Advances in Thyroid Organoids Research and Applications.

INTRODUCTION: Organoids are three-dimensional cellular aggregates derived from stem cells or primary tissues that can self-organize into organotypic structures and showcase the physiological functions of that organ. Organoids typically comprise multiple organ-specific cell types that are responsible for organ function in vivo. They may also incorporate various cellular and molecular stromal components to recapitulate the in vivo microenvironment of the target organ. METHODS: All articles related to thyroid-like organs were synthesized. Articles published between 1959 and 2023 were assessed, categorized, and analyzed using relevant keywords. RESULTS: As such, organoids provide a model of greater physiological relevance than 2D cell culture for basic and translational research. Murine and human organoids of the thyroid have been established from embryonic stem cells (ESCs), pluripotent stem cells (PSCs) and from various healthy or diseased thyroid tissues. These thyroid organoids have been used in basic and translation research on thyroid-related diseases including hyperthyroidism, Graves' disease, and Hashimoto's thyroiditis. In addition, organoids derived from patients with thyroid cancer retain histopathological features and mutational profile of the original tumor. These patient-derived organoids have been successfully used in in vitro evaluation of drug response of individual patients, demonstrating their potential application in personalized treatment of thyroid cancer. CONCLUSION: In this review article, we have discussed various techniques for establishing thyroid organoids and their applications in thyroid-related diseases as disease models, regenerative medicines, or a tool for drug testing.

Aging-related NOX4-Nrf2 redox imbalance increases susceptibility to cisplatin-induced acute kidney injury by regulating mitophagy.

BACKGROUND: During aging, excessive ROS production in the kidneys leads to redox imbalance, which contributes to oxidative damage and impaired organ homeostasis. However, whether and how aging-related NOX4-Nrf2 redox imbalance increases susceptibility to cisplatin-induced acute kidney injury remain largely unknown. METHODS: In this study, we used cisplatin-challenged aging mouse models and senescent HK-2 cells to investigate the effects and mechanisms of aging on susceptibility to cisplatin-induced acute kidney injury. RESULTS: In vivo, we found that cisplatin stimulation caused more severe renal damage, oxidative stress, mitochondrial dysfunction and mitophagy impairment in aging mice than in young mice. Moreover, Nrf2 deficiency aggravated cisplatin-induced acute kidney injury by exacerbating NOX4-Nrf2 redox imbalance and defective mitophagy. In vitro experiments on D-gal-treated human renal tubular epithelial cells (HK-2) demonstrated that senescent renal epithelial cells exhibited increased susceptibility to cisplatin-induced apoptosis, NOX4-Nrf2 redox imbalance-mediated oxidative stress and defective mitophagy. Mechanistically, we found that knockdown of Nrf2 in HK2 cells resulted in increased ROS and aggravated mitophagy impairment, whereas these effects were reversed in NOX4-knockdown cells. CONCLUSION: The present study indicates that NOX4-Nrf2 redox imbalance is critical for mitophagy deficiency in aged renal tubular epithelial cells and is a therapeutic target for alleviating cisplatin-induced acute kidney injury in elderly patients.

Characteristics of denitrification activity, functional genes, and denitrifying community composition in the composting process of kitchen and garden waste.

N2O can be easily produced during the co-composting of kitchen waste (KW) and garden waste (GW). This study investigated the effects of the co-composting of KW and GW at different ratios (1:2, 1:1.5, 1:1, and 1.5:1) on the denitrifying activities, functional genes, and community composition of denitrifiers. The results showed that the denitrification activity of KW and GW at a 1:2 ratio was the lowest. The gene abundances of nirS, nirK, nosZI, and nosZII were high on days 12 and 28 under the four different ratios. Network analysis demonstrated that nosZ-type denitrifiers could construct a complex and reciprocal bacterial network to promote the reduction of N2O to N2. Mantel test results revealed that nirS-, nirK-, nosZI-, and nosZII-type denitrifiers were significantly positively correlated with pH, C/N, and moisture content. These findings demonstrated that composting with appropriate proportions of KW and GW could reduce N2O emissions caused by denitrification.

