Histopathological growth pattern and vessel co-option in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) exhibits different blood imaging features and prognosis depending on histology. To clarity histopathological growth patterns (HGPs) and vascularization processes of iCCA, we collected 145 surgical specimens and histologically classified them into large bile duct (LBD) (20 cases), small bile duct (SBD) (54), cholangiolocarcinoma (CLC) (35), combined SBD-CLC (cSBD-CLC) (26), and ductal plate malformation (DPM) (10) (sub)types. According to the invasive pattern at the interface between tumor and adjacent background liver, HGPs were classified into desmoplastic, pushing, and replacing HGPs. Desmoplastic HGP predominated in LBD type (55.5%), while replacing HGP was common in CLC (82.9%) and cSBD-CLC (84.6%) subtypes. Desmoplastic HGP reflected angiogenesis, while replacing HGP showed vessel co-option in addition to angiogenesis. By evaluating microvessel density (MVD) using vascular markers, ELTD1 identified vessel co-option and angiogenesis, and ELTD1-positive MVD at invasive margin in replacing HGP was significantly higher than those in desmoplastic and pushing HGPs. REDD1, an angiogenesis-related marker, demonstrated preferably higher MVD in the tumor center than in other areas. iCCA (sub)types and HGPs were closely related to vessel co-option and immune-related factors (lymphatic vessels, lymphocytes, and neutrophils). In conclusion, HGPs and vascular mechanisms characterize iCCA (sub)types and vessel co-option linked to the immune microenvironment.

Oxidative Coupling of Hydroquinone Derivatives with Olefins to Dihydrobenzofurans.

Dihydrobenzofuran is an important skeleton for bioactive compounds and natural products. Hydroquinones can be easily modified into substituted hydroquinones, which effectively undergo oxidation to produce the corresponding benzoquinone derivatives. Benzoquinones are reactive electrophiles that are frequently utilized in coupling with olefins to dihydrobenzofurans. Herein, we report the one-pot oxidative coupling of hydroquinones bearing an electron-withdrawing group at the C2 position with olefins to dihydrobenzofurans in the presence of the Lewis acidic FeCl3 and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) oxidant. Furthermore, this method was applied to the oxidative coupling of N-electron-withdrawing group-substituted 4-aminophenol.

Three-dimensional analysis of partial restoration of spermatogenesis in vitamin A-deficient mice.

BACKGROUND: An animal model of the partial restoration of spermatogenesis may be useful in the field of reproductive biology and medicine. Vitamin A deficiency (VAD) induces the restorable arrest of spermatogenesis at the level of spermatogonia and is used as a mouse model of spermatogenesis disorder. OBJECTIVE: We aimed to establish an animal model in which spermatogenesis is partially restored by switching a vitamin A deficiency diet to a normal vitamin A-containing diet and conduct a comprehensive analysis to identify vulnerable sites in the seminiferous tubules that affect the efficient restoration of spermatogenesis in this model. MATERIALS AND METHODS: Mice fed a vitamin A deficiency diet until 12 weeks old and then reared with a normal diet for 15 weeks served as the restoration model. We performed three-dimensional reconstructions of the seminiferous tubules and analyzed the three-dimensional distribution of restored spermatogenesis throughout the testis. RESULTS: Fifteen weeks after the switch to the normal diet, spermatogenesis was restored in 78% of the length of seminiferous tubules. The percentage of restored spermatogenesis was lower in longer seminiferous tubules. An analysis of the distribution of spermatogenesis throughout the testis in this model revealed that it was restored less in portions of seminiferous tubules near the rete testis and hairpin curves and also in those located in the caudal region of the testis. These sites tended to correspond to sites with fewer spermatogonia in the vitamin A deficiency testis. DISCUSSION AND CONCLUSIONS: We established an animal model of the partial restoration of spermatogenesis and examined the three-dimensional distribution of restored spermatogenesis in seminiferous tubules. The results obtained provide insights into the mechanisms underlying spermatogenesis disorders and may contribute to better clinical practices, such as the screening of drugs or therapeutic interventions for human male infertility and improvements in fertility preservation techniques for individuals undergoing chemotherapy.

Effects of inter-stimulus and inter-trial intervals on somatosensory gating.

