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In brief: In this study, we examined the relationship between BMAL1 expression and the genes regulating steroid biosynthesis in human luteinized granulosa cells. BMAL1 function is crucial for steroid production and proper ovarian function, highlighting the importance of circadian clock regulation in female reproductive health. Abstract: Human luteinized granulosa cells were collected to analyze circadian clock gene expression and its effect on the genes regulating steroid biosynthesis. We used siRNA to knock down the expression of BMAL1 in KGN cells. We measured the expression levels of genes regulating steroid biosynthesis and circadian clock RT-qPCR. We demonstrated that BMAL1 expression positively correlates with genes regulating steroid biosynthesis (CYP11A1, CYP19A1, STAR, and ESR2). The knockdown of BMAL1 in KGN cells revealed a significant decrease in steroid synthase expression. In contrast, when BMAL1 was overexpressed in KGN and HGL5 cells, we observed a significant increase in the expression of steroid synthases, such as CYP11A1 and CYP19A1. These results indicated that BMAL1 positively controls 17ß-estradiol (E2) secretion in granulosa cells. We also demonstrated that dexamethasone synchronization in KGN cells enhanced the rhythmic alterations in circadian clock genes. Our study suggests that BMAL1 plays a critical role in steroid biosynthesis in human luteinized granulosa cells, thereby emphasizing the importance of BMAL1 in the regulation of reproductive physiology.
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Fatores de Transcrição ARNTL , Enzima de Clivagem da Cadeia Lateral do Colesterol , Feminino , Humanos , Fatores de Transcrição ARNTL/genética , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Estradiol/metabolismo , Células da Granulosa/metabolismo , Progesterona/metabolismoRESUMO
This paper introduces an optical-mechanical system designed for the dynamic detection and analysis of lunar dust, typically characterized as particles under 20 micrometers on the lunar surface. The system's design is both compact and lightweight, aligning with the payload constraints of lunar exploration missions. It is capable of real-time tracking and recording the motion of lunar dust at various altitudes, a crucial capability for understanding the environmental dynamics of the lunar surface. By capturing images and applying sophisticated algorithms, the system accurately measures the velocity and size of dust particles. This approach significantly advances the quantitative analysis of lunar dust, especially during agitation events, filling a critical gap in our current understanding of lunar surface phenomena. The insights gained from this study are not only pivotal for developing theoretical models of lunar surface air flow disturbances and dust movement but also instrumental in designing effective dust mitigation and hazard avoidance strategies for future lunar missions, thereby enhancing both scientific knowledge and the engineering applications in lunar exploration.
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Multi-spectral imaging technologies have made great progress in the past few decades. The development of snapshot cameras equipped with a specific multi-spectral filter array (MSFA) allow dynamic scenes to be captured on a miniaturized platform across multiple spectral bands, opening up extensive applications in quantitative and visualized analysis. However, a snapshot camera based on MSFA captures a single band per pixel; thus, the other spectral band components of pixels are all missed. The raw images, which are captured by snapshot multi-spectral imaging systems, require a reconstruction procedure called demosaicing to estimate a fully defined multi-spectral image (MSI). With increasing spectral bands, the challenge of demosaicing becomes more difficult. Furthermore, the existing demosaicing methods will produce adverse artifacts and aliasing because of the adverse effects of spatial interpolation and the inadequacy of the number of layers in the network structure. In this paper, a novel multi-spectral demosaicing method based on a deep convolution neural network (CNN) is proposed for the reconstruction of full-resolution multi-spectral images from raw MSFA-based spectral mosaic images. The CNN is integrated with the channel attention mechanism to protect important channel features. We verify the merits of the proposed method using 5 × 5 raw mosaic images on synthetic as well as real-world data. The experimental results show that the proposed method outperforms the existing demosaicing methods in terms of spatial details and spectral fidelity.
