A combination of laparoscopy and bilateral uterine artery occlusion for the treatment of type II cesarean scar pregnancy: a retrospective analysis.

OBJECTIVE: We investigated the efficacy of a combination of laparoscopy and bilateral uterine artery occlusion (BUAO) for the treatment of type II cesarean scar pregnancy (CSP). METHODS: Patients with type II CSP underwent laparoscopy + bilateral uterine artery embolization (control group) or laparoscopy + BUAO (study group). Data regarding the duration of surgery, intraoperative hemorrhage, postoperative complications, the duration of the hospital stay, and the costs of hospitalization were retrospectively collected. One year later, the time to the return of the ß-human chorionic gonadotropin (ß-hCG) concentration to normal and to the return of menstruation were compared. RESULTS: The duration of surgery, time to the return of menstruation, and incidence of postoperative complications in the study group were significantly less than in the control group, but there was no significant difference in the time for ß-hCG to return to normal or the volume of intraoperative hemorrhage. The duration of hospitalization and costs for the control group were higher than those for the study group. CONCLUSION: Laparoscopy in combination with BUAO is associated with minimal trauma, rapid recovery, a short duration of surgery, low cost of hospitalization, and a low postoperative complication rate. Thus, it represents a useful new surgical treatment for type II CSP.

Circulating cell-free DNA sequencing for early detection of lung cancer.

INTRODUCTION: Lung cancer is a leading cause of death in patients with cancer. Early diagnosis is crucial to improve the prognosis of patients with lung cancer. Plasma circulating cell-free DNA (cfDNA) contains comprehensive genetic and epigenetic information from tissues throughout the body, suggesting that early detection of lung cancer can be done non-invasively, conveniently, and cost-effectively using high-sensitivity techniques such as sequencing. AREAS COVERED: In this review, we summarize the latest technological innovations, coupled with next-generation sequencing (NGS), regarding genomic alterations, methylation, and fragmentomic features of cfDNA for the early detection of lung cancer, as well as their clinical advances. Additionally, we discuss the suitability of study designs for diagnostic accuracy evaluation for different target populations and clinical questions. EXPERT OPINION: Currently, cfDNA-based early screening and diagnosis of lung cancer faces many challenges, such as unsatisfactory performance, lack of quality control standards, and poor repeatability. However, the progress of several large prospective studies employing epigenetic features has shown promising predictive performance, which has inspired cfDNA sequencing for future clinical applications. Furthermore, the development of multi-omics markers for lung cancer, including genome-wide methylation and fragmentomics, is expected to play an increasingly important role in the future.

MoS2/CoS heterostructures grown on carbon cloth as free-standing anodes for high-performance sodium-ion batteries.

Heterostructure construction with mixed transition metal sulfides has been recognized as a promising strategy to boost the performance of sodium-ion batteries (SIBs). Herein, a carbon-decorated MoS2/CoS heterostructure on carbon cloth (MoS2/CoS@CC) as a free-standing anode for SIBs was synthesized via a facile growth-carbonization strategy. In the composite, the generated built-in electric field at MoS2 and CoS heterointerfaces is beneficial for elevating the electron conductivity, thus expediting the Na-ion transport rate. Moreover, different redox potentials between MoS2 and CoS can effectively mitigate the mechanical strain induced by repeated Na+ de-/intercalation, thus ensuring the structural integrity. In addition, the carbon skeleton derived from the carbonization of glucose can enhance the conductivity of the electrode and maintain the structural integrity. Consequently, the resulting MoS2/CoS@CC electrode delivers a reversible capacity of 605 mA h g-1 at 0.5 A g-1 after 100 cycles, and prominent rate performance (366 mA h g-1 at 8.0 A g-1). Theoretical calculations also confirm that the establishment of a MoS2/CoS heterojunction can powerfully promote the electron conductivity, thereby enhancing the Na-ion diffusion kinetics.

Comparison of the two routes of video endoscopic inguinal lymphadenectomy in vulvar cancer: a systematic review and a single-center experience.

