Complete continuum of care for maternal health services and determinants among mothers who gave birth in the last year in Chiro City, Eastern Ethiopia: a community-based cross-sectional study (2024).

Introduction: Ethiopia has one of the highest maternal death rates in the world, with 412 deaths for every 100,000 live births. A qualified healthcare professional's care during pregnancy, delivery, and the postnatal period is crucial to saving the lives of the mother and her child. The continuum of maternity health services in Ethiopia is still shallow, despite efforts to increase the use of these services. This study's goal was to evaluate the magnitude and factors influencing the entire continuum of care for maternal health services in Chiro City in 2024. Methods: A community-based cross-sectional study was conducted from 15 January to 15 February 2024, among mothers who gave birth in the last year preceding the data collection period in Chiro City, Eastern Ethiopia. Data were collected through face-to-face interviews using a structured questionnaire. Multivariable logistic regression analysis was done to identify determinants of the complete continuum of care. A P-value of <0.05 was considered statistically significant in this study. Result: The prevalence of a complete continuum of care among mothers who gave birth in the last year in Chiro District was 37.0%. Accordingly, women who received ANC were 5.24 times more likely to complete the maternal health services continuum of care compared with their counterparts (AOR: 5.24, 95% CI: 1.94, 14.15). Compared with their counterparts, women who received health education were 4.36 times more likely to complete the continuum of care (AOR: 4.36, 95% CI: 2.0, 9.51). Similarly, women who had planned pregnancies were 4.32 times more likely to complete the maternal health services continuum of care than those who had unplanned pregnancies (AOR: 4.32, 95% CI: 2.38, 7.85). Conclusion and recommendation: The continuum of care was favorably correlated with ANC usage, health education, and planned pregnancies. To increase the coverage of the entire continuum of maternal care, it is desirable to develop programs that encourage women to initiate ANC contacts, provide health education, and promote planned pregnancies.

The effect of nanobubbles on Langmuir-Blodgett films.

Nanobubbles (NBs) are classified in two distinct categories: surface and bulk. Surface NBs are readily observed using atomic force microscopy (AFM), while the existence of bulk NBs has been a subject of debate, conflicting with the diffusion theory's predictions. Current methodologies for identifying bulk NBs yield inconclusive results. In this study, Langmuir Blodgett (LB) technique and AFM, are utilized to visualize NB imprints on anionic, cationic and zwitterionic lipid films deposited on glass-slide substrates. Our analysis of Langmuir monolayers compression isotherms reveals the impact of bulk NBs on lipid monolayer development. AFM scans of the deposited lipid films consistently show NB imprints. Notably, cationic and zwitterionic film depositions exhibit NB formations from the 1st layer, whereas in anionic films, these formations are observed only after the 3rd layer. These results suggest that the origin of these imprinted formations may be attributed to bulk NBs.

Carboxymethyl chitosan and octadecylamine-coated liposome-containing WPTS: design, optimization, and evaluation.

Liposomes (LPs) are a delivery system for stabilizing pharmaceuticals with limited use due to their propensity to congregate and fuse. A proposed method of addressing these problems is polymer coating. In this study, the potential of octadecylamine (ODA)-coated liposomes and carboxymethyl chitosan (CMCS/ODA-LPs) for enhancing Wacao pentacyclic triterpene saponin (WPTS) transport capacity was investigated. CMCS/ODA-LPs were produced by electrostatic adsorption and thin-film hydration. Response surface methodology (RSM) was employed to enhance the process and encapsulation efficiency (EE) for optimum drug encapsulation efficiency. The synthesized WPTS-CMCS/ODA-LPs were uniformly dispersed in a circular shape, and during 14 days of storage at 4 °C, the particle size and morphology did not significantly change. Vesicle size, zeta potential, polydispersity index (PDI), and entrapment efficiency (%) were 179.1 ± 7.31 nm, -29.6 ± 1.35 mV, 0.188 ± 0.052, and 75.62 ± 0.43, respectively. The hemolysis test revealed that WPTS-CMCS/ODA-LPs were sufficiently biocompatible. Compared to WPTS-LPs, WPTS-CMCS/ODA-LPs consistently showed a much more significant cytotoxic effect on cancer cells. Early and WPTS-CMCS/ODA-LPs-induced apoptosis resulted in almost seven times more cell death than the control. Compared to physiological pH 7.3, the pH-sensitive CMCS coupled LPs increased drug release at acidic pH 6.5. These findings suggest the efficacy of pH-sensitive CMCS/ODA-LPs as a medication delivery method for WPTS.

