Bi2Te3-Based Thermoelectric Modules for Efficient and Reliable Low-Grade Heat Recovery.

Bismuth-telluride-based alloy has long been considered as the most promising candidate for low-grade waste heat power generation. However, optimizing the thermoelectric performance of n-type Bi2Te3 is more challenging than that of p-type counterparts due to its greater sensitivity to texture, and thus limits the advancement of thermoelectric modules. Herein, the thermoelectric performance of n-type Bi2Te3 is enhanced by incorporating a small amount of CuGaTe2, resulting in a peak ZT of 1.25 and a distinguished average ZT of 1.02 (300-500 K). The decomposed Cu+ strengthens interlayer interaction, while Ga+ optimizes carrier concentration within an appropriate range. Simultaneously, the emerged numerous defects, such as small-angle grain boundaries, twin boundaries, and dislocations, significantly suppresses the lattice thermal conductivity. Based on the size optimization by finite element modelling, the constructed thermoelectric module yields a high conversion efficiency of 6.9% and output power density of 0.31 W cm-2 under a temperature gradient of 200 K. Even more crucially, the efficiency and output power little loss after subjecting the module to 40 thermal cycles lasting for 6 days. This study demonstrates the efficient and reliable Bi2Te3-based thermoelectric modules for broad applications in low-grade heat harvest.

Strong electron-phonon coupling and high lattice thermal conductivity in half-Heusler thermoelectric materials.

Traditional half-Heusler thermoelectric materials, identified as 18-electron compounds, are characterized by the high power factor and the high lattice thermal conductivity. Interestingly, the emerging 19-electron half-Heusler compounds were also found to be promising thermoelectric materials, but with a 5-10 times lower lattice thermal conductivity. Since the two kinds of compounds have similar chemical and physical structures, such as TiCoSb and VCoSb, the large difference in lattice thermal conductivity is a puzzling question. Here, we present a theoretical study to clarify the lattice thermal transport in half-Heusler thermoelectric materials. Based on electronic band structure analysis, we show that the two transition-metal elements in half-Heusler compounds form the strong and direct d-d interaction that is responsible for the high lattice thermal conductivity of 18-electron compounds. In 19-electron half-Heusler compounds, however, the extra valence electron enters the d-d antibonding states, which significantly weakens the atomic bond strength, leading to a large decrease in the cohesive energy. The resulting softened acoustic phonons enhance the phonon-phonon scattering, and thus reduce the lattice thermal conductivity significantly. By constructing an artificial 18-e compound V0.5Sc0.5CoSb, it is proved that the one less electron relative to VCoSb increases the lattice thermal conductivity significantly.

A surface strategy boosting the ethylene selectivity for CO2 reduction and in situ mechanistic insights.

Electrochemical reduction of carbon dioxide into ethylene, as opposed to traditional industrial methods, represents a more environmentally friendly and promising technical approach. However, achieving high activity of ethylene remains a huge challenge due to the numerous possible reaction pathways. Here, we construct a hierarchical nanoelectrode composed of CuO treated with dodecanethiol to achieve elevated ethylene activity with a Faradaic efficiency reaching 79.5%. Through on in situ investigations, it is observed that dodecanethiol modification not only facilitates CO2 transfer and enhances *CO coverage on the catalyst surfaces, but also stabilizes Cu(100) facet. Density functional theory calculations of activation energy barriers of the asymmetrical C-C coupling between *CO and *CHO further support that the greatly increased selectivity of ethylene is attributed to the thiol-stabilized Cu(100). Our findings not only provide an effective strategy to design and construct Cu-based catalysts for highly selective CO2 to ethylene, but also offer deep insights into the mechanism of CO2 to ethylene.

Prognostic value of geriatric nutritional risk index in patients with diffuse large B-cell lymphoma: a meta-analysis

Background Geriatric nutritional risk index (GNRI) on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) remains unclear. The purpose of this meta-analysis was to discuss the value of the GNRI in evaluating long-term outcomes in DLBCL. Methods We systematically and roundly retrieved PubMed, Cochrane Library, Embase, Scopus and Web of Science electronic databases from inception of the databases to March 20, 2023. At the same time, we calculated the pool hazard ratios (HRs) with their 95% confidence interval (CI) for overall survival and progression-free survival to assess the effect of GNRI on the prognosis of DLBCL patients. Results In our primary meta-analysis, 7 trials with a total of 2448 patients were enrolled. Results showed that lower level of GNRI was related to poorer overall survival (HR = 1.78, 95% CI 1.27, 2.50, p < 0.01) and worse progression-free survival (HR = 2.31, 95% CI 1.71, 3.13, p < 0.01) in DLBCL patients. Conclusion The results of our meta-analysis indicate that a lower GNRI significantly associated with poorer prognosis for DLBCL. It is believed that GNRI was a promisingly predictive indicator of survival outcomes in DLBCL patients. However, large multicenter prospective studies are necessary to verify the results (AU)

Prognostic value of geriatric nutritional risk index in patients with diffuse large B-cell lymphoma: a meta-analysis.