AIM OF THE STUDY: Sensory gating is a human higher cognitive function that serves to suppress excessive sensory information and prevent brain overactivity. To elucidate this function, a paired-pulse stimulation paradigm has been used while recording electroencephalography (EEG), and evaluated as an amplitude ratio of responses to a second stimulus (S2) over responses to the first stimulus (S1). The present study investigated the effects of the inter-stimulus interval (ISI) and inter-trial interval (ITI) on somatosensory gating using somatosensory-evoked potentials (SEPs). METHODS: In Experiment 1, ISI was set at five conditions: 200, 400, 600, 800, and 1000 ms. In Experiment 2, ITI was set at four conditions: 1, 2, 4, and 8 s. RESULTS: ISI affected the S2/S1 amplitude ratios of P22 and N27 at C3' and N30 at Fz, and these S2/S1 amplitude ratios decreased the most under the 200 and 400-ms conditions. ITI affected the S2/S1 amplitude ratios of P22, N27, and N60 at C3', and especially, the somatosensory gating did not work under the 1-s condition. These results suggest that not all SEP components are modulated in the same manner with changing ISI and ITI. The effects of ISI and ITI independently affected the somatosensory gating. CONCLUSIONS: Based on our findings, preferable parameters are 200-400 ms for ISI and 4 s or longer for ITI to evaluate the functional mechanisms on somatosensory gating in SEPs.

Fast and Stable Responses during Decision Making Require Strong Inhibitory Processes in Soccer Players.

Quick decision making is a vital factor for a successful pass in soccer games. Many previous studies of decision making in soccer focused on motor execution, but inhibitory processing has remained unclear. This study aimed to clarify the differences in motor execution and inhibitory among Japanese collegiate soccer players with different skill levels. We evaluated the behavioral data and event-related potentials in the high-skilled, low-skilled, and novice groups during the Go/No-go and pass choice reaction tasks. The reaction time (RT) was significantly shorter in the high group than in the novice group, and RT variability was small in the high group. The amplitude of the N2 component was significantly larger in the high group than in the low and novice groups, and the latency of the P3 component was significantly shorter in the high and low groups than in the novice group during the pass choice reaction task. The subtracted No-go N2 amplitude was also significantly larger in the high and low groups than in the novice group, and correlations existed between the RT, RT variability, and the subtracted No-go N2 amplitude during these tasks. These data indicate that soccer players' behavioral responses and inhibition processing decision-making activities are associated with skill levels.

Three-dimensional analysis of junctions between efferent and epididymal ducts in the human caput epididymis.

BACKGROUND: Due to the scarcity of studies using human tissues, the limited information is currently available on the gross structure of the caput epididymis in humans, at which efferent ducts connect to the epididymal duct. OBJECTIVE: The present study investigated the three-dimensional structures of efferent and caput epididymal ducts in humans, with a focus on junctions between the former and the latter. MATERIALS AND METHODS: We examined three sets of human efferent and caput epididymal ducts in specimens obtained from prostatic carcinoma patients. They were reconstructed from serial paraffin sections using a segmentation model created by a deep learning protocol and high-performance three-dimensional reconstruction software. RESULTS: Serial sections and three-dimensional images of human efferent and caput epididymal ducts were combined to obtain the detailed anatomical information. When a single efferent duct was defined as a duct connecting to both the extra-testicular rete testis and epididymal duct, there were 14.7 efferent ducts with a total length of 3.0 m per specimen on average. The cranial portion of the efferent ducts joined to a single duct and terminated at the end of the epididymal duct, whereas other efferent ducts terminated independently on the side of the epididymal duct. These two types of junctions between the efferent and epididymal ducts differed in the patterns of the epithelial-type switch. The epididymal duct consisted of multiple segments, which were separated by a minimal amount of connective tissue septa or even without them. Efferent ducts occupied most of the volume of the caput epididymis. DISCUSSION AND CONCLUSIONS: By utilizing deep learning, we reconstructed human efferent and caput epididymal ducts and revealed their precise three-dimensional structures, which differed from those of rodents in several aspects. The present results may be useful for analyzing anatomical abnormalities related to some types of male infertility.

Sphingosine kinase 1 is involved in triglyceride breakdown by maintaining lysosomal integrity in brown adipocytes.