Insights from the COVID-19 pandemic: trends in development assistance committee countries' aid allocation, 2011-2021.

BACKGROUND: Official Development Assistance (ODA) significantly aids sustainable development in low- and middle-income countries (LMICs). However, the COVID-19 pandemic has impacted aid allocation, posing challenges for attaining the Sustainable Development Goals (SDGs). OBJECTIVE: This study explores and underscores the profound implications of shifts in ODA allocation by Development Assistance Committee (DAC) member countries, resulting from the COVID-19 pandemic, offering a unique perspective on the evolving landscape of international aid. METHODS: Drawing from the gross ODA disbursement data for LMICs by DAC member countries from 2011 to 2021, a linear regression analysis assessed the changes in ODA amount, ODA-to-gross national income (GNI) ratio, sectoral aid allocation, and the balance between bilateral and multilateral aid, primarily focusing on the differences pre- and post-COVID-19. For non-specialised multilateral agencies' core funding, the OECD's methodology for calculating imputed multilateral ODA was employed to estimate ODA flows. RESULTS: The study found an increasing trend in the total ODA provided by DAC member countries from 2011 to 2021. However, the average ODA/GNI ratio showed a slight but significant decrease before the pandemic, followed by an increase after the COVID-19 pandemic. The health sector received the highest percentage of aid after the pandemic, with a marked increase in both bilateral and multilateral aid. However, other sectors such as humanitarian aid, water and sanitation, and energy experienced a significant decrease in sectoral aid share. CONCLUSIONS: Emerging from this analysis is a strong recommendation for DAC members to re-evaluate aid objectives and escalate their financial commitments to reinforce SDGs and sustainable development efforts. While the rise in health aid is essential, other sectors also require equal focus to offset the ramifications of the COVID-19 pandemic. Understanding the intricacies of aid allocation can improve aid efficacy, culminating in greater, transformative results for recipient countries.

ATP-induced conformational change of axonemal outer dynein arms revealed by cryo-electron tomography.

Axonemal outer dynein arm (ODA) motors generate force for ciliary beating. We analyzed three states of the ODA during the power stroke cycle using in situ cryo-electron tomography, subtomogram averaging, and classification. These states of force generation depict the prepower stroke, postpower stroke, and intermediate state conformations. Comparison of these conformations to published in vitro atomic structures of cytoplasmic dynein, ODA, and the Shulin-ODA complex revealed differences in the orientation and position of the dynein head. Our analysis shows that in the absence of ATP, all dynein linkers interact with the AAA3/AAA4 domains, indicating that interactions with the adjacent microtubule doublet B-tubule direct dynein orientation. For the prepower stroke conformation, there were changes in the tail that is anchored on the A-tubule. We built models starting with available high-resolution structures to generate a best-fitting model structure for the in situ pre- and postpower stroke ODA conformations, thereby showing that ODA in a complex with Shulin adopts a similar conformation as the active prepower stroke ODA in the axoneme.

Pathogenic variants in CLXN encoding the outer dynein arm docking-associated calcium-binding protein calaxin cause primary ciliary dyskinesia.

