Iron accumulation in ovarian microenvironment damages the local redox balance and oocyte quality in aging mice.

Accumulating oxidative damage is a primary driver of ovarian reserve decline along with aging. However, the mechanism behind the imbalance in reactive oxygen species (ROS) is not yet fully understood. Here we investigated changes in iron metabolism and its relationship with ROS disorder in aging ovaries of mice. We found increased iron content in aging ovaries and oocytes, along with abnormal expression of iron metabolic proteins, including heme oxygenase 1 (HO-1), ferritin heavy chain (FTH), ferritin light chain (FTL), mitochondrial ferritin (FTMT), divalent metal transporter 1 (DMT1), ferroportin1(FPN1), iron regulatory proteins (IRP1 and IRP2) and transferrin receptor 1 (TFR1). Notably, aging oocytes exhibited enhanced ferritinophagy and mitophagy, and consistently, there was an increase in cytosolic Fe2+, elevated lipid peroxidation, mitochondrial dysfunction, and augmented lysosome activity. Additionally, the ovarian expression of p53, p21, p16 and microtubule-associated protein tau (Tau) were also found to be upregulated. These alterations could be phenocopied with in vitro Fe2+ administration in oocytes from 2-month-old mice but were alleviated by deferoxamine (DFO). In vivo application of DFO improved ovarian iron metabolism and redox status in 12-month-old mice, and corrected the alterations in cytosolic Fe2+, ferritinophagy and mitophagy, as well as related degenerative changes in oocytes. Thereby in the whole, DFO delayed the decline in ovarian reserve and significantly increased the number of superovulated oocytes with reduced fragmentation and aneuploidy. Together, our findings suggest that aging-related disturbance in ovarian iron homeostasis contributes to excessive ROS production and that iron chelation may improve ovarian redox status, and efficiently delay the decline in ovarian reserve and oocyte quality in aging mice. These data propose a novel intervention strategy for preserving the ovarian reserve function in elderly women.

PLD1 promotes spindle assembly and migration through regulating autophagy in mouse oocyte meiosis.

PLD1 has been implicated in cytoskeletal reorganization and vesicle trafficking in somatic cells; however, its function remains unclear in oocyte meiosis. Herein, we found PLD1 stably expresses in mouse oocytes meiosis, with direct interaction with spindle, RAB11A+ vesicles and macroautophagic/autophagic vacuoles. The genetic or chemical inhibition of PLD1 disturbed MTOC clustering, spindle assembly and its cortical migration, also decreased PtdIns(4,5)P2, phosphorylated CFL1 (p-CFL1 [Ser3]) and ACTR2, and their local distribution on MTOC, spindle and vesicles. Furthermore in PLD1-suppressed oocytes, vesicle size was significantly reduced while F-actin density was dramatically increased in the cytoplasm, the asymmetric distribution of autophagic vacuoles was broken and the whole autophagic process was substantially enhanced, as illustrated with characteristic changes in autophagosomes, autolysosome formation and levels of ATG5, BECN1, LC3-II, SQSTM1 and UB. Exogenous administration of PtdIns(4,5)P2 or overexpression of CFL1 hyperphosphorylation mutant (CFL1S3E) could significantly improve polar MTOC focusing and spindle structure in PLD1-depleted oocytes, whereas overexpression of ACTR2 could rescue not only MTOC clustering, and spindle assembly but also its asymmetric positioning. Interestingly, autophagy activation induced similar defects in spindle structure and positioning; instead, its inhibition alleviated the alterations in PLD1-depleted oocytes, and this was highly attributed to the restored levels of PtdIns(4,5)P2, ACTR2 and p-CFL1 (Ser3). Together, PLD1 promotes spindle assembly and migration in oocyte meiosis, by maintaining rational levels of ACTR2, PtdIns(4,5)P2 and p-CFL1 (Ser3) in a manner of modulating autophagy flux. This study for the first time introduces a unique perspective on autophagic activity and function in oocyte meiotic development.Abbreviations: ACTR2/ARP2: actin related protein 2; ACTR3/ARP3: actin related protein 3; ATG5: autophagy related 5; Baf-A1: bafilomycin A1; BFA: brefeldin A; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GOLGA2/GM130: golgin A2; GV: germinal vesicle; GVBD: germinal vesicle breakdown; IVM: in vitro maturation; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MI: metaphase of meiosis I; MII: metaphase of meiosis II; MO: morpholino; MTOC: microtubule-organizing center; MTOR: mechanistic target of rapamycin kinase; PB1: first polar body; PLA: proximity ligation assay; PLD1: phospholipase D1; PtdIns(4,5)P2/PIP2: phosphatidylinositol 4,5-bisphosphate; RAB11A: RAB11A, member RAS oncogene family; RPS6KB1/S6K1: ribosomal protein S6 kinase B1; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TUBA/α-tubulin: tubulin alpha; TUBG/γ-tubulin: tubulin gamma; UB: ubiquitin; WASL/N-WASP: WASP like actin nucleation promoting factor.