BACKGROUND: Video endoscopic inguinal lymphadenectomy (VEIL) has fewer complications than open surgery for vulva cancer. No high-level evidence comparing the efficacy and safety of the two routes of VEIL (VEIL-H and VEIL-L) is available. METHODS: We performed a comprehensive literature search for reports on VEIL for vulva cancer from 2000 to 2020 and reviewed our experience. Data extraction includes patients' characteristics, perioperative indicators, postoperative complications, and cancer recurrence. RESULTS: A total of 11 eligible studies were included in the systematic review. Nine studies included only one route of VEIL, and the other two studies directly compared the two routes of VEIL. The average operation time of the VEIL-L group was 85 (range, 33-180.12) minutes, and that of the VEIL-H group was 112 (range, 35-170.79) minutes. The average blood loss of the VEIL-L group was 9 (range, 5-30) mL, and that of the VEIL-H group was 96 (range, 5.5-214.8) mL. The average number of intraoperatively removed lymph nodes in the VEIL-L group was 9 (range, 7.5-13.2), and that in the VEIL-H group was 14 (range, 9.5-16). No significant difference was observed in the cancer recurrence rate between the two groups. We found similar results in our cohort study. CONCLUSIONS: The operation time, intraoperative blood loss, and time of drainage of the VEIL-L procedure seemed less than those of the VEIL-H procedure. VEIL-L and VEIL-H were equivalent in the efficacy of lymph node dissection, surgery-related complications, and cancer recurrence rate.

The long non-coding RNA LOC285758 promotes invasion of acute myeloid leukemia cells by down-regulating miR-204-5p.

Acute myeloid leukemia (AML) is the second most common type of leukemia worldwide. It was previously reported that expression of the long noncoding RNA LOC285758 is positively associated with AML cell proliferation, but the underlying mechanisms have not previously been reported. Here, we report that LOC285758 expression is higher in clinical AML blood samples and cultured AML cells. miR-204-5p was confirmed to be a target gene of LOC285758 by bioinformatics analysis and luciferase assay. LOC285758 overexpression promoted AML cell viability and invasion abilities, which were effectively inhibited by miR-204-5p overexpression; moreover, miR-204-5p overexpression also regulated the expression of E-cadherin, N-cadherin and Twist1. The data also showed that increased LOC285758 expression could effectively suppress the earlier effects of miR-204-5p on AML cells. Our findings suggest that targeting of miR-204-5p by LOC285758 promotes the cell viability and invasion of AML cells, and thus LOC285758 may have potential as a therapeutic target for AML treatment.

Intelligent Management of Chemical Warehouses with RFID Systems.

At present, most chemical warehouses rely on human management, which is a time-consuming and laborious process. Therefore, it is very meaningful to use radio frequency identification (RFID) systems for the intelligent management of chemicals. Detecting the remaining amount of chemicals is an important process in the management of a chemical warehouse. It helps managers find the chemicals that are going to run out and replenish them in time. However, in a traditional chemical warehouse, managers usually inspect each chemical on the shelf in turn manually, which is a waste of time and labor. Although some solutions using RFID technology have been proposed, they are expensive and difficult to deploy in a real environment. In order to solve this problem, we propose an intelligent system called the RF-Detector in this paper, which combines robotics and RFID technology. An RFID reader and an antenna are installed on the robot, which achieves automatic scanning of the chemicals. The RF-Detector can achieve two functions: One function is to detect the remaining amount of chemicals using the changes in received signal strength indication (RSSI) and read rate, and the other is to locate chemicals using the phase curve, so that managers can quickly find the chemicals with an insufficient amount remaining. In this paper we implement the RF-Detector and evaluate its performance. The experimental results show that the RF-Detector achieves about 93% detection accuracy and 92% positioning accuracy for chemicals.

Coordination polymer derived general synthesis of multi-shelled hollow metal oxides for lithium-ion batteries.

Multi-shelled hollow metal oxide nanostructures have attracted tremendous attention in energy storage devices owing to their high specific capacity, rate capability and ameliorated cycling performance. Although great progress has been made in synthesizing multi-shelled hollow structures, most methods still depend on tedious template mediated strategies to generate complex interior structures. Herein, we developed a facile universal self-templated approach to synthesize a series of multi-shelled hollow metal oxide spheres with tailored compositions. This strategy involved the solvothermal preparation of uniform spherical coordination polymers (CPs) as precursors and a subsequent thermal treatment in air. Single-, binary- and ternary-metal multi-shelled hollow oxide spheres (Co, Mn-Co, Ni-Co, Ni-Co-Mn, etc.) were successfully obtained. To demonstrate their applications in energy storage, the electrochemical properties of ZnCo2O4 were investigated by testing the lithium-ion-storage performance. Owing to the unique structures, the multi-shelled hollow ZnCo2O4 spheres exhibited high specific capacity, excellent cycling durability (1200 mA h·g-1 after 200 cycles at 0.1 A g-1) and prominent rate capability (730 mA h·g-1 at 5.0 A g-1).