PURPOSE: Primary ciliary dyskinesia (PCD) is a heterogeneous disorder that includes respiratory symptoms, laterality defects, and infertility caused by dysfunction of motile cilia. Most PCD-causing variants result in abnormal outer dynein arms (ODAs), which provide the generative force for respiratory ciliary beating and proper mucociliary clearance. METHODS: In addition to studies in mouse and planaria, clinical exome sequencing and functional analyses in human were performed. RESULTS: In this study, we identified homozygous pathogenic variants in CLXN (EFCAB1/ODAD5) in 3 individuals with laterality defects and respiratory symptoms. Consistently, we found that Clxn is expressed in mice left-right organizer. Transmission electron microscopy depicted ODA defects in distal ciliary axonemes. Immunofluorescence microscopy revealed absence of CLXN from the ciliary axonemes, absence of the ODA components DNAH5, DNAI1, and DNAI2 from the distal axonemes, and mislocalization or absence of DNAH9. In addition, CLXN was undetectable in ciliary axonemes of individuals with defects in the ODA-docking machinery: ODAD1, ODAD2, ODAD3, and ODAD4. Furthermore, SMED-EFCAB1-deficient planaria displayed ciliary dysmotility. CONCLUSION: Our results revealed that pathogenic variants in CLXN cause PCD with defects in the assembly of distal ODAs in the respiratory cilia. CLXN should be referred to as ODA-docking complex-associated protein ODAD5.

Analysis of orphan designation status for FDA approved drugs, and case studies in oncology, neuroscience and metabolic diseases.

Many new drugs have been approved over the past decade for rare or orphan diseases. The passage of the Orphan Drug Act (ODA) in 1983 has provided key economic and regulatory incentives to provide medicines for patients who are suffering from rare diseases that may not be commercially attractive for research and development. We have analyzed 497 novel drugs approved from 2010 - June 13, 2022, of which 220 were given orphan designation status. We discuss trends over this time period, potential risks for long development times, and provide example case studies of successful development and launch of novel drugs for rare diseases.

Analysis of health overseas development aid for internally displaced persons in low- and middle-income countries.

Background: There are an estimated 55 million internally displaced persons (IDPs) globally. IDPs commonly have worse health outcomes than host populations and other forcibly displaced populations such as refugees. Official development assistance (ODA) is a major source of the global financial response for health in low- and middle-income countries (LMICs), including for populations affected by armed conflict and forced displacement. Analysis of ODA supports efforts to improve donor accountability, transparency and the equitable use of ODA. The aim of this study is to examine international donor support and responsiveness to IDP health needs through analysis of ODA disbursements to LMICs between 2010 and 2019. Methods: ODA disbursement data to LMICs from 2010 to 2019 were extracted from the Creditor Reporting System (CRS) database and analysed with Stata software using a combination of: (i) text searching for IDP and refugee related terms; and (ii) relevant health and humanitarian CRS purpose codes. Descriptive analysis was used to examine patterns of ODA disbursement, and nonlinear least squared regression analysis was used to examine responsiveness of ODA disbursement to recipient country IDP population size and health system capacity and health characteristics. Findings: The study highlighted declining per IDP capita health ODA from USD 5.34 in 2010 to USD 3.72 in 2019 (with annual average decline of -38% from the 2010 baseline). In contrast, health ODA for refugees in LMICs increased from USD 18.55 in 2010 to USD 23.31 in 2019 (with an annual average increase of +14%). Certain health topics for IDPs received very low ODA, with only 0.44% of IDP health ODA disbursed for non-communicable diseases (including mental health). There was also weak evidence of IDP health ODA being related to recipient country IDP population size, and health system capacity and health characteristics. The paper highlights the need for increased investment by donors in IDP health ODA and to ensure that it is responsive to their health needs.

Donors' Interest in Water and Sanitation Subsectors.

International efforts have taken place to alleviate poverty by adopting several obligations within the international society; one of these obligations is the provision of safe access to water and sanitation. The MDGs helped people around the world to gain improved water sources and better sanitation. Although the sectoral aid increased from 20% between 1990 and 1992 (only 4.9% distributed for water supply and sanitation (W&S)) to 35% between 2002 and 2004 (only 3.9% allocated for W&S), facts showed that the allocated aid was biased to social aims rather than infrastructural targets. In this study, I am focusing on the donors' commitment for W&S, whether their ODA for these two sub-sectors is aligned with the intentions of the SDGs. I find that donors allocated W&S aid by focusing on governments in general with higher governance indicators, and that poorer countries received a higher allocation of aid.