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BACKGROUND: Our web-based training program called "Educating Medical Professionals about Reproductive Issues in Cancer Healthcare" aims to help healthcare professionals communicate promptly with patients and survivors who are adolescents and young adults, with information pertinent to reproductive health issues such as the risk of infertility and fertility preservation. METHODS: The study participants were professional healthcare providers, including physicians, nurses, pharmacists, social workers, midwives, psychologists, laboratory technicians, genetic counselors, and dieticians. Pre- and post- and 3-month follow-up tests consisting of 41 questions were administered to measure changes in knowledge and confidence. The participants also received a follow-up survey that covered confidence, communication techniques, and practice habits. A total of 820 healthcare providers participated in this program. RESULTS: The mean total score from the pre-test to the post-test grew significantly (p < 0.01), and participants' self-confidence increased. In addition, there was a change in the behavior of healthcare providers, who began asking about patients' marital status and parity. CONCLUSION: Our web-based fertility preservation training program improved knowledge and self-confidence regarding fertility preservation issues among healthcare providers caring for adolescents and young adult cancer patients and survivors.
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Preservação da Fertilidade , Neoplasias , Médicos , Feminino , Adolescente , Adulto Jovem , Gravidez , Humanos , Preservação da Fertilidade/métodos , Japão , Neoplasias/terapia , InternetRESUMO
The poor prognosis after surgery for pancreatic cancer or extrahepatic bile duct cancer has mainly been attributed to early lymph node metastasis, as well as a high frequency of perineural invasion along the peripancreatic neural plexuses or extrahepatic bile duct plexus. However, there has been no detailed morphological description of the anterior and posterior hepatic plexuses (AHP and PHP). In addition, the concepts of the pancreatic plexus and PHP are confused by surgeons. To assess the relations of the pancreatic plexus and hepatic plexuses from the morphological, developmental, and clinical perspectives, these plexuses were dissected in 24 cadavers. The PHP was found to be completely independent of the AHP. The PHP ran behind the portal vein, with most nerve fibers ascending along the bile duct to the gallbladder and the liver or descending to the distal common bile duct and duodenal papilla. Some branches of the PHP contributed to the pancreatic plexus, corresponding to pancreatic head plexus I as defined by the Japan Pancreas Society. The differences between the PHP and pancreatic head plexus I should be understood, even though liver function is not obviously affected after PHP excision for pancreatic head cancer. Further study is needed to determine whether there are functional differences between the AHP and PHP. Clin. Anat., 33:630-636, 2020. © 2019 Wiley Periodicals, Inc.
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Duodeno/anatomia & histologia , Vesícula Biliar/anatomia & histologia , Fígado/anatomia & histologia , Pâncreas/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Cadáver , Feminino , Humanos , MasculinoRESUMO
PURPOSE: Total mesopancreas excision has been found to be helpful for increasing no residual tumor resection rate and improving the prognosis of pancreatic cancer. This study analyzed the relationships among the mesopancreas and pancreatic head plexus from the morphological, developmental, and clinical perspectives. METHODS: Twenty-four cadavers were employed. The upper abdominal viscera were resected en-bloc with the hepatoduodenal ligament, abdominal aorta, and nerve plexuses, and the innervation of the pancreas was dissected. Ten additional cadavers were used for histological examination of the pancreatic head and neck, part of the duodenum, the superior mesenteric artery (SMA) and its surrounding tissues, and the related arteries and veins. RESULTS: As results, cross-sections of the SMA revealed 6-9 layers of membranous structures resembling the layers of an onion, and the nerve fibers of the superior mesenteric plexus ran between the layers. Loose areolar tissue, adipose tissue, and lymphatics existed between the SMA and the pancreatic head/uncinate process, along with abundant thin blood vessels and capillaries, but very few nerves were found approaching the pancreas. Several parallel layers of collagen fibers (so-called Treitz's fusion fascia) existed between the dorsal aspect of the pancreatic head and the aortocaval plane. CONCLUSION: The mesopancreas was continuous and connected with the para-aortic area. It may be better termed the mesopancreatoduodenum than the mesopancreas, as the duodenum-pancreas-SMA forms a complex morphological, developmental, functional, and pathological structure.
