Ca2+ is a key secondary messenger that determines sperm motility patterns. Mammalian sperm undergo capacitation, a process to acquire fertilizing ability, in the female reproductive tract. Capacitated sperm change their flagellar waveform to develop hyperactivated motility, which is crucial for successful sperm navigation to the eggs and fertilization. The sperm-specific channel, CATSPER, and an ATPase transporter, PMCA4, serve as major paths for Ca2+ influx and efflux, respectively, in sperm. The ionic paths coordinate Ca2+ homeostasis in the sperm, and their loss-of-function impairs sperm motility, to cause male infertility. In this review, we summarize the physiological significance of these two Ca2+ gates and suggest their potential applications in novel male contraceptives.
Over the past two decades, studies have discovered a special form of alternative splicing (AS) that produces a circular form of RNA. This stands in contrast to normal AS, which produces a linear form of RNA. Although these circRNAs have garnered considerable attention in the scientific community for their biogenesis and functions, the focus of these studies has been on the regulatory role of circRNAs with the assumption that circRNAs are non-coding. As non-coding RNAs, they may regulate mRNA transcription, tumor initiation, and translation by sponging miRNAs and RNA-binding proteins (RBPs). In addition to these regulatory roles of circRNAs, however, recent studies have provided strong evidence for their translation. The translation of circRNAs is expected to have an important role in promoting cancer cell growth and activating molecular pathways related to cancer development. In some cases, the translation of circRNAs is shown to be efficiently driven by an internal ribosome entry site (IRES). The development of a computational tool for identifying and characterizing the translation of circRNAs using high-throughput sequencing and IRES increases identifiable proteins translated from circRNAs. In turn, it has a substantial impact on helping researchers understand the functional role of proteins derived from circRNAs. New web resources for aggregating, cataloging, and visualizing translational information of circRNAs derived from previous studies have been developed. In this paper, general concepts of circRNA, circRNA biogenesis, translation of circRNA, and existing circRNA tools and databases are summarized to provide new insight into circRNA studies.
Ca2+ is a key secondary messenger that modulates sperm motility by tuning flagellar movement in various species. The sperm-specific Ca2+ channel, CatSper, is a primary Ca2+ gate that is essential for male fertility in mammals. CatSper-mediated Ca2+ signaling enables sperm to develop hyperactivated motility and fertilize the eggs in the female tract. Therefore, altered CatSper function compromises the entry of Ca2+ into the sperm, followed by impairing hyperactivation and male fertility. However, methods to evaluate the function of the CatSper channel are limited to patch clamping and functional imaging using Ca2+ dye. Previous studies have revealed that various parameters for sperm motility are highly correlated with intracellular Ca2+ levels in mouse. Here, I cover a step-by-step protocol to analyze the change in Ca2+-mediated sperm motility by using computer-assisted semen analysis (CASA) to evaluate the functional normality of the CatSper channel in sperm. This approach analyzes sperm motility parameters during intracellular Ca2+ chelation followed by in vitro capacitation to recover intracellular Ca2+ via the activated CatSper channel. Thus, this Ca2+-handling method is handy and could be broadly applied in reproductive biology labs and clinics that have CASA equipment to examine the functional normality of the CatSper channel.
