Reconsideration of the Diagnostic Criteria for an Atypical Placental Site Nodule Comparing Typical Placental Site Nodule of the Uterus: A Report of Two Cases.

Placental site nodules (PSNs) are non-neoplastic remnants of chorionic-type intermediate trophoblastic cells from a previous gestation that form a well-defined single nodule or multiple nodules in the uterine and extrauterine sites. As the cases of PSNs transformed into gestational trophoblastic tumors were described in the literature, "atypical placental site nodules" (APSNs) have been considered as putative transitional lesions between PSNs and gestational trophoblastic tumors. Although histologic criteria and cutoff point of Ki-67 proliferation index for differentiating an APSN from a typical PSN have not been clearly defined, nodules larger than 5 mm with increased cellularity, a corded or nested appearance, marked nuclear atypia, increased mitotic activity, and an increased Ki-67 proliferation index (>5% or >8%) of intermediate trophoblastic cells seem to be accepted as diagnostic criteria for APSNs. However, some of the criteria, including lesion size and histologic features of the trophoblastic cells in the nodule are not only subjective but have features inherent of the intermediate trophoblastic cells of the fetal membrane and a typical PSN. We thought that it is not reasonable to consider them as diagnostic features of APSNs, if not associated with cellular proliferation. We present 2 cases of incidentally identified PSNs that were larger than 10 mm in size with a corded or nested arrangement of trophoblastic cells, which could have been categorized as APSNs according to the currently proposed criteria to discuss whether the currently proposed diagnostic criteria for APSNs are appropriate.

Highly Stable Bulk Perovskite for Blue LEDs with Anion-Exchange Method.

To date, the light emitting diode (LED) based halide perovskite was rapidly developed due to the outstanding property of perovskite materials. However, the blue perovskite LEDs based on the bulk halide perovskites have been rarely researched and showed low efficiencies. The bulk blue perovskite LEDs suffered from insufficient coverage on the substrate due to the low solubility of the inorganic Cl sources or damaged by the structural instability with participation of organic cations. Here, we show the new method of fabricating stable inorganic bulk blue perovskite LEDs with the anion exchange approach to avoid use of insoluble Cl precursors. The devices showed nice operational spectral stability at the desired blue emission peak. The bulk perovskite blue LEDs showed a maximum luminance of 1468 and 494 cd m-2 for the 490 and 470 nm emission peaks, respectively.

Short-term serial assessment of electronic patient-reported outcome for depression and anxiety in breast Cancer.

PURPOSE: The incidence of depression and anxiety is higher in patients with breast cancer than in the general population. We evaluated the degree of depression and anxiety and investigated the changes in patients with breast cancer during the treatment period and short-term follow-up period. METHODS: Overall, 137 patients with breast cancer were evaluated using the Patient Health Questionnaire 9-item depression scale (PHQ-9) and Generalized Anxiety Disorder scale (GAD-7). The scales were developed as a web-based electronic patient-reported outcome measure, and serial results were assessed before the operation, after the operation, in the post-treatment period, and in the 6-month follow-up period after surgery. RESULTS: The degree of depression and anxiety increased during treatment and decreased at 6-month follow-up, even if there were no statistical differences among the four periods (PHQ-9: p = 0.128; GAD-7: p = 0.786). However, daily fatigue (PHQ-9 Q4) and insomnia (PHQ-9 Q3) were the most serious problems encountered during treatment and at 6-month follow-up, respectively. In the GAD-7, worrying too much (Q3) consistently showed the highest scores during the treatment and follow-up periods. Of the patients, 7 (5.11%) and 11 (8.03%) patients had a worsened state of depression and anxiety, respectively, after treatment compared with before treatment. CONCLUSION: Most factors associated with depression and anxiety improved after treatment. However, factors such as insomnia and worrying too much still disturbed patients with breast cancer, even at 6-month follow-up. Therefore, serial assessment of depression and anxiety is necessary for such patients.

Generic Strategy to Synthesize High-Tap Density Anode and Cathode Structures with Stratified Graphene Pliable Pockets via Monomeric Polymerization and Evaporation, and Their Utilization to Enable Ultrahigh Performance in Hybrid Energy Storages.