Effects of dam building on N2O-producing and N2O-reducing community structures in river sediments and the associated N2O emission potential.

Dam construction is regarded as the greatest anthropogenic disturbance in aquatic ecosystems, and it promotes denitrification, through which large N2O emissions occur. However, the effect of dams on N2O producers and other N2O-reducing microorganisms (especially for nosZ II), and the associated denitrification rates remain poorly understood. This study systematically investigated the spatial variation of potential denitrification rates in dammed river sediments in winter and summer and the microbial processes driving N2O production and reduction. Sediments in the transition zone of dammed rivers were found to be critical for N2O emission potential, with lower potential denitrification rate and N2O production rate in winter than in summer. In dammed river sediments, the dominant N2O-producing microorganisms and N2O-reducers were nirS-harboring bacteria and nosZ I-harboring bacteria, respectively. Diversity analysis showed that diversity of N2O-producing did not differ significantly between upstream and downstream sediments, whereas the population size and diversity of N2O-reducing microbial communities in upstream sediments significantly decreased, leading to biological homogenization. Further ecological network analysis revealed that the ecological network of nosZ II microbes was more complex than that of nosZ I microbes, and both exhibited more cooperation in the downstream sediments than in the upstream sediments. Mantel analysis showed that the potential N2O production rate was mainly influenced by electrical conductivity (EC), NH4+, and TC content, and that higher nosZ II/nosZ I ratios contributed to improved N2O sinks in dammed river sediments. Moreover, the Haliscomenobacter genus from the nosZ II-type community in the downstream sediments contributed significantly to N2O reduction. Collectively, this study elucidates the diversity and community distribution of nosZ-type denitrifying microorganisms influenced by dams, and also highlights the non-negligible role played by nosZ II-containing microbial groups in mitigating N2O emissions from dammed river sediments.

IDOD-YOLOV7: Image-Dehazing YOLOV7 for Object Detection in Low-Light Foggy Traffic Environments.

Convolutional neural network (CNN)-based autonomous driving object detection algorithms have excellent detection results on conventional datasets, but the detector performance can be severely degraded in low-light foggy weather environments. Existing methods have difficulty in achieving a balance between low-light image enhancement and object detection. To alleviate this problem, this paper proposes a foggy traffic environment object detection framework, IDOD-YOLOV7. This network is based on joint optimal learning of image defogging module IDOD (AOD + SAIP) and YOLOV7 detection modules. Specifically, for low-light foggy images, we propose to improve the image quality by joint optimization of image defogging (AOD) and image enhancement (SAIP), where the parameters of the SAIP module are predicted by a miniature CNN network and the AOD module performs image defogging by optimizing the atmospheric scattering model. The experimental results show that the IDOD module not only improves the image defogging quality for low-light fog images but also achieves better results in objective evaluation indexes such as PSNR and SSIM. The IDOD and YOLOV7 learn jointly in an end-to-end manner so that object detection can be performed while image enhancement is executed in a weakly supervised manner. Finally, a low-light fogged traffic image dataset (FTOD) was built by physical fogging in order to solve the domain transfer problem. The training of IDOD-YOLOV7 network by a real dataset (FTOD) improves the robustness of the model. We performed various experiments to visually and quantitatively compare our method with several state-of-the-art methods to demonstrate its superiority over the others. The IDOD-YOLOV7 algorithm not only suppresses the artifacts of low-light fog images and improves the visual effect of images but also improves the perception of autonomous driving in low-light foggy environments.

The role of MEOX1 in non-neoplastic and neoplastic diseases.

