Search

Anovulation is the most prominent cause of infertility in polycystic ovary syndrome (PCOS) patients. Although ovulation can be corrected pharmacologically, the number of pregnancies remains low. Even if excellent embryos are transferred by IVF, it does not change the high miscarriage rate of PCOS patients. These facts collectively indicate that there is a disorder of endometrial development and receptivity to the embryo in PCOS patients, including the decrease of receptive ability, inhibition of embryo adhesion, undersupply of energy, poor blood perfusion, and pro-inflammatory status in the endometrium. However, it has never received the same attention as ovulatory dysfunction. Here we list some alternations of endometrial receptivity in women with PCOS, discuss the underlying intricate mechanisms, and try to find out the possible therapeutic targets, which may bring new perspectives to those who are able to provide high-quality embryos.

The vegetable sponge-like Bi2O3 was prepared using a microwave-ultrasonic strategy, with in situ reconstruction boosting the CO2RR performance.

Zn-BTC survived reconstruction with the possession of slightly reduced Zn2+ and carboxyl groups at negative potential, resulting in a steady H2/CO ratio (∼1 : 2) in a wide potential window (−0.96 to −1.96 V vs. RHE).

A Cu-BTC-CP precatalyst with asymmetric building units, which in situ reconstructs to low-coordinated Cu during the CO2RR, delivers an ethylene faradaic efficiency of 65.2 ± 3% at 350 mA cm−2 in a flow cell.

The increased hypothalamic neurokinin B (NKB) level may contribute to the hyperactive LH pulse secretion in Polycystic ovary syndrome (PCOS). However, the expression and role of the neurokinin B-neurokinin 3 receptor (NKB-NK3R) system in the local ovarian tissue of PCOS have not been clarified. We constructed in vivo and in vitro models to elucidate the mechanism of the NKB-NK3R pathway in reproductive endocrine disorders of PCOS.The granulosa cell line-KGN cells were set in palmitic acid (PA) and dihydrotestosterone (DHT) to simulate the PCOS-like conditions. And we used the high-fat/high-glucose diet to build a PCOS-like mice model and neurokinin 3 receptor antagonist (NK3Ra) was administered to half of the mice. The expression of the NKB-NK3R system, mitochondrial functions, hormone levels, and inflammatory state was evaluated.The PCOS-like stimulations induced the NKB-NK3R system and MAPK-ERK pathway overexpression in KGN cells, in an approximate dose and time-dependent manner. The NKB-NK3R system overactivated the MAPK-ERK pathway to increase NNT overexpression, disturb NADH/NADPH pools, aggravate the oxidation state, and decrease ATP production. With overexpression of the NKB-NK3R system in the local ovarian tissue, ovulatory dysfunction, progesterone deficiency, and pro-inflammatory states were apparent in PCOS-like mice. Antagonizing the receptor, NK3R, reversed the adverse reproductive endocrine phenotypes via improving mitochondrial dysfunction.In addition to the central regulation, local ovarian overexpression of the NKB-NK3R system participated in the adverse reproductive endocrine phenotypes, supporting the therapeutic implications of NK3Ra for PCOS.

Researchers have been studying the pain sensation extensively in the past few decades. Quantitative simulation and theoretical modeling of pain sensation based on experimental results are necessary for pain research. Many theories have been proposed to explain the mechanism of pain from molecular, cellular, and neuron network perspectives. But some phenomena in pain sensation are not fully understood, including wind-up and ramp-off. This paper focused on the theoretical model of wind-up and ramp-off phenomena in the pain sensation. With the addition of the transduction model, the generation mechanism of wind-up and ramp-off is better explained. The simulations were carried out to analyze the skin pain sensation under the mechanical stimulus, consisting of four different parts: the mechanical model of skin, transduction, transmission, modulation, and perception. The stress distribution on the skin was obtained based on the elastic theory. And the modified Hodgkin and Huxley model and the mathematical model of gate control theory were utilized to analyze the process of transduction, modulation, and perception, respectively. The numerical experiments demonstrated the wind-up occurs with a frequent stimulus of 1 Hz and 2 Hz, and ramp-off appears with the withdrawal of constant mechanical stimulus, which could contribute to the understanding of the pain sensation mechanism.