Hybrid energy storage systems have shown great promise for many applications; however, achieving high energy and power densities with long cycle stability remains a major challenge. Here, a strategy to synthesize high-tap density anode and cathode structures that yield ultrahigh performance in hybrid energy storage is reported. First, vinyl acetate monomers are polymerized into molecular sizes via chain reactions controlled by the surface free radicals of graphene and metals. Subsequently, molecular-size polymers are thermally evaporated to construct battery-type anode structures with encapsulated tin metals for high-capacity and stratified graphene pliable pockets (GPPs) for fast charge transfer. Similarly, sulfur particles are attached to GPPs via monomeric polymerization, and capacitor-type hollow GPP (H@GPP) cathode structures are produced by evaporating sulfur, where sublimated S particles yield mesopores for rapid anion movement and micropores for high capacity. Moreover, hybrid full-cell devices with high-tap density anodes and cathodes show high gravimetric energy densities of up to 206.9 Wh kg-1 , exceeding those of capacitors by ≈16-fold, and excellent volumetric energy densities of up to 92.7 Wh L-1 . Additionally, they attain high power densities of up to 23 678 W kg-1 , outperforming conventional devices by a factor of ≈100, and long cycle stability over 10 000 cycles.

Recurrent KRAS mutations identified in papillary renal neoplasm with reverse polarity-a comparative study with papillary renal cell carcinoma.

Comprehensive molecular analyses revealed that papillary renal cell carcinoma (PRCC) is a heterogenous entity. Papillary renal neoplasm with reverse polarity (PRNRP) is a subset of PRCC with characteristic histomorphologies such as low-grade nuclear features, inverted nuclear location, eosinophilic cytoplasm, and indolent clinical behavior. We tried to define the molecular, clinicopathological, histologic, and immunohistochemical features of PRNRP by comparing them with type 1 PRCC (PRCC1) and type 2 PRCC (PRCC2). A cohort of 30 PRNRP, 23 PRCC1, and 26 PRCC2 cases was used. Targeted sequencing of 90 cancer-related genes including KRAS was performed in 26 PRNRP tumor samples. PNA-mediated clamping PCR of KRAS was performed using paired normal and tumor DNA from 30 PRNRP, 23 PRCC1, and 26 PRCC2 cases. Tissue microarray slides were made in three cores per tumor, which were stained with cytokeratin 7 (CK7), alpha-methylacyl-CoA racemase (AMACR), epithelial membrane antigen (EMA), E-cadherin, vimentin, and CD10. Recurrent mutations in KRAS were detected in 28 of the 30 PRNRPs. However, there were no KRAS mutations in any PRCC1 or PRCC2 cases. PRNRP exhibited distinct clinicopathological features: small tumor size, lower pathologic T stage, and no disease-specific death during the follow-up period. Histologically, peritumoral lymphoid aggregation, prominent papillary architecture (>80% of tumor), hyalinized papillae, inverted nuclear location, and lower nuclear grade were observed. PRNRP was usually positive for CK7, AMACR, EMA, and E-cadherin, and negative for CD10. The findings suggest that PRNRP is a subtype of papillary renal neoplasm that is different from PRCC1 or PRCC2 in terms of molecular, clinicopathological, histological, and immunohistochemical features.

Hepatocyte Growth Factor Improves the Therapeutic Efficacy of Human Bone Marrow Mesenchymal Stem Cells via RAD51.

Human embryonic stem cell-derived mesenchymal stem cells (hE-MSCs) have greater proliferative capacity than other human mesenchymal stem cells (hMSCs), suggesting that they may have wider applications in regenerative cellular therapy. In this study, to uncover the anti-senescence mechanism in hE-MSCs, we compared hE-MSCs with adult bone marrow (hBM-MSCs) and found that hepatocyte growth factor (HGF) was more abundantly expressed in hE-MSCs than in hBM-MSCs and that it induced the transcription of RAD51 and facilitated its SUMOylation at K70. RAD51 induction/modification by HGF not only increased telomere length but also increased mtDNA replication, leading to increased ATP generation. Moreover, HGF-treated hBM-MSCs showed significantly better therapeutic efficacy than naive hBM-MSCs. Together, the data suggest that the RAD51-mediated effects of HGF prevent hMSC senescence by promoting telomere lengthening and inducing mtDNA replication and function, which opens the prospect of developing novel therapies for liver disease.

Fluorine Functionalized Graphene Nano Platelets for Highly Stable Inverted Perovskite Solar Cells.