Targeted gene therapy has shown durable efficacy in non-neoplastic and neoplastic patients. Therefore, finding a suitable target has become a key area of research. Mesenchyme homeobox 1 (MEOX1) is a transcriptional factor that plays a significant role in regulation of somite development. Evidence indicates that abnormalities in MEOX1 expression and function are associated with a variety of pathologies, including non-neoplastic and neoplastic diseases. MEOX1 expression is upregulated during progression of most diseases and plays a critical role in maintenance of the cellular phenotypes such as cell differentiation, cell cycle arrest and senescence, migration, and proliferation. Therefore, MEOX1 may become an important molecular target and therapeutic target. This review will discuss the current state of knowledge on the role of MEOX1 in different diseases.

Effects of dam building on the occurrence and activity of comammox bacteria in river sediments and their contribution to nitrification.

The recent discovery of complete ammonia oxidizers (comammox) has fundamentally changed our understanding of nitrification. However, studies on the occurrence and activity of comammox bacteria and their contribution to nitrification remain unclear. Here, we investigated the abundance, activity, and diversity of comammox bacteria and their contribution to nitrification in sediments from dammed rivers in winter and summer. Our results indicated that comammox clade A was ubiquitous in all sediment samples and the community structure in comammox varied between the upper and lower reaches, but not on the time scale (winter and summer). Comammox activity in the dammed river sediments in summer was prominently higher than in winter (summer: 1.08 ±â€¯0.52; winter: 0.197 ±â€¯0.148 mg N kg-1 day-1). Furthermore, the activity of comammox bacteria in summer appeared higher in the vicinity of the dammed river and in the Sanjiang estuary, which is located downstream of the dammed river. The activity of ammonia-oxidizing bacteria (AOB) (0.77 ±â€¯0.478 mg N kg-1 day-1) was higher compared to comammox (0.639 ±â€¯0.588 mg N kg-1 day-1) and ammonia-oxidizing archaea (AOA) (0.026 ±â€¯0.022 mg N kg-1 day-1) in both winter and summer. In terms of contribution to the nitrification process, AOB (winter: 67.13 ±â€¯12.21 %; summer: 50.57 ±â€¯16.14 %) outperformed comammox (winter: 28.59 ±â€¯12.51 %; summer: 48.38 ±â€¯16.62 %) and AOA (winter: <7.39 %; summer: <2.09 %). These findings indicated that the nitrification process in dammed river sediments was mainly dominated by AOB. Additionally, comammox activity was significantly affected by temperature and NH4+, suggesting that these variables were key determinants of the niche partitioning of comammox. Collectively, our findings provide novel perspectives into the widespread distribution and contribution of comammox to nitrification in dammed river ecosystems, thus broadening our understanding of the nitrification processes.

Bacteriostasis and cleaning effect of trace ozone replacing personal care products.

Ozone is widely used to inactivate bacteria, fungi, and viruses. In recent years, the treatment of itchy skin diseases (eczema and atopic dermatitis) using trace ozone has also received attention. However, the feasibility of using trace ozone to replace personal care products (PCPs) has rarely been analyzed. In this study, the applicability of trace ozone was evaluated in terms of its efficiency for microbial inactivation in three types of skin microbiomes, cleaning performance on simulated human hair and epidermis, safety for simulated human hair, and contribution to emission reduction. The results revealed that at a 10:1 ratio of ozonated water to bacterial suspension, the inactivation ratios of Malassezia, C. albicans, and S. epidermidis reached 99.63%, 83.47%, and 100%, respectively. In addition, the cleaning performance of an ozone solution (0.4 mg/L) for simulated human skin contaminated with carbon black and sebum could reach 95.89% and 95.63%, respectively, with 5 min of washing. The average scores were 0.40 and 0.37 after 5 min and 10 min of ozone treatments, respectively, indicating that trace ozone does not significantly damage simulated human hair. Results also revealed that the total emissions of COD, TP, and TN would be reduced by 1.29×106, 3.55×103, and 3.63×103 mg/ (household · year), respectively, if PCPs are replaced by trace ozone. In short, our findings indicate that trace ozone is a potential alternative to PCPs. By replacing PCPs with trace ozone, the use of synthetic chemical products can be reduced and carbon emissions from oil extraction can be countered.