Objective. The imaging photoplethysmography (IPPG), which is applied to heart rate measurement, is susceptible to interference caused by illumination variations during photography. To improve the accuracy, robustness, and real-time performance of IPPG, a new method combined with modified ensemble empirical mode decomposition (EEMD) and fast independent component analysis (FastICA) was proposed. Approach. On the modified EEMD, to reduce the error caused by the residual white noise of the algorithm, it was characterized by recurrently updating zero-mean white noise for ensemble averaging based on the standard deviation of the input signal. On the modified FastICA, its constructed nonlinear function was superseded by Huber’s approximation function to improve the robustness and running speed. Main results. Comparison experiments were conducted between the MAHNOB-HCI database and own collected data. In the hybrid natural light and computer screen light scenario, the mean absolute error (MAE) of heart rate amounted to 0.93 beats per minute and the correlation coefficient r reached 0.85. In the experiments of MAHNOB-HCI database, the MAE amounted to 6.03 beats per minute and the correlation coefficient r reached 0.75. Furthermore, the modified method decreased the running time by approximately ten times compared to the original algorithms. Significance. Various experimental results demonstrated that the proposed method significantly improves the accuracy, timeliness, and interference resistance.

As thermal protection substrates for wearable electronics, functional soft composites made of polymer materials embedded with phase change materials and metal layers demonstrate unique capabilities for the thermal protection of human skin. Here, we develop an analytical transient phase change heat transfer model to investigate the thermal performance of a wearable electronic device with a thermal protection substrate. The model is validated by experiments and the finite element analysis (FEA). The effects of the substrate structure size and heat source power input on the temperature management efficiency are investigated systematically and comprehensively. The results show that the objective of thermal management for wearable electronics is achieved by the following thermal protection mechanism. The metal thin film helps to dissipate heat along the in-plane direction by reconfiguring the direction of heat flow, while the phase change material assimilates excessive heat. These results will not only promote the fundamental understanding of the thermal properties of wearable electronics incorporating thermal protection substrates, but also facilitate the rational design of thermal protection substrates for wearable electronics.

Objective: Anti-Müllerian hormone (AMH) expression is elevated in patients with polycystic ovary syndrome (PCOS), however, its clinical significance is not clear. Owing to the strong correlation between AMH and polycystic ovarian morphology (PCOM), some studies believe that AMH alone can be used to diagnose PCOS. The aim of this study was to explore whether AMH can be used to diagnose PCOS and to differentiate the various PCOS subtypes. Methods: This was a retrospective study of 503 patients with PCOS. Patients were divided into eight subtypes based on the presence/absence of hyperandrogenemia (HA), insulin resistance (IR), or obesity (OB). The expression characteristics of AMH in each subtype were analyzed. Due to the small number of patients with subtypes 7 and 8, only patients with subtypes 1–6 were included in the analysis. Results: AMH showed a good positive correlation with PCOM (P = 0.000) and negative correlations with OB (P = 0.000) and IR (P = 0.003). The free testosterone index showed no correlation with AMH (P = 0.803). The percentages of patients with each subtype (excluding subtypes 7–8) and their respective AMH levels were as follows: Type 1 (HA + NIR + OB) 4.77% and 9.12 ng/mL; Type 2 (HA + IR + NOB) 20.68% and 10.34 ng/mL; Type 3 (HA + NIR + NOB) 23.66% and 9.47 ng/mL; Type 4 (HA + IR + OB) 30.82% and 8.32 ng/mL; Type 5 (NHA + NIR + NOB) 11.73% and 10.0 ng/mL; and Type 6 (NHA + IR + NOB) 6.16% and 9.76 ng/mL. The diagnostic rates of AMH (>8.09 ng/mL) and ultrasound for PCOM were 60.10% and 85.60%, respectively, suggesting that AMH did not completely predict PCOM. Conclusions: High AMH levels can be used to evaluate the incidence trend of PCOS. However, due to clinical heterogeneity, accurately evaluating the severity of PCOS and identifying the subtype of PCOS in Chinese patients are difficult. Individualized treatment should be administered based on accurate clinical subtypes and other clinical characteristics.