A generalized strategy for the synthesis of two-dimensional metal oxide nanosheets based on a thermoregulated phase transition.

Two-dimensional (2D) metal oxide (MO) nanomaterials, like graphene, possess unique electrical, mechanical, optical and catalytic performances, and have attracted substantial research interest recently. However, it remains a challenge to easily obtain 2D MO nanosheets by a generalized synthetic pathway. Here, we report a general and facile strategy for the synthesis of 2D MO nanosheets induced by nonionic surfactant micelles. Notably, the novel strategy primarily relies on the thermoregulated phase transition of the micelles. The resulting 2D MO nanosheets show high specific surface areas. As a demonstration, Sb2O3 nanosheets synthesized by our method as anodes for sodium-ion batteries (SIBs) have a high reversible capacity of 420 mA h g-1 and a high capacity retention of 99% after 150 cycles at 0.1 A g-1. Mn3O4 nanosheets for supercapacitors have a remarkable specific capacitance of 127 F g-1 at a current density of 0.5 A g-1. Even at a large current density of 5 A g-1 after 10 000 cycles, 96% of the specific capacitance is retained, demonstrating the remarkable performance of these nanosheets for energy storage applications.

MicroRNA-21 attenuates oxygen and glucose deprivation induced apoptotic death in human neural stem cells with inhibition of JNK and p38 MAPK signaling.

Neural stem cells (NSCs) persist in the mammalian brain throughout life and protect against hypoxia-ischemia injury. NSCs are being increasingly recognized as a novel therapeutic target for various neurological disorders. Previous research indicates that miR-21 attenuates hypoxia-ischemia induced apoptotic death in various cell types. However, whether miR-21 plays a role in this protective effect mediated by NSCs is unknown, particularly in human NSCs (hNSCs). The present study investigated whether miR-21 could prevent hNSC injury induced by oxygen and glucose deprivation (OGD). Upon challenge with OGD treatment, loss of cell viability was observed in cultured hNSCs, as shown by CCK-8 assay. Moreover, quantitative real-time PCR (qRT-PCR) analysis indicated that expression of miR-21 increased in a time-dependent manner. TUNEL staining and Western blotting analysis showed that overexpression of miR-21 inhibited excessive hNSCs death induced by OGD treatment. Accordingly, knock down of miR-21 attenuated the neuroprotective effect observed in response to OGD treatment. Furthermore, JNK and p38 MAPKs inhibition was observed after overexpression of miR-21, and knock down of miR-21 had the opposite effect. We suggest that miR-21 prevents OGD-induced hNSCs death and apoptotic-associated protein activities through inhibiting JNK and p38 pathways in cultured hNSCs. Our findings may help to develop strategies for enhancing resident and transplanted NSCs survival after hypoxia-ischemic brain damage.

Aggregation-induced emission enhancement of gold nanoclusters triggered by silicon nanoparticles for ratiometric detection of protamine and trypsin.

Metal nanoclusters protected by glutathione (GSH) have attracted a wide attention due to the unique aggregation-induced emission (AIE) feature. However, the "trigger" effects of ethanol, temperature, pH values, and metal ions may restrict the application of these particles. In this work, the amino modified silicon nanoparticles (SiNPs) and GSH-capped gold nanoclusters (GSH-AuNCs) can self-assemble into well-defined spherical particles due to the electrostatic interaction. As a result, the unique aggregation-induced emission enhancement (AIEE) of GSH-AuNCs arises at 570 nm, and the SiNPs keep their own blue fluorescence at 450 nm, so a novel nanohybrid probe (SiNPs@GSH-AuNCs) with dual-emission property has been constructed. When protamine is added to SiNPs@GSH-AuNCs, the cationic protamine can compete with SiNPs and absorb onto the surface of GSH-AuNCs, which inhibits the self-assembly and leads to the fluorescence quenching of GSH-AuNCs; while trypsin can catalyze the hydrolysis of protamine, the self-assembly starts again, producing the AIEE recovery. In the whole process, the SiNPs act as an internal standard and their emission stays constant. By means of the fluorescence intensity ratios I570/I450, the linear range of protamine is from 0.15 to 3.00 µg mL-1 with the limit of detection (LOD) of 0.07 µg mL-1, and trypsin shows a linear response in the range from 10 to 100 ng mL-1 with LOD of 4.50 ng mL-1. Furthermore, this strategy exhibits good sensitivity and selectivity, and has been further validated by applying it for the determination of protamine and trypsin in serum samples.