Les efforts internationaux pour la réduction de la pauvreté ont pris forme à travers de plusieurs obligations adoptés par la société internationale. Une de ces obligations est l'approvisionnement d'accès sécuritaire à l'eau et à l'assainissement (en anglais, water supply and sanitation, W&S). Les Objectifs du Millénaire pour le Développement (en anglais : Millenuim Development Goals, MDGs) ont aidé des gens partout dans le monde à bénéficier d'un meilleur approvisionnement d'eau, et d'accès a des installations sanitaires. Même si l'aide dédié e ce secteur a augmenté du 20% en 1990-1992 (que 4.9% distribué pour W&S) au 35% en 2002-2004 (que 3.9% dédié à W&S), les faits nous démontrent que cet aide est biaisé vers des finalités sociales plutôt que des objectifs d'infrastructure. Dans cet étude, nous nous focalisons sur l'engagement des donneurs envers W&S, pour voir si leur aide officielle au développement (en anglais : Official Development Assistance, ODA) pour ces deux secteurs est aligné avec les intentions des objectifs de développement durable (en anglais : Sustainable Development Goals, SDGs). Nous trouvons que les donneurs affectent leur aide W&S se focalisant généralement sur les gouvernements avec des meilleurs indicateurs de gouvernance, et que les pays les plus pauvres reçoivent une affectation d'aide supérieure.

Japan's development cooperation for health in Vietnam: a first holistic assessment on Japan's ODA and non-ODA public resources cooperation.

BACKGROUND: Japan strives to strengthen its development cooperation by mobilizing various resources to assist partner countries advance on Universal Health Coverage by 2030. However, the involvement and roles of various actors for health are not clear. This study is the first to map Japan's publicly funded projects by both Official Development Assistance (ODA) and other non-ODA public funds, and to describe the intervention areas. Further, the policy implications for country-specific cooperation strategies are discussed. The development cooperation for health in Vietnam is used as a case in this study. METHODS: A cross-sectional analysis of the Japanese publicly funded health projects that were being implemented in Vietnam during December 2016 was conducted. A framework of analysis based on the World Health Organization six health systems building blocks was adopted. The projects' qualitative information was also assessed. RESULTS: Overall, 68 projects implemented through Japanese public funding were analyzed. These 68 projects under 15 types of schemes were managed by seven different scheme-operating organizations and funded by five ministries. Of these 44 (64.7%) were ODA and 24 (35.3%) were non-ODA projects. Among the recategorized six building blocks of the health system, the largest proportion of projects was health service delivery (44%), followed by health workforces (25%), and health information systems (15%). Almost half the projects were implemented together with the central hospitals as Vietnamese counterparts, which suggests that this is one area in which the specificities of Japanese cooperation are demonstrated. No synergetic effects of potential collaboration or harmonization among Japanese funded projects were captured. CONCLUSIONS: Several Japanese-funded projects addressed a wide range of health issues across all six building blocks of the health system in Vietnam. However, there is room for improvement in developing coordination and harmonization among the diversified Japanese projects. Establishing a country-specific mechanism for strategic coordination across Japanese ministries' schemes can yield efficient and effective development cooperation for health. While Vietnam's dependence on external funding is low, the importance of coordination across domestic actors of the donor countries can serve as an important lesson, especially in beneficiary countries with high external funding dependency.

Field monitoring data on a residential exhaust air heat pump system (air-to-air heat pump).

This data article presents the raw data used in the article "Experimental and analytical evaluation of exhaust air heat pumps in ventilation-based heating systems" [1]. The data set contains measurement results of a field monitoring on a residential exhaust air heat pump system (air-to-air heat pump) in Germany. This data could be used to investigate the dynamic behavior and performance of the exhaust air heat pump systems. The data set contains air temperature and humidity of all four sides of the heat pump unit. Moreover, the electrical consumption of the unit and the dynamic pressure difference on the exhaust side (as indication of the air volume rate) could be also found in the data set.

