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This in vivo study aimed to investigate local and systemic immune responses induced by sperm in cows after artificial insemination (AI). Initially, 12 multiparous Japanese Black cows were subjected to intrauterine AI (AI group, n = 6) or saline infusion (control group, n = 6). The uterine body and horn ipsilateral to the ovulatory follicle were mini-flushed with 2 ml of RPMI-1640 medium at different time points (0, 1, 6, 10, 24, 48 h, and 7 days after AI), centrifuged, and the sediments were examined under a light microscope. Vaginal smears were prepared at 0, 1, 6, and 10 h after AI to investigate the sperm backflow. Subsequently, another experiment was conducted by assigning cows to three groups: intrauterine AI (AI group, n = 5), heat-inactivated AI (Heat-AI group, n = 5), or saline infusion (control group, n = 5). Blood samples were collected, and polymorphonuclear neutrophils (PMNs) and peripheral blood mononuclear cells (PBMCs) were separated and analyzed for gene expression using real-time PCR. The results showed that most sperm were rapidly transported either forward into the uterine horn or backward into the vagina within 1 h after AI. The PMNs migrated into the uterine lumen 6 hours after AI. Only active sperm-induced proinflammatory responses in PMNs and PBMCs via upregulation of TNFa, IL8, IL1B, and PGES and downregulation of IL10 at 6 h after AI. These data provide evidence that sperm generate transient proinflammatory responses locally in the uterus and systemically in the peripheral immune cells, which may be prerequisites for uterine clearance, embryo receptivity, and implantation in cows.
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Leucocitos Mononucleares , Semen , Femenino , Bovinos , Masculino , Animales , Útero/fisiología , Espermatozoides/metabolismo , Inseminación Artificial/veterinaria , Inseminación Artificial/métodosRESUMEN
A radio is adaptive if it can autonomously analyze the communications environment and instantly modify its settings to achieve the best possible efficiency. In orthogonal frequency division multiplexing (OFDM) transmissions, identifying the space frequency block coding (SFBC) category utilized is one of the most important tasks of an adaptive receiver. Previous approaches to this problem did not take into consideration the fact that real systems typically suffer from transmission defects. This study offers a novel maximum likelihood recognizer capable of distinguishing between SFBC OFDM waveforms in the context of inphase and quadrature phase differences (IQDs). The theoretical findings show that IQDs arising from the transmitter and recipient can be combined with channel paths to generate so-called effective channel paths. The conceptual examination demonstrates that the outlined maximum likelihood strategy of the SFBC recognition and effective channel estimation processes is implemented by an expectation maximization tool utilizing the error control decoders' soft outputs. The simulations results reveal that the suggested strategy delivers a much greater recognition accuracy than the typical approaches outlined in the comparable literature. At a signal-to-noise ratio (SNR) of 14 dB, for example, the proposed approach achieves a bit error rate (BER) of 0.00002, which is very close to the case of perfect estimation and compensation for IQDs, outperforming the previous reported works which achieved BERs of 0.01 and 0.02.
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The intelligent reflecting surface (IRS) is a cutting-edge technology for cost-effectively achieving future spectrum- and energy-efficient wireless communication. In particular, an IRS comprises many low-cost passive devices that can independently reflect the incident signal with a configurable phase shift to produce three-dimensional (3D) passive beamforming without transmitting Radio-Frequency (RF) chains. Thus, the IRS can be utilized to greatly improve wireless channel conditions and increase the dependability of communication systems. This article proposes a scheme for an IRS-equipped GEO satellite signal with proper channel modeling and system characterization. Gabor filter networks (GFNs) are jointly proposed for the extraction of distinct features and the classification of these features. Hybrid optimal functions are used to solve the estimated classification problem, and a simulation setup was designed along with proper channel modeling. The experimental results show that the proposed IRS-based methodology provides higher classification accuracy than the benchmark without the IRS methodology.
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This paper presents the design of an arc-shaped near-isotropic self-complementary antenna for spectrum sensing application. An arc-shaped dipole with horizontal and vertical arms is used to achieve a near isotropic radiation pattern. The radiation pattern improved by adjusting the horizontal and vertical arm lengths. Simulated and experimental results show that the proposed antenna has an impedance bandwidth of 146% (2.4-18.4 GHz) for VSWR ≤ 2 with a good radiation pattern. In order to quantify the antenna performance, antenna gain variation, bandwidth, efficiency, and size have been compared with previously reported designs. It is shown that the proposed arc-shaped antenna can achieve nearly isotropic radiation patterns with a maximum radiation efficiency of 92%. The isotropic performance of the antenna has been characterized by observing the radiation pattern and solid angle. The FR4 substrate is used as a dielectric with relative permittivity 4.4 and loss tangent of 0.02. (εr = 4.4, h = 1.6 mm) The simulated and measured results are in good comparison, and the proposed design is a suitable candidate for spectrum sensing.