BACKGROUND: Geriatric nutritional risk index (GNRI) on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) remains unclear. The purpose of this meta-analysis was to discuss the value of the GNRI in evaluating long-term outcomes in DLBCL. METHODS: We systematically and roundly retrieved PubMed, Cochrane Library, Embase, Scopus and Web of Science electronic databases from inception of the databases to March 20, 2023. At the same time, we calculated the pool hazard ratios (HRs) with their 95% confidence interval (CI) for overall survival and progression-free survival to assess the effect of GNRI on the prognosis of DLBCL patients. RESULTS: In our primary meta-analysis, 7 trials with a total of 2448 patients were enrolled. Results showed that lower level of GNRI was related to poorer overall survival (HR = 1.78, 95% CI 1.27, 2.50, p < 0.01) and worse progression-free survival (HR = 2.31, 95% CI 1.71, 3.13, p < 0.01) in DLBCL patients. CONCLUSION: The results of our meta-analysis indicate that a lower GNRI significantly associated with poorer prognosis for DLBCL. It is believed that GNRI was a promisingly predictive indicator of survival outcomes in DLBCL patients. However, large multicenter prospective studies are necessary to verify the results.

High Performance Thermoelectric Power of Bi0.5 Sb1.5 Te3 Through Synergistic Cu2 GeSe3 and Se Incorporations.

Bi2 Te3 -based alloys are the benchmark for commercial thermoelectric (TE) materials, the widespread demand for low-grade waste heat recovery and solid-state refrigeration makes it imperative to enhance the figure-of-merits. In this study, high-performance Bi0.5 Sb1.5 Te3 (BST) is realized by incorporating Cu2 GeSe3 and Se. Concretely, the diffusion of Cu and Ge atoms optimizes the hole concentration and raises the density-of-states effective mass (md * ), compensating for the loss of "donor-like effect" exacerbated by ball milling. The subsequent Se addition further increases md * , enabling a total 28% improvement of room-temperature power factor (S2 σ), reaching 43.6 µW cm-1  K-2 compared to the matrix. Simultaneously, the lattice thermal conductivity is also significantly suppressed by multiscale scattering sources represented by Cu-rich nanoparticles and dislocation arrays. The synergistic effects yield a peak ZT of 1.41 at 350 K and an average ZT of 1.23 (300-500 K) in the Bi0.5 Sb1.5 Te2.94 Se0.06 + 0.11 wt.% Cu2 GeSe3 sample. More importantly, the integrated 17-pair TE module achieves a conversion efficiency of 6.4%, 80% higher than the commercial one at ΔT = 200 K. These results validate that the facile composition optimization of the BST/Cu2 GeSe3 /Se is a promising strategy to improve the application of BST-based TE modules.

Optimized Thermoelectric Cooler Performance by the Structure-Matching Design of Asymmetrical p/n-Type Legs.

Commercial Bi2Te3-based thermoelectric (TE) coolers typically comprise equal-size p- and n-type legs. However, this traditional structure limits the cooling temperature differences of TE coolers (TECs) due to identical current density, when their electrical or thermal characteristics differ significantly. This work presents a novel design of p- and n-type TE legs to optimize the performance of TECs. The cooling properties of the materials are initially calculated by theoretical equations and then evaluated by using a combination of finite element simulations and experiments. The research findings suggest that by utilizing higher ZT p-type materials to enhance the TEC cooling performance, further optimization of the ratio of the cross-sectional area of the TE legs (Ap/An) improves the structural matching of the legs, which achieves the maximum figure of merit Z and leads to a 5.4% increase in cooling power density. Additionally, the TEC with optimized Ap/An increases the cooling temperature difference by 3.3 and 2.7 K for the same current at hot side temperatures of 300 and 315 K, respectively, while the coefficient of performance remains unchanged. Moreover, the maximum cooling temperature difference reaches 70 and 74 K, respectively. We anticipate that our results will guide the design and optimization of the TECs.