Crystallographically Textured and Magnetic LaCu-Substituted Ba-Hexaferrite with Excellent Gyromagnetic Properties.

Excellent gyromagnetic properties of textured, bulk Ba-hexaferrite samples are required for low-loss, self-biased applications for microwave and millimeter-wave (MMW) devices. However, conventionally processed bulk Ba-hexaferrite ceramics typically demonstrate low remanent magnetization values, 4πMr, of 2.0~3.0 kG, and relatively large ferromagnetic resonance (FMR) linewidths, ΔHFMR, of 0.8~2 kOe. These properties lead to the development of high-performance, practical devices. Herein, crystallographically textured Ba-hexaferrite samples, of the composition Ba0.8La0.2Fe11.8Cu0.2O19, having excellent functional properties, are proposed. These materials exhibit strong anisotropy fields, Ha, of ~14.6 kOe, high remanent magnetization, 4πMr, of 3.96 kGs, and a low ΔHFMR of 401 Oe at zero-bias field at the Q-band. Concomitantly, the broadband millimeter-wave transmittance was utilized to determine the complex permeability, µ*, and permittivity, ε*, of textured hexaferrites. Based on Schlöemann's theory of complex permeability, µ*, the remanent magnetization, 4πMr, anisotropy field, Ha, and effective linewidth, ΔHeff, were estimated; these values agree well with measured values.

High N2O reduction potential by denitrification in the nearshore site of a riparian zone.

As a potent atmospheric greenhouse gas and a major source of ozone depletion, nitrous oxide (N2O) emission has been given increasing attention in aquatic systems, particularly at the aquatic-terrestrial interfaces, such as riparian zones. However, the microbial mechanisms regulating N2O emission in riparian zones remain unknown. Here, we measured the contributions of denitrification and ammonium oxidation to N2O emission along with the abundance and community structure of nirK-, nirS-, nosZ I- and nosZ II-harbouring bacteria in both surface sediments (0-10 cm) and overlying water along a lake riparian zone (including nearshore sites and offshore sites). Overall, the nearshore sites of the riparian zones emitted less N2O than the offshore sites. Nearshore N2O emission was dominated by denitrification with a high N2O reduction rate, whereas offshore N2O emission was driven by ammonium oxidation. Furthermore, N2O derived from ammonium oxidation was influenced by the NH4+-N content, and denitrification N2O was modulated by denitrifier communities. The N2O-producing community was dominated by nirS-harbouring bacteria, while the N2O-reducing community was dominated by nosZ I-harbouring bacteria. The relative abundance of Hydrogenophilales from nirS-denitrifiers and Chloroflexi unclassified from nosZ II-type communities influenced the N2O produced by denitrification, according to high-throughput sequencing analysis. Additionally, we also found lower levels of N2O production per unit volume in overlying water, which were 3-4 orders of magnitude less than in the surface sediment. Overall, we propose that using riparian zones can be an effective management tool for N2O mitigation by enhancing the N2O reduction process of denitrification and decreasing ammonium oxidation.

Inhibitory effect of pirfenidone on pulmonary fibrosis in patients with acute paraquat poisoning.

OBJECTIVE: To study the efficacy of pirfenidone (PFD) on patients with pulmonary fibrosis caused by acute paraquat (PQ) poisoning. METHODS: A total of 86 patients with pulmonary fibrosis caused by acute PQ poisoning admitted to our hospital were analyzed retrospectively. All of them successfully received the standard 21-day treatment based on "Taishan Consensus", and they were assigned to the PFD group or the NO-PFD group according to whether they received PFD treatment (at 200 mg/time, 3 times/day) for 6 months after discharge. The two groups were compared in effective treatment rate, mortality and incidence of adverse reactions such as liver and kidney function damage, pulmonary fibrosis-associated indexes, pulmonary function-associated indexes, and arterial blood gas indexes before and after therapy. RESULTS: The PFD group showed a notably higher effective treatment rate than the NO-PFD group (P<0.05). Additionally, the PFD group showed notably lower levels of serum hyaluronic acid (HA), laminin (LN), type IV collagen (CIV), and type III procollagen (PCIII), and notably higher levels of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC than the NO-PFD group (all P<0.001), and the PFD group also showed significantly higher levels of arterial blood gas indexes including arterial partial pressure of oxygen (PaO2) and PaO2/inspired oxygen (FIO2) than the NO-PFD group (both P<0.001). Moreover, the Kaplan-Meier survival curves showed that the survival rate of the patients in PFD group was significantly higher than that in the NO-PFD group (P<0.05). CONCLUSION: With a high safety, PFD can effectively improve the treatment efficacy in patients with pulmonary fibrosis caused by acute PQ poisoning. PFD can improve the pulmonary function and arterial blood gas status of patients, without causing obvious liver and kidney damage.