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Registros , Impedancia EléctricaRESUMEN
Modulation awareness and cooperative transmissions have individually received a significant amount of research in the scholarly literature. However, a limited number of works are principally concerned with the combination of the two topics, and they are restricted to frequency-flat wireless channels. In this study, we propose a new modulation awareness method applicable to dual-hop amplify-and-forward cooperative broadcasts. The suggested method is built on the creation of theoretical representations of cross-correlation functions of the received signals. We conceptually prove that a family of modulation types generates spikes for certain cross-correlation functions, while others do not. We create a numerous layer hypothesis evaluation for the purpose of making judgments centered on this attribute. The suggested method has a number of benefits, such as the ability to operate on both frequency-flat and frequency-selective channels, as well as the absence of the necessity of channel awareness or noise power. Computer simulations analyze the performance of the proposed method, which delivers adequate awareness performance in a variety of operational scenarios.
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Algoritmos , Tecnología Inalámbrica , Simulación por ComputadorRESUMEN
Automatic modulation recognition (AMR) is an essential component in the design of smart radios that can intelligently communicate with their surroundings in order to make the most efficient use of available resources. Throughout the last few decades, this issue has been subjected to in-depth examination in the published research literature. To the best of the authors' knowledge, there have only been a few studies that have been specifically devoted to the task of performing AMR across cooperative wireless transmissions. In this contribution, we examine the AMR problem in the context of amplify-and-forward (AAF) two-path consecutive relaying systems (TCRS) for the first time in the literature. We leverage the property of data redundancy associated with AAF-TCRS signals to design a decision feedback iterative modulation recognizer via an expectation-maximization procedure. The proposed recognizer incorporates the soft information produced by the data detection process as a priori knowledge to generate the a posteriori expectations of the information symbols, which are employed as training symbols. The proposed algorithm additionally involves the development of an estimate of the channel coefficients as a secondary activity. The simulation outcomes have validated the feasibility of the proposed design by demonstrating its capacity to achieve an excellent recognition performance under a wide range of running conditions. According to the findings, the suggested technique converges within six rounds, achieving perfect recognition performance at a signal-to-noise ratio of 14 dB. Furthermore, the minimal pilot-to-frame-size ratio necessary to successfully execute the iterative procedure is 0.07. In addition, the proposed method is essentially immune to time offset and performs well throughout a broad range of frequency offset. Lastly, the proposed strategy beats the existing techniques in recognition accuracy while requiring a low level of processing complexity.
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Algoritmos , Simulación por Computador , Retroalimentación , Relación Señal-RuidoRESUMEN
Previously, we reported that the presence of multiple day 7 (D7) bovine embryos in the uterus induces systemic immune responses in circulating polymorphonuclear neutrophils (PMNs), but with unknown mechanism. Thus, this study aimed to investigate the direct impact of D7 bovine embryo on PMNs' immune responses in vitro and whether these PMNs can amplify and transfer embryo signals further to another PMN population. PMNs were directly stimulated by embryo culture media (ECM) or interferon tau (IFNT) (10 ng/ml) followed by evaluating mRNA expression by real-time PCR and phenotypic analysis by flow cytometry. To test whether PMNs can transfer embryo signals to a new PMN population, PMNs triggered by ECM or IFNT, were thoroughly washed and diluted to remove any media components, and again were incubated in fresh culture media for 3 h, from which culture supernatants were collected and used as PMN conditioned media (CM) to stimulate a new PMN population. Similar to ECM, IFNT directly stimulated expressions of IFNs (IFNA, IFNG), interferon-stimulated genes (ISGs; OAS1, ISG15, MX1), STAT1, TGFB and IL8, and downregulated TNFA in PMNs. Flow cytometrical analyses demonstrated that IFNT stimulated expressions of pregnancy-related phenotypic markers, CD16 and arginase-1 (ARG1), in PMNs. Most importantly, PMN CM induced ISGs and STAT1 mRNA in fresh PMNs. Since IFNT directly upregulated IFNA expression in PMNs, the impact of IFNA on PMNs' immune responses was further tested. Stimulation of PMNs with IFNA, especially at a low level (1 pg/ml), induced IFNT-like immune responses comparable to those induced by PMN CM. Together, these findings indicated that D7 bovine embryos induce direct anti-inflammatory responses with upregulation of ISGs expressions in PMNs mainly via IFNT. Additionally, PMNs can amplify and transfer embryo signals to a new PMN population in a cell-to-cell communication mechanism possibly mediated in part by IFNA. Such a novel immunological crosstalk might contribute to embryo tolerance and pregnancy establishment in cattle.