Sphingosine 1-phosphate (S1P) has been implicated in brown adipose tissue (BAT) formation and energy consumption; however, the mechanistic role of sphingolipids, including S1P, in BAT remains unclear. Here, we showed that, in mice, BAT activation by cold exposure upregulated mRNA and protein expression of the S1P-synthesizing enzyme sphingosine kinase 1 (SphK1) and S1P production in BAT. Treatment of wild-type brown adipocytes with exogenous S1P or S1P receptor subtype-selective agonists stimulated triglyceride (TG) breakdown only marginally, compared with noradrenaline. However, genetic deletion of Sphk1 resulted in hypothermia and diminished body weight loss upon cold exposure, suggesting that SphK1 is involved in thermogenesis through mechanisms different from receptor-mediated, extracellular action of S1P. In BAT of wild-type mice, SphK1 was localized largely in the lysosomes of brown adipocytes. In the brown adipocytes of Sphk1-/- mice, the number of lysosomes was reduced and lysosomal function, including proteolytic activity, acid esterase activity, and motility, was impaired. Concordantly, nuclear translocation of transcription factor EB, a master transcriptional regulator of lysosome biogenesis, was reduced, leading to decreased mRNA expression of the lysosome-related genes in Sphk1-/- BAT. Moreover, BAT of Sphk1-/- mice showed greater TG accumulation with dominant larger lipid droplets in brown adipocytes. Inhibition of lysosomes with chloroquine resulted in a less extent of triglyceride accumulation in Sphk1-/- brown adipocytes compared with wild-type brown adipocytes, suggesting a reduced lysosome-mediated TG breakdown in Sphk1-/- mice. Our results indicate a novel role of SphK1 in lysosomal integrity, which is required for TG breakdown and thermogenesis in BAT.

Expression patterns of sex steroid receptors in developing mesonephros of the male mouse: three-dimensional analysis.

The androgen pathway via androgen receptor (AR) has received the most attention for development of male reproductive tracts. The estrogen pathway through estrogen receptor (ESR1) is also a major contributor to rete testis and efferent duct formation, but the role of progesterone via progesterone receptor (PGR) has largely been overlooked. Expression patterns of these receptors in the mesonephric tubules (MTs) and Wolffian duct (WD), which differentiate into the efferent ductules and epididymis, respectively, remain unclear because of the difficulty in distinguishing each region of the tracts. This study investigated AR, ESR1, and PGR expressions in the murine mesonephros using three-dimensional (3-D) reconstruction. The receptors were localized in serial paraffin sections of the mouse testis and mesonephros by immunohistochemistry on embryonic days (E) 12.5, 15.5, and 18.5. Specific regions of the developing MTs and WD were determined by 3-D reconstruction using Amira software. AR was found first in the specific portion of the MTs near the MT-rete junction at E12.5, and the epithelial expression showed increasing strength from cranial to the caudal regions. Epithelial expression of ESR1 was found in the cranial WD and MTs near the WD first at E15.5. PGR was weakly positive only in the MTs and cranial WD starting on E15.5. This 3-D analysis suggests that gonadal androgen acts first on the MTs near the MT-rete junction but that estrogen is the first to influence MTs near the WD, while potential PGR activity is delayed and limited to the epithelium.

The relationship between pitching parameters and release points of different pitch types in major league baseball players.

Objectives: The purpose of this study was to deepen our understanding of pitches and to obtain basic knowledge about pitches by comparing 4-seam and other pitches in Major League Baseball (MLB). Methods: We analyzed big data for 1,820 professional baseball pitchers of MLB on release speed, spin rate, release point 3D coordinates (X, Y, and Z axes), amount of change for 4-seam, and seven changing ball types (sinker, slider, changeup, cutter, curve, split finger, and knuckle curve), using PITCHf/x and TrackMan. We also evaluated three relationships: (1) between the release points and the ball types of pitch; (2) between the amount of change in the ball and the release speed; and (3) between the release speed and the spin rate. Results: The release speed was significantly slower in seven changing ball types than in the 4-seam (p < 0.01, respectively). The spin rate and the amount of change (ΔX and ΔZ) were significantly different between 4-seam and seven changing ball types (p < 0.01, respectively). Release point 3D coordinates (X, Y, and Z axes) were significantly different between 4-seam and slider, cutter, and curve (p < 0.01, respectively). Based on these findings, the eight pitch types were mainly divided into three groups: 4-seam, curve, and off-speed pitch types. Conclusion: Seven changing ball types included specific characteristics for each parameter. The correspondence among the release speed, ΔX, and ΔZ at the 3D coordinates is an arch with 4-seam as the apex. Our results suggest an effective strategy for changing the release point and displacement of a ball's trajectory to improve the performance of baseball pitchers.