Neurokinin-B (NKB)-Neurokinin-3-receptor (NK3R) pathway is remarkably sensitive to energy equilibrium; however, its role in metabolic regulation remains unexplored in polycystic ovary syndrome (PCOS). Therefore, this work aimed to investigate the role of NK3R antagonists (NK3Ra) on metabolic dysfunction and obesity in in vitro and in vivo PCOS models.First, an observational study using serum samples collected from 19 PCOS patients was performed. Second, prospective case-control experimental studies where NK3Ra (SB222200) was used to treat PCOS-like mice (BALB/c mice), ovariectomized+estrogen implanted obese mice (C57BL/6J mice) and 3T3-L1 murine preadipocytes were carried out to investigate its effect on metabolism in vivo and in vitro. The fat volumes, serum biochemical indexes, adipokines and inflammatory cytokines, metabolism-related gene expression and the concentrations of ATP, NAD+, NADPH…etc. were studied.We found a positive correlation between serum NKB and lipid metabolism indicators in PCOS women. Using the mouse models, we demonstrated that administration of NK3Ra regulates serum adipokines, inhibits weight gain with a marked decrease in fat volume, adipocyte size, and inflammatory cytokines, and promotes oxidative metabolism and energy consumption. NK3Ra reduces lipid accumulation in mature murine adipocytes by inhibiting the expression of peroxisome proliferator- activated receptor gamma (PPAR-γ) and fatty acid binding protein 4 (FABP4) genes. NK3Ras also enhances oxidative metabolism and energy consumption by maintaining intracellular redox homeostasis.This study backs the use of NK3Ras as a potential therapeutic for PCOS since it ameliorates both reproductive and metabolic aberrations.

At present, Imaging Photoplethysmography (IPPG) has attracted extensive attention on heart rate measurement, because of its non-contact, non-invasive and safe characteristics. However, in reality, the IPPG signal is extremely feeble and susceptible to be submerged by ambient interference such as illumination. To this end, we propose a new IPPG signal processing approach to enhance the anti-interference capability of measuring heart rate through a modified EEMD algorithm with updated white-noise iterating. In the modified EEMD algorithm, based on the standard deviation of the input IPPG signal, zero-mean white noises are generated randomly for iterative ensemble averaging. Through this new method, the fault caused by the residual white noise of traditional EEMD is solved. Lastly, through the comparative experiments of our own acquisition statistics, the approach proposed by this paper has significantly improved the performance in terms of accuracy, timeliness and anti-interference under various scenarios. The mean absolute error reaches 1.4 beats per minute and the correlation coefficient r reaches 0.8089. In addition, the modified EEMD algorithm reduces the running time by more than 10 times compared to the original method, approximately 0.16s per time.

High dielectric constant materials are of particular current interests as indispensable components in transistors, capacitors, etc. In this context, there are emerging trends to exploit defect engineering in dielectric ceramics for enhancing the performance. However, demonstrations of similar high dielectric performance in integration-compatible crystalline films are rare. Herein, such a breakthrough via the functionalization of donor–acceptor dipoles by compositional tuning in GaCu codoped ZnO films is reported. The dielectric constant reaches ~200 at 1 kHz and the optical transmittance in visible light reaches ~80%. Importantly, by analyzing the impedance spectroscopy data, prominent relaxation mechanisms in correlation with the dipole properties, enabling consistent explanations of the dielectric constant as a function of frequency are discriminated. The atomistic nature of the dipoles is revealed by the systematic X-ray spectroscopy analysis. Spectacularly, similar trends for the dielectric properties are observed, while synthesizing samples by pulsed laser deposition and ion implantation, indicating the general character of the phenomena.

Objective: This study aimed at elucidating the therapeutic effectiveness of metformin in polycystic ovary syndrome (PCOS) patients with normal clinical indices of insulin sensitivity. Methods: This study was a retrospective cohort study. Based on their homeostasis model of assessment of insulin resistance (HOMA-IR) results, PCOS patients (n = 113) were allocated to either the IR Group (IR, HOMA-IR >2.69) or the non-IR Group (NIR, HOMA-IR ≤2.69). Metformin was administered to all patients, and their medical history, menstrual status, and endocrine and metabolic characteristics were obtained before and after treatment. The one-way analysis of variance was used to determine the differences between the IR and NIR groups. The paired t-test was used to determine the differences between pre- and posttreatment results. Results: Analyses of baseline characteristics showed that the incidence of IR and glycolipid metabolism is higher within elder PCOS patients. Metformin improved menstrual cycle and ovulation rate in NIR patients, similar to those in IR patients. In the NIR group, metformin decreased luteinizing hormone (LH) levels, free androgen index (FAI) levels, body mass index, and waist circumference, but had no obvious effect on glucose, insulin, and lipid profiles. Whereas in the IR group, metformin not only decreased LH and FAI levels, but also improved glycolipid metabolism. Conclusions: The effect of metformin on PCOS patients with normal insulin sensitivity index suggests that the mechanism of menstrual improvement may not be related to IR. In addition, metformin can improve glycolipid metabolism. Therefore, metformin is suitable for long-term treatment of PCOS and should be more widely used.