Synergistic effects of adsorption and chemical reduction towards the effective Cr(VI) removal in the presence of the sulfur-doped biochar material.

In this study, the anaerobic sludge withdrawn from thickener in a sewage treatment plant served as the precursor for sludge-based biochar fabrication, which was further modified via sulfur (S) heteroatom doping (i.e., S-BC). The S atom doping resulted in the adjustment of the physicochemical properties towards the carbon material, endowment of abundant functional groups on biochar surface, and increasing the binding sites between biochar and Cr(VI). Compared to the primary biochar (i.e., biochar without heteroatomic doping, named BC), S-BC exhibited a rough surface and possessed remarkable advantages in ash content, specific surface area, and pore volume. The existence of graphene carbon crystal structure for S-BC was confirmed through S-BC by XRD and FTIR analysis. The studies of adsorption kinetics and isotherms showed that pseudo-second-order kinetics and the Langmuir model more fitted the Cr(VI) removal behavior in the presence of S-BC. Therefore, the chemisorption and monolayer adsorption were the primary mechanisms involved in the Cr(VI) removal process. Additionally, XPS analysis results illustrated the aqueous Cr(VI) was efficiently eliminated through the synergistic effect of chemisorption and reduction to Cr(III) in the presence of S-BC. Moreover, S-BC could still achieve the Cr(VI) eliminating efficiency of 85.31% undergoing five cycles with unchanged functional group and crystal structure via FTIR and XRD analysis. Thus, the results of this study may shed light on a new approach for simultaneous economical sludge disposal and the sustainable remediation of the Cr(VI)-contaminated wastewater.

Chondroprotective effects of bone marrow mesenchymal stem cell-derived exosomes in osteoarthritis.

Chondrocyte ferroptosis constitutes a major cause of the development of osteoarthritis (OA). Bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) have a protective role against ferroptosis in various diseases. Hence, we aimed to determine whether BMSC-Exos alleviated chondrocyte ferroptosis and its effect on OA, and to dissect out the possible mechanisms. An OA rat chondrocyte model was established by interleukin-1ß (IL-1ß) exposure, and treated with BMSC-Exos/ferroptosis inhibitor Ferrostatin-1. Cell viability/ferroptosis-related index levels [reactive oxygen species (ROS)/malondialdehyde (MDA)/glutathione (GSH)]/cell death/ACSL4 mRNA and protein levels and METTL3 levels were assessed by MTT/kits/immunohistochemical method and TUNEL staining/RT-qPCR and Western blot. METTL3/ACSL4 were overexpressed in rat chondrocytes to evaluate their role in BMSC-Exo-produced repression on chondrocyte ferroptosis. Bioinformatics website predicted the presence of m6A modification sites on ACSL4 mRNA, with the m6A level enriched on it assessed by MeRIP/RT-qPCR. ACSL4 mRNA stability was detected by actinomycin D assay. A surgical destabilized medial meniscus rat OA model was also established, followed by injection with BMSC-Exos to verify their function. IL-1ß stimulation in rat chondrocytes inhibited cell viability, elevated Fe2+/ROS/MDA levels, declined GSH levels and increased TUNEL positive cell number and ACSL4 level, which were neutralized by BMSC-Exos. BMSC-Exos limited chondrocyte ferroptosis by down-regulating METTL3, with the effect abrogated by METTL3 overexpression. METTL3 regulated the m6A modification of ACSL4 mRNA, increasing ACSL4 mRNA stability and ACSL4 expression. BMSC-Exos reduced chondrocyte ferroptosis and prevented OA progression via disruption of the METTL3-m6A-ACSL4 axis. BMSC-Exos might exert a chondroprotective effect by attenuating chondrocyte ferroptosis and alleviate OA progression.

Highly Stable Perovskite Solar Cells Based on the Efficient Interaction between Pb2+ and Cyano Groups of 4-Aminophthalonitrile.