Novel α-Trifluoromethyl Chalcone Exerts Antitumor Effects Against Prostate Cancer Cells.

BACKGROUND/AIM: Despite treating advanced prostate cancer (PCa) with androgen deprivation therapy, it eventually progresses to castration-resistant PCa. Subsequently, taxanes are administered, but when PCa becomes resistant to taxanes, another treatment is needed, which has not yet been established. We previously synthesized a novel α-trifluoromethyl chalcone, YS71, and reported its antitumor effects against PCa cells. In this study, we confirmed its efficacy against androgen-sensitive, androgen-independent, and taxane-resistant PCa cells. MATERIALS AND METHODS: The PCa cell lines used were LNCaP, PC-3, DU145, PC-3-TxR (paclitaxel-resistant), PC-3-TxR/CxR (paclitaxel- and cabazitaxel-resistant), DU145-TxR, and DU145-TxR/CxR. The antiproliferative effects of YS71 were evaluated using proliferation assay. The reverse transcriptase transcription-polymerase chain reaction and western blot were performed to determine the expression level of androgen receptor (AR), whereas luciferase assay was performed to determine the AR activity. Furthermore, TUNEL assay and western blot were performed to investigate the mechanism of the antiproliferative effect. RESULTS: YS71 exerted a dose-dependent antitumor effect, inhibited AR activity, and induced apoptosis in all PCa cells in a dose-dependent manner. Western blot showed that YS71 increased the levels of apoptosis-related proteins, cleaved caspase-3, and cleaved PARP, and decreased the levels of the antiapoptotic proteins, Bcl-xL and Bcl-2. In addition, microarray analysis revealed that YS71 decreased several cancer-related genes. CONCLUSION: YS71 exhibits antitumor activity by inducing apoptosis in PCa cells, including taxane-resistant cells. It could be a potential future therapeutic option for hormone- and chemotherapy-resistant PCa.

The CCL2-CCR2 Axis Contributes to Migration of Cabazitaxel-resistant Prostate Cancer Cells.

BACKGROUND/AIM: Developing resistance to cabazitaxel is a major challenge in patients with docetaxel- and castration-resistant prostate cancer (CRPC) since it is frequently administered as a last resort. We have previously reported that CCL2 induces resistance to the antiproliferative effect of cabazitaxel in DU145-TxR/CxR prostate cancer cell lines. However, how CCL2 induces resistance to the antimigration effect of cabazitaxel remains unclear. MATERIALS AND METHODS: We established a cabazitaxel-resistant cell line, DU145-TxR/CxR, from a previously established paclitaxel-resistant cell line, DU145-TxR, which was confirmed to show docetaxel resistance. We performed migration assay and analyzed the expression of epithelial-mesenchymal transition markers using DU145-TxR/CxR with or without CCL2 silencing with small interfering RNA (siRNA) transfection. RESULTS: Cabazitaxel inhibited the migration of DU145 cells through the inactivation of STAT3. A CCR2 (a specific receptor of CCL2) antagonist suppressed the migration of DU145-TxR and DU145-TxR/CxR cells under cabazitaxel treatment. Western blotting revealed that the CCR2 antagonist inhibited STAT3 phosphorylation in DU145-TxR and DU145-TxR/CxR cells under cabazitaxel treatment. CCL2 silencing with siRNA in DU145-TxR and DU145-TxR/CxR cells decreased migration through STAT3 and p38 inactivation. Furthermore, CCL2 activated AKT, and CCR2 antagonist inhibited AKT phosphorylation in DU145-TxR and DU145-TxR/CxR cells with recovery of sensitivity to cabazitaxel under cabazitaxel treatment. CONCLUSION: The CCL2-CCR2 axis is a key contributor to resistance to the antimigration effect of cabazitaxel in prostate cancer cells. CCL2-CCR2 axis inhibition may be a potential therapeutic target against chemoresistant CRPC in combination with cabazitaxel.