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Pâncreas/inervação , Idoso , Idoso de 80 Anos ou mais , Variação Anatômica , Plexo Celíaco/anatomia & histologia , Fáscia/anatomia & histologia , Feminino , Humanos , MasculinoRESUMO
Over the past few decades, researchers have attempted to simplify and accelerate the process of sleep stage classification through various approaches; however, only a few such approaches have gained widespread acceptance. Artificial intelligence technology, particularly deep learning, is promising for earning the trust of the sleep medicine community in automated sleep-staging systems, thus facilitating its application in clinical practice and integration into daily life. We aimed to comprehensively review the latest methods that are applying deep learning for enhancing sleep staging efficiency and accuracy. Starting from the requisite "data" for constructing deep learning algorithms, we elucidated the current landscape of this domain and summarized the fundamental modeling process, encompassing signal selection, data pre-processing, model architecture, classification tasks, and performance metrics. Furthermore, we reviewed the applications of automated sleep staging in scenarios such as sleep-disorder screening, diagnostic procedures, and health monitoring and management. Finally, we conducted an in-depth analysis and discussion of the challenges and future in intelligent sleep staging, particularly focusing on large-scale sleep datasets, interdisciplinary collaborations, and human-computer interactions.
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Inteligência Artificial , Aprendizado Profundo , Humanos , Eletroencefalografia/métodos , Sono , Algoritmos , Fases do SonoRESUMO
Background: Post-viral olfactory dysfunction (PVOD) is the common symptoms of long COVID, lacking of effective treatments. Traditional Chinese medicine (TCM) is claimed to be effective in treating olfactory dysfunction, but the evidence has not yet been critically appraised. We conducted a systematic review to evaluate the effectiveness and safety of TCM for PVOD. Methods: We searched eight databases to identified clinical controlled studies about TCM for PVOD. The Cochrane risk of bias tools and GRADE were used to evaluate the quality of evidence. Risk ratio (RR), mean differences (MD), and 95 % confidence interval (CI), were used for effect estimation and RevMan 5.4.1 was used for data analysis. Results: Six randomized controlled trials (RCTs) (545 participants), two non-randomized controlled trials (non-RCTs) (112 participants), and one retrospective cohort study (30 participants) were included. The overall quality of included studies was low. Acupuncture (n = 8) and acupoint injection (n = 3) were the mainly used TCM therapies. Five RCTs showed a better effect in TCM group. Four trials used acupuncture, and three trials used acupoint injection. The results of two non-RCTs and one cohort study were not statistically significant. Two trials reported mild to moderate adverse events (pain and brief syncope caused by acupuncture or acupoint injection). Conclusions: Limited evidence focus on acupuncture and acupoint injection for PVOD and suggests that acupuncture and acupoint injection may be effective in improving PVOD. More well-designed trials should focus on acupuncture to confirm the benefit. Protocol registration: The protocol of this review was registered at PROSPERO: CRD42022366776.
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OBJECTIVE: Insufficient placental development causes various obstetric complications, including fetal growth restriction (FGR). The Sirtuin 1 (SIRT1) and insulin-like 4 (INSL4) protein-coding genes have been demonstrated to play an important role in placental development. However, no treatment for FGR is available due to placental dysfunction. Therefore, this study aimed to examine the potential of the SIRT1-INSL4 axis as a treatment candidate for FGR caused by insufficient placental development. METHODS: Twenty patients were enrolled, including 10 with FGR and 10 full-term controls. FGR and control placental samples were collected. Quantitative real-time polymerase chain reaction, immunohistochemical analysis, and western blotting were used to analyze INSL4 and SIRT1 expression. An in-vitro loss-of-function approach with the human choriocarcinoma cell line BeWo was applied for functional analyses of SIRT1 in placental development. BeWo cells were differentiated into syncytiotrophoblasts by silencing SIRT1 using small interfering RNA. SIRT1 activator was added during differentiation of SIRT1-knockdown BeWo cells into syncytiotrophoblasts. RESULTS: The FGR samples had lower INSL4 and SIRT1 mRNA and protein expression levels than the control samples. Immunohistochemistry showed that both SIRT1 and INSL4 were expressed mainly in syncytiotrophoblasts. In-vitro analyses showed that SIRT1 knockdown decreased INSL4 expression; however, SIRT1 activator restored SIRT1 expression in SIRT1-silenced BeWo cells. CONCLUSIONS: SIRT1 and INSL4 are downregulated in the placenta of FGR, and INSL4 is regulated by SIRT1. These findings indicate that the SIRT1-INSL4 axis may be a potential therapeutic target for FGR.