Defects present on the top surface of perovskite films have a pronounced detrimental impact on the photovoltaic performance and stability of perovskite solar cells (PSCs). Consequently, the development of effective defect passivation strategies has become key in enhancing both the power conversion efficiency (PCE) and stability of PSCs. In this study, a small molecule material, 4-Aminophthalonitrile (4-APN), was introduced as a means to mitigate surface defects within perovskite films. Obviously, 4-APN effectively passivates the defects at grain boundaries by combining cyano groups (-C≡N) with Pb2+ , significantly reducing the density of defect states, inhibiting non-radiative recombination at the interface, and promoting the charge transfer efficiency from the perovskite layer to the hole transport layer. The 4-APN modification led to a significant upswing in the PCE, while concurrently bolstering the overall device stability. Importantly, the devices on 4-APN as passivation additive exhibited negligible performance degradation aging for 1200 h.

High-Fill-Factor Perovskite Solar Cells via Pseudohalide Salt Modification of the Substrate to Mitigate Nonradiative Recombination at the Interface.

The utilization of the sol-gel method for fabricating planar SnO2 as the electron transport layer (ETL) induces numerous defects on the SnO2 layer surface and perovskite film bottom, causing considerable deterioration of the device performance. Conventional inorganic salt-doped SnO2 precursor solutions used for passivation may cause incomplete substrate coverage due to the presence of inorganic salt crystals, further degrading the device performance. Here, a substrate modification approach involving the pretreatment of a fluorine-doped SnO2 (FTO) substrate with NH4PF6 is proposed. The interaction between PF6- ions and the FTO substrate enhances SnO2 film quality; excess PF6- ions decrease the number of defects on the film surface. NH4+ ions react with an -OH stabilizing agent in the SnO2 solution and are eliminated during annealing. The combined effects suppress nonradiative recombination and ion migration at the ETL-perovskite interface. The corresponding high-quality perovskite solar cells (PSCs) exhibit a fill factor of ∼0.825; PSC efficiency increases from 19.59% to 22.32%.

Effective automatic detection of anterior cruciate ligament injury using convolutional neural network with two attention mechanism modules.

BACKGROUND: To develop a fully automated CNN detection system based on magnetic resonance imaging (MRI) for ACL injury, and to explore the feasibility of CNN for ACL injury detection on MRI images. METHODS: Including 313 patients aged 16 - 65 years old, the raw data are 368 pieces with injured ACL and 100 pieces with intact ACL. By adding flipping, rotation, scaling and other methods to expand the data, the final data set is 630 pieces including 355 pieces of injured ACL and 275 pieces of intact ACL. Using the proposed CNN model with two attention mechanism modules, data sets are trained and tested with fivefold cross-validation. RESULTS: The performance is evaluated using accuracy, precision, sensitivity, specificity and F1 score of our proposed CNN model, with results of 0.8063, 0.7741, 0.9268, 0.6509 and 0.8436. The average accuracy in the fivefold cross-validation is 0.8064. For our model, the average area under curves (AUC) for detecting injured ACL has results of 0.8886. CONCLUSION: We propose an effective and automatic CNN model to detect ACL injury from MRI of human knees. This model can effectively help clinicians diagnose ACL injury, improving diagnostic efficiency and reducing misdiagnosis and missed diagnosis.

Visual Cascaded-Progressive Convolutional Neural Network (C-PCNN) for Diagnosis of Meniscus Injury.

OBJECTIVE: The objective of this study is to develop a novel automatic convolutional neural network (CNN) that aids in the diagnosis of meniscus injury, while enabling the visualization of lesion characteristics. This will improve the accuracy and reduce diagnosis times. METHODS: We presented a cascaded-progressive convolutional neural network (C-PCNN) method for diagnosing meniscus injuries using magnetic resonance imaging (MRI). A total of 1396 images collected in the hospital were used for training and testing. The method used for training and testing was 5-fold cross validation. Using intraoperative arthroscopic diagnosis and MRI diagnosis as criteria, the C-PCNN was evaluated based on accuracy, sensitivity, specificity, receiver operating characteristic (ROC), and evaluation performance. At the same time, the diagnostic accuracy of doctors with the assistance of cascade- progressive convolutional neural networks was evaluated. The diagnostic accuracy of a C-PCNN assistant with an attending doctor and chief doctor was compared to evaluate the clinical significance. RESULTS: C-PCNN showed 85.6% accuracy in diagnosing and identifying anterior horn injury, and 92% accuracy in diagnosing and identifying posterior horn injury. The average accuracy of C-PCNN was 89.8%, AUC = 0.86. The diagnosis accuracy of the attending physician with the aid of the C-PCNN was comparable to that of the chief physician. CONCLUSION: The C-PCNN-based MRI technique for diagnosing knee meniscus injuries has significant practical value in clinical practice. With a high rate of accuracy, clinical auxiliary physicians can increase the speed and accuracy of diagnosis and decrease the number of incorrect diagnoses.