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Embrión de Mamíferos/inmunología , Embrión de Mamíferos/metabolismo , Regulación de la Expresión Génica , Interferón Tipo I/inmunología , Neutrófilos/inmunología , Proteínas Gestacionales/inmunología , Embarazo/genética , Embarazo/inmunología , Animales , Arginasa/genética , Bovinos , Medios de Cultivo Condicionados/farmacología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Inmunidad Innata , Técnicas In Vitro , Interferón Tipo I/farmacología , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Fenotipo , Proteínas Gestacionales/farmacología , Receptores de IgG/genéticaRESUMEN
During the passage through the female reproductive tract, sperm interact with various compartments and their immune systems. The immune system that protects the female against pathogens also could destroy sperm or prevent them from reaching the site of fertilisation. In particular, the uterine innate immune response is crucial from the perspectives of both the sperm and the uterus. Following insemination, sperm immediately start to trigger inflammation in the uterus by entering uterine glands and activating an innate immune response. In cattle, the activation occurs mainly via TLR2 signalling, if not the only one, between sperm and the uterine epithelium lining the glands. This acute immune response is manifested as the upregulation of mRNA expression of IL8, TNFA, IL1B , and PGES . As a consequence, many sperm are trapped by polymorphonuclear neutrophils, the first and major component of innate immunity. The sperm-induced uterine innate immune responses apparently serve to clear the uterus of excess sperm and, importantly, prepare the endometrium for implantation. Pathophysiological conditions in the uterus seriously disrupt this phenomenon, and thus could directly decrease fertility.
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Espermatozoides , Receptor Toll-Like 2 , Animales , Bovinos , Endometrio/metabolismo , Femenino , Sistema Inmunológico , Inmunidad Innata , Masculino , Espermatozoides/metabolismo , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/metabolismo , ÚteroRESUMEN
Uterine infection with bacteria and the release of peptidoglycan (PGN), antigenic cell wall components of both Gram-negative and Gram-positive bacteria, can cause early pregnancy losses in ruminants, but the associated mechanisms remain unsolved. Day 7 blastocyst starts to secrete a minute amount of interferon-tau (IFNT) in the uterine horn which is required for early stage of maternal recognition of pregnancy (MRP) in ruminants, and it induces interferon stimulated genes (ISGs) for driving uterine receptivity in cows. This study investigated if PGN disrupts IFNT response through modulation of endometrial ISGs expressions. Cultured bovine endometrial epithelial cells (BEECs) were treated with embryo culture medium (ECM) or IFNT (1 ng/ml) in the presence or absence of a low level of PGN (10 pg/ml) for 24 h. A real-time PCR analyses revealed that the presence of PGN suppressed IFNT-induced ISGs (OAS1 and ISG15) and STAT1 expressions in BEECs. To visualize the impact of PGN in an ex-vivo model that resembles the in vivo status, endometrial explants were treated by IFNT (1 ng/ml) with or without PGN (10 pg/ml) for 12 h. PGN suppressed IFNT-induced gene expressions of the above factors, but not for IFNA receptor type1 (IFNAR1) or type2 (IFNAR2) in explants. Immunofluorescence analysis illustrated that PGN completely suppressed the IFNT-triggered OAS1 protein expression in the luminal epithelium of explants. Of note, PGN did not stimulate pro-inflammatory cytokines (TNFA and IL1B) or TLR2 mRNA expression in both models. These findings indicate that the presence of low levels of PGN suppresses ISGs expression induced by IFNT secreted from early embryo, at the luminal epithelium of the bovine endometrium. This could severely interfere with early stage of MRP processes in cows, leading to pregnancy failure.