Synesthesia has specific cognitive processing during Go/No-go paradigms.

Grapheme-color synesthesia is a consistent and automatic perception of non-physical color when presented with a grapheme. Many previous studies focused on the synesthetic visual system, but other cognitive functions in grapheme-color synesthetes have remained unclear. Therefore, the objective of the present study was to investigate the characteristics of cognitive processing for motor execution and inhibition during Go/No-go paradigms in grapheme-color synesthesia using event-related potentials (ERPs). Six grapheme-color synesthetes and 24 non-synesthetes performed visual, auditory, and somatosensory Go/No-go paradigms. Omission errors were higher in grapheme-color synesthetes than non-synesthetes. Group-trial interactions (i.e., synesthetes-non-synesthetes × Go-No-go) were observed for the latency of the visual N2 component and amplitude of the somatosensory N2 component. Latencies of auditory and somatosensory P3 components were shorter in grapheme-color synesthetes than non-synesthetes. These findings suggest that grapheme-color synesthetes have specific cognitive processing in motor execution and inhibition as well as synesthetic color perception. Our data advance understanding of cognitive processing in grapheme-color synesthesia.

Fabrication and Characterization of Acicular Micro-Textured Copper Sheet Device for Low-Temperature Heat Radiation.

An acicular microtextured sheet was developed as a heat radiation device from the high-temperature source to the cooling medium in the infrared (IR) spectrum. The copper surface was modified by acicular micro-texturing to place a semi-regular micro-/nano-cone structure onto it. FT-IR (Fourier transformation IR) spectroscopy was utilized to measure the transmittance diagram in near-IR to far-IR wavelengths. The wavelength (λ) of 6.7 µm, where the highest absorbance valley was detected in the diagram, was equivalent to the doubled size of the micro-cone average height, with Have = 3.3 µm; λ ~ 2 × Have. The electromagnetic waves in the far-IR wavelength were emitted by acicular micro-textured metallic sheets. The heat radiation transfer experiment was performed to describe this low-temperature heat radiation behavior. No temperature rise was detected on the black-colored polycarbonate (BC-PC) plate away from the bare copper sheet without textures, located on the high-temperature source. The temperature increased by 4 K on the BC-PC plate using the acicular textured copper sheet device. The emitter temperature also decreased significantly by 50 K or 50% of the heat source temperature.

Effects of hypocapnia and hypercapnia on human somatosensory processing.

The present study investigated the effects of hypocapnia and hypercapnia on human somatosensory processing by utilizing somatosensory evoked magnetic fields (SEFs) with magnetoencephalography (MEG). Thirteen volunteers participated in two experiments separately to measure respiratory and cardiovascular data and SEFs. Both experiments consisted of a combination of normal and rapid respiratory rhythms and two inspiratory gas conditions (air and a hypercapnic gas); normal breathing with air (NB), rapid breathing with air (RB), normal breathing with the hypercapnic gas (NB+Gas), and rapid breathing with gas (RB+Gas). Partial pressures of end-tidal CO2 (PETCO2) increased during inhaling the hypercapnic gas and decreased during RB, but the RB+Gas condition continued to cause elevated PETCO2 compared with the baseline. Subsequently, middle cerebral artery blood (MCA) velocity using transcranial Doppler changed as well, while mean MCA velocity increased under the RB+Gas condition. The peak amplitude of the M60 component in SEFs was also significantly larger under with-gas than without-gas conditions, irrespective of the respiratory frequency. These results suggest that there is a close relationship between cerebral blood flow and neural activity of the M60 component in SEFs. This study provides evidence to further understanding on one of the neural mechanisms of hypercapnia.

Suppression of androgen receptor signaling induces prostate cancer migration via activation of the CCL20-CCR6 axis.