Overexpressed circ_0067934 acts as an oncogene to facilitate cervical cancer progression via the miR-545/EIF3C axis.

Circular RNAs were recently identified as a novel type of noncoding RNAs. An increasing number of reports have demonstrated their essential regulatory roles in various biological processes and human diseases, including cancer. However, the role of circRNA in cervical cancer (CC) remains largely unknown. In the current study, we investigated the physiological functions of circ_0067934 during CC development and progression. We found that circ_0067934 was overexpressed in CC tissues and cell lines. Circ_0067934 upregulation was associated with advanced stage, lymph node metastasis, and poor prognosis in CC patients. Knockdown of circ_0067934 suppressed the proliferation, colony formation, migration, invasion, and epithelial-mesenchymal transition of CC cells in vitro. Circ_0067934 loss also inhibited CC tumor growth in vivo. Mechanistically, silencing circ_0067934 increased miR-545 expression. MiR-545 repressed EIF3C expression through targeting its 3'-untranslated region. MiR-545 suppressed the proliferation, migration, and invasion of CC cells, whereas restoration of EIF3C could rescue the effects of circ_0067934 knockdown. Taken together, our findings revealed that circ_0067934 promotes CC progression via miR-545/EIF3C axis. Our study may provide a new insight into the pathogenesis of CC.

Construction of humanized anti-HER2 single-chain variable fragments (husFvs) and achievement of potent tumor suppression with the reconstituted husFv-Fdt-tBid immunoapoptotin.

As HER2 is frequently overexpressed in various malignancies, targeting HER2 is considered an efficient, highly selective antitumor therapy. HER2-targeted immunoconjugates are being developed and result in persistent remission of HER2-overexpressing tumors. However, many of the antibodies used as the targeting moiety are of murine origin and exhibit risk of inducing immunogenicity, limiting their antitumor therapeutic efficacy. Here, we humanized e23sFv, an HER2-targeting murine scFv with excellent affinity and specificity, using a human antibody consensus sequence engraftment strategy. The affinity of the initially humanized e23sFv was then rescued and improved by selective mutagenesis followed by phage-display-based affinity panning of the mutant pool. The resulting humanized e23sFv candidates (husFvs) exhibited up-to-94-fold increased affinity to recombinant HER2. The immunogenicity of e23sFv was dramatically alleviated after humanization, as indicated by the impaired production of cytokines by husFv-stimulated human PBMCs. Two internalizable husFvs with optimal affinity were applied to generate humanized immunoapoptotins by infusion with the translocation domain Fdt and the proapoptotic domain truncated Bid. The husFv-immunoapoptotins demonstrated improved HER2-targeting and tumor-killing capacities in vitro and in vivo compared with the e23sFv-immunoapoptotins and would enable the administration of multiple treatment cycles to patients, resulting in improved antitumor efficacy. Furthermore, the husFvs recognized distinct HER2 epitopes and could thus be used in combination with trastuzumab or pertuzumab to achieve robust synergistic antitumor effects in HER2-positive malignancies.

Photoinduced electron transfer from polymer-templated Ag nanoclusters to G-quadruplex-hemin complexes for the construction of versatile biosensors and logic gate applications.