PURPOSE: This study explored the feasibility of utilizing a deep learning artificial intelligence (AI) model to detect ileocolic intussusception on grayscale ultrasound images. METHODS: This retrospective observational study incorporated ultrasound images of children who underwent emergency ultrasonography for suspected ileocolic intussusception. After excluding video clips, Doppler images, and annotated images, 40,765 images from two tertiary hospitals were included (positive-to-negative ratio: hospital A, 2,775:35,373; hospital B, 140:2,477). Images from hospital A were split into a training set, a tuning set, and an internal test set (ITS) at a ratio of 7:1.5:1.5. Images from hospital B comprised an external test set (ETS). For each image indicating intussusception, two radiologists provided a bounding box as the ground-truth label. If intussusception was suspected in the input image, the model generated a bounding box with a confidence score (0-1) at the estimated lesion location. Average precision (AP) was used to evaluate overall model performance. The performance of practical thresholds for the modelgenerated confidence score, as determined from the ITS, was verified using the ETS. RESULTS: The AP values for the ITS and ETS were 0.952 and 0.936, respectively. Two confidence thresholds, CTopt and CTprecision, were set at 0.557 and 0.790, respectively. For the ETS, the perimage precision and recall were 95.7% and 80.0% with CTopt, and 98.4% and 44.3% with CTprecision. For per-patient diagnosis, the sensitivity and specificity were 100.0% and 97.1% with CTopt, and 100.0% and 99.0% with CTprecision. The average number of false positives per patient was 0.04 with CTopt and 0.01 for CTprecision. CONCLUSION: The feasibility of using an AI model to diagnose ileocolic intussusception on ultrasonography was demonstrated. However, further study involving bias-free data is warranted for robust clinical validation.
Radial spokes (RS) are T-shaped multiprotein complexes on the axonemal microtubules. Repeated RS1, RS2, and RS3 couple the central pair to modulate ciliary and flagellar motility. Despite the cell type specificity of RS3 substructures, their molecular components remain largely unknown. Here, we report that a leucine-rich repeat-containing protein, LRRC23, is an RS3 head component essential for its head assembly and flagellar motility in mammalian spermatozoa. From infertile male patients with defective sperm motility, we identified a splice site variant of LRRC23. A mutant mouse model mimicking this variant produces a truncated LRRC23 at the C-terminus that fails to localize to the sperm tail, causing male infertility due to defective sperm motility. LRRC23 was previously proposed to be an ortholog of the RS stalk protein RSP15. However, we found that purified recombinant LRRC23 interacts with an RS head protein RSPH9, which is abolished by the C-terminal truncation. Evolutionary and structural comparison also shows that LRRC34, not LRRC23, is the RSP15 ortholog. Cryo-electron tomography clearly revealed that the absence of the RS3 head and the sperm-specific RS2-RS3 bridge structure in LRRC23 mutant spermatozoa. Our study provides new insights into the structure and function of RS3 in mammalian spermatozoa and the molecular pathogenicity of LRRC23 underlying reduced sperm motility in infertile human males.
Infertility, Male , Sperm Motility , Mice , Animals , Male , Humans , Semen , Axoneme/metabolism , Sperm Tail , Proteins/metabolism , Spermatozoa , Infertility, Male/genetics , Flagella/metabolism , Mammals
OBJECTIVE: To develop a deep-learning-based bone age prediction model optimized for Korean children and adolescents and evaluate its feasibility by comparing it with a Greulich-Pyle-based deep-learning model. MATERIALS AND METHODS: A convolutional neural network was trained to predict age according to the bone development shown on a hand radiograph (bone age) using 21036 hand radiographs of Korean children and adolescents without known bone development-affecting diseases/conditions obtained between 1998 and 2019 (median age [interquartile range {IQR}], 9 [7-12] years; male:female, 11794:9242) and their chronological ages as labels (Korean model). We constructed 2 separate external datasets consisting of Korean children and adolescents with healthy bone development (Institution 1: n = 343; median age [IQR], 10 [4-15] years; male: female, 183:160; Institution 2: n = 321; median age [IQR], 9 [5-14] years; male: female, 164:157) to test the model performance. The mean absolute error (MAE), root mean square error (RMSE), and proportions of bone age predictions within 6, 12, 18, and 24 months of the reference age (chronological age) were compared between the Korean model and a commercial model (VUNO Med-BoneAge version 1.1; VUNO) trained with Greulich-Pyle-based age as the label (GP-based model). RESULTS: Compared with the GP-based model, the Korean model showed a lower RMSE (11.2 vs. 13.8 months; P = 0.004) and MAE (8.2 vs. 10.5 months; P = 0.002), a higher proportion of bone age predictions within 18 months of chronological age (88.3% vs. 82.2%; P = 0.031) for Institution 1, and a lower MAE (9.5 vs. 11.0 months; P = 0.022) and higher proportion of bone age predictions within 6 months (44.5% vs. 36.4%; P = 0.044) for Institution 2. CONCLUSION: The Korean model trained using the chronological ages of Korean children and adolescents without known bone development-affecting diseases/conditions as labels performed better in bone age assessment than the GP-based model in the Korean pediatric population. Further validation is required to confirm its accuracy.