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Endometrio/metabolismo , Interferón Tipo I/metabolismo , Peptidoglicano/metabolismo , Proteínas Gestacionales/metabolismo , 2',5'-Oligoadenilato Sintetasa/genética , 2',5'-Oligoadenilato Sintetasa/metabolismo , Aborto Veterinario/inmunología , Aborto Veterinario/metabolismo , Aborto Veterinario/microbiología , Animales , Blastocisto/inmunología , Blastocisto/metabolismo , Blastocisto/microbiología , Bovinos , Enfermedades de los Bovinos/genética , Enfermedades de los Bovinos/metabolismo , Enfermedades de los Bovinos/microbiología , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Endometrio/inmunología , Endometrio/microbiología , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Femenino , Expresión Génica , Técnicas In Vitro , Interferón Tipo I/farmacología , Intercambio Materno-Fetal/inmunología , Peptidoglicano/inmunología , Embarazo , Proteínas Gestacionales/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factor de Transcripción STAT1/genética , Enfermedades Uterinas/genética , Enfermedades Uterinas/metabolismo , Enfermedades Uterinas/veterinaria , Útero/inmunología , Útero/metabolismo , Útero/microbiologíaRESUMEN
We previously reported that sperm binding to cultured monolayers of bovine uterine epithelial cells induces an acute inflammatory response involving the Toll-like receptor (TLR2) signaling pathway. This response serves to clear the uterus of sperm and thereby prepares the endometrium for implantation. The endometrium is lined by surface epithelial cells; however, epithelial cells also line uterine glands. To investigate the source of the immune response, we used an explant model. Explants of bovine endometrium were incubated with bull sperm illuminated by JC1 fluorescent labeling in their mitochondria. The sperm glided over the surface epithelium until they encountered and entered uterine glands, where they remained. Scanning electron microscopy of explants revealed polymorphonuclear neutrophils (PMNs) in uterine glands along with sperm. In the absence of sperm, PMNs were not seen in glands. The incubation of sperm with explants resulted in an acute inflammatory response, seen as the upregulation of mRNA expression of IL8, TNFA, IL1B, PGES and TLR2 in whole explants, as well as increased TNFA protein expression in uterine glands. TLR1/2 antagonist reduced sperm numbers in the glands and inhibited the increase of TNFA. Our observations suggest that uterine glands serve as a site where sperm interact with the uterine epithelium to trigger the innate immune response to clear excess sperm from the uterus.
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We previously reported that sperm binding to cultured bovine oviduct epithelial cells induces an anti-inflammatory immune response. Now we have developed a differentiated explant model to focus on the oviductal ampulla, where fertilization occurs, and to study the effect of sperm capacitation on the immune response. We used heparin to stimulate bovine sperm capacitation. Fluorescence imaging showed that 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide-labeled sperm pretreated with (Hep(+) ) or without (Hep(-) ) heparin rapidly attached to the explant ciliated epithelium in similar numbers. However, only Hep(+) sperm upregulated explant messenger RNA (mRNA) transcription of TLR2, IL8, TGFB1, and PGES, without changes in TNFA and IL-10 expression, while Hep(-) sperm only upregulated PGES. The responses were primarily anti-inflammatory, with a greater response produced by Hep(+) sperm, which also produced a substantial increase in TLR2 protein expression in the epithelium. The addition of TLR1/2 (toll-like receptor 1/2) antagonist to the Hep(+) and (Hep(-) ) sperm-explant coincubations reduced sperm attachment to the epithelium and inhibited TLR2 protein expression and some of the Hep(+) sperm-induced mRNA transcription. Our observations suggest that the ampullar epithelium immunologically reacts more strongly to sperm that have undergone heparin stimulation of capacitation. This anti-inflammatory response could serve to protect capacitated sperm as they approach the oocyte in the ampulla.