In this paper, fluorescent Ag nanoclusters (Ag NCs) templated by hyperbranched polyethyleneimine (PEI) are utilized as a versatile probe through the photoinduced electron transfer (PET) between PEI-Ag NCs and G-quadruplex-hemin complexes. In the presence of hemin and target molecule, the specific conjugation with its aptamer induces the conformational change of the DNA sequence, releasing the G-quadruplex sequence part. Once the G-quadruplex-hemin complexes are introduced, electron transfer from the PEI-Ag NCs to G-quadruplex-hemin complexes occurs, resulting in fluorescence quenching. Through changing the sensing DNA sequence, this novel PET system enables the specific detection of target DNA and adenosine triphosphate (ATP) with the wide linear range of 1-200 nM and 5-500 nM, respectively, and the corresponding limit of detection as low as 0.3 nM for target DNA and 1.5 nM for ATP. In addition, the proposed method is successfully applied to the determination of ATP in human serum samples with satisfactory recoveries, and a logic gate is fabricated using target molecules and hemin as inputs and the fluorescence signal of PEI-Ag NCs as an output.

Nano-in-Micro Delivery System Prepared by Co-Axial Air Flow for Oral Delivery of Conjugated Linoleic Acid.

The preparation of a nano-in-micro delivery system (NiMDS) under mild conditions without using toxic organic solvents and expensive equipment still faces challenges. In this study, we introduced the co-axial air flow method to prepare NiMDS for the oral delivery of conjugated linoleic acid (CLA). The chitosan nanoparticles were prepared using the stearic-acid-modified chitosan through self-aggregation. Then, the chitosan nanoparticles were incorporated into alginate microparticles by the co-axial air flow method. The obtained chitosan nanoparticles and NiMDS were spherical in shape with the average sizes of 221⁻243 nm and 130⁻160 µm, respectively. Compared with alginate microparticles, the hybrid particles were of fewer fragments, were bigger in size, had a higher mechanical strength, and showed a controlled release in the phosphate buffer solution (pH 1.2 or 7.4). The release kinetics study showed that encapsulating the chitosan nanoparticles into the alginate microparticles inhibited the dissolution of alginate microparticles at the initial stage. These results revealed the potential of NiMDS as an ideal oral carrier for the sustained release of CLA in the gastrointestinal environment.

eIF2 alpha phosphorylation alleviates UVA-induced HO-1 expression in mouse epidermal cells.

Ultraviolet A (UVA) irradiation is a potential environmental stressor, which contributes to inflammation, photoaging, and carcinogenesis. UVA causes endoplasmic reticulum stress, hence phosphorylates the α subunit of eIF2. Meanwhile, UVA also induces expression of haem oxygenase-1 (HO-1) and nuclear factor erythroid-derived two related factor 2 (Nrf2) in human skin cells. In mouse JB6 cell, we found high dose UVA could change cell morphology, cause cell viability loss. UVA irradiation activated phosphorylation of eIF2α and Nrf2-HO-1 pathway in a dose-dependent manner. Besides, modulation of eIF2α phosphorylation status could alter expression pattern of Nrf2-HO-1 signalling. Salubrinal, a selective inhibitor of eIF2α dephosphorylation, increased the S phase in cell cycle of JB6 cells after UVA irradiation, suggesting phosphorylation status of eIF2α may affect cellular homeostasis under UVA irradiation. The study directed to further acknowledge about the relationship of UVA-induced eIF2α phosphorylation and Nrf2-HO-1 pathway, which may play a role in phototherapy and photo protection.

Hypoxia stimulates proliferation of rat neural stem/progenitor cells by regulating mir-21: an in vitro study.

Neural stem/progenitor cells (NSPCs) reside not only in the developing brain, but also in the adult brain within specialized microenvironments that regulate their function. In vitro and in vivo studies have revealed strong regulatory links between hypoxic/ischemic insults and activation of NSCPs. However, the underlying mechanisms of this activation remain unclear. In this study, we found that cell proliferation is promoted by hypoxia, and accompanied by increasing expression of miR-21 in cultured rat NSPCs. Moreover, qRT-PCR analysis indicated that expression of miR-21 increases in a time-dependent manner. 5-Bromo-2-deoxyUridine (BrdU) staining and flow cytometry showed that overexpression of miR-21 further promoted proliferation of NSPCs in the presence of hypoxia. Knocking down of miR-21 partially abolished the proliferative effect of hypoxia treatment on cell proliferation. Western blot demonstrated that overexpression of miR-21 enhanced expression of cyclin D1, while knock down of miR-21 suppressed cyclin D1 expression under hypoxic conditions. Furthermore, overexpression of miR-21 also increased levels of p-AKT. These results demonstrate that miR-21 plays a role in regulating the proliferation of cultured rat NSPCs undergoing hypoxia, and the activation of the PI-3-K signaling pathway might be one of the underlying mechanisms. These findings prompt a molecular study investigating potential mechanisms for stem cell treatment of cerebral ischemia.