Artificial Intelligence , Deep Learning , Adolescent , Humans , Child , Male , Female , Infant , Age Determination by Skeleton , Radiography , Republic of Korea
Non-alcoholic fatty liver disease (NAFLD) is associated with human environmental exposure to polychlorinated biphenyls (PCBs). Alternative splicing (AS) is dysregulated in steatotic liver disease and is regulated by splicing factors (SFs) and N-6 methyladenosine (m6A) modification. Here integrated analysis of hepatic mRNA-sequencing data was used to identify differentially expressed SFs and differential AS events (ASEs) in the livers of high fat diet-fed C57BL/6 J male mice exposed to Aroclor1260, PCB126, Aroclor1260 + PCB126, or vehicle control. Aroclor1260 + PCB126 co-exposure altered 100 SFs and replicate multivariate analysis of transcript splicing (rMATS) identified 449 ASEs in 366 genes associated with NAFLD pathways. These ASEs were similar to those resulting from experimental perturbations in m6A writers, readers, and erasers. These results demonstrate specific hepatic SF and AS regulatory mechanisms are disrupted by HFD and PCB exposures, contributing to the expression of altered isoforms that may play a role in NAFLD progression to NASH.
PURPOSE: In microscopic lumbar discectomy in obese patients, a correlation is found between the operation time and increase in estimated blood loss according to the increase in body mass index; however, no studies have investigated the outcomes of biportal endoscopic lumbar discectomy in obese patients. Therefore, this study aimed to compare the clinical and radiographic outcomes of microscopic and endoscopic discectomy in obese patients with lumbar herniated discs. METHODS: In this multicenter, retrospective study, clinical and radiological data were compared and analyzed in 73 obese patients with a body mass index of > 30 kg/m2 who underwent microscopic or biportal endoscopic lumbar discectomy. Clinical data on the visual analog scale (VAS), Oswestry disability index (ODI), and EuroQol-5D (EQ-5D) scores were measured, and radiological data were obtained using magnetic resonance imaging (MRI). RESULTS: This study enrolled 43 patients who underwent microscopic discectomy and 30 who underwent biportal endoscopic discectomy. The VAS, ODI, and EQ-5D scores in both groups improved after surgery compared with those before surgery, although there was no difference between the two groups. Although there was a difference in the incidence of recurrent disc herniation confirmed by MRI after surgery, no difference was found in the number of patients requiring surgery between the two groups. CONCLUSION: In obese patients with lumbar disc herniation that was not improved with conservative treatment, no significant clinical or radiological differences in outcomes were noted between microscopic and biportal endoscopic surgery methods. In contrast, minor complications were less common in the biportal group.