BKM120 sensitizes BRCA-proficient triple negative breast cancer cells to olaparib through regulating FOXM1 and Exo1 expression.

Poly (ADP-ribose) polymerase (PARP) inhibitors offer a significant clinical benefit for triple-negative breast cancers (TNBCs) with BRCA1/2 mutation. However, the narrow clinical indication limits the development of PARP inhibitors. Phosphoinositide 3-kinase (PI3K) inhibition sensitizes BRCA-proficient TNBC to PARP inhibition, which broadens the indication of PARP inhibitors. Previously researches have reported that PI3K inhibition induced the defect of homologous recombination (HR) mediated repair by downregulating the expression of BRCA1/2 and Rad51. However, the mechanism for their synergistic effects in the treatment of TNBC is still unclear. Herein, we focused on DNA damage, DNA single-strand breaks (SSBs) repair and DNA double-strand breaks (DSBs) repair three aspects to investigate the mechanism of dual PI3K and PARP inhibition in DNA damage response. We found that dual PI3K and PARP inhibition with BKM120 and olaparib significantly reduced the proliferation of BRCA-proficient TNBC cell lines MDA-MB-231 and MDA231-LM2. BKM120 increased cellular ROS to cause DNA oxidative damage. Olaparib resulted in concomitant gain of PARP1, forkhead box M1 (FOXM1) and Exonuclease 1 (Exo1) while inhibited the activity of PARP. BKM120 downregulated the expression of PARP1 and PARP2 to assist olaparib in blocking PARP mediated repair of DNA SSBs. Meanwhile, BKM120 inhibited the expression of BRAC1/2 and Rad51/52 to block HR mediated repair through the PI3K/Akt/NFκB/c-Myc signaling pathway and PI3K/Akt/ FOXM1/Exo1 signaling pathway. BKM120 induced HR deficiency expanded the application of olaparib to HR proficient TNBCs. Our findings proved that PI3K inhibition impaired the repair of both DNA SSBs and DNA DSBs. FOXM1 and Exo1 are novel therapeutic targets that serves important roles in DNA damage response.

Renal cell carcinoma associated with Xp11.2 translocation/transcription factor E3 gene fusion: an adult case report and literature review.

Renal cell carcinoma (RCC) associated with Xp11.2 translocation/transcription factor E3 (TFE3) gene fusion is a rare and independent subtype of RCC included in the classification of MiT (microphthalmia-associated transcriptional factor) family translocation RCC. Herein, we report an adult case of Xp11.2 translocation RCC, and review the relevant literature to improve our understanding of the pathogenesis, epidemiology, clinical manifestations, diagnosis, differential diagnosis, treatment, and other aspects of the disease.

Dissimilatory nitrate/nitrite reduction to ammonium (DNRA) pathway dominates nitrate reduction processes in rhizosphere and non-rhizosphere of four fertilized farmland soil.