Objective To evaluate the association between CD16++ monocytes in peripheral blood and the clinical features and short-term therapeutic effects of polycystic ovary syndrome (PCOS). Methods This prospective cross-sectional study included women diagnosed with PCOS at a University Hospital in Shanghai, China, between June 4 and November 28, 2016. Patients received Diane-35, metformin, or both combined for 3 months. We collected anthropometric measures and used flow cytometry to detect CD16++ monocytes. Results The final analysis included 70 patients: 18 in the Diane-35 group, 30 in the metformin group, and 22 in the Diane-35 plus metformin group. The control group comprised 60 women without PCOS. The proportion of CD16++ monocytes was significantly higher in patients with PCOS than in those with no PCOS (16.05% vs 10.73%; P=0.001). The proportion differed significantly between patients with and those without hyperandrogenism (13.12% vs 17.30%; P=0.002) and showed moderate accuracy in diagnosing hyperandrogenism before treatment. We noted a decrease in monocytes post-treatment in patients given metformin and Diane-35 plus metformin. Conclusions The proportion of CD16++ monocytes was most significantly associated with hyperandrogenism before treatment. Our findings suggest that the proportion of CD16++ monocytes in peripheral blood might be related to the inflammatory condition of PCOS.

Background: Neuroendocrine (NE) phenotype contributes to 25 to 30% androgen deprivation resistant prostate cancer cases. Until now, this aggressive phenotype is untreatable. Therefore, it is urgent to study the molecular mechanism of NE development to reveal therapeutic strategies. Methods: Data were downloaded from CCLE, cBioPortal, and GEO and analyzed by R. RT-qPCR, western-blot, Immunohistochemistry, and Immunofluorescence were used to assess gene expression. Results: Neuroendocrine prostate cancer (NEPCa) develops from prostate adenocarcinoma (AdPCa). We screened and identified the consensus differentially expressed genes across all public NEPCa transcriptome datasets. We found several HOX genes are included. HOXB13 is deceased but HOXB3, HOXD8 are increased in NEPCa. Based on the HOX code (total 39 HOX genes expression) theory, different cell lineages have distinct HOX codes and HOX codes can represent tissue identities, we established 42 HOX codes for 42 cells lineages including prostate through bioinformatics analysis of 1019 cancer cell lines transcriptome. We found NEPCa samples have changed prostatic HOX code. We also found YAP1, a previously characterized oncogene, is decreased in mRNA level in NEPCa than AdPCa. We confirmed the YAP1 protein is not detected in NEPCa human/mouse samples, PDX samples, and cell line samples (NCI-H660). We used YAP1 as a model. We hypothesized that the signaling involved in silencing YAP1 expression can also contribute to NE development. We first confirmed the loss of YAP1 expression in NEPCa cells is under epigenetic control by inducing YAP1 mRNA expression in primary mouse NEPCa cells through epigenetic inhibitors treatments (HDACs/DNA methyltransferase inhibitors). We characterized the YAP1 promoter through data mining chromatin ChIP-seq data and DNA methylation-seq data. We identified and cloned a 3kb DNA fragment across the YAP1 transcription start site as YAP1 regulatory element. We then built a YAP1-promoter-luciferase reporter using this fragment. We also generated a list of transcription factors that can bind the YAP1 regulatory element. We will then confirm the roles of these transcriptional factors in both regulating YAP1 and NE development. We also found YAP1 expression is co-expressed with many HOX genes in human samples. This suggested the potential regulatory function of HOX code to YAP1 expression. Conclusion: We proposed 2 critical events during NE development, changed prostatic HOX code and loss of YAP expression. We identified HOX code change as one of the potential regulatory mechanisms of YAP1. We then proposed to use YAP1 regulatory element as a model system to study the NE development mechanism. Funding: The LSUHS Office of Research SEED awards, NIH R01 CA226285, and Feist-Weiller Cancer Center pre-doc fellowship to SC. Acknowledgment: We acknowledge Feist-Weiller Cancer Center for travel support to SC. Citation Format: Siyuan Cheng, Shu Yang, Yingli Shi, Xiuping Yu. Altered prostatic HOX code is associated with decreased YAP1 expression during neuroendocrine prostate cancer development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3751.