Diskectomy, Percutaneous , Intervertebral Disc Displacement , Humans , Intervertebral Disc Displacement/complications , Intervertebral Disc Displacement/diagnostic imaging , Intervertebral Disc Displacement/surgery , Retrospective Studies , Treatment Outcome , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Diskectomy/methods , Endoscopy/methods , Diskectomy, Percutaneous/methods
Left pulmonary artery (LPA) stenosis with acute angulation commonly necessitates surgical revision in the treatment of tetralogy of Fallot (TOF). We investigated the clinical characteristics of acute angulation of the LPA in patients with TOF via computed tomography (CT). Between 2011 and 2022, 160 patients were diagnosed with TOF using CT. After excluding 28 patients due to insufficient records or age, 132 patients were included in the present analysis. The patients were divided into two groups according to the presence or absence of acute angulation of the LPA: group I (TOF with an acute angle of the LPA, n = 53) and group II (TOF without an acute angle of the LPA, n = 79). We retrospectively collected clinical data from electronic medical records. T-tests were used to analyze continuous variables (i.e., age, sex, weight, right ventricular outflow tract [RVOT] pressure on echocardiography, and distance to bifurcation), and Fisher's exact and chi-square tests were used to analyze categorical data (i.e., presence of the right aortic arch, pulmonary arterial atresia/hypoplasia, atrial septal defect [ASD], patent ductus arteriosus [PDA], and pulmonary valve). The groups did not differ significantly in terms of sex, weight, presence of the right aortic arch, pulmonary arterial atresia/hypoplasia, ASD, or distance to the bifurcation. Moreover, there was no significant difference between the presence and absence of PDA (P = 0.057); however, patients in group I were significantly older (143.2 ± 97.8 days) than those in group II (91.1 ± 76.0 days, P = 0.002). Furthermore, RVOT pressure was significantly higher among patients in group I (45.1 ± 22.5 mmHg) than in group II (25.0 ± 12.4 mmHg, P < 0.001). In the current study, acute angulation of the LPA in patients with TOF, as observed on CT, was associated with older age and higher RVOT pressure on echocardiography.
Ductus Arteriosus, Patent , Heart Septal Defects, Atrial , Hypertension, Pulmonary , Pulmonary Atresia , Stenosis, Pulmonary Artery , Tetralogy of Fallot , Humans , Aged, 80 and over , Pulmonary Artery/diagnostic imaging , Tetralogy of Fallot/diagnostic imaging , Tetralogy of Fallot/surgery , Retrospective Studies , Tomography, X-Ray Computed
Radial spokes (RS) are T-shaped multiprotein complexes on the axonemal microtubules. Repeated RS1, RS2, and RS3 couple the central pair to modulate ciliary and flagellar motility. Despite the cell type specificity of RS3 substructures, their molecular components remain largely unknown. Here, we report that a leucine-rich repeat-containing protein, LRRC23, is an RS3 head component essential for its head assembly and flagellar motility in mammalian spermatozoa. From infertile male patients with defective sperm motility, we identified a splice site variant of LRRC23. A mutant mouse model mimicking this variant produces a truncated LRRC23 at the C-terminus that fails to localize to the sperm tail, causing male infertility due to defective sperm motility. LRRC23 was previously proposed to be an ortholog of the RS stalk protein RSP15. However, we found that purified recombinant LRRC23 interacts with an RS head protein RSPH9, which is abolished by the C-terminal truncation. Evolutionary and structural comparison also shows that LRRC34, not LRRC23, is the RSP15 ortholog. Cryo-electron tomography clearly revealed that the absence of the RS3 head and the sperm-specific RS2-RS3 bridge structure in LRRC23 mutant spermatozoa. Our study provides new insights into the structure and function of RS3 in mammalian spermatozoa and the molecular pathogenicity of LRRC23 underlying reduced sperm motility in infertile human males.
The cochlea's ability to discriminate sound frequencies is facilitated by a special topography along its longitudinal axis known as tonotopy. Auditory hair cells located at the base of the cochlea respond to high-frequency sounds, whereas hair cells at the apex respond to lower frequencies. Gradual changes in morphological and physiological features along the length of the cochlea determine each region's frequency selectivity, but it remains unclear how tonotopy is established during cochlear development. Recently, sonic hedgehog (SHH) was proposed to initiate the establishment of tonotopy by conferring regional identity to the primordial cochlea. Here, using mouse genetics, we provide in vivo evidence that regional identity in the embryonic cochlea acts as a framework upon which tonotopy-specific properties essential for frequency selectivity in the mature cochlea develop. We found that follistatin (FST) is required for the maintenance of apical cochlear identity, but dispensable for its initial induction. In a fate-mapping analysis, we found that FST promotes expansion of apical cochlear cells, contributing to the formation of the apical cochlear domain. SHH, in contrast, is required both for the induction and maintenance of apical identity. In the absence of FST or SHH, mice produce a short cochlea lacking its apical domain. This results in the loss of apex-specific anatomical and molecular properties and low-frequency-specific hearing loss.