Stable expression and multi-site location of Odf2 in mouse oocytes, sperm and early embryos.

In mammals, centriole is degenerated during early oogenesis, but it is still not known about the expression and function of centriolar structural components in oocyte meiosis. Here we found that Odf2 (outer dense fiber of sperm tails 2), a key centriolar appendage protein, was stably expressed in mouse oocytes during meiotic progression. Distinct from its single location at centrosomes in somatic mitosis, Odf2 was multiply located at microtubule organizing centers (MTOCs), chromosome centromeres and vesicles in oocyte meiosis. In addition, the vesicle-associated Odf2 disappeared in oocytes treated with the vesicle inhibitor Brefeldin A. Odf2 was mainly co-localized with the mitochondrial sheath in the sperm tail and presented as double spots, similar to γ-tubulin, in the sperm neck region. After fertilization, Odf2 remained on vesicles in embryos from 1-cell to 4-cell stage but was only detected on centrosomes at blastocyst stage. Taken together, Odf2 is expressed precisely in mouse oocytes even in the absence of intact centriole structure, and may regulate oocyte spindle assembly and positioning, additionally, the sperm motility and early embryo development.

Adverse effects of 2-Methoxyestradiol on mouse oocytes during reproductive aging.

2-Methoxyestradiol (2-ME2) is a metabolite of 17ß-estradiol and is currently in clinical trials as an antitumor agent. Here we found 2-ME2 level remains stable in the local environment of ovaries but declines in serum in aging mice, and exogenous 2-ME2 impacts the meiotic maturation of mouse oocytes in dose-dependent manner. In vitro 2-ME2 application arrested oocytes at metaphase I (MI), with abnormal spindle structure and chromosome alignment. 2-ME2 exposure induced excessive production of reactive oxygen species (ROS) and malondialdehyde, as well as accelerated apoptosis progression. 2-ME2 unbalanced mitochondrial dynamics by increasing DRP1 and MFN1 while decreasing Opa1. Similar phenotypes were also observed in oocytes from mice injected intraperitoneally with 2-ME2. Taken together, this study indicates 2-ME2 exposure impairs oocyte meiotic maturation through inducing mitochondrial imbalance, oxidative stress and apoptosis. The gradual decline in oocyte quality and quantity may be associated with the stable 2-ME2 in ovaries during female reproductive aging.

Enhancing the Efficiency of Perovskite Solar Cells by Bidirectional Modification of the Perovskite and Electron Transport Layer.

In perovskite solar cells (PSCs), the numerous defects present on the surface of the SnO2 electron transport layer (ETL) and the bottom of the perovskite film limit their power conversion efficiency (PCE) and stability. In view of this, a bidirectional modification strategy is designed using formamidine acetate (FAAc) to passivate the defects on the SnO2 ETL surface and bottom of the perovskite simultaneously. FA+ cations act on the harmful hydroxyl groups on the SnO2 ETL surface, whereas Ac- anions act on the iodine vacancy defect at the bottom of the perovskite. Because the interface defect is well passivated by FAAc, the interfacial charge recombination is restrained. This results in a significant increase in the filling factor of the PSC to ∼0.83 and the consequent increase in PCE to 23.05%, which considerably improves the stability. Bidirectional modification technology is an effective strategy for improving the PCE and stability of PSCs.

Ste20-like kinase activity promotes meiotic resumption and spindle microtubule stability in mouse oocytes.