Problem Excess caloric intake and irregular circadian rhythm could severely impair female reproductive, metabolic, and immune function. However, the similarities and differences between their individual and combined effects and mechanisms have not been fully elucidated. Due to limitations and confounding factors in clinical research, we used these two kinds of unhealthy factors to intervene the mice singly or in combination to explore their effects on individuals. Method of study We used a high-calorie diet (HCD), constant light exposure (CLE), and a high-calorie diet combined with constant light exposure (HCD + CLE) to build three different mouse models. During the 9 weeks modeling period, the estrous cycles were monitored, and after modeling, the indicators of glycolipid metabolism, inflammation, and reproductive endocrine function were tested. Results We found that both HCD and CLE alone could induce ovulatory disorders, obesity, and chronic low-grade inflammation and inhibit melatonin secretion. The difference was that HCD significantly reduced the serum luteinizing hormone (LH) and testosterone (T) levels, inhibited the expression of FSH β and LH β in pituitary, increased cytochrome P450 enzymes and LH receptor expression in ovary, as well causing impaired glucose tolerance and hyperlipidemia, and significantly promoted the secretion of leptin and inhibited the secretion of adiponectin. However, CLE significantly increased blood LH and T, prompted the expression of kisspeptin in hypothalamus and LH β in pituitary, and had no effect on glycolipid metabolic indexes or the secretion of leptin or adiponectin. The phenotype of HCD + CLE model was basically the same as that of HCD model, associated with more severe visceral obesity and chronic inflammation. Conclusions In conclusion, we found that unhealthy lifestyle determines the phenotype of reproductive endocrine, immune, and metabolic disorders. These findings can provide theoretical support for the subsequent study of PCOS-like features.

HOXB13, the most posterior HOX B gene, is primarily expressed in the prostate. Using immunohistochemical staining, we evaluated the expression of HOXB13 in prostatic tissues. We found that HOXB13 was expressed in both benign prostatic tissues and prostate adenocarcinoma (AdPCa) but its expression was reduced or lost in neuroendocrine prostate cancer (NEPCa). Additionally, using RNAseq data of HOXs in cell lines derived from various tissue origins, we established HOX codes for these tissue types. We applied the HOX codes to PCa samples and found that the majority of AdPCa samples sustained the prostate-specific HOX code but the majority of NEPCa samples lost it. Our analysis also showed that the NEPCa samples did not correlate well with the HOX codes of any other tissue type. This indicates that NEPCa tumors lose prostate identity but do not gain a clear-cut new tissue identity. Finally, we treated PCa cells with all trans retinoic acid and found that the reduced/lost HOXB13 expression can be reverted, as can AR and AR targets. Taken together, our data indicate that HOXB13 expression is reduced or lost in NEPCa and a loss of prostate-specific HOX code in NEPCa represents a loss of prostatic identity.

As phase change functional polymer composites, polydimethylsiloxane (PDMS) and paraffin composites exhibit excellent performance on temperature dependent thermal and mechanical properties. In this paper, PDMS/paraffin composites with uniform microstructure are prepared by the melting mixing method with paraffin as filler and PDMS as matrix. The modification of PDMS by paraffin components owns both advantages on excellent flexibility and heat absorption capacity. Systematic experiments results are performed to illustrate the DSC specter, stress-strain curves and other properties varying with temperature. The obtained composites can be an ideal material for soft thermal management substrate of flexible electronics or phase change heat sink of batteries and this study might be helpful for the design and fabrication in the wide potential applications. Keywords: Phase change polymer composites, Thermal properties, Thermal management, Mechanical properties, Temperature sensitive

Various known and unknown viral diseases can threaten crustacean aquaculture. To develop prophylactic and therapeutic strategies against viruses, crustacean cell lines are urgently needed for immunology and virology studies. However, there are currently no permanent crustacean cell lines available. In this study, we developed a new method for preparing crayfish plasma (CP) and found that CP enhanced the proliferative capacity of haematopoietic tissue (hpt) cells from Cherax quadricarinatus by an EdU (5-ethynyl-2'-deoxyuridine) assay. The optimal CP concentration for hpt cell culture and the optimal subculture method are discussed. To achieve efficient expression of a foreign gene in hpt cells cultured in vitro, different transfection methods and vectors were analysed. We found that Lipofectamine 2000 could be used to efficiently transfect a foreign vector into hpt cells and exhibited a lower level of cytotoxicity than the other methods tested, and transfection of pEGFP-N1/w249 and pDHsp70-EGFP-FLAG resulted in high EGFP expression. By transmission electron microscopy (TEM) and virus copy number analysis, we found that white spot syndrome virus (WSSV) could infect hpt cells and multiply efficiently. Our results implied that the crayfish hpt cell culture system we improved could be used as a replacement for immortal crustacean cell lines in viral infection studies. Our findings provide a solid foundation for future immortalization and gene function studies in crustacean cells.