The suppression of androgen receptor (AR) expression exacerbates the migration potential of prostate cancer. This study identified a previously unrecognized regulation of the AR-controlled pathway that promotes migration potential in prostate cancer cells. Prostate cancer cells that pass through a transwell membrane (mig cells) have a higher migration potential with a decreased AR expression than parental cells. In this study, we aimed to elucidate the mechanism of migration enhancement associated with the suppression of AR signaling. Expression of C-C motif ligand 20 (CCL20) is upregulated in mig cells, unlike in the parental cells. Knockdown of AR with small interfering RNA (siAR) in LNCaP and C4-2B cells increased CCL20 secretion and enhanced the migration of cancer cells. Mig cells, CCL20-treated cells, and siAR cells promoted cell migration with an enhancement of AKT phosphorylation and Snail expression, while the addition of a C-C chemokine receptor 6 (CCR6, the specific receptor of CCL20) inhibitor, anti-CCL20 antibody, and AKT inhibitor suppressed the activation of AKT and Snail. With 59 samples of prostate cancer tissue, CCL20 secretion was profuse in metastatic cases despite low AR expression levels. Snail expression was associated with the expression of CCL20 and CCR6. A xenograft study showed that the anti-CCL20 antibody significantly inhibited Snail expression, thereby suggesting a new therapeutic approach for castration-resistant prostate cancer with the inhibition of the axis between CCL20 and CCR6.

Are bladder washing samples suitable for investigation of HPV infection in urinary bladder? Comparison in HPV prevalence between urine and washing samples.

Although urine and bladder washing samples are commonly used for the cytological evaluation of the bladder mucosa, it has been unknown whether these samples are likely suitable to investigate human papillomavirus (HPV) prevalence in the urinary bladder. The present study aimed to elucidate the appropriateness of spontaneously voided urine or bladder washing in screening HPV infection in the urinary bladder. Urine and bladder washing samples were obtained from 201 patients who underwent transurethral bladder tumor resection. After extracting DNA from both samples, HPV-DNA was examined using a nested polymerase chain reaction with GP5+/6+ and MY09/11 primers. HPV genotyping was performed in the HPV-positive samples. In situ hybridization (ISH) was performed to observe the HPV-DNA localization in urothelial cells among cytological samples and paraffin-embedded tumor tissues in HPV-positive washing samples. HPV prevalence in urine and washing samples were 9.5% and 7.0%, respectively. High-risk HPV prevalence in urine and washing samples was 7.5% and 4.0%, respectively. The most common HPV type was HPV 16, followed by HPV 52 and HPV 18 in both samples. HPV type distribution in both samples was not in agreement (κ = -0.431). The ISH analysis revealed that HPV-DNA signal was observed in urothelial cells of five (55.7%) of nine detectable HPV-positive cytological samples. Six (66.7%) of nine HPV-positive cases had HPV-DNA signals in tumor tissue. The use of washing samples was likely applicable for investigating HPV prevalence in the urinary bladder. HPV-DNA detected in washing samples might be frequently derived from the urinary bladder.

A Single Administration of Progesterone during the Neonatal Period Shows No Structural Changes in Male Reproductive Tracts in Mice.

The concentration of female-dominant steroid hormones, such as progesterone and estrogen, drops after birth in neonates. We have reported that neonatal estrogen treatment results in inflammation in the epididymis after puberty in male mice. Our recent study discovered that progesterone receptor was specifically expressed in efferent ducts just before birth in male mice. Therefore, this study aimed to reveal the impact of neonatal progesterone administration on the efferent ducts after puberty. Progesterone was subcutaneously administered to neonatal mice on their birthday in three groups: high-dose (200 mg/kg), low-dose (8 mg/kg), and control (cottonseed oil). Their testis and epididymis were collected at 12 weeks old. Semi-serial paraffin sections of these tissues were prepared and evaluated through PAS-hematoxylin staining. Efferent ducts were reconstructed into a three-dimensional structure, and their length and volume were analyzed. Spermatogenesis in the testis and epithelium of the tracts appeared normal, even in individuals administered with progesterone. There were no significant differences in the length and volume of the efferent ducts among the three groups. This study suggests that progesterone treatment in neonatal mice does not cause any structural changes in the male reproductive tracts at puberty, unlike the neonatal estrogen treatment.

Performance-environment mutual flow model using big data on baseball pitchers.