Ste20-like kinase (SLK) is involved in cell proliferation and migration in somatic cells. This study aims to explore SLK expression and function in mouse oocyte meiosis. Western blot, immunofluorescence, Co-immunoprecipitation, drug treatment, cRNA construct and in vitro transcription, microinjection of morpholino oilgo (MO) and cRNA were performed in oocytes. High and stable protein expression of SLK was detected in mouse oocyte meiosis, with dynamic distribution in the nucleus, chromosomes and spindle apparatus. SLK phosphorylation emerges around meiotic resumption and reaches a peak during metaphase I (MI) and metaphase II. SLK knockdown with MO or expression of kinase-dead SLK K63R dramatically delays meiotic resumption due to sequentially suppressed phosphorylation of Polo-like kinase 1 (Plk1) and cell division cycle 25C (CDC25C) and dephosphorylation of cyclin-dependent kinase 1 (CDK1). SLK depletion promotes ubiquitination-mediated degradation of paxillin, an antagonist to α-tubulin deacetylation, and thus destroys spindle assembly and chromosome alignment; these phenotypes can be substantially rescued by exogenous expression of SLK kinase active fragment. Additionally, exogenous SLK effectively promotes meiotic progression and spindle assembly in aging oocytes with reduced SLK. Collectively, this study reveals SLK is required for meiotic resumption and spindle assembly in mouse oocyte meiosis.

Defect management by a cesium fluoride-modified electron transport layer promotes perovskite solar cells.

SnO2 is a candidate material for electron transport layers (ETLs) in perovskite solar cells (PSCs). However, a large number of defects at the SnO2/perovskite interface lead to notable non-radiative interfacial recombination. Moreover, the energy level arrangement between SnO2/perovskite does not match well. In this study, a SnO2/CsF-SnO2 double-layer ETL was prepared by doping CsF into SnO2, effectively passivating the defects of the SnO2 ETL and SnO2/perovskite interface. The formation of a good energy level arrangement with the perovskite layer reduces the interface non-radiative recombination and improves the performance of the interface charge extraction. The photoelectric conversion efficiency of the optimal CsF-modified PSC reached 22.18%, owing to the significant increase in the open-circuit voltage to 1.180 V.

Efficient and Stable Perovskite Solar Cells via CsPF6 Passivation of Perovskite Film Defects.

Polycrystalline perovskite films have many fatal defects; defect passivation can improve the performance of perovskite solar cells (PSCs). In this study, the defects in perovskite films are passivated by introducing the pseudohalide salt CsPF6 into the films. Because the ionic radii of Cs+ and PF6- are close to those of FA+ and I-, respectively, they can be uniformly doped into perovskite films to passivate the bulk, surface, and grain boundary defects. The photovoltaic performance of the PSCs significantly improved after passivation. Moreover, the photoelectric conversion efficiency increased significantly from 21.36% to 23.15% after passivation. Because of defect passivation, PSCs also exhibit good environmental stability. This study introduces a scheme for improving the photovoltaic performance of PSCs via passivation.

Implication of exogenous abscisic acid (ABA) application on phytoremediation: plants grown in co-contaminated soil.

Abscisic acid (ABA) may play an important role in alleviating negative effects of heavy metal stress on growth performance of plants. A pot experiment was conducted to investigate differential effects of exogenous ABA with different concentrations (0, 20, 40, and 60 µmol/L) on heavy metal accumulation and physiological response of Cd/Zn hyperaccumulator Sedum alfredii Hance and non-hyperaccumulator Hylotelephium spectabile (Boreau) H. Ohba grown in co-contaminated soil. In the experiment, Cd, Zn, or Pb concentration in stem and leaf of H. spectabile was significantly increased by exogenous ABA application than control. However, the opposite pattern was observed for S. alfredii. With decrease of Cd concentration, Zn or Pb concentration in root of H. spectabile grown in co-contaminated soil was significantly increased by exogenous ABA application than control. Cd, Zn, or Pb concentration in root of S. alfredii was significantly increased by exogenous ABA application than control. Compared with S. alfredii, BCF and TF of Cd, Zn, or Pb for H. spectabile were significantly increased by exogenous ABA application. With negative effect on root growth, total biomass of the two species, especially H. spectabile, was significantly increased by exogenous ABA application than control. With increase of their total chlorophyll content, antioxidant capacity of the two species subjected to heavy metal stress was improved by exogenous ABA application than control. Heavy metal-induced growth inhibition was significantly alleviated by exogenous ABA application when the two species were grown in co-contaminated soil. We tentatively concluded that differential effects of exogenous ABA application on transport pathway of ions incurred different patterns of heavy metal accumulation between Cd/Zn hyperaccumulator S. alfredii and non-hyperaccumulator H. spectabile. It is suggested that compared with Cd/Zn hyperaccumulator S. alfredii, exogenous ABA application may improve heavy metal uptake in root and transport of heavy metal ions between different organs for non-hyperaccumulator H. spectabile grown in co-contaminated soil. Our results provide insight into effects of exogenous ABA application on phytoremediation of Cd-, Pb-, and Zn-co-contaminated soil.