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Comunicación Celular/inmunología , Trompas Uterinas , Espermatozoides/metabolismo , Receptor Toll-Like 2/fisiología , Animales , Bovinos , Comunicación Celular/genética , Células Cultivadas , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Trompas Uterinas/inmunología , Trompas Uterinas/metabolismo , Femenino , Inmunidad/fisiología , Masculino , Capacitación Espermática/fisiología , Espermatozoides/inmunologíaRESUMEN
This study aimed to investigate the possible effects of the vasoactive peptide angiotensin II (ANG II), secreted by bovine oviduct epithelial cells, on the in vitro phagocytic activity of polymorphonuclear leukocytes, specifically neutrophils, towards sperm. The measured concentrations of ANG II in oviduct flushes and conditioned medium from primary bovine oviduct epithelial culture ranged from 10(-10) to 10(-11) M. In our experiments, neutrophils were incubated for 2 hr with ANG II (0, 10(-11) , 10(-10) , 10(-9) , and 10(-8) M). Phagocytosis and superoxide production were then assessed by co-incubation of these neutrophils with sperm pretreated to induce capacitation, revealing a dose-dependent increase in both metrics by ANG II. This stimulatory effect of ANG II was eliminated by losartan, an angiotensin receptor type 1 (AGTR1) antagonist. ANG II also suppressed neutrophil transcription of angiotensin converting enzyme-1 (ACE) and AGTR1, but not AGTR2, suggesting the involvement of the AGTR1 receptor-mediated pathway in the response to sperm. Scanning electron microscopy further revealed that incubation of neutrophils with ANG II stimulated the formation of DNA-based extracellular traps for sperm entanglement. The addition of prostaglandin E2 at concentrations found in the oviduct suppressed the ANG II-stimulated phagocytic activity of neutrophils towards sperm. Thus the physiological levels of ANG II stimulate neutrophil phagocytosis of sperm in vitro, and suggest that an angiotensin/prostaglandin E2 system may fine-tune the local immune response that fosters sperm survival in the bovine oviduct. Mol. Reprod. Dev. 83: 630-639, 2016. © 2016 Wiley Periodicals, Inc.
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Angiotensina II/metabolismo , Células Epiteliales/metabolismo , Neutrófilos/metabolismo , Oviductos/metabolismo , Fagocitosis , Espermatozoides , Animales , Bovinos , Células Epiteliales/citología , Trampas Extracelulares/metabolismo , Femenino , Losartán/farmacología , Masculino , Oviductos/citología , Peptidil-Dipeptidasa A/metabolismo , Receptor de Angiotensina Tipo 1/metabolismo , Receptor de Angiotensina Tipo 2/metabolismo , Superóxidos/metabolismoRESUMEN
The oviduct is an active contractile tube that provides the proper environment for sperm transport, capacitation and survival. Oviductal contractions are regulated by autocrine/paracrine secretion of several factors, such as prostaglandins (PGs) and endothelin-1 (EDN-1). We have previously shown that during the preovulatory stage, sperm are exposed to polymorphonuclear neutrophils (PMNs) in the bovine oviduct, and the bovine oviduct epithelial cells (BOECs) secrete molecules including PGE2 that suppress sperm phagocytosis by PMNs in vitro. In this study, we investigated the possible effects of EDN-1 on the phagocytic activity of PMNs toward sperm. The local concentrations of EDN-1 in oviduct fluid and BOEC culture medium ranged from 10(-10) to 10(-11) M as determined by EIA. Phagocytosis and superoxide production were assayed by co-incubation of sperm pretreated to induce capacitation with PMNs exposed to EDN-1 (0, 10(-11), 10(-10), 10(-9), and 10(-8) M) for 2 h. EDN-1 suppressed dose dependently (10(-11) to 10(-8) M) the phagocytic activity for sperm and superoxide production of PMNs in response to capacitated sperm. Moreover, this suppression was eliminated by an ETB receptor antagonist (BQ-788). EDN-1 suppressed mRNA expression of EDN-1 and ETB but not ETA receptors in PMNs, suggesting the ETB receptor-mediated pathway. Scanning electron microscopic observation revealed that incubation of PMNs with EDN-1 (10(-9) M) completely suppressed the formation of DNA-based neutrophil extracellular traps for sperm entanglement. The results provide evidence indicating that EDN-1 may be involved in the protection of sperm from phagocytosis by PMNs in the bovine oviduct, supporting sperm survival until fertilization.