Clinical and molecular characteristics of primary ciliary dyskinesia: A tertiary care centre experience.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a ciliopathy with diverse clinical and genetic findings caused by abnormal motile cilia structure and function. In this study, we describe the clinical characteristics of confirmed PCD cases in our population and report the radiological, genetic, and laboratory findings. METHODS: This was a retrospective, observational, single-centre study. We enrolled 18 patients who were diagnosed with confirmed PCD between 2015 and 2019. We then analyzed their data, including clinical findings and workup. RESULTS: In our cohort, 56% of patients had molecularly confirmed PCD, and RSPH9 was the most common gene identified. Transmission electron microscopy (TEM) showed an ultrastructural defect in 64% of samples, all of which matched the genetic background of the patient. Situs inversus (SI) was observed in 50% of patients, and congenital heart disease was observed in 33%. The median body mass index (BMI) was 15.87 kg/m2, with a median z score of -1.48. The median FEV1 value was 67.6% (z score - 2.43). Radiologically, bronchiectasis was noted in 81% of patients at a variable degree of severity. Lung bases were involved in 91% of patients. We were unable to correlate the genotype-phenotype findings. CONCLUSION: We describe the clinical and molecular characteristics of patients with confirmed PCD in a tertiary centre in Saudi Arabia and report 9 new pathogenic or likely pathogenic variants in one of the PCD-associated genes.

Bioefficacy of Epaltes divaricata (L.) n-Hexane Extracts and Their Major Metabolites against the Lepidopteran Pests Spodoptera litura (fab.) and Dengue Mosquito Aedes aegypti (Linn.).

The present research investigated the chemical characterization and insecticidal activity of n-Hexane extracts of Epaltes divaricata (NH-EDx) along with their chief derivatives n-Hexadecanoic acid (n-HDa) and n-Octadecanoic acid (n-ODa) against the dengue vector Aedes aegypti and lepidopteran pest Spodoptera litura. Chemical screening of NH-EDx through GC-MS analysis delivered nine major derivatives, and the maximum peak area percentage was observed in n-Hexadecanoic acid (14.63%) followed by n-Octadecadienoic acid (6.73%). The larvicidal activity of NH-EDx (1000 ppm), n-HDa (5 ppm), and n-ODa (5 ppm) against the A. aegypti and S. litura larvae showed significant mortality rate in a dose-dependent way across all the instars. The larvicidal activity was profound in the A. aegypti as compared to the S. litura across all the larval instars. The sublethal dosages of NH-EDx (500 ppm), n-HDa (2.5 ppm), and n-ODa (2.5 ppm) also showed alterations in the larval/pupal durations and adult longevity in both the insect pests. The enzyme activity revealed that the α- and ß-carboxylesterase levels were decreased significantly in both the insect pests, whereas the levels of GST and CYP450 uplifted in a dose-dependent manner of NH-EDx, n-HDa, and n-ODa. Correspondingly, midgut tissues such as the epithelial layer (EL), gut lumen (GL), peritrophic matrix (Pm), and brush border membrane (BBM) were significantly altered in their morphology across both A. aegypti and S. litura against the NH-EDx and their bioactive metabolites. NH-EDx and their bioactive metabolites n-HDa and n-ODa showed significant larvicidal, growth retardant, enzyme inhibition, and midgut toxicity effects against two crucial agriculturally and medically challenging insect pest of ecological importance.

Antibacterial and corrosion protection properties of SA-CuZnO@ODA-GO composite in circulating cooling water.

The suitable temperature of circulating cooling water is conducive to the reproduction of bacteria, which will cause corrosion to the pipe and form slime on its surface. Therefore, the sterilization of circulating cooling water is an essential step. In this work, a new type of SA-CuZnO@ODA-GO composite antibacterial material with hydrophobic properties was prepared by ultrasonic treatment method. The composite was characterized and analyzed by SEM, TEM, XPS, XRD, and FT-IR. Then, the CuZnO@ODA-GO@PU hydrophobic and antibacterial coating was prepared. The antibacterial properties and mechanism of the composite were investigated by gram-positive bacteria S. aureus and gram-negative bacteria E. coli. The result shows that the best antibacterial rate of SA-CuZnO@ODA-GO composite antibacterial material is up to 99.10%. As for the SA-CuZnO@ODA-GO@PU composite antibacterial coating, the corrosion resistance of the antibacterial coating is up to 99.99%. The anticorrosion property is due to the hydrophobic modification of the composite, which can insulate the steel sheet from water. Secondly, due to the rigidity of the SA-CuZnO@ODA-GO, it combines with epoxy resin to form a compact structure.