The concept of mimicking natural materials to design novel lightweight structures with high capacity of energy absorption is of great interest at present. Enormous natural structures exhibit fascinating mechanical performance after hundreds of millions of years of convergent evolution. Odontodactylus scyllarus, known as the peacock mantis shrimp, whose dactyl strike is recognized as one of the rapidest and powerful creatures found in nature, has an enormous potential to act as excellent biomimetic protective system. In this paper, a novel lightweight bio-inspired double-sine corrugated (DSC) sandwich structure has been proposed to enhance the impact resistance. The out-of-plane uniform compression of the bio-inspired bi-directionally sinusoidal corrugated core sandwich panel has been conducted under the quasi-static crushing load. Compared with the regular triangular and sinusoidal corrugated core sandwich panels, the bio-inspired DSC core sandwich panels significantly improve the structural crashworthiness as well as reducing the initial peak force greatly. Finally, the influences of the wave amplitude, wave number and corrugated core layer thickness on the mechanical performance of the bio-inspired DSC core sandwich panel are investigated to seek for the appropriate structural parameters to optimize the energy absorption behavior. Keywords: Bio-inspired, Sandwich structure, Crashworthiness, Energy absorption, FE simulation

Background: HOX genes encode Homeobox-containing proteins. There are 39 HOX genes organized into 4 clusters in human. The nested and partially overlapping expression of HOX genes in an anatomic region can determine its tissue specificity, which is termed as “HOX code”. In this study, we examined the expression of HOX genes in neuroendocrine prostate cancer (NEPCa), an aggressive subtype prostate cancer that arises from prostate adenocarcinoma (AdPCa) trough trans-differentiation. Methods: The HOX genes expression data were extracted from Cancer Cell Line Encyclopedia (CCLE) dataset. All in silico analysis were performed by using R language. Immunohistochemistry (IHC), dual immunofluorescence staining, Western blot and RT-qPCR were conducted to access the expression of HOXs. Results: Using the HOXs' mRNA expression data from CCLE, we generated HOX codes for 25 different types of tissues. These HOX codes were validated in TCGA pan cancer. By calculating the Pearson correlation, we were able to use 9 HOX codes including prostatic HOX code to identify the tissue origins of the cancer samples. Further, we found that in prostate cancer, the NEPCa samples have lost prostatic HOX code while majority of the AdPCa samples maintain the prostatic HOX code. The expression of HOXB13, the most prominent HOX expressed in prostatic tissues, was increased in AdPCa along with PCa progression but was decreased in NEPCa. Similarly, we found that in breast cancer, a sub-group of samples correlated well with the HOX code of mammary gland, but the rest did not. By comparing the differentially expressed genes in these two subgroups of samples, we found that the neuroendocrine markers including CHGA, CHGB and SYP were higher in HOX code-negative samples compared with HOX code-positive ones. Additionally, we observed a similar phenomenon in colorectal cancer samples: The expression of neurogenesis genes were enriched in HOX code-negative subgroup. Conclusions: 1) The expression of HOXB13 is decreased in NEPCa. 2) NEPCa has changed HOX code, suggesting the loss of prostatic identity in these samples. 3) The association of neuroendocrine phenotype with the changes in HOX code is not limited to prostate cancer but also is observed in other types of cancer. Significance: The HOX codes we established can be used in pan cancer research to identify the tissue origins of cancer samples and to study the trans-differentiation of cancer cells. Funding: This study is supported by: The LSUHS Office of Research SEED awards, NIH R01 CA226285 and Feist-Weiller Cancer Center. Citation Format: Siyuan Cheng, Shu Yang, Yingli Shi, Runhua Shi, Yunshin Yeh, Xiuping Yu. Neuroendocrine cancer cells have changed HOX code during trans-differentiation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2151.