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Endotelina-1/fisiología , Neutrófilos/citología , Oviductos/fisiología , Fagocitosis , Espermatozoides/citología , Animales , Bovinos , Medios de Cultivo/química , Regulación hacia Abajo , Antagonistas de los Receptores de la Endotelina B/farmacología , Femenino , Fertilización , Masculino , Microscopía Electrónica de Rastreo , Oligopéptidos/química , Piperidinas/química , ARN Mensajero/metabolismo , Receptor de Endotelina B/fisiología , Superóxidos/metabolismoRESUMEN
This study aimed to investigate the presence of polymorphonuclear neutrophils (PMNs) in bovine oviduct fluid under physiological conditions and to determine the possible role of bovine oviduct epithelial cells (BOECs) in the regulation of the phagocytic activity of PMNs for sperm. During the pre-ovulatory stage, PMNs were identified in the bovine oviduct fluid in relatively constant numbers. In our experiments, PMNs were incubated for 4âh with the supernatant of cultured BOECs stimulated for 24âh by LH (10âng/ml). Phagocytosis was then assayed by co-incubation of these PMNs with sperm treated to induce capacitation. The BOEC supernatant significantly suppressed sperm phagocytosis by PMNs, and the LH-stimulated BOEC supernatant further suppressed phagocytosis. Importantly, in the BOEC culture, LH stimulated the secretion of prostaglandin E2 (PGE2), which dose-dependently (10(-6), 10(-7), and 10(-8)âM) suppressed sperm phagocytosis by PMNs. Furthermore, a PGEP2 receptor antagonist significantly abrogated the inhibition of phagocytosis by the LH-stimulated BOEC supernatant. Additionally, using scanning electron microscopy, incubation of PMNs with either PGE2 or LH-stimulated BOEC supernatant before phagocytosis was found to prevent the formation of DNA-based neutrophil extracellular traps for sperm entanglement. The results indicate that sperm are exposed to PMNs in the oviduct and PGE2 released into the oviduct fluid after LH stimulation may play a major role in the suppression of the phagocytic activity of PMNs for sperm via interaction with EP2 receptors. Thus, the bovine oviduct provides a PGE2-rich microenvironment to protect sperm from phagocytosis by PMNs, thereby supporting sperm survival in the oviduct. Free Japanese abstract A Japanese translation of this abstract is freely available at http://www.reproduction-online.org/content/147/2/211/suppl/DC1.
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Bovinos , Dinoprostona/fisiología , Células Epiteliales/fisiología , Trompas Uterinas/citología , Neutrófilos/fisiología , Fagocitosis/fisiología , Espermatozoides , Animales , Células Cultivadas , Medios de Cultivo Condicionados/farmacología , Dinoprostona/análisis , Trompas Uterinas/metabolismo , Femenino , Hormona Luteinizante/farmacología , Masculino , Fagocitosis/efectos de los fármacos , Subtipo EP2 de Receptores de Prostaglandina E/antagonistas & inhibidores , Subtipo EP2 de Receptores de Prostaglandina E/fisiología , Capacitación EspermáticaRESUMEN
We have previously shown that polymorphonuclear neutrophils (PMNs) are present in bovine oviduct fluid under physiological conditions, and that the oviduct provides a microenvironment that protects sperm from phagocytosis by PMNs. Alpha 1-acid glycoprotein (AGP) is a major acute-phase protein produced mainly in the liver that has immunomodulatory functions. AGP mRNA is expressed in extrahepatic organs, such as the lung, kidney, spleen, lymph node, uterus, and ovary. Therefore, in this study, we investigated, 1) the local production of AGP in the bovine oviduct, 2) the effect of AGP on the phagocytic activity of PMNs for sperm and superoxide production and 3) the impact of AGP desialylation on the PMN phagocytosis of sperm. The AGP gene was expressed in cultured bovine oviduct epithelial cells (BOECs) and AGP protein was detected in oviduct fluid. Preexposure of PMNs to AGP at physiological levels impaired PMN phagocytosis for sperm and superoxide generation. The desialylation of AGP eliminated these suppressive effects of AGP on PMN. Scanning electron microscopy revealed that AGP drastically reduced the formation of DNA-based neutrophil extracellular traps (NETs) for sperm entanglement. Additionally, AGP dose-dependently stimulated BOECs to produce prostaglandin E2 (PGE2) which has been shown to partially contribute to the regulation of sperm phagocytosis in the bovine oviduct. AGP and PGE2 at concentrations detected in the oviducts additively suppressed sperm phagocytosis by PMNs. These results provide evidence that locally produced AGP may be involved in protecting sperm from phagocytosis by PMNs in the bovine oviduct.