Nitrate (NO3-) reduction partitioning between denitrification, anaerobic ammonium oxidation (anammox), denitrifying anaerobic methane oxidation (DAMO), and dissimilatory nitrate reduction to ammonium (DNRA), can influence the nitrogen (N) use efficiency and crop production in arid farmland. The microbial structure, function and potential rates of denitrification, anammox, DAMO and DNRA, and their respective contributions to total NO3- reduction were investigated in rhizosphere and non-rhizosphere soil of four typical crops in north China by functional gene amplification, high-throughput sequencing, network analysis and isotopic tracing technique. The measured denitrification and DNRA rate varied from 0.0294 to 20.769 nmol N g-1 h-1and 2.4125-58.682 nmol N g-1 h-1, respectively, based on which DNRA pathway contributed to 84.44 ± 14.40% of dissimilatory NO3- reduction, hence dominated NO3- reduction processes compared to denitrification. Anammox and DAMO were not detected. High-throughput sequencing analysis on DNRA nrfA gene, and denitrification nirS and nirK genes demonstrated that these two processes did not correlate to corresponding gene abundance or dominant genus. RDA and Pearson's correlation analysis illustrated that DNRA rate was significantly correlated with the abundance of Chthiniobacter, as well as total organic matter (TOM); denitrification rate was significantly correlated with the abundance of Lautropia, so did TOM. Network analysis showed that the genus performed DNRA was the key connector in the microbial community of dissimilatory nitrate reducers. This study simultaneously investigated the dissimilatory nitrate reduction processes in rhizosphere and non-rhizosphere soils in arid farmland, highlighting that DNRA dominated NO3- reduction processes against denitrification. As denitrification results in N loss, whereas DNRA contributes to N retention, the relative contributions of DNRA versus denitrification activities should be considered appropriately when assessing N transformation processes and N fertilizer management in arid farmland fields.

Safety and Efficacy of Right Retroperitoneal Laparoscopic Live Donor Nephrectomy: A Retrospective Single-Center Study.

BACKGROUND The aim of this study was to investigate the efficacy and safety of right retroperitoneal laparoscopic live donor nephrectomy (LDN) in 81 cases of living-related renal transplant. MATERIAL AND METHODS We retrospectively reviewed all living-related donors who underwent right retroperitoneoscopic living donor nephrectomy between June 2010 and December 2017 at the First Hospital of Jilin University and their corresponding recipients. Demographic and clinical data were collected from the hospital's electronic clinical data system. Data on preoperative renal retention parameters, operative time, and donor kidney warm ischemia time, the trimmed length of the renal artery and vein of donor kidney, and the time to extubation were recorded. Complications in both donors and recipients were recorded. RESULTS We included 81 donors who underwent successful right-sided retroperitoneoscopic LDN, with 31 males and 50 females and a mean age of 47.1 years (range 21-63 years). There was no intraoperative conversion to open donor nephrectomy. The mean operative time was 120.68±29.8 min. The mean warm ischemic time was 49.26±3.86 s. The estimate blood loss was 54.32 mL (range 50-400 mL). The median length of hospital stay was 7 days (range 4-13 days). There was neither intraoperative complication such as hemorrhage or lymph fistula nor kidney graft injury. There was no graft renal vein thrombosis and ureteral stricture or other complications. No graft rejection occurred. CONCLUSIONS Right retroperitoneal laparoscopic live donor nephrectomy is safe and effective for renal transplant in living-related renal transplant by laparoscopic excision and extraction of the right kidney with vena cava flap.

The clinicopathological and prognostic value of CD44 expression in bladder cancer: a study based on meta-analysis and TCGA data.