Follistatin , Hedgehog Proteins , Animals , Mice , Follistatin/genetics , Hedgehog Proteins/genetics , Hedgehog Proteins/metabolism , Cochlea/physiology , Hearing/physiology , Mammals/metabolism
The flagellar-specific Ca2+ channel CatSper is the predominant Ca2+ entry site in mammalian sperm. CatSper-mediated Ca2+ signaling affects nearly every event that regulates sperm to acquire fertilizing capability. In this review, we summarize some of the main findings from 20 years of CatSper research and highlight recent progress and prospects.
Calcium Channels , Semen , Animals , Humans , Male , Calcium Channels/metabolism , Semen/metabolism , Spermatozoa/metabolism , Calcium Signaling , Calcium/metabolism , Mammals
This study successfully prepared and tested sulfur- and nitrogen-co-doped TiO2-coated α-Al2O3 (S,N-doped TiO2/Al2O3) hollow fiber (HF) membranes for efficient photocatalytic degradation of gaseous ammonia (NH3). Thiourea was used as a sulfur- and nitrogen-doping source to produce a S,N-doped TiO2 photocatalyst powder. For comparative purposes, undoped TiO2 powder was also synthesized. Through the application of a phase-inversion technique combined with high-temperature sintering, hollow fibers composed of α-Al2O3 were developed. Undoped TiO2 and S,N-doped TiO2 photocatalyst powders were coated on the α-Al2O3 HF surface to obtain undoped TiO2/Al2O3 and S,N-doped TiO2/Al2O3 HF membranes, respectively. All prepared samples were characterized using XRD, TEM, XPS, UV-Vis, SEM, BET, FT-IR, and EDS. S and N dopants were confirmed using XPS and UV-Vis spectra. The crystal phase of the undoped TiO2 and S,N-doped TiO2 photocatalysts was a pure anatase phase. A portable air purifier photocatalytic filter device was developed and tested for the first time to decrease the amount of indoor NH3 pollution under the limits of the lachrymatory threshold. The device, which was made up of 36 S,N-doped TiO2/Al2O3 HF membranes, took only 15-20 min to reduce the level of NH3 in a test chamber from 50 ppm to around 5 ppm, confirming the remarkable performance regarding the photocatalytic degradation of gaseous NH3.
The Korean Society of Radiology and Medical Guidelines Committee amended the existing 2016 guidelines to publish the "Korean Clinical Practice Guidelines for Adverse Reactions to Iodide Contrast for Injection and Gadolinium Contrast for MRI: The Revised Clinical Consensus and Recommendations (2022 Third Edition)." Expert members recommended and approved by the Korean Society of Radiology, the Korean Academy of Asthma, Allergy and Clinical Immunology, and the Korean Nephrology Society participated together. According to the expert consensus or systematic literature review, the description of the autoinjector and connection line for the infection control while using contrast medium, the acute adverse reaction, and renal toxicity to iodized contrast medium were modified and added. We would like to introduce the revised contents.