Isolation and Antitrypanosomal Characterization of Furoquinoline and Oxylipin from Zanthoxylum zanthoxyloides.

In the absence of vaccines, there is a need for alternative sources of effective chemotherapy for African trypanosomiasis (AT). The increasing rate of resistance and toxicity of commercially available antitrypanosomal drugs also necessitates an investigation into the mode of action of new antitrypanosomals for AT. In this study, furoquinoline 4, 7, 8-trimethoxyfuro (2, 3-b) quinoline (compound 1) and oxylipin 9-oxo-10, 12-octadecadienoic acid (compound 2) were isolated from the plant species Zanthoxylum zanthoxyloides (Lam) Zepern and Timler (root), and their in vitro efficacy and mechanisms of action investigated in Trypanosomabrucei (T. brucei), the species responsible for AT. Both compounds resulted in a selectively significant growth inhibition of T. brucei (compound 1, half-maximal effective concentration EC50 = 1.7 µM, selectivity indices SI = 74.9; compound 2, EC50 = 1.2 µM, SI = 107.3). With regards to effect on the cell cycle phases of T. brucei, only compound 1 significantly arrested the second growth-mitotic (G2-M) phase progression even though G2-M and DNA replication (S) phase arrest resulted in the overall reduction of T. brucei cells in G0-G1 for both compounds. Moreover, both compounds resulted in the aggregation and distortion of the elongated slender morphology of T. brucei. Analysis of antioxidant potential revealed that at their minimum and maximum concentrations, the compounds exhibited significant oxidative activities in T. brucei (compound 1, 22.7 µM Trolox equivalent (TE), 221.2 µM TE; compound 2, 15.0 µM TE, 297.7 µM TE). Analysis of growth kinetics also showed that compound 1 exhibited a relatively consistent growth inhibition of T. brucei at different concentrations as compared to compound 2. The results suggest that compounds 1 and 2 are promising antitrypanosomals with the potential for further development into novel AT chemotherapy.

Cyber and Offline Dating Abuse in a Portuguese Sample: Prevalence and Context of Abuse.

The increasing use of information and communication technologies (ICT) and networking has promoted the occurrence of different forms of victimization, specifically in terms of interpersonal interaction (e.g., cyberbullying or online risk-taking behaviour), which also includes cyber dating abuse (CDA). Some studies report that CDA is an extension of offline dating abuse (ODA). Because Portuguese studies in this area are scarce, this study aims to bridge this knowledge gap, seeking to investigate the extent and the context of CDA occurrence, and the relationship between CDA and all forms of ODA, i.e., physical, verbal-emotional and control. A convenience sample of 173 Portuguese adolescents and young adults was studied. This sample is mostly female (86.7%), has a mean (M) age of 25.36 years old and a standard deviation (SD) of 6.88 years of age. The results show that CDA and ODA among the Portuguese are very prevalent and related. Control (31.8 vs. 20.8%) and verbal-emotional ODA (26.7 vs. 20.2%) as well as control CDA (38.2 vs. 43.4%) were the most prevalent forms of abuse, either in terms of victimization or in terms of perpetration. The results also showed that CDA usually appears in a context of jealousy, also explaining control CDA and CDA direct aggression. A significant relationship between control CDA and CDA direct aggression and physical, verbal-emotional and control ODA was found. Experiencing control and verbal-emotional ODA are the main risk factors of control CDA victimization. This study allows to lay the groundwork for further research on dating victimization and perpetration through ICT, and has important practical implications at the level of Portuguese prevention strategies and intervention policies, thus emphasizing the role of the official authorities and the law itself.

COVID-19 and International Food Assistance: Policy proposals to keep food flowing.

