co-delivery of Chlorhexidine and Silver Nanoparticles.

Sealing the therapeutic agents in the root canal is considered to be an essential step in root canal therapy. The lyotropic liquid crystalline precursor (LLCP) incorporated with chlorhexidine (CHX) and silver nanoparticles (Ag-NPs) has been confirmed as a promising candidate for root canal therapy in the previous study. Importantly, the stability of the LLCP system was a significant determinant for its therapeutic effect and further application. The objective of this study was to comprehensively investigate the stability of the LLCP incorporated with CHX and Ag-NPs. The oil-water partition coefficient of CHX and Ag-NPs was measured. The water absorption and the physical stability of drug-loaded LLCP solution were studied. Stability under high temperature, high humidity, and strong light irradiation was also investigated. The results demonstrated that CHX and Ag-NPs could be entrapped in the water channel of LLCP, indicating the low tendency of drugs leakage. The drug-loaded LLCP was a pseudoplastic fluid and it showed an excellent physical stability with a sedimentation rate of 0.981 and a settling time of 26~28 h. The payload of LLCP was confirmed to weaken the water absorption behavior, which facilitated its transformation to cubic liquid crystal. The stress testing under high temperature, high humidity, and strong light irradiation also manifested that the LLCP was stable when stored under moisture-proof condition. In conclusion, the developed LLCP incorporated with CHX and Ag-NPs was highly stable during storage and qualified for further application.

Presence of voids after three obturation techniques in band-shaped isthmuses: a micro-computed tomography study.

BACKGROUND: The objective of the present micro-computed tomography (micro-CT) study was to assess the presence of voids in band-shaped isthmuses obturated using three different filling techniques. METHODS: Twenty-four artificial molar teeth with a band-shaped isthmus were allocated to three groups (n = 8) for obturation, according to the filling technique: single-cone (SC), continuous wave of condensation (CWC) or lateral condensation (LC). Obturation was performed with gutta-percha (GP) cones and iRoot SP (Innovative Bioceramix, Vancouver, Canada). Post-filling micro-CT scanning was performed. The percentage of filling materials and void volumes were calculated in the isthmus areas and data were analyzed using one-way ANOVA and Tukey tests. RESULTS: The mean percentage of void volumes and corresponding filling percentages in the isthmus areas after obturation in the SC groups was 22.98 % ± 1.19 %, 77.02 % ± 1.19 %; in the CWC groups 10.46 % ± 2.28 %, 89.54 % ± 2.28 %; and in the LC groups was 13.14 % ± 1.85 %, 86.86 % ± 1.85 %, respectively. CONCLUSIONS: In band-shaped isthmus area, the obturation quality of CWC was superior to SC and LC techniques.

Calcitriol tablets with hybrid lipid-based solid dispersions with enhanced stability and content uniformity.

Calcitriol, as the biologically active form of vitamin D3, is essential for patients with renal osteopathy. The solubilization, stabilization, and content uniformity are key issues in its formulation development. In our previous study, the incomplete release of calcitriol was solved by using the hybrid lipid-based solid dispersion (SD) for calcitriol. However, good stability and content uniformity are still urgently needed. In this study, solid lipid with antioxidant properties and liquid lipid compatible with calcitriol were employed as hybrid lipid carrier (HLC) to establish a solid dispersion. Moreover, the content uniformity of tablets with hybrid lipid carrier based SDs (HLCTs) was further guaranteed due to the multi-dispersion of calcitriol in HLC, solidification, and blank granules. Additionally, the compression of the blank granules was adjusted by the water content. The mixing method of calcitriol-containing and blank granules was also optimized. The obtained HLCTs were evaluated for hardness, disintegration time, in vitro drug dissolution, content uniformity, and stability. Satisfactory HLCTs were developed successfully in this study with superior content uniformity and better stability than the commercial soft capsule (Rocaltrol®). It was proved to be a promising formulation for drugs with poor water-solubility, instability to oxygen and heat, and dose-related toxicity.