The epithelial splicing regulatory proteins, ESRP1 and ESRP2, are essential for mammalian development through the regulation of a global program of alternative splicing of genes involved in the maintenance of epithelial cell function. To further inform our understanding of the molecular functions of ESRP1, we performed enhanced crosslinking immunoprecipitation coupled with high-throughput sequencing (eCLIP) in epithelial cells of mouse epidermis. The genome-wide binding sites of ESRP1 were integrated with RNA-Seq analysis of alterations in splicing and total gene expression that result from epidermal ablation of Esrp1 and Esrp2. These studies demonstrated that ESRP1 functions in splicing regulation occur primarily through direct binding in a position-dependent manner to promote either exon inclusion or skipping. In addition, we also identified widespread binding of ESRP1 in 3' and 5' untranslated regions (UTRs) of genes involved in epithelial cell function, suggesting that its post-transcriptional functions extend beyond splicing regulation.
Due to its greater physical-chemical stability, ceramic nanofiltration (NF) membranes were used in a number of industrial applications. In this study, a novel NF membrane was prepared by co-depositing a titanium dioxide (TiO2) and graphene oxide (GO) composite layer directly onto a porous α-Al2O3 hollow fiber (HF) support. An 8 µm-thick TiO2/GO layer was deposited to the surface of α-Al2O3 HF support by vacuum deposition method to produce advanced TiO2/GO-Al2O3 HF NF membrane. Scanning electron microscope (SEM) micrographs, energy dispersive spectrometer (EDS), X-ray powder diffraction (XRD), thermogravimetric analyzer (TGA), porosity, 3-point bending strength, zeta potential analysis, and hydrophilic properties by water contact angle are used for TiO2/GO-Al2O3 HF NF membrane characterization. The results show that the developed membrane's MWCO ranged from 600 to 800 Da. The water flux, rejection of lignin, and sodium ions were 5.6 L/m2 h·bar, ~92.1%, and ~5.5%, respectively. In a five-day NF process, the TiO2/GO-Al2O3 HF NF membrane exhibits good lignin permeation stability of about 14.5 L/m2 h.
BACKGROUND: Several recent studies have reported that deep learning reconstruction "TrueFidelity" (TF) improves computed tomography (CT) image quality. However, no study has compared adaptive statistical repeated reconstruction (ASIR-V) using TF in pediatric cardiac CT angiography (CTA) with a low peak kilovoltage. OBJECTIVE: This study aimed to determine whether ASIR-V or TF CTA image quality is superior in children with congenital heart disease (CHD). MATERIALS AND METHODS: Fifty children (median age, 2 months; interquartile range, 0-5 months; 28 men) with CHD who underwent CTA were enrolled between June and September 2020. Images were reconstructed using 2 ASIR-V blending factors (80% and 100% [AV-100]) and 3 TF settings (low, medium, and high [TF-H] strength levels). For the quantitative analyses, 3 objective image qualities (attenuation, noise, and signal-to-noise ratio [SNR]) were measured of the great vessels and heart chambers. The contrast-to-noise ratio (CNR) was also evaluated between the left ventricle and the dial wall. For the qualitative analyses, the degree of quantum mottle and blurring at the upper level to the first branch of the main pulmonary artery was assessed independently by 2 radiologists. RESULTS: When the ASIR-V blending factor level and TF strength were higher, the noise was lower, and the SNR was higher. The image noise and SNR of TF-H were significantly lower and higher than those of AV-100 (Pâ <â .01), except for noise in the right atrium and left pulmonary artery and SNR of the right ventricle. Regarding CNR, TF-H was significantly better than AV-100 (Pâ <â .01). In addition, in the objective assessment of the degree of quantum mottle and blurring, TF-H had the best score among all examined image sets (Pâ <â .01). CONCLUSION: TF-H is superior to AV-100 in terms of objective and subjective image quality. Consequently, TF-H was the best image set for cardiac CTA in children with CHD.