Enhanced Thermoelectric Performance of P-Type (Bi,Sb)2 Te3 by Incorporating Non-Stoichiometric Ag5 Te3 and Refining Te-Se Ratio.

Power generation modules utilizing thermoelectric (TE) materials are suitable for recycling widespread low-grade waste heat (<600 K), highlighting the immediate necessity for advanced Bi2 Te3 -based alloys. Herein, the substantial enhancement in TE performance of the p-type Bi0.4 Sb1.6 Te3 (BST) sintered sample is realized by subtly incorporating the non-stoichiometric Ag5 Te3 and counteractive Se. Specifically, Ag atoms diffused into the BST lattice improve the density-of-states effective mass (md * ) and boost the hole concentration for the suppressed bipolar effect. The addition of Se further improves md * prompting the room-temperature power factor upgrade to 46 W cm-1  K-2 . Concurrently, the lattice thermal conductivity is considerably lowered by multiple scattering sources exemplified by Sb-rich nanoprecipitates and dense dislocations. These synergistic results yield a high peak ZT of 1.44 at 375 K and an average ZT of 1.28 between 300 and 500 K in the Bi0.4 Sb1.6 Te2.95 Se0.05 + 0.05 wt.% Ag5 Te3 sample. More significantly, when coupled with n-type zone-melted Bi2 Te2.7 Se0.3 , the integrated 17-pair TE module achieves a competitive conversion efficiency of 6.1% and an output power density of 0.40 W cm-2 at a temperature difference of 200 K, demonstrating great potential for practical applications.

High-Performance Industrial-Grade p-Type (Bi,Sb)2 Te3 Thermoelectric Enabled by a Stepwise Optimization Strategy.

As the sole dominator of the commercial thermoelectric (TE) market, Bi2 Te3 -based alloys play an irreplaceable role in Peltier cooling and low-grade waste heat recovery. Herein, to improve the relative low TE efficiency determined by the figure of merit ZT, an effective approach is reported for improving the TE performance of p-type (Bi,Sb)2 Te3 by incorporating Ag8 GeTe6 and Se. Specifically, the diffused Ag and Ge atoms into the matrix conduce to optimized carrier concentration and enlarge the density-of-states effective mass while the Sb-rich nanoprecipitates generate coherent interfaces with little loss of carrier mobility. The subsequent Se dopants introduce multiple phonon scattering sources and significantly suppress the lattice thermal conductivity while maintaining a decent power factor. Consequently, a high peak ZT of 1.53 at 350 K and a remarkable average ZT of 1.31 (300-500 K) are attained in the Bi0.4 Sb1.6 Te0.95 Se0.05  + 0.10 wt% Ag8 GeTe6 sample. Most noteworthily, the size and mass of the optimal sample are enlarged to Ø40 mm-200 g and the constructed 17-couple TE module exhibits an extraordinary conversion efficiency of 6.3% at ΔT = 245 K. This work demonstrates a facile method to develop high-performance and industrial-grade (Bi,Sb)2 Te3 -based alloys, which paves a strong way for further practical applications.

Enhanced Thermoelectric Properties of p-Type Bi0.5Sb1.5Te3-Cu8GeSe6 Composite Materials.

Bismuth-telluride-based thermoelectric materials have been applied in active room-temperature cooling, but the mediocre ZT value of ∼1.0 limits the thermoelectric (TE) device's conversion efficiency and determines its application. In this work, we show the obviously improved thermoelectric properties of p-type Bi0.5Sb1.5Te3 by the Cu8GeSe6 composite. The addition of Cu8GeSe6 effectively boosts the carrier concentration and thus limits the bipolar thermal conductivity as the temperature is elevated. With the Cu8GeSe6 content of 0.08 wt %, the hole concentration reaches 5.0 × 1019 cm-3 and the corresponding carrier mobility is over 160 cm2 V-1 s-1, resulting in an optimized power factor of over 42 µW cm-1 K-2 at 300 K. Moreover, the Cu8GeSe6 composite introduces multiple phonon-scattering centers by increasing dislocations and element and strain field inhomogeneities, which reduce the thermal conductivity consisting of a lattice contribution and a bipolar contribution to 0.51 W m-1 K-1 at 350 K. As a consequence, the peak ZT of the Bi0.5Sb1.5Te3-0.08 wt % Cu8GeSe6 composite reaches 1.30 at 375 K and the average ZT between 300 and 500 K is improved to 1.13. A thermoelectric module comprised of this composite and commercial Bi2Te2.5Se0.5 exhibits a conversion efficiency of 5.3% with a temperature difference of 250 K, demonstrating the promising applications in low-grade energy recovery.