The COVID-19 pandemic is increasing the need for international food assistance, and disrupting the supply and delivery of food assistance. A series of unprecedented shocks is straining the capacity of food assistance organizations to reach vulnerable populations. We discuss how the COVID-19 pandemic is affecting the demand and the supply of international food assistance, and we propose three policy changes that can keep food flowing to those in need. First, donor countries can prioritize humanitarian spending in aid-allocation decisions. Second, governments can exempt food assistance from trade barriers that impede procurement (export restrictions) and delivery (import tariffs). Third, donor countries can allow flexibility for implementing agencies by untying food assistance from domestic procurement and shipping restrictions. All of these proposals are regulatory changes that can be made without requiring increased spending. These options are particularly relevant now because donor-country governments are entering economic recessions, and foreign aid budgets will be constrained.

Hyaluronic acid derivative-modified nano-structured lipid carrier for cancer targeting and therapy.

To reduce the problems of poor solubility, high in vivo dosage requirement, and weak targeting ability of paclitaxel (PTX), a hyaluronic acid-octadecylamine (HA-ODA)-modified nano-structured lipid carrier (HA-NLC) was constructed. HA-ODA conjugates were synthesized by an amide reaction between HA and ODA. The hydrophobic chain of HA-ODA can be embedded in the lipid core of the NLC to obtain HA-NLC. The HA-NLC displayed strong internalization in cluster determinant 44 (CD44) highly expressed MCF-7 cells, and endocytosis mediated by the CD44 receptor was involved. The HA-NLC had an encapsulation efficiency of PTX of 72.0%. The cytotoxicity of the PTX-loaded nanoparticle HA-NLC/PTX in MCF-7 cells was much stronger than that of the commercial preparation Taxol®. In vivo, the HA-NLC exhibited strong tumor targeting ability. The distribution of the NLCs to the liver and spleen was reduced after HA modification, while more nanoparticles were aggregated to the tumor site. Our results suggest that HA-NLC has excellent properties as a nano drug carrier and potential for in vivo targeting.

Purification and crystal structure of human ODA16: Implications for ciliary import of outer dynein arms by the intraflagellar transport machinery.

Motile cilia protrude from cell surfaces and are necessary to create movement of cells and fluids in the body. At the molecular level, cilia contain several dynein molecular motor complexes including outer dynein arms (ODAs) that are attached periodically to the ciliary axoneme, where they hydrolyse ATP to create the force required for bending and motility of the cilium. ODAs are preassembled in the cytoplasm and subsequently trafficked into the cilium by the intraflagellar transport (IFT) system. In the case of the green alga Chlamydomonas reinhardtii, the adaptor protein ODA16 binds to ODAs and directly to the IFT complex component IFT46 to facilitate the ciliary import of ODAs. Here, we purified recombinant human IFT46 and ODA16, determined the high-resolution crystal structure of the ODA16 protein, and carried out direct interaction studies of IFT46 and ODA16. The human ODA16 C-terminal 320 residues adopt the fold of an eight-bladed ß-propeller with high overall structural similarity to the Chlamydomonas ODA16. However, the small 80 residue N-terminal domain, which in Chlamydomonas ODA16 is located on top of the ß-propeller and is required to form the binding cleft for IFT46, has no visible electron density in case of the human ODA16 structure. Furthermore, size exclusion chromatography and pull-down experiments failed to detect a direct interaction between human ODA16 and IFT46. These data suggest that additional factors may be required for the ciliary import of ODAs in human cells with motile cilia.

Role of the Novel Hsp90 Co-Chaperones in Dynein Arms' Preassembly.

The outer and inner dynein arms (ODAs and IDAs) are composed of multiple subunits including dynein heavy chains possessing a motor domain. These complex structures are preassembled in the cytoplasm before being transported to the cilia. The molecular mechanism(s) controlling dynein arms' preassembly is poorly understood. Recent evidence suggests that canonical R2TP complex, an Hsp-90 co-chaperone, in cooperation with dynein axonemal assembly factors (DNAAFs), plays a crucial role in the preassembly of ODAs and IDAs. Here, we have summarized recent data concerning the identification of novel chaperone complexes and their role in dynein arms' preassembly and their association with primary cilia dyskinesia (PCD), a human genetic disorder.