Deep Learning , Heart Defects, Congenital , Male , Humans , Child , Infant , Radiographic Image Interpretation, Computer-Assisted/methods , Radiation Dosage , Tomography, X-Ray Computed/methods , Heart Defects, Congenital/diagnostic imaging , Heart Atria , Algorithms , Image Processing, Computer-Assisted
Coronavirus disease 2019 (COVID-19) is usually less severe in children and adolescents than in adults. However, it can cause severe respiratory illness in a small proportion of children with risk factors. Here, we report a rare case of a 10-year-old boy with postinfectious bronchiolitis obliterans that developed after pneumonia caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This patient was previously healthy apart from a high body mass index (BMI, 30.13; 99.6th percentile for the age bracket), history of preterm birth (35 weeks), and low birth weight (1,850 g). He had persistent exertional dyspnea after recovering from SARS-CoV-2-related pneumonia. Spirometry revealed obstructive lung disease with the following results: predicted forced vital capacity (FVC%pred), 71%; forced expiratory volume in 1 second (FEV1%pred), 63%; FEV1/FVC, 0.81; and forced expiratory flow25-75%pred, 55%. Chest computed tomography showed multifocal areas of parenchymal hyperlucency and mosaic attenuation in both lungs. This case suggests that careful observation of children with obesity and low birth weight is necessary after recovery from SARS-CoV-2-related pneumonia.
Bronchiolitis Obliterans , COVID-19 , Pneumonia , Premature Birth , Adolescent , Adult , Bronchiolitis Obliterans/diagnosis , Bronchiolitis Obliterans/etiology , COVID-19/complications , Child , Female , Forced Expiratory Volume , Humans , Infant, Newborn , Lung/diagnostic imaging , Male , Pneumonia/complications , SARS-CoV-2 , Spirometry , Vital Capacity
In recent years, reactive ammonia (NH3) has emerged as a major source of indoor air pollution. In this study, Al2O3-based hollow fiber membranes functionalized with nitrogen-doped titanium dioxide were produced and successfully applied for efficient heterogeneous photocatalytic NH3 gas degradation. Al2O3 hollow fiber membranes were prepared using the phase inversion process. A dip-coating technique was used to deposit titanium dioxide (TiO2) and nitrogen-doped titanium dioxide (N-TiO2) thin films on well-cleaned Al2O3-based hollow fiber membranes. All heterogeneous photocatalytic degradation tests of NH3 gas were performed with both UV and visible light irradiation at room temperature. The nitrogen doping effects on the NH3 heterogeneous photocatalytic degradation capacity of TiO2 were investigated, and the effect of the number of membranes (30, 36, 42, and 48 membranes) of the prototype lab-scale photocatalytic membrane reactor, with a modular design, on the performances in different light conditions was also elucidated. Moreover, under ultraviolet and visible light, the initial concentration of gaseous NH3 was reduced to zero after only fifteen minutes in a prototype lab-scale stage with a photocatalytic membrane reactor based on an N-TiO2 photocatalyst. The number of Al2O3-based hollow fiber membranes functionalized with N-TiO2 photocatalysts increases the capacity for NH3 heterogeneous photocatalytic degradation.
The intestinal microbiome releases a plethora of small molecules. Here, we show that the Ruminococcaceae metabolite isoamylamine (IAA) is enriched in aged mice and elderly people, whereas Ruminococcaceae phages, belonging to the Myoviridae family, are reduced. Young mice orally administered IAA show cognitive decline, whereas Myoviridae phage administration reduces IAA levels. Mechanistically, IAA promotes apoptosis of microglial cells by recruiting the transcriptional regulator p53 to the S100A8 promoter region. Specifically, IAA recognizes and binds the S100A8 promoter region to facilitate the unwinding of its self-complementary hairpin structure, thereby subsequently enabling p53 to access the S100A8 promoter and enhance S100A8 expression. Thus, our findings provide evidence that small molecules released from the gut microbiome can directly bind genomic DNA and act as transcriptional coregulators by recruiting transcription factors. These findings further unveil a molecular mechanism that connects gut metabolism to gene expression in the brain with implications for disease development.
Bacteriophages , Cognitive Dysfunction , Gastrointestinal Microbiome , Amines , Animals , Bacteria , Bacteriophages/genetics , Humans , Mice , Microglia , Tumor Suppressor Protein p53