Introduction: The study investigated the baseball pitching performance in terms of release speed, spin rate, and 3D coordinate data of the release point depending on the ball and strike counts. Methods: We used open data provided on the official website of Major League Baseball (MLB), which included data related to 580 pitchers who pitched in the MLB between 2015 and 2019. Results: The results show that a higher ball count corresponds to a slower release speed and decreased spin rate, and a higher strike count corresponds to a faster release speed and increased spin rate. For a higher ball count, the pitcher's release point tended to be lower and more forward, while for a higher strike count, the pitcher's release point tended to be to the left from the right pitcher's point of view. This result was more pronounced in 4-seam pitches, which consisted the largest number of pitchers. The same tendency was confirmed in other pitches such as sinker, slider, cut ball, and curve. Discussion: Our findings suggest that the ball count is associated with the pitcher's release speed, spin rate, and 3D coordinate data. From a different perspective, as the pitcher's pitching performance is associated with the ball and strike count, the ball and strike count is associated with pitching performance. With regard to the aforementioned factor, we propose a "performance-environment flow model," indicating that a player's performance changes according to the game situation, and the game situation consequently changes the player's next performance.

Differences in the neural networks of thermal sensation with and without evaluation process.

Several neuroimaging studies have analyzed the neural networks involved in thermal sensation. In some of these studies, participants were instructed to evaluate and report the thermal sensation using a point scale, visual analog scale, or other psychophysical rating tool while the imaging data were obtained. Therefore, the imaging data may reflect signals involved in the processes of both sensation and evaluation. The present study aimed to discriminate the neural networks involved in identifying different temperature stimuli and the two different processes by using functional magnetic resonance imaging (fMRI). We applied four different thermal stimuli ("hot," 40C; "warm," 36 °C, "cool," 27 °C; and "cold," 22 °C) to the left forearm using Peltier apparatus. During the stimuli, participants were instructed to either evaluate (evaluation task) or not evaluate (no-evaluation task) and report the thermal sensation. We found brain activation in the medial prefrontal cortex/anterior cingulate gyrus, inferior frontal gyrus, bilateral insula, and posterior parietal cortex during the four thermal stimuli both with and without the evaluation task. Additionally, the stimuli with the evaluation task induced stronger and broader activation, including the right fronto-parietal and anterior insula regions. These results indicate that thermal stimulation activates the common neural networks, independent of the thermal conditions and evaluation process. Moreover, the evaluation process may increase the attention to the thermal stimuli, resulting in the activation of the right lateralized ventral attentional network.

Three-dimensional analysis and in vivo imaging for sperm release and transport in the murine seminiferous tubule.

Spermatozoa released from Sertoli cells must be transported to the epididymis. However, the mechanism of the luminal flow in seminiferous tubules has remained unclear to date. Therefore, in this study, we investigated luminal flow and movements in the seminiferous tubules by three-dimensional analysis and in vivo imaging. Serial 5-µm-thick mouse testicular sections at 50-µm-intervals were prepared and stained by Periodic Acid-Schiff-hematoxylin. After three-dimensional reconstruction of the seminiferous tubules, the localization of the released spermatozoa and the stages observed in the sections were recorded in each reconstructed tubule. Luminal movements in the seminiferous tubules were observed by in vivo imaging using a fluorescent-reporter mouse and two-photon excitation microscopy system. Spermatozoa without contact to the seminiferous epithelium were not accumulated toward the rete testis. Additionally, such spermatozoa were found on their way not only to the most proximal rete testis but also a more distant rete testis from any stage VIII seminiferous epithelia. In vivo imaging demonstrated that the direction of the flagella of spermatozoa attached to the seminiferous epithelium was repeatedly reversed. The epithelium at the inner curve of the seminiferous tubule was shaken more actively and had fewer spermatozoa attached compared with the epithelium at the outer curve. Our results hence suggest that the luminal flow in the seminiferous tubules is repeatedly reversed and that this physical force helps spermatozoa to be released from Sertoli cells. In brief: Spermatozoa are released from Sertoli cells and flow in the seminiferous tubule to the rete testis. Our results suggest that the luminal flow in the tubules is repeatedly reversed and that this physical force helps spermatozoa release from the Sertoli cells.