Edged-selectively fluorine (F) functionalized graphene nanoplatelets (EFGnPs-F) with a p-i-n structure of perovskite solar cells achieved 82% stability relative to initial performance over 30 days of air exposure without encapsulation. The enhanced stability stems from F-substitution on EFGnPs; fluorocarbons such as polytetrafluoroethylene are well-known for their superhydrophobic properties and being impervious to chemical degradation. These hydrophobic moieties tightly protect perovskite layers from air degradation. To directly compare the effect of similar hydrophilic graphene layers, edge-selectively hydrogen functionalized graphene nanoplatelet (EFGnPs-H) treated devices were tested under the same conditions. Like the pristine MAPbI3 perovskite devices, EFGnPs-H treated devices were completely degraded after 10 days. The hydrophobic properties of EFGnPs-F were characterized by contact angle measurement. The test results showed great water repellency compared to pristine perovskite films or EFGnPs-H coated films. This resulted in highly air-stable p-i-n perovskite solar cells.

Colloidal Quantum Dot Photovoltaics Enhanced by Perovskite Shelling.

Solution-processed quantum dots are a promising material for large-scale, low-cost solar cell applications. New device architectures and improved passivation have been instrumental in increasing the performance of quantum dot photovoltaic devices. Here we report photovoltaic devices based on inks of quantum dot on which we grow thin perovskite shells in solid-state films. Passivation using the perovskite was achieved using a facile solution ligand exchange followed by postannealing. The resulting hybrid nanostructure created a more intrinsic CQD film, which, when incorporated into a photovoltaic device with graded bandstructure, achieved a record solar cell performance for single-step-deposited CQD films, exhibiting an AM1.5 solar power conversion efficiency of 8.95%.

High-Efficiency Colloidal Quantum Dot Photovoltaics via Robust Self-Assembled Monolayers.

The optoelectronic tunability offered by colloidal quantum dots (CQDs) is attractive for photovoltaic applications but demands proper band alignment at electrodes for efficient charge extraction at minimal cost to voltage. With this goal in mind, self-assembled monolayers (SAMs) can be used to modify interface energy levels locally. However, to be effective SAMs must be made robust to treatment using the various solvents and ligands required for to fabricate high quality CQD solids. We report robust self-assembled monolayers (R-SAMs) that enable us to increase the efficiency of CQD photovoltaics. Only by developing a process for secure anchoring of aromatic SAMs, aided by deposition of the SAMs in a water-free deposition environment, were we able to provide an interface modification that was robust against the ensuing chemical treatments needed in the fabrication of CQD solids. The energy alignment at the rectifying interface was tailored by tuning the R-SAM for optimal alignment relative to the CQD quantum-confined electron energy levels. This resulted in a CQD PV record power conversion efficiency (PCE) of 10.7% with enhanced reproducibility relative to controls.

Colloidal CdSe(1-x)S(x) Nanoplatelets with Narrow and Continuously-Tunable Electroluminescence.

Colloidal nanoplatelets, quasi-two-dimensional quantum wells, have recently been introduced as colloidal semiconductor materials with the narrowest known photoluminescence line width (∼10 nm). Unfortunately, these materials have not been shown to have continuously tunable emission but rather emit at discrete wavelengths that depend strictly on atomic-layer thickness. Herein, we report a new synthesis approach that overcomes this issue: by alloying CdSe colloidal nanoplatelets with CdS, we finely tune the emission spectrum while still leveraging atomic-scale thickness control. We proceed to demonstrate light-emitting diodes with sub-bandgap turn-on voltages (2.1 V for a device emitting at 2.4 eV) and the narrowest electroluminescence spectrum (FWHM ∼12.5 nm) reported for colloidal semiconductor LEDs.

Pure Cubic-Phase Hybrid Iodobismuthates AgBi2 I7 for Thin-Film Photovoltaics.

Bismuth-based hybrid perovskites are candidates for lead-free and air-stable photovoltaics, but poor surface morphologies and a high band-gap energy have previously limited these hybrid perovskites. A new materials processing strategy to produce enhanced bismuth-based thin-film photovoltaic absorbers by incorporation of monovalent silver cations into iodobismuthates is presented. Solution-processed AgBi2 I7 thin films are prepared by spin-coating silver and bismuth precursors dissolved in n-butylamine and annealing under an N2 atmosphere. X-ray diffraction analysis reveals the pure cubic structure (Fd3m) with lattice parameters of a=b=c=12.223 Å. The resultant AgBi2 I7 thin films exhibit dense and pinhole-free surface morphologies with grains ranging in size from 200-800 nm and a low band gap of 1.87 eV suitable for photovoltaic applications. Initial studies produce solar power conversion efficiencies of 1.22 % and excellent stability over at least 10 days under ambient conditions.