EAST upper divertor has been upgraded to ITER-like actively-cooled W/Cu components in May 2014. In the manufacture, assembling and disassembling of this W/Cu divertor, it was found that more than 10 support legs have dropped from the W/Cu-monoblock. In this work, the welding technique and drop reason of the support leg have been summarized and analyzed. To replant the dropped legs, some weld methods, including the middle-temperature brazing, electric resistance welding and 3D printing, have been performed and compared. Finally, the replantation technique based on 3D printing with laser beam has been developed and the nickel leg has successfully been printed on W block without the copper interface. In the development of the replantation technique, the microstructure and mechanical properties of the nickel leg have been researched to modify the printing technique. It is considered that this replantation technique also could be used in the ITER W divertor project.

Objective This study was aimed to explore the potential of a non-invasive monocytes-based delivery system to transport therapeutic genes into the diseased brain. The study was conducted by first establishing the optimized conditions for lentiviral vector (LV)-mediated gene transfer into freshly isolated monocytes, followed by investigating the inflamed-brain homing efficiency and in vivo cell-mediated transgene expression by carrier monocytes in a mouse model with acute sub-regional neuroinflammation. Materials & methods Using a newly optimized spin-infection method, up to 35% of freshly isolated monocytes were successfully transduced with the LV system DHIV-101 at M.O.I. of 10. Meanwhile, cell trafficking and accumulation were detected in the inflamed brain regions in high density following intravenous (IV) administration of freshly isolated monocytes, confirming the suitability of using monocytes as cellular vehicles targeting the brain. However, LV transduced monocytes (TD-MO) displayed significantly reduced homing efficiency into the brain, possibly due to the initial unhealthy cellular states following LV transduction. Although the presence of transgene in the brain was confirmed by PCR, transgene expression was not detected within the inflammatory central nervous system (CNS) sites by RT-PCR or ELISA. Instead, high density of functional TD-MO and their transgene products were detected in the spleen. Conclusion In conclusion, this study demonstrated that IV-infused monocytes were able to migrate into the brain, and remain viable and functional in vivo following LV transduction, warranting more indepth research to fully establish the conditions in order to reduce cellular toxicity induced by vector transduction, and thus enhance the brain homing efficiency of carrier monocytes.

Follicle-stimulating hormone (FSH), as the main indicator of ovarian function, plays an important role in the clinical activities of gynecologic endocrinology. Although anti-Mullerian hormone and antral follicle count are also the indictors evaluating ovarian function, many clinicians are still relentless in their decision to impose the death penalty of ovaries when high FSH levels (especially more than 40 IU/L) are observed. We recently encountered four patients whose FSH levels were inconsistent with actual fertility because all patients had successfully conceived after treatment. In our study, we found the culprit (macro-FSH) of false-positive FSH levels by applying the polyethylene glycol protein precipitation technique. The biological functions of macro-FSH were further evaluated by using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. This study suggests that ovarian reserve function should be comprehensively assessed in clinic, and the causes of serum test indicators inconsistent with clinic should be identified. Key words: Fertility; Macro-Follicle-Stimulating Hormone; Ovarian Function; Polyethylene Glycol Precipitation

In order to avoid the occurrence of two types of longitudinal defects (strain localization and folding flaws), which were observed in the CuCrZr tubes of EAST W/Cu upper divertor components, in the future manufacturing of monoblock components using hot isostatic pressing (HIP), a new CuCrZr tube forming protocol is proposed. The evolution of Cu grains and Cr-rich particles is monitored by scanning electron microscopy throughout the new tube forming processes. The final microstructures of the newly developed tubes are totally different from those of the EAST project previously chosen tubes and the elongation of Cr-rich precipitates has been substantially suppressed by using the new tube forming protocol. The newly developed tubes show better HIP performance than the EAST previously chosen ones. Since circumferential mechanical properties, especially ductility, are of great importance, a circumferential ductility testing manner for small-diameter tubes, which might be a supplement to longitudinal tensile testing, has been utilized and the preliminary testing results are given. The recrystallization behavior of the newly developed tubes is also investigated.