Assessing the activity of antibodies conjugated to upconversion nanoparticles for immunolabeling.

Surface modification and functionalization is typically required to engineer upconversion nanoparticles (UCNPs) for biosensing and bioimaging applications. Nevertheless, despite various antibody conjugation methods having been applied to UCNPs, no consensus has been reached on the best choice, as the results from individual studies are largely unable to be compared due to inadequate assessment of the properties of the conjugated products. Here, we introduce a systematic approach to quantitatively evaluate the biological activity of antibody-conjugated UCNPs. We determine that the optimal antibody conjugation efficiency to our colominic acid polysaccharide-coated UCNPs via 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxy succinimide (EDC/NHS) coupling is approximately 70%, corresponding to 16 antibodies per nanoparticle of 63 nm hydrodynamic diameter, with on average 12 of the 16 antibodies maintaining their affinity to the target antigens. The binding ability of the antibody-conjugated UCNPs to the antigen was well preserved, as verified by enzyme-linked immunosorbent assay (ELISA), flow cytometry, and cellular imaging. This is the first study to quantitate the active antibody binding capacity of polysaccharide coated UCNP nanoparticles, offering a practical guideline for benchmarking functionalised UCNPs in future studies.

[Application of optimized catheter management strategy in interhospital patients transition with extracorporeal membrane oxygenation].

OBJECTIVE: To discuss the effect of optimized catheter management strategy on reducing the incidence of catheter-related adverse events in interhospital patients transition with extracorporeal membrane oxygenation (ECMO). METHODS: A historical control trial was conducted. The patients transferred with ECMO to the Second Affiliated Hospital of Nanchang University from January 2018 to December 2020 were enrolled. From January 2019 to December 2020, 38 patients with interhospital transport using optimized catheter management strategy were as observation group; from January to December in 2018, 30 patients with routine catheter management method were selected as the control group. The incidence of catheter-related adverse events during transition was compared between the two groups. RESULTS: There were no significant differences in clinical data such as age, number of catheters, transit time, transit distance, ECMO operation time between the observation group and the control group [age (years old): 58.26±10.38 vs. 54.00±16.61, number of catheters (roots): 6.03±1.32 vs. 5.51±1.37, transit time (hours): 2.48±0.30 vs. 2.51±0.39, transfer distance (kilometers): 155.27±20.45 vs. 165.56±25.62, ECMO operating time (days): 8.47±1.28 vs. 9.11±1.99, all P > 0.05]. The incidence of catheter-related adverse events in the control group was 26.67% (8/30), among them, 2 patients had ECMO catheter discount after getting over the bed, causing the flow alarm; 1 patient's central venous catheter (CVC) was not placed with U-shape and twisted, the vasopressors were not entered in time, which caused hypotension; 3 patients had more bleeding at the puncture points and film crimping; the urinary catheters were clamped in 2 patients and not opened in time. In the observation group, the patients did not have catheter-related adverse events during transition. There was statistically significant difference in the incidence of catheter-related adverse events between the two groups (χ2 = 7.814, P < 0.05). CONCLUSIONS: The implementation of optimized catheter management strategy can greatly reduce the incidence of catheter-related adverse events and provide an effective safety guarantee for the interhospital transit of ECMO patients.

The feasibility of Miltuximab®-IRDye700DX-mediated photoimmunotherapy of solid tumors.