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Insulinas , Sirtuína 1 , Feminino , Gravidez , Humanos , Sirtuína 1/genética , Retardo do Crescimento Fetal/genética , Retardo do Crescimento Fetal/terapia , Placenta , Western BlottingRESUMO
Uterine leiomyomas are smooth-muscle tumors originating in the myometrium and are the most common pelvic tumors in women of reproductive age. Symptomatic tumors may result in abnormal uterine bleeding, bladder dysfunction, pelvic discomfort, and reproductive issues, such as infertility and miscarriage. There are currently few non-invasive treatments for leiomyoma, but there are no practical early intervention or preventive methods. In this study, human uterine leiomyoma and myometrial tissues were used to detect the protein and mRNA expression levels of UCHL1. To explore the effects of UCHL1 knockdown and inhibition in leiomyoma and myometrial cells, we determined the mRNA expressions of COL1A1 and COL3A1. Collagen gel contraction and wound-healing assays were performed on myometrial and leiomyoma cells. We found that UCHL1 expression was considerably higher in uterine leiomyomas than in the myometrium. COL1A1 and COL3A1 expression levels were downregulated after inhibition of UCHL1 in human leiomyoma cells. Furthermore, the elimination of UCHL1 significantly decreased the migration and contractility of leiomyoma cells. In conclusion, these results indicate that UCHL1 is involved in the growth of leiomyoma in humans. For the treatment of uterine leiomyoma, targeting UCHL1 activity may be a unique and possible therapeutic strategy.
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Leiomioma , Neoplasias Uterinas , Feminino , Humanos , Neoplasias Uterinas/genética , Leiomioma/metabolismo , Leiomioma/patologia , Leiomioma/terapia , RNA Mensageiro/metabolismo , Ubiquitinas , Hidrolases , Ubiquitina TiolesteraseRESUMO
Purpose: Macrophage polarization contributes to the mechanisms of treating knee osteoarthritis (KOA). In previous studies, fire needling acupuncture has been shown to affect KOA favorably. However, the mechanism of fire needling acupuncture on macrophage polarization is not well-defined. Thus, this study was conducted to determine that fire needling acupuncture exerts a therapeutic role in KOA by modulating macrophage polarization. Methods: Thirty mice were allocated at random into three groups of ten. The groups were labeled as "control", "model", and "fire needling acupuncture". Each group consisted of ten mice. From the second day of intra-articular injection MIA, the right "xiyan" (EX-LE5), "dubi" (ST35), "liangqiu" (ST34), and "xuehai" (SP10) acupoints were manipulated once every other day for two weeks in the fire needling acupuncture group. Mechanical withdrawal threshold and weight distribution were evaluated for behavioral testing in each group. The synovial morphology was monitored by HE staining. Pathological morphology was observed by HE staining, Saf-O staining, and toluidine blue staining. The polarization of macrophages in synovial tissue was detected using immunofluorescence (F4/80, CD86, and CD206). Results: Fire needling acupuncture increased the percentage weight-bearing difference and the mechanical withdrawal threshold, and improved synovial inflammation and cartilage damage in MIA-induced KOA mice. F4/80 and CD86 expression were downregulated by fire needling acupuncture, but CD206 was increased. Conclusion: Fire needling acupuncture decreases pain behaviors in KOA mice and improves synovial membrane injury and pathological cartilage damage. The macrophage polarization is involved in the mechanism of fire needling acupuncture's amelioration of articular cartilage damage.