CD44 is reported to be involved in tumor invasion and metastasis. However, the role of cancer stem cell marker CD44 in bladder cancer still remains controversial. Hence, the correlations between CD44 expression and the clinicopathological features and the prognosis of bladder cancer were investigated. Publications using immunohistochemical methods were identified. The Cancer Genome Atlas (TCGA) data were also analyzed. The odds ratios (ORs) or hazard ratios (HRs) with their 95% confidence intervals (95% CIs) were calculated. 14 studies involving 1107 tissue samples were included. CD44 expression in bladder cancer was lower than in non-tumor tissue samples (OR = 0.14, P = 0.005), which was consistent with TCGA data. CD44 expression was correlated with advanced T stage (OR = 1.76, P = 0.029) and lymph node metastasis (OR = 4.09, P < 0.001). Multivariate survival analysis showed that CD44 expression was not linked to tumor-specific survival, overall survival, and recurrence/relapse-free survival, but was associated with disease failure (HR = 2.912, 95% CI = 1.51-5.61). No relationships of CD44 expression with the clinicopathological features and overall survival were found from TCGA data. Our finding suggested that CD44 expression may be correlated with progression, metastasis, and disease failure of bladder cancer. However, further large-scale studies are needed.Abbreviations: CD44: Cluster of Differentiation 44; CIs: Confidence Intervals; CSCs: Cancer Stem Cells; EMT: Epithelial-mesenchymal Transition; HRs: Hazard Ratios; ORs: Odds Ratios; TCGA: The Cancer Genome Atlas.

A meta-analysis and The Cancer Genome Atlas data of prostate cancer risk and prognosis using epithelial cell adhesion molecule (EpCAM) expression.

BACKGROUND: Epithelial cell adhesion molecule (EpCAM) expression has been reported in many types of cancer, including prostate cancer (PCa). However, the role of EpCAM expression remains inconsistent. We conducted a meta-analysis to assess the clinicopathological and prognostic significance of EpCAM expression in PCa. METHODS: Publications were searched online using electronic databases. The available data were obtained from The Cancer Genome Atlas (TCGA). The odds ratios (ORs) or hazard ratios (HRs) with their 95% confidence intervals (CIs) were calculated. RESULTS: We identified seven studies in which immunohistochemistry was used and that included 871 prostatic tissue samples. EpCAM expression was significantly higher in PCa samples than in benign and normal tissue samples (OR = 77.93, P = 0.002; OR = 161.61, P <  0.001; respectively). No correlation of EpCAM overexpression with pT stage and lymph node metastasis was observed; however, EpCAM overexpression showed a significant correlation with Gleason score (OR = 0.48, P = 0.012) and bone metastasis (OR = 145.80, P <  0.001). Furthermore, TCGA data showed that EpCAM overexpression was not closely correlated with age, pT stage, lymph node metastasis, number of lymph node, prostate-specific antigen level, Gleason score, biochemical recurrence, and overall survival. Based on multivariate Cox proportional-hazards regression analysis, a significant correlation was observed between EpCAM overexpression and 5-year worse biochemical recurrence free-survival. CONCLUSIONS: EpCAM overexpression may be correlated with the development of bone metastasis and worse biochemical recurrence free-survival of PCa. Further studies are needed to verify these findings.

Elimination of donor CD47 protects against vascularized allograft rejection in mice.

CD47 is a ubiquitously expressed transmembrane glycoprotein that plays a complex role in regulation of cell survival and function. We have previously shown that the interspecies incompatibility of CD47 plays an important role in triggering rejection of cellular xenografts by macrophages. However, the role of CD47 in solid organ transplantation remains undetermined. Here, we explored this question in mouse models of heart allotransplantation. We observed that the lack of CD47 in donor hearts had no deleterious effect on graft survival in syngeneic or single MHC class I-mismatched recipients, in which both wild-type (WT) and CD47 knockout (CD47 KO) mouse hearts survived long term with no sign of rejection. Paradoxically, elimination of donor CD47 was beneficial for graft survival in signal MHC class II- and class I- plus class II-mismatched combinations, in which CD47 KO donor hearts showed significantly improved survival compared to WT donor hearts. Similarly, CD47 KO donor hearts were more resistant than WT hearts to humoral rejection in α1,3-galactosyltransferase-deficient mice. Moreover, a significant prolongation of WT allografts was observed in recipient mice treated with antibodies against a CD47 ligand thrombospondin-1 (TSP1) or with TSP1 deficiency, indicating that TSP1-CD47 signaling may stimulate vascularized allograft rejection. Thus, unlike cellular transplantation, donor CD47 expression may accelerate the rejection of vascularized allografts.