BACKGROUND: Photoimmunotherapy (PIT) is an emerging method of cancer treatment based on the use of a photosensitizer near-infrared dye IRDye700DX (IR700) conjugated to a monoclonal antibody. The antibody selectively delivers IR700 to cancer cells, which can then be killed after photoexcitation. Glypican-1 (GPC-1) is a novel target expressed specifically in malignant tumors. We aimed to investigate whether anti-GPC-1 antibody Miltuximab® (Glytherix Ltd., Sydney, Australia) can be conjugated with IR700 for PIT of solid tumors. METHODS: The dye IR700 was conjugated with Miltuximab® and characterized by spectrophotometry and flow cytometry. Miltuximab®-IR700-mediated PIT was tested in prostate (DU-145), bladder (C3 and T-24), brain (U-87 and U-251) and ovarian (SKOV-3) cancer cell lines. After 1 h incubation with Miltuximab®-IR700, the cells were washed by PBS and illuminated using a 690-nm light-emitting diode. The viability of the cells was assessed by a CCK-8 viability kit 24 h later. RESULTS: Miltuximab®-IR700-mediated PIT caused 67.3-92.3% reduction in viability of cells with medium-high GPC-1 expression and did not affect the viability of GPC-1-low cells. Cytotoxicity was attributed to the targeted binding of the conjugate with subsequent photoactivation, as the conjugate or light exposure alone had no effect on the cell viability. Miltuximab®-IR700 did not induce cytotoxicity in cells blocked by unconjugated Miltuximab®. CONCLUSIONS: PIT with Miltuximab®-IR700 appears to be highly specific and effective against GPC-1-expressing cancer cells, indicating that it holds promise for an effective and safe treatment of early stage solid tumors or as adjuvant therapy following surgical resection. These findings necessitate further investigation of PIT with Miltuximab®-IR700 in other GPC-1-expressing cancer cell lines in vitro and in vivo in xenograft tumor models.

Near-Infrared Molecular Imaging of Glioblastoma by Miltuximab®-IRDye800CW as a Potential Tool for Fluorescence-Guided Surgery.

Glioblastoma (GBM) is one of the most aggressive tumors and its 5-year survival is approximately 5%. Fluorescence-guided surgery (FGS) improves the extent of resection and leads to better prognosis. Molecular near-infrared (NIR) imaging appears to outperform conventional FGS, however, novel molecular targets need to be identified in GBM. Proteoglycan glypican-1 (GPC-1) is believed to be such a target as it is highly expressed in GBM and is associated with poor prognosis. We hypothesize that an anti-GPC-1 antibody, Miltuximab®, conjugated with the NIR dye, IRDye800CW (IR800), can specifically accumulate in a GBM xenograft and provide high-contrast in vivo fluorescent imaging in rodents following systemic administration. Miltuximab® was conjugated with IR800 and intravenously administered to BALB/c nude mice bearing a subcutaneous U-87 GBM hind leg xenograft. Specific accumulation of Miltuximab®-IR800 in subcutaneous xenograft tumor was detected 24 h later using an in vivo fluorescence imager. The conjugate did not cause any adverse events in mice and caused strong fluorescence of the tumor with tumor-to-background ratio (TBR) reaching 10.1 ± 2.8. The average TBR over the 10-day period was 5.8 ± 0.6 in mice injected with Miltuximab®-IR800 versus 2.4 ± 0.1 for the control group injected with IgG-IR800 (p = 0.001). Ex vivo assessment of Miltuximab®-IR800 biodistribution confirmed its highly specific accumulation in the tumor. The results of this study confirm that Miltuximab®-IR800 holds promise for intraoperative fluorescence molecular imaging of GBM and warrants further studies.

Pentosan polysulfate binds to STRO-1+ mesenchymal progenitor cells, is internalized, and modifies gene expression: a novel approach of pre-programing stem cells for therapeutic application requiring their chondrogenesis.

BACKGROUND: The pharmaceutical agent pentosan polysulfate (PPS) is known to induce proliferation and chondrogenesis of mesenchymal progenitor cells (MPCs) in vitro and in vivo. However, the mechanism(s) of action of PPS in mediating these effects remains unresolved. In the present report we address this issue by investigating the binding and uptake of PPS by MPCs and monitoring gene expression and proteoglycan biosynthesis before and after the cells had been exposed to limited concentrations of PPS and then re-established in culture in the absence of the drug (MPC priming). METHODS: Immuno-selected STRO-1+ mesenchymal progenitor stem cells (MPCs) were prepared from human bone marrow aspirates and established in culture. The kinetics of uptake, shedding, and internalization of PPS by MPCs was determined by monitoring the concentration-dependent loss of PPS media concentrations using an enzyme-linked immunosorbent assay (ELISA) and the uptake of fluorescein isothiocyanate (FITC)-labelled PPS by MPCs. The proliferation of MPCs, following pre-incubation and removal of PPS (priming), was assessed using the Wst-8 assay method, and proteoglycan synthesis was determined by the incorporation of 35SO4 into their sulphated glycosaminoglycans. The changes in expression of MPC-related cell surface antigens of non-primed and PPS-primed MPCs from three donors was determined using flow cytometry. RNA sequencing of RNA isolated from non-primed and PPS-primed MPCs from the same donors was undertaken to identify the genes altered by the PPS priming protocol. RESULTS: The kinetic studies indicated that, in culture, PPS rapidly binds to MPC surface receptors, followed by internalisation and localization within the nucleus of the cells. Following PPS-priming of MPCs and a further 48 h of culture, both cell proliferation and proteoglycan synthesis were enhanced. Reduced expression of MPC-related cell surface antigen expression was promoted by the PPS priming, and RNA sequencing analysis revealed changes in the expression of 42 genes. CONCLUSION: This study has shown that priming of MPCs with low concentrations of PPS enhanced chondrogenesis and MPC proliferation by modifying their characteristic basal gene and protein expression. These findings offer a novel approach to re-programming mesenchymal stem cells for clinical indications which require the repair or regeneration of cartilaginous tissues such as in osteoarthritis and degenerative disc disease.