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BACKGROUND: Tamarix chinensis Lour (TCL) is a shrub that usually grows in arid or semiarid desert areas and saline-alkali fields. It is a traditional Chinese herbal medicine with hepatoprotective, antioxidant, antibacterial, and antitumor activities. AIM: To investigate the possible protective effects of TCL against liver injury induced by chronic ethanol intake. METHODS: C57BL/6J male mice were fed a Lieber-DeCarli lipid diet containing alcohol and received (by gavage) a water-alcohol extract (80%) of TCL (100 and 200 mg/kg BW) or distilled water for 4 wk. After euthanasia, liver tissues were observed histologically with hematoxylin and eosin staining and Oil red O staining, and the levels of alanine aminotransferase, aspartate transaminase, hepatic lipids, reactive oxygen species, malondialdehyde, and superoxide dismutase were measured. In addition, expression of the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome and downstream proinflammatory cytokines were determined. RESULTS: Compared with the ethanol group, mice in the TCL-treated group (200 mg/kg) had significantly lower serum levels of alanine aminotransferase (mean, 34.1 IU/L vs 45.3 IU/L, P < 0.01) and aspartate transaminase (mean, 89.6 IU/L vs 115.7 IU/L, P < 0.01), as well as marked reduction of hepatic tissue reactive oxygen species (decreased by 27.5%, P < 0.01) and malondialdehyde (decreased by 76.6%, P < 0.01) levels, with a significant increase of superoxide dismutase (Increased by 73.2%, P < 0.01). Expression of the NLRP3 inflammasome and its downstream cytokines [interleukin (IL)-1ß, tumor necrosis factor-α, and IL-6], and recruitment of natural killer T cells to the liver, were reduced in the TCL-treated incubation with a Lieber-DeCaril ethanol lipid diet group. CONCLUSION: These findings suggest that a TCL extract (200 mg/kg) protects against chronic ethanol-induced liver injury, probably by inhibiting the NLRP3-caspase-1-IL-1ß signaling pathway and suppressing oxidative stress.
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Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Medicamentos de Ervas Chinesas/uso terapêutico , Hepatopatias Alcoólicas/prevenção & controle , Substâncias Protetoras/uso terapêutico , Tamaricaceae , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Modelos Animais de Doenças , Etanol/efeitos adversos , Inflamassomos/metabolismo , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismoRESUMO
In this study, 94 fetal pigs were used to comprehensively investigate the origins, number, location, and distribution of the coronary arteries to enrich knowledge on the coronary circulation in fetal pigs, and allow comparison with adult pigs and humans. In fetal pigs, the posterior interventricular sulcus branch always arose from the right coronary artery and the circumflex artery was rarely extended to the posterior interventricular sulcus, while it is variable in humans. In fetal pigs, there was sometimes anastomosis (8.5%) between the left and right conus branches as nutrient arteries of the pulmonary cone. Other branches were not significantly different between fetal pigs and humans, including the acute marginal branch, obtuse marginal branch, and sinoatrial nodal artery. Coronary dominance was also similar. In conclusion, compared with adult pigs, dissection of the coronary arteries in fetal pigs provided a more faithful overview of the porcine coronary circulation. The coronary arteries in fetal pigs were also more suitable for comparison with humans when pigs are used as experimental animals for studying the coronary vessels, which could be an important reference for investigation of clinical treatment of the coronary arteries. In summary, our data provide reliable information about the distribution and ramifications of the coronary arteries, and could be useful for clinicians and surgeons who wish to comprehensively understand coronary anatomy.