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Bovinos , Trompas Uterinas/inmunología , Neutrófilos/inmunología , Orosomucoide/fisiología , Fagocitosis , Espermatozoides/inmunología , Animales , Líquidos Corporales/química , Supervivencia Celular , Células Cultivadas , Dinoprostona/biosíntesis , Células Epiteliales/metabolismo , Trampas Extracelulares/efectos de los fármacos , Trompas Uterinas/citología , Trompas Uterinas/metabolismo , Femenino , Expresión Génica , Inmunidad/efectos de los fármacos , Masculino , Microscopía Electrónica de Rastreo , Ácido N-Acetilneuramínico , Neutrófilos/efectos de los fármacos , Neutrófilos/ultraestructura , Orosomucoide/química , Orosomucoide/genética , Orosomucoide/farmacología , Fagocitosis/efectos de los fármacos , ARN Mensajero/análisis , Espermatozoides/fisiología , Relación Estructura-Actividad , Superóxidos/metabolismoRESUMEN
BACKGROUND: Non-alcoholic steatohepatitis (NASH) is an advanced subtype of non-alcoholic fatty liver disease (NAFLD). NASH prevalence is increasing exponentially and carries a high risk for disease progression, cirrhosis, and liver-related mortality. Aldafermin, a fibroblast growth factor 19 (FGF19) analog, is one of the evolving therapeutic agents with the potential to regulate multiple pathways involved in the pathogenesis of NASH. We aimed to investigate the efficacy and safety of aldafermin in patients with NASH. METHODS: PubMed, Scopus, Cochrane Library, and Web of Science were searched till November 2023 to identify eligible randomized controlled trials (RCTs). Continuous data were pooled as mean difference (MD), while dichotomous data were pooled as risk ratios (RR) with a 95 % confidence interval. A subgroup meta-analysis was conducted to evaluate the efficacy of the two doses (1 mg and 3 mg) of aldafermin. RESULTS: Four RCTs with a total of 491 patients were included. Aldafermin showed a dose-dependent improvement in the ≥30 % reduction in the liver fat content (RR: 2.16, 95 % CI [1.41 to 3.32]) and (RR: 5.00, 95 % CI [1.34 to 18.64]), alanine aminotransferase levels (MD: -19.79, 95 % CI [-30.28 to -9.3]) and (MD: -21.91, 95 % CI [-29.62 to -14.21]), aspartate aminotransferase levels (MD: -11.79, 95 % CI [-18.06 to -5.51]) and (MD: -13.9, 95 % CI [-18.59 to -9.21]), and enhanced liver fibrosis score (ELF) (MD: -0.13, 95 % CI [-0.29 to 0.02]) and (MD: -0.33, 95 % CI [-0.50 to -0.17]), in the 1 mg and 3 mg subgroups respectively. No significant differences were detected in the aldafermin group regarding histologic endpoints, lipid profile, metabolic parameters, and overall adverse effects, except for the increased occurrence of diarrhea in the aldafermin 3 mg subgroup. CONCLUSION: Aldafermin is a promising well-tolerated therapeutic agent for NASH with evidence supporting its ability to reduce liver fat content, fibrosis serum biomarkers, and liver enzymes. However, its effectiveness in improving histologic fibrosis, while showing numerical trends, still lacks statistical significance. Larger and longer NASH trials are warranted to enhance the robustness of the evidence.
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Enfermedad del Hígado Graso no Alcohólico , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Resultado del Tratamiento , Factores de Crecimiento de Fibroblastos/sangre , Factores de Crecimiento de Fibroblastos/uso terapéutico , Propionatos , ChalconasRESUMEN
In this article, we propose a light weight, low profile Multiple Input Multiple Output (MIMO) antenna system for compact 5th Generation (5G) mmwave devices. Using a RO5880 substrate that is incredibly thin, the suggested antenna is made up of circular rings stacked vertically and horizontally on top of one another. The single element antenna board has dimensions of 12 × 12 × 0.254 mm3 while the size of the radiating element is 6 × 2 × 0.254 mm3 (0.56λ0 × 0.19λ0 × 0.02λ0). The proposed antenna showed dual band characteristics. The first resonance showed a bandwidth of 10 GHz with a starting frequency of 23 GHz to an ending frequency point of 33 GHz followed by a second resonance bandwidth of 3.25 GHz ranging from 37.75 to 41 GHz, respectively. The proposed antenna is transformed into a four element Linear array system with size of 48 × 12 × 0.254 mm3 (4.48λ0 × 1.12λ0 × 0.02λ0). The isolation levels at both resonance bands were noted to be >20 dB which shows high levels of isolation among radiating elements. The MIMO parameters such as Envelope Correlation Co-efficient (ECC), Mean Effective Gain (MEG) and Diversity Gain (DG) were derived and were found to be in satisfactory limits. The proposed MIMO system model is fabricated and through validation and testing of the prototype, the results were found to be in good agreement with simulations.