Potential role of circulating microRNAs as a biomarker for unexplained recurrent spontaneous abortion.

OBJECTIVE: To compare circulating microRNA (miRNA) profiles between unexplained recurrent spontaneous abortion (URSA) and normal early pregnancies (NEP) and to evaluate the potential role of circulating miRNA as a biomarker for URSA. DESIGN: Laboratory study using human plasma samples. SETTING: Special hospital and research institutes. PATIENT(S): From September 2012 to April 2013, samples of plasma were obtained from 27 URSA patients and 28 NEP patients at 6-10 weeks of gestation at the Department of Reproductive Immunology in Family Planning Special Hospital of Guangdong Province. INTERVENTION(S): Differential miRNA profiling analysis of plasma collected from URSA and NEP patients was performed with the use of microarray. MAIN OUTCOME MEASURE(S): The circulating miRNA expression profile was assessed by means of microarray and real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis. RESULT(S): Twenty-five circulating miRNAs were expressed differentially in URSA compared with NEP. Of these, nine were overexpressed and 16 down-regulated. Six differentially expressed circulating miRNAs were selected to validate the microarray results, and qRT-PCR data confirmed the reliability of the microarray results. Further analysis showed that four circulating miRNAs (miR-320b, miR-146b-5p, miR-221-3p, miR-559) were up-regulated. In URSA, one circulating miRNA (miR-101-3p) was down-regulated in other larger scale samples according to qRT-PCR. Based on target gene analysis, we speculate that these circulating miRNAs regulate URSA by targeting immune, apoptosis, and angiogenic gene functions. CONCLUSION(S): Circulating microRNAs may be involved in URSA pathogenesis and provide a promising new diagnostic biomarker for URSA.

Reconstitution of degenerated ovine lumbar discs by STRO-3-positive allogeneic mesenchymal precursor cells combined with pentosan polysulfate.

OBJECTIVE Disc degeneration and associated low-back pain are major causes of suffering and disability. The authors examined the potential of mesenchymal precursor cells (MPCs), when formulated with pentosan polysulfate (PPS), to ameliorate disc degeneration in an ovine model. METHODS Twenty-four sheep had annular incisions made at L2-3, L3-4, and L4-5 to induce degeneration. Twelve weeks after injury, the nucleus pulposus of a degenerated disc in each animal was injected with ProFreeze and PPS formulated with either a low dose (0.1 million MPCs) or a high dose (0.5 million MPCs) of cells. The 2 adjacent injured discs in each spine were either injected with PPS and ProFreeze (PPS control) or not injected (nil-injected control). The adjacent noninjured L1-2 and L5-6 discs served as noninjured control discs. Disc height indices (DHIs) were obtained at baseline, before injection, and at planned death. After necropsy, 24 weeks after injection, the spines were subjected to MRI and morphological, histological, and biochemical analyses. RESULTS Twelve weeks after the annular injury, all the injured discs exhibited a significant reduction in mean DHI (low-dose group 17.19%; high-dose group 18.01% [p < 0.01]). Twenty-four weeks after injections, the discs injected with the low-dose MPC+PPS formulation recovered disc height, and their mean DHI was significantly greater than the DHI of PPS- and nil-injected discs (p < 0.001). Although the mean Pfirrmann MRI disc degeneration score for the low-dose MPC+PPS-injected discs was lower than that for the nil- and PPS-injected discs, the differences were not significant. The disc morphology scores for the nil- and PPS-injected discs were significantly higher than the normal control disc scores (p < 0.005), whereas the low-dose MPC+PPS-injected disc scores were not significantly different from those of the normal controls. The mean glycosaminoglycan content of the nuclei pulposus of the low-dose MPC+PPS-injected discs was significantly higher than that of the PPS-injected controls (p < 0.05) but was not significantly different from the normal control disc glycosaminoglycan levels. Histopathology degeneration frequency scores for the low-dose MPC+PPS-injected discs were lower than those for the PPS- and Nil-injected discs. The corresponding high-dose MPC+PPS-injected discs failed to show significant improvements in any outcome measure relative to the controls. CONCLUSIONS Intradiscal injections of a formulation composed of 0.1 million MPCs combined with PPS resulted in positive effects in reducing the progression of disc degeneration in an ovine model, as assessed by improvements in DHI and morphological, biochemical, and histopathological scores.