Production of pristine, sulfur-coated and silicon-alloyed germanium nanoparticles via laser pyrolysis.

Here we demonstrate production of three types of germanium containing nanoparticles (NPs) by laser pyrolysis of GeH4 and characterize their sizes, structures and composition. Pristine Ge NPs were fabricated with 50 standard cubic centimeter per minute (sccm) of GeH4 and 25 sccm of SF6 as a photosensitizer gas, while sulfur-coated Ge NPs were produced with 25 sccm of GeH4 and 50 sccm of SF6. The laser pyrolysis of SiH4/GeH4 mixtures produced Si1-xGex alloy NPs. Effects of key process parameters including laser intensity and gas flow rates on NP properties have been investigated. The ability of the laser pyrolysis technique to flexibly produce a variety of germanium-containing NPs, as illustrated in this study shows promise for commercial-scale production of new nanomaterials as high purity dry powders.

Optimal top electrodes for inverted polymer solar cells.

Although polymer solar cells (PSCs) have received a tremendous amount of attention in recent years, a number of criteria must be met in order for them to be suitable as practical and commercially feasible power sources, including high performance, good air stability and inexpensive manufacturing. In this contribution, we determine the optimal top electrode for practical PSC fabrication by investigating the influence of the electrode material on the optical properties and performance of PSC devices. The optical properties of eight metals were considered, out of which three metal electrodes (aluminum (Al), silver (Ag), gold (Au)) with the best optical properties were used to prepare inverted PSC devices comprising a blended polymer thieno[3,4-b]thiophene/benzodithiophene (PTB7) and [6,6]-phenyl C71-butyric acid methyl ester (PC71BM). Among the photovoltaic parameters, the short circuit current density (JSC) was most strongly affected by the optical properties of the top electrode. In the results of the experiment, the J(SC) of the Al and Ag electrode devices was found to be approximately 13% (13.4 → 15.1 mA cm(-2)) higher than the Au electrode device due to the significant parasitic absorption of light by Au at wavelengths below 600 nm. In contrast, Al and Ag electrodes have high reflectance throughout the visible spectrum, which leads to high J(SC). Ag electrodes have relatively good stability to ambient exposure, maintaining over 96% of the original efficiency after 170 hours; this stability is comparable to Au. These data lead to the conclusion that Ag is the optimal top electrode material for use in inverted devices.

Effect of mild alkali pretreatment on structural changes of reed (Phragmites communis Trinius) straw.

The effect of dilute sodium hydroxide (NaOH) on reed straw structural change at 105 degreeC temperature was evaluated in this study. Various concentrations of NaOH (1% to 2.5%) were used for pretreatment of reed straw at 105 degreeC for 10min. Scanning electron microscopy, atomic force microscopy and Fourier transform infrared spectroscopy studies showed that 2% and 2.5% NaOH pretreated sample exposed more cellulose fibers compared with other treatments. The cellulose crystalline index was increased by the 1% to 2.0% NaOH treatments and slightly lowered by the 2.5% NaOH treatment due to destructing cellulose fibres. Two per cent NaOH pretreatment caused 69.9% lignin removal, whereas 2.5% NaOH pretreatment removed 72.4% lignin. Besides, reed straw, when pretreated at 2% and 2.5% NaOH, resulted 56.4% and 60.5% hemicellulose removal, respectively. However, the difference in removal of lignin and hemicellulose between 2% and 2.5% NaOH treated reed straw was very marginal. In addition, very negligible increase of cellulose level was estimated, amounting 78.8% and 76.6% in 2.5% and 2% NaOH-treated sample, respectively. Moreover, after 72 h, reducing sugar yield was 81.2% and 83.3% using enzyme loading of 15 FPU (g dry biomass)-' and 30 IU (g dry biomass)- and xylanase 4 FXU (g dry biomass)-1 from 2% and 2.5% NaOH pretreated reed straw, respectively. Reducing sugar yield was increased very marginally when NaOH concentration increased from 2% to 2.5% for reed straw pretreatment. Therefore, 2% NaOH is supposed to be effective for reed straw pretreatment at this mentioned condition.

Enhanced Free Li-Ion Mobility in Solid-State Electrolytes via Long-Range Assembly of Porous Materials.