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This research work presents a compact design of a Multiple-Input Multiple-Output (MIMO) multiband antenna along with high-isolation characteristics. The presented antenna was designed for 3.50 GHz, 5.50 GHz, and 6.50 GHz frequencies for 5G cellular, 5G WiFi, and WiFi-6, respectively. The fabrication of the aforementioned design was undertaken using FR-4 (1.6 mm thickness) substrate material with a loss tangent and relative permittivity of about 0.025 and 4.30, respectively. The two-element MIMO multiband antenna was miniaturized to 16 × 28 × 1.6 mm3, making it desirable for devices operating in 5G bands. High isolation (>15 dB) was attained with thorough testing without employing a decoupling scheme in the design. Laboratory measurements resulted in a peak gain of 3.49 dBi and an efficiency of around 80% in the entire operating band. The evaluation of the presented MIMO multiband antenna was carried out in terms of the envelope correlation coefficient (ECC), diversity gain (DG), total active reflection coefficient (TARC), and Channel Capacity Loss (CCL). The measured ECC was less than 0.04, and the DG was well above 9.50. The observed TARC was also lower than -10 dB, and the CCL was below 0.4 bits/s/Hz in the entire operating band. The presented MIMO multiband antenna was analyzed and simulated using CST Studio Suite 2020.
RESUMEN
It is known that sperm and seminal plasma (SP) affect uterine immunity. In cattle, artificial insemination enables breeding by depositing frozen and largely diluted sperm with a negligible amount of SP into the uterus. Thus, the present study focused on the impact of frozen-thawed sperm on bovine uterine immunity. We have previously shown that in the bovine uterus, sperm swim smoothly over the luminal epithelium and some sperm interact with uterine glands to induce a weak inflammatory response mainly via the endometrial Toll-like receptor 2 (TLR2) signaling. However, the process by which sperm is encountered in the uterine glands is not completely clear. The present study intended to evaluate the role of sperm-TLR2 in sperm-uterine mucus penetration for reaching the glandular epithelium to induce the uterine immune response. To activate and block sperm-TLR2, they were treated with TLR2 agonist and antagonist, respectively. TLR2 activation enhanced sperm hyperactivation and improved its capacity to penetrate the artificial viscoelastic fluid and estrous-uterine-mucus. In contrast, TLR2-blocked sperm showed completely opposite effects. It is noteworthy, that the TLR2-activated sperm that penetrated the uterine mucus exhibited increased motile activity with hyperactivation. In the sperm-endometrial ex-vivo model, a greater amount of TLR2-activated sperm entered the uterine glands with an immune response, which was seen as the upregulation of mRNA expression for TNFA, IL1B, IL8, PGES, and TLR2 similar to those in control sperm. On the other hand, a lesser amount of TLR2-blocked sperm entered the uterine glands and weakened the sperm-induced increase only in PGES, suggesting that penetration of a certain number of sperm in the uterine gland is necessary enough to trigger the inflammatory response. Altogether, the present findings indicate that activation of sperm-TLR2 promotes their hyperactivation and mucus penetration with greater motility, allowing them to enter into the uterine glands more. This further suggests that the hyperactivated sperm contributes to triggering the pro-inflammatory cascade partly via TLR2 in the uterus.
Asunto(s)
Semen , Receptor Toll-Like 2 , Femenino , Bovinos , Masculino , Animales , Receptor Toll-Like 2/metabolismo , Moco/fisiología , Espermatozoides/metabolismo , Útero/metabolismoRESUMEN
Modulation recognition (MR) has become an essential topic in today's wireless communications systems. Recently, convolutional neural networks (CNNs) have been employed as a potent tool for MR because of their ability to minimize the feature's susceptibility to its surroundings and reduce the need for human feature extraction and evaluation. In particular, these investigations rely on the unrealistic assumption that the channel coefficient is typically one. This motivates us to overcome the previous constraint by providing a novel MR suited to fading wireless channels. This paper proposes a novel MR algorithm that is capable of recognizing a broad variety of modulation types, including M-ary QAM and M-ary PSK, without enforcing any restrictions on the modulation size, M. The analysis has shown that each modulation choice has a distinct two-dimensional in-phase quadrature histogram. This property is beneficially utilized to design a convolutional neural-network-based MR algorithm. When compared to the existing techniques, Monte Carlo simulations demonstrated the success of the proposed design.