Mesenchymal progenitor cells combined with pentosan polysulfate mediating disc regeneration at the time of microdiscectomy: a preliminary study in an ovine model.

OBJECT: Following microdiscectomy, discs generally fail to undergo spontaneous regeneration and patients may experience chronic low-back pain and recurrent disc prolapse. In published studies, formulations of mesenchymal progenitor cells combined with pentosan polysulfate (MPCs+PPS) have been shown to regenerate disc tissue in animal models, suggesting that this approach may provide a useful adjunct to microdiscectomy. The goal of this preclinical laboratory study was to determine if the transplantation of MPCs+PPS, embedded in a gelatin/fibrin scaffold (SCAF), and transplanted into a defect created by microdiscectomy, could promote disc regeneration. METHODS: A standardized microdiscectomy procedure was performed in 18 ovine lumbar discs. The subsequent disc defects were randomized to receive either no treatment (NIL), SCAF only, or the MPC+PPS formulation added to SCAF (MPCs+PPS+SCAF). Necropsies were undertaken 6 months postoperatively and the spines analyzed radiologically (radiography and MRI), biochemically, and histologically. RESULTS: No adverse events occurred throughout the duration of the study. The MPC+PPS+SCAF group had significantly less reduction in disc height compared with SCAF-only and NIL groups (p < 0.05 and p < 0.01, respectively). Magnetic resonance imaging Pfirrmann scores in the MPC+PPS+SCAF group were significantly lower than those in the SCAF group (p = 0.0213). The chaotropic solvent extractability of proteoglycans from the nucleus pulposus of MPC+PPS+SCAF-treated discs was significantly higher than that from the SCAF-only discs (p = 0.0312), and using gel exclusion chromatography, extracts from MPC+PPS+SCAF-treated discs also contained a higher percentage of proteoglycan aggregates than the extracts from both other groups. Analysis of the histological sections showed that 66% (p > 0.05) of the MPC+PPS+SCAF-treated discs exhibited less degeneration than the NIL or SCAF discs. CONCLUSIONS: These findings demonstrate the capacity of MPCs in combination with PPS, when embedded in a gelatin sponge and sealed with fibrin glue in a microdiscectomy defect, to restore disc height, disc morphology, and nucleus pulposus proteoglycan content.

[Predictive value of endometrial receptivity and pregnancy outcome by hysteroscopy examination at the phase of implantation window in unexplained infertile women].