Electron Transport Assisted by Transparent Conductive Oxide Elements in Perovskite Solar Cells.

Fluorine and indium elements in F-doped SnO2 (FTO) and Sn-doped In2 O3 (ITO), respectively, significantly contribute toward enhancing the electrical conductivity of these transparent conductive oxides. In this study, fluorine was combined with indium to modify the SnO2 electron transport layer (ETL) through InF3 . Consequently, the modified perovskite solar cells (PSCs) showe the favorable alignment of energy levels, improved absorption and utilization of light, enhanced interfacial charge extraction, and suppressed interfacial charge recombination. After InF3 modification, the open circuit voltage (Voc ) and fill factor (FF) of the PSC were significantly improved, and the photoelectric conversion efficiency (PCE) reached 21.39 %, far exceeding that of the control PSC (19.62 %).

Precursor Engineering of the Electron Transport Layer for Application in High-Performance Perovskite Solar Cells.

The electron transport layer (ETL) is a key component of regular perovskite solar cells to promote the overall charge extraction efficiency and tune the crystallinity of the perovskite layer for better device performance. The authors present a novel protocol of ETL engineering by incorporating a composition of the perovskite precursor, methylammonium chloride (MACl), or formamidine chloride (FACl), into SnO2 layers, which are then converted into the crystal nuclei of perovskites by reaction with PbI2 . The SnO2 -embedded nuclei remarkably improve the morphology and crystallinity of the optically active perovskite layers. The improved ETL-to-perovskite electrical contact and dense packing of large-grained perovskites enhance the carrier mobility and suppress charge recombination. The power conversion efficiency increases from 20.12% (blank device) to 21.87% (21.72%) for devices with MACl (FACl) as an ETL dopant. Moreover, all the precursor-engineered cells exhibit a record-high fill factor (82%).

Enhanced crystallization of solution-processed perovskite using urea as an additive for large-grain MAPbI3perovskite solar cells.

Perovskite crystal quality plays an important role in perovskite solar cells, given that multiple grain boundaries and trap states in the perovskite films hamper further enhancement of solar cell efficiency. Using the solution method to prepare perovskite films with large grains and high coverage requires further improvements. Herein, we introduce Lewis base urea as an additive into the precursor of perovskite to control the crystallization dynamics, allowing for large-grain crystal growth. As a result, MAPbI3films with urea as an additive are well crystallized with large crystal grains of sizes >3µm. The large-grain perovskite is found to simultaneously improve the power-conversion efficiency (PCE) and device stability. With an optimal urea additive of 20 mol%, the PCE is significantly increased from 15.47% for the reference MAPbI3solar cell to 18.53% for the device with MAPbI3with urea as an additive. Finally, the optimized device demonstrates excellent stability and maintains 80% of the initial PCE after 60 days.

Preparation of bilayer-core osmotic pump tablet by coating the indented core tablet.

In this paper, a bilayer-core osmotic pump tablet (OPT) which does not require laser drilling to form the drug delivery orifice is described. The bilayer-core consisted of two layers: (a) push layer and (b) drug layer, and was made with a modified upper tablet punch, which produced an indentation at the center of the drug layer surface. The indented tablets were coated by using a conventional pan-coating process. Although the bottom of the indentation could be coated, the side face of the indentation was scarcely sprayed by the coating solution and this part of the tablet remained at least partly uncoated leaving an aperture from which drug release could occur. Nifedipine was selected as the model drug. Sodium chloride was used as osmotic agent, polyvinylpyrrolidone as suspending agent and croscarmellose sodium as expanding agent. The indented core tablet was coated by ethyl cellulose as semipermeable membrane containing polyethylene glycol 400 for controlling the membrane permeability. The formulation of core tablet was optimized by orthogonal design and the release profiles of various formulations were evaluated by similarity factor (f(2)). It was found that the optimal OPT was able to deliver nifedipine at an approximate zero-order up to 24 h, independent on both release media and agitation rates. The preparation of bilayer-core OPT was simplified by coating the indented core tablet, by which sophisticated technology of the drug layer identification and laser drilling could be eliminated. It might be promising in the field of preparation of bilayer-core OPT.