Metal-organic frameworks (MOFs), with their tunable pore sizes and high surface areas, are gaining prominence in Li metal battery applications, including their use as nanofillers in solid composite electrolytes (SCEs) for enhanced ionic conductivity. Yet, when used in SCEs, individual dispersed MOF particles in isolation as nanofillers can impede efficient ion transport in all-solid-state batteries due to the insufficient supply of ionic transport pathways within SCEs. Here, we introduced a continuous SCE nanofiller with long-range assembly interconnected porous MOFs (IMOF_SCE) for effective ion transport pathway supply along the interface between the nanofiller and the polymer matrix. IMOF_SCE achieved Li-ion conductivity (6.72 × 10-5 S cm-1 at 20 °C) and Li-ion transference number (tLi+ = 0.855), resulting in the improved electrochemical performance of Li metal batteries. Additionally, the Li/LiFePO4 full cell integrated with IMOF_SCE achieved an outstanding stable capacity retention of 98.8% in 300 cycles. This work offers insights into the design strategy of effective nanofillers for SCEs and can be adapted for other porous materials.

Oxyntic Gland Neoplasms - From Adenoma to Advanced Gastric Cancer: A Review of 29 Cases.

PURPOSE: Oxyntic gland neoplasm (OGN) is a rare condition that can be classified as oxyntic gland adenoma (OGA) or gastric adenocarcinoma of fundic-gland type (GA-FG). GA-FG primarily presents as early gastric cancer, with only a few reported cases of advanced gastric cancer (AGC). We aimed to investigate the clinicopathological features of OGN and describe an aggressive variant. MATERIALS AND METHODS: We investigated a total of 29 cases, including a patient with double primary cases, diagnosed with OGN or differentiated-type adenocarcinoma with GA-FG morphology, between November 2016 and April 2022. We analyzed 54 pathological specimens and reviewed their clinicopathological, endoscopic, and histological features. The lesions were reclassified as OGA or GA-FG, and immunohistochemical (IHC) staining for MUC-5AC and MUC-6 was performed on available resected GA-FG cases. RESULTS: The median patient age was 65 years and males accounted for 58.6% of patients. Most cases occurred in the body horizontally (69.0%) and on the greater curvature side cross-sectionally (48.3%). Endoscopically, type 0-IIa (41.4%) and a subepithelial tumor-like appearance (24.1%) were the most common findings. Histologically, there were 8 cases of OGA (27.6%) and 21 cases of GA-FG (72.4%). In GA-FG, MUC-6 was positive in 13 cases (81.3%), whereas MUC-5AC was positive in 8 cases (50.0%). Three cases presented as AGCs. CONCLUSIONS: Although OGNs are generally considered low-grade, they can present as AGCs and may exhibit features of lymphovascular or perineural invasion. Recognizing the clinicopathological features and accurately diagnosing OGN are important for providing adequate treatment.

Hole transport layer engineering in high performance quasi-2D perovskite blue light emitting diodes.

Quasi-2D perovskites have emerged as highly promising materials for application in perovskite light-emitting diodes (PeLEDs), garnering significant attention due to their outstanding semiconductor properties. These materials boast an inherent multi-quantum well structure that imparts a robust confinement effect, particularly advantageous for blue emission. However, the development of blue emitters utilizing quasi-2D perovskites encounters challenges, notably colour instability, multipeak emission, and suboptimal fluorescence yield. The hole transfer layer (HTL) on which the perovskite layer is deposited in PeLEDs further affects the performance and efficiency. In this review, we delve into the evolution of blue PeLEDs and elucidate the optical properties of quasi-2D perovskites with the primary focus on HTL materials. We explore different HTL materials like PEDOT:PSS, metal oxides, and conjugated polyelectrolytes as well as ionic liquids, and their role in enhancing the colour stability, minimizing interfacial defects and increasing the fluorescence yield. This review endeavours to provide a holistic perspective of the different HTLs and serve as a valuable reference for researchers navigating the realm of HTL engineering towards the realization of high-performance blue quasi-2D PeLEDs.

Clinical Outcomes of Small Cell Carcinoma of the Genitourinary Tract and the Prognostic Significance of the Tumor Immune Microenvironment.