OBJECTIVE: To explore predictive value of endometrial receptivity and pregnancy outcome by hysteroscopy examination at the phase of implantation window in unexplained infertile women. METHODS: From Oct. 2007 to Mar. 2009, 93 unexplained infertile women underwent hysteroscopy examination at 7 approximately 9 days after a spontaneous ovulation in Family Planning Research Institute of Guangdong Province. According to the endometrial glandular openings and vascular shape, 79 cases without pathological endometrial changes were divided into 60 cases in good endometrium group and 19 cases in poor endometrium group. The following clinical parameters were analyzed and compared between two groups, including endometrial configuration, thickness, secretion, the development and number of pinopodes, vascular distribution, and the level of sex hormone, leukemia inhibitory factor (LIF) and glycodelin in the uterine flushing, and pregnancy outcome. RESULTS: (1) There was no statistical difference in the level of serum estrogen and progesterone at the phase of implantation window, which were (518 +/- 176) pmol/L, (40 +/- 20) nmol/L in good group and (513 +/- 244) pmol/L, (37 +/- 19) nmol/L in poor group (P < 0.05). The endometrium thickness at periovulatroy and implantation window days (1.06 +/- 0.10) cm/(1.16 +/- 0.08) cm in good group did not show significant difference with (0.93 +/- 0.12) cm/(1.02 +/- 0.10) cm in poor group (P > 0.05). The proportion of type A, B and C endometrium at periovulatory days were 63% (12/19), 37% (7/19) and 0 (0/19) in good group and 23% (14/60), 77% (46/60) and 0 (0/60) in poor group. When compared with those of type A or B between two groups respectively, it all showed statistical difference (P < 0.05). However, at phase of implantation window, endometrium configurations were all type B at both groups. (2) 90% (17/19) of women in good group and 7% (4/60) of women in poor group showed normal endometrial secretion function, which showed significant differences (P < 0.01). (3) The percentage of fully developed pinopodes and abundant pinopodes [84% (16/19) and 90% (17/19)] in good group were significantly higher than 42% (25/60) and 57% (34/60) in poor group (P < 0.05). (4) The level of CD(34) expression and microvessel density [MVD; (40.1 +/- 1.2) positive unit (PU) and (21.7 +/- 4.0)/high power field (HP)] in good group were significantly higher than (18.1 +/- 1.3) PU and (8.5 +/- 1.3)/HP in poor group (P < 0.01). (5) The level of LIF and glycodelin in uterine flushing [(72 +/- 54) ng/L and (196 +/- 20) microg/L] in good group were significantly higher than (15 +/- 16) ng/L and (116 +/- 26) microg/L in poor group (P < 0.05). (6) The rate of clinical pregnancy, spontaneous abortion and term delivery were 74% (14/19), 0 (0/14) and 100% (14/14) in good group and 23% (14/60), 14% (2/14) and 86% (12/14) in poor group, the rate of clinical pregnancy and term delivery in good group were significantly increased when compared with those in poor group (P < 0.01). CONCLUSIONS: Hysteroscopy examination at the phase of implantation window could reflect the development of glandular openings and vasculature. It is a preferable method to evaluate the endometrial receptivity and predict pregnancy outcome.

Pentosan polysulfate promotes proliferation and chondrogenic differentiation of adult human bone marrow-derived mesenchymal precursor cells.

INTRODUCTION: This study was undertaken to determine whether the anti-osteoarthritis drug pentosan polysulfate (PPS) influenced mesenchymal precursor cell (MPC) proliferation and differentiation. METHODS: Human MPCs were maintained in monolayer, pellet or micromass cultures (MMC) for up to 10 days with PPS at concentrations of 0 to 20 microg/ml. MPC viability and proliferation was assessed using the WST-1 assay and 3H-thymidine incorporation into DNA, while apoptosis was monitored by flow cytometry. Proteoglycan (PG) biosynthesis was determined by 35SO42- incorporation and staining with Alcian blue. Proteoglycan and collagen type I and collagen type II deposition in pellet cultures was also examined by Toluidine blue and immunohistochemical staining, respectively. The production of hyaluronan (HA) by MPCs in MMC was assessed by ELISA. The relative outcome of PPS, HA, heparin or dextran sulfate (DS) on PG synthesis was compared in 5-day MMC. Gene expression of MPCs in 7-day and 10-day MMC was examined using real-time PCR. MPC differentiation was investigated by co-culturing with PPS in osteogenic or adipogenic inductive culture media for 28 days. RESULTS: Significant MPC proliferation was evident by day 3 at PPS concentrations of 1 to 5 microg/ml (P < 0.01). In the presence of 1 to 10 microg/ml PPS, a 38% reduction in IL-4/IFNgamma-induced MPC apoptosis was observed. In 5-day MMC, 130% stimulation of PG synthesis occurred at 2.5 microg/ml PPS (P < 0.0001), while 5.0 microg/ml PPS achieved maximal stimulation in the 7-day and 10-day cultures (P < 0.05). HA and DS at > or = 5 microg/ml inhibited PG synthesis (P < 0.05) in 5-day MMC. Collagen type II deposition by MMC was significant at > or = 0.5 microg/ml PPS (P < 0.001 to 0.05). In MPC-PPS pellet cultures, more PG, collagen type II but less collagen type I was deposited than in controls. Real-time PCR results were consistent with the protein data. At 5 and 10 microg/ml PPS, MPC osteogenic differentiation was suppressed (P < 0.01). CONCLUSIONS: This is the first study to demonstrate that PPS promotes MPC proliferation and chondrogenesis, offering new strategies for cartilage regeneration and repair in osteoarthritic joints.