Nrf2- and Bach1 May Play a Role in the Modulation of Ultraviolet A-Induced Oxidative Stress by Acetyl-11-Keto-ß-Boswellic Acid in Skin Keratinocytes.

BACKGROUND: Exposure of human skin to solar ultraviolet A (UVA) irradiation causes severe oxidative stress with damage to various cellular components and concomitant inflammation and carcinogenesis. OBJECTIVE: The aim of this study is to investigate the protective effect of acetyl-11-keto-ß-boswellic acid (AKBA) against UVA radiation on human skin keratinocytes. METHODS: HaCaT cells were pretreated with AKBA followed by UVA irradiation. Radiation effects on cell morphology, cell viability, intracellular reactive oxygen species (ROS) levels, and antioxidant enzymes were examined. RESULTS: AKBA reduces UVA irradiation-induced cell viability loss, accompanied by a decreased production of UVA-induced ROS, decreased malondialdehyde, and increased superoxide dismutase expression. In addition, AKBA increased basal and UVA-induced levels of Nrf2 (NF-E2-related factor 2), the redox-sensitive factor, and its target genes NQO1 and heme oxygenase-1 (HO-1), whereas expression of the transcriptional repressor Bach1 (BTB and CNC homology 1) was reduced. Furthermore, the cytoprotective effects of AKBA against UVA-derived oxidative damage were accompanied by modulating expression of inflammatory mediators (i.e., cyclooxygenase-2 and nuclear factor-κB) and NOX1. CONCLUSIONS: AKBA protects skin cells from UVA-induced damage by modulating inflammatory mediators and/or ROS production. Therefore, AKBA has potential in the development of skin care products.

Synthesis and spectroscopic characterization of water-soluble Mn-doped ZnO(x)S(1-x) quantum dots.

A non-cadmium and water-soluble Mn-doped ZnO(x)S(1-x) QDs was synthesized with denatured bovine serum albumin (dBSA) as stabilizer under nitrogen atmosphere, and the as-prepared products were characterized by X-ray powder diffraction (XRD), UV-vis absorption spectroscopy, fluorescence (FL) emission spectroscopy, high resolution transmission electronmicroscopy (HRTEM) and Raman spectrum. XRD patterns indicate that the Mn-doped ZnO(x)S(1-x) QDs have a zinc-blende structure, and that manganese emerges in the form of divalent manganese (Mn(2+)) and trivalent manganese (Mn(3+)) (the intermediate of the reaction). The size of Mn-doped ZnO(x)S(1-x) QDs is about 3.2±0.7 nm according to HRTEM imaging. The FL spectra reveal that the Mn-doped ZnO(x)S(1-x) QDs have two distinct emission bands: the defect-related emission and the Mn(2+)-related emission, which exhibit a competing process. A good FL signal of the transition of Mn(2+) ((4)T(1)-(6)A(1)) is observed when the doping amounts are 1.0% and 20% respectively, and the as-prepared solutions are stable for more than 6 months at 4°C. This method has the advantages of good stability and environment-friendly stabilizer, for involving no heavy metal ions or toxic reagents.

Preparation and characterization of nanoparticles based on hydrophobic alginate derivative as carriers for sustained release of vitamin D3.

Hydrophobic alginate derivative was prepared by modification of alginate by acid chloride reaction using oleoyl chloride without organic solvents. The conjugate of oleoyl alginate ester (OAE) was confirmed by FT-IR and (1)H NMR. The degree of substitution (DS) of OAE was determined by (1)H NMR, and it ranged from 0.84 to 3.85. In distilled water, OAE formed self-assembled nanoparticles at low concentrations in aqueous medium, and nanoparticles retained their structural integrity both in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The loading and release characteristics of nanoparticles based on OAE were investigated using vitamin D(3) as a model nutraceutical. As the concentration of vitamin D(3) increased, the loading capacity (LC) increased, whereas the loading efficiency (LE) decreased. Nanoparticles could release vitamin D(3) at a sustained rate in gastrointestinal fluid. These results revealed the potential of OAE nanoparticles as oral carriers for sustained release of vitamin D(3).