PURPOSE: Small cell carcinoma of the genitourinary tract (GU SCC) is a rare disease with a poor prognosis. There are only limited treatment options due to insufficient understanding of the disease. In this study, we analyzed the clinical outcomes of patients with GU SCC and their association with the tumor immune phenotype. MATERIALS AND METHODS: Patients diagnosed with GU SCC were included. Survival outcomes according to the primary location (prostate and non-prostate) and stages (limited disease [LD] and extensive disease [ED]) were analyzed. We performed multiplex immunohistochemistry (IHC) in non-prostate SCC patients and analyzed the immune cell population. RESULTS: A total of 77 patients were included in this study. Their median age was 71 years, 67 patients (87.0%) were male, and 48 patients (62.3%) had non-prostate SCC. All patients with ED (n=31, 40.3%) received etoposide plus platinum (EP) as initial treatment and median overall survival (OS) was 9.7 months (95% confidence interval [CI], 7.1 to 18.6). Patients with LD (n=46, 59.7%) received EP followed by radiotherapy or surgery, and 24-months OS rate was 63.6% (95% CI, 49.9 to 81.0). The multiplex IHC analysis of 21 patients with non-prostate SCC showed that patients with a higher density of programmed death-ligand 1-expressing CD68+CD206+ M2-like macrophages had significantly worse OS outcomes with an adjusted hazards ratio of 4.17 (95% CI, 1.25 to 14.29; adjusted p=0.02). CONCLUSION: Patients with GU SCC had a poor prognosis, even those with localized disease. The tumor immune phenotypes were significantly associated with survival. This finding provides new insights for treating GU SCC.

Artificial intelligence algorithm for neoplastic cell percentage estimation and its application to copy number variation in urinary tract cancer.

BACKGROUND: Bladder cancer is characterized by frequent mutations, which provide potential therapeutic targets for most patients. The effectiveness of emerging personalized therapies depends on an accurate molecular diagnosis, for which the accurate estimation of the neoplastic cell percentage (NCP) is a crucial initial step. However, the established method for determining the NCP, manual counting by a pathologist, is time-consuming and not easily executable. METHODS: To address this, artificial intelligence (AI) models were developed to estimate the NCP using nine convolutional neural networks and the scanned images of 39 cases of urinary tract cancer. The performance of the AI models was compared to that of six pathologists for 119 cases in the validation cohort. The ground truth value was obtained through multiplexed immunofluorescence. The AI model was then applied to 41 cases in the application cohort that underwent next-generation sequencing testing, and its impact on the copy number variation (CNV) was analyzed. RESULTS: Each AI model demonstrated high reliability, with intraclass correlation coefficients (ICCs) ranging from 0.82 to 0.88. These values were comparable or better to those of pathologists, whose ICCs ranged from 0.78 to 0.91 in urothelial carcinoma cases, both with and without divergent differentiation/ subtypes. After applying AI-driven NCP, 190 CNV (24.2%) were reclassified with 66 (8.4%) and 78 (9.9%) moved to amplification and loss, respectively, from neutral/minor CNV. The neutral/minor CNV proportion decreased by 6%. CONCLUSIONS: These results suggest that AI models could assist human pathologists in repetitive and cumbersome NCP calculations.

Spherical bullet formation via E-cadherin promotes therapeutic potency of mesenchymal stem cells derived from human umbilical cord blood for myocardial infarction.

The beneficial effects of stem cells in clinical applications to date have been modest, and studies have reported that poor engraftment might be an important reason. As a strategy to overcome such a hurdle, we developed the spheroid three dimensional (3D) bullet as a delivery method for human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) through the maintenance of cell-cell interactions without additional xenofactors, cytokines, or matrix. We made spheroid 3D-bullets from hUCB-MSCs at 24 hours' anchorage-deprived suspension culture. To investigate the in vivo therapeutic efficacy of 3D-bullets, we used rat myocardial infarction (MI) model. Transplantation of 3D-bullet was better than that of single cells from monolayer culture or from 3D-bullet in improving left ventricular (LV) contractility [LV ejection fraction (LVEF) or LV fractional shortening (LVFS)] and preventing pathologic LV dilatation [LV end-systolic diameter (LVESD) or LV end-diastolic diameter (LVEDD)] at 8 weeks. In the mechanism study of 3D-bullet formation, we found that calcium-dependent cell-cell interaction was essential and that E-cadherin is a key inducer mediating hUCB-MSC 3D-bullet formation among several calcium-dependent adhesion molecules which were nominated as candidates after cDNA array analysis. In more specific experiments with E-cadherin overexpression using adenoviral vector or with E-cadherin neutralization using blocking antibody, we found that E-cadherin regulates vascular endothelial growth factor (VEGF) secretion via extracellular signal-regulated kinase (ERK)/v-akt murine thymoma viral oncogene homolog1 (AKT) pathways. During formation of spheroid 3D-bullets, activation of E-cadherin in association with cell-cell interaction turns on ERK/AKT signaling pathway that are essential to proliferative and paracrine activity of MSCs leading to the enhanced therapeutic efficacy.