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Vasos Coronários/anatomia & histologia , Vasos Coronários/embriologia , Suínos/anatomia & histologia , Suínos/embriologia , Animais , HumanosRESUMO
Developmentally, the uncinate process of the pancreas is derived from the ventral pancreatic anlagen, supplied by the superior mesenteric artery (SMA), and contains pancreatic polypeptide (PP)-rich islets of Langerhans. In contrast, the other parts of the pancreas originate from the dorsal anlagen supplied by the celiac system and contain PP-poor islets. This study was performed to investigate whether morphogenesis of the ventral pancreas anlagen is associated with the pattern of SMA branching. SMA branches to the pancreatic body were dissected in 44 cadavers. The cadavers were divided into two groups: the SMA group in which the SMA gave off branches to the pancreatic body and the General group in which it did not. In the SMA group, the ratio of the diameter of the SMA branch supplying the pancreatic body (SMA branch) to that of the SMA itself was calculated. After dissection was completed, tissues were collected from all pancreatic specimens for HE staining and for immunohistochemistry with PP and insulin antibodies. There were 25 cadavers in the General group and 19 in the SMA group. In 10/19 cadavers from the SMA group, PP-rich islets were confirmed in the pancreatic body. The SMA branch diameter ratio was significantly smaller in the SMA group cadavers with PP-poor islets (n = 9) than in cadavers with PP-rich islets (n = 10) (P < 0.001). These findings suggest a relation between the SMA branching pattern and the distribution of PP cells.
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Artéria Mesentérica Superior/anatomia & histologia , Pâncreas/anatomia & histologia , Pâncreas/irrigação sanguínea , Idoso , Idoso de 80 Anos ou mais , Cadáver , Feminino , Imunofluorescência , Corantes Fluorescentes , Humanos , Imunoquímica , Imuno-Histoquímica , Ilhotas Pancreáticas/anatomia & histologia , Masculino , Pessoa de Meia-IdadeRESUMO
Chronic testicular pain remains an important challenge for urologists. Investigation of the innervation of male gonads thus becomes essential for deepening our understanding of their regulatory roles in male reproductive physiology and pathophysiology. Studies of testicular innervation are mainly limited to the intratesticular peptidergic nerves of the testis by immunohistochemical and acetylcholinesterase histochemical investigations in some animals. Little is known about the detailed, overall distribution in general experimental animal testis. In this study, the distribution of nerves supplying the testis, epididymis and accessory sex glands of Suncus murinus was investigated by whole mount immunohistochemistry staining using a neurofilament protein antibody. Testicular nerves arose through three routes: nerves deriving from the mesenteric and renal plexuses accompanied the testicular artery, entering into the testicular hilum through the superior ligament of the testis. The nerves originating from the hypogastric plexus then ran along the internal iliac artery, deferential artery, and passed through the mesoductus deferens or mesoepididymis, innervating the cauda and corpus of the epididymis, the vas deferens and the inferior pole of the testis. The third route arose from the pelvic plexus, distributed in the seminal vesicle and the prostate. The density of nerve fibers was higher in the cauda epididymidis than in the testis, and more abundant in the vas deferens. The different origins and distribution densities of testicular nerves in S. murinus may serve different neuronal regulatory functions, and, therefore, S. murinus may be an important model animal for understanding the different characteristics of testicular pain.
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Epididimo/inervação , Plexo Hipogástrico/anatomia & histologia , Proteínas de Neurofilamentos/análise , Musaranhos/anatomia & histologia , Testículo/inervação , Animais , Imageamento Tridimensional , Imuno-Histoquímica/métodos , Masculino , Modelos Animais , Dor/etiologia , Próstata/inervação , Glândulas Seminais/inervação , Doenças Testiculares/etiologia , Ducto Deferente/inervaçãoRESUMO
This work describes the whole-mount immunohistochemistry staining method in detail, using neurofilament protein antibody to label the innervation of the biliary tract in Suncus murinus (S. murinus ). First, the specimen was dissected from S. murinus and fixed in 4% paraformaldehyde (PFA). Second, an enzymatic treatment and potential endogenous peroxidase inactivation were performed. The specimen was then exposed to the primary antibody, anti-neurofilament protein antibody, for 3-6 days. It was then incubated with the secondary antibody conjugated with horseradish peroxidase. The color reaction was revealed by reacting the specimen with a 3,3'-diaminobenzidine (DAB) substrate. This method can be applied to analyze the innervation of all visceral organs. Furthermore, this protocol can also be adapted to test other neuronal antibodies, but optimization of the antibodies should be done first. This method was originally introduced by Kuratani and Tanaka1,2,3.