Early embryonic arrest is one of the major causes of female infertility. However, because of difficulties in phenotypic evaluation, genetic determinants of human early embryonic arrest are largely unknown. With the development of assisted reproductive technology, the phenotype of early human embryonic arrest can now be carefully evaluated. Here, we describe a consanguineous family with a recessive inheritance pattern of female infertility characterized by recurrent early embryonic arrest in cycles of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). We have identified a homozygous PADI6 nonsense mutation (c.1141C>T [p.Gln381 ∗ ]) that is responsible for the phenotype. Mutational analysis of PADI6 in a cohort of 36 individuals whose embryos displayed developmental arrest identified two affected individuals with compound-heterozygous mutations (c.2009_2010del [p.Glu670Glyfs ∗ 48] and c.633T>A [p.His211Gln]; c.1618G>A [p.Gly540Arg] and c.970C>T [p.Gln324 ∗ ]). Immunostaining indicated a lack of PADI6 in affected individuals' oocytes. In addition, the amount of phosphorylated RNA polymerase II and expression levels of seven genes involved in zygotic genome activation were reduced in the affected individuals' embryos. This phenotype is consistent with Padi6 knockout mice. These findings deepen our understanding of the genetic basis of human early embryonic arrest, which has been a largely ignored Mendelian phenotype. Our findings lay the foundation for uncovering other genetic causes of infertility resulting from early embryonic arrest.

A newly isolated Pacific white shrimp (Litopenaeus vannamei) beta-actin promoter SbaP and its derivative compact construct SbaP (ENX) have recently been demonstrated to promote ectopic gene expression in vitro and in vivo. To further explore the potential transduction application, this newly isolated shrimp promoter SbaP was comparatively tested with cytomegalovirus (CMV), simian virus 40 (SV40), polyhedrin (Polh), and white spot syndrome virus immediate early gene 1 (WSSV ie1) four constitutive promoters and a beta-actin promoter (TbaP) from tilapia fish to characterize its promoting function in eight different cell lines. Luciferase quantitation assays revealed that SbaP can drive luciferase gene expression in all eight cell lines including sf21 (insect), PAC2 (zebrafish), EPC (carp), CHSE-214 (chinook salmon), GSTEF (green sea turtle), MS-1 (monk seal), 293T (human), and HeLa (human), but at different levels. Comparative analysis revealed that the promoting activity of SbaP was lower (

Prostate cancer (PCa) is the most common non-cutaneous cancer among American men. In 2019, 174,650 new patients will be diagnosed from this disease. Most patients with localized PCa could be treated successfully. However, when PCa develops into castrate-resistant prostate cancer (CRPCa), the five-year survival rate drops below 30%. Neuroendocrine prostate cancer (NEPCa) is an aggressive subtype of PCa observed in 20%-30% CRPCa patients. Understanding how NEPCa progressed from prostate adenocarcinoma could reveal novel therapeutic targets. Previous studies indicate that activation of Wnt/beta-Catenin signaling promotes the progression to CRPCa with an increased NE differentiation. Additionally, animal studies suggest that Wnt/beta-Catenin signaling is active in NEPCa. Here we explored the mechanisms that promote Wnt/beta-Catenin signaling in NEPCa. Using TRAMP mice, which develop NEPCa after castration, we assessed the expression of Wnt-related genes and found that after androgen deprivation, the expression of Wnt7A is increased in prostate derived from both wild type and TRAMP mice but the expression of DKK1, a Wnt inhibitor, is decreased in wild type prostate but not in TRAMP prostate. The elevated expression of Wnt7a in combination with the lack of induction of Dkk1 in TRAMP tumors provides a mechanism to activate Wnt/beta-Catenin signaling in these tumors. Furthermore, we found the expression of YES-associated Protein (YAP1), a key transcriptional coactivator of Hippo pathway, is lost in NEPCa, in contrast to the elevated expression of YAP1 in high-grade prostate adenocarcinoma. YAP1 knockdown activated Wnt/beta-Catenin activity in PCa PC3 and 22Rv1 cells, indicating that the loss of YAP1 expression provides another mechanism to activate Wnt/beta-Catenin signaling, promoting NEPCa phenotype in PCa cells. Funding: This study is supported by: FWCC/Foundation Legacy Funds, DOD New Investigator Award, The Office of Research SEED awards, NIH R01 AND R03. Citation Format: Siyuan Cheng, Shu Yang, Nestor Prieto-Dominguez, Zachary M. Connelly, Yingli Shi, Xiuping Yu. Loss of YAP1 activates Wnt/beta-Catenin signaling in prostate cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4861.

To evaluate the association between CD16This prospective cross-sectional study included women diagnosed with PCOS at a University Hospital in Shanghai, China, between June 4 and November 28, 2016. Patients received Diane-35, metformin, or both combined for 3 months. We collected anthropometric measures and used flow cytometry to detect CD16The final analysis included 70 patients: 18 in the Diane-35 group, 30 in the metformin group, and 22 in the Diane-35 plus metformin group. The control group comprised 60 women without PCOS. The proportion of CD16The proportion of CD16