RESUMEN

The storage and periodic voiding of urine in the lower urinary tract are regulated by a complex neural control system that includes the brain, spinal cord, and peripheral autonomic ganglia. Investigating the neuromodulation mechanisms of the lower urinary tract helps to deepen our understanding of urine storage and voiding processes, reveal the mechanisms underlying lower urinary tract dysfunction, and provide new strategies and insights for the treatment and management of related diseases. However, the current understanding of the neuromodulation mechanisms of the lower urinary tract is still limited, and further research methods are needed to elucidate its mechanisms and potential pathological mechanisms. This article provides an overview of the research progress in the functional study of the lower urinary tract system, as well as the key neural regulatory mechanisms during the micturition process. In addition, the commonly used research methods for studying the regulatory mechanisms of the lower urinary tract and the methods for evaluating lower urinary tract function in rodents are discussed. Finally, the latest advances and prospects of artificial intelligence in the research of neuromodulation mechanisms of the lower urinary tract are discussed. This includes the potential roles of machine learning in the diagnosis of lower urinary tract diseases and intelligent-assisted surgical systems, as well as the application of data mining and pattern recognition techniques in advancing lower urinary tract research. Our aim is to provide researchers with novel strategies and insights for the treatment and management of lower urinary tract dysfunction by conducting in-depth research and gaining a comprehensive understanding of the latest advancements in the neural regulation mechanisms of the lower urinary tract.

Asunto(s)

RESUMEN

Micturition serves an essential physiological function that allows the body to eliminate metabolic wastes and maintain water-electrolyte balance. The urine spot assay (VSA), as a simple and economical assay, has been widely used in the study of micturition behavior in rodents. However, the traditional VSA method relies on manual judgment, introduces subjective errors, faces difficulty in obtaining appearance time of each urine spot, and struggles with quantitative analysis of overlapping spots. To address these challenges, we developed a deep learning-based approach for the automatic identification and segmentation of urine spots. Our system employs a target detection network to efficiently detect each urine spot and utilizes an instance segmentation network to achieve precise segmentation of overlapping urine spots. Compared with the traditional VSA method, our system achieves automated detection of urine spot area of micturition in rodents, greatly reducing subjective errors. It accurately determines the urination time of each spot and effectively quantifies the overlapping spots. This study enables high-throughput and precise urine spot detection, providing important technical support for the analysis of urination behavior and the study of the neural mechanism underlying urination.

Asunto(s)

RESUMEN

It has been strongly suggested that selenium deficiency and T-2 toxin contamination have a strong relationship with the occurrence and development of Kashin-Beck disease (KBD). In order to provide information for understanding the high prevalence of KBD in Tibet, this study collected the responses to a cubital venous blood and dietary questionnaire of 125 subjects including 75 KBD patients and 50 healthy controls in a KBD-prevalent county (Luolong County) in Tibet, China. A total of 10 household local families were randomly selected in this area, and local diet samples of brick tea, Zanba powder, milk residue, and hulless Barley were collected from these residents. Selenium content in blood was detected by inductively coupled plasma mass spectrometry (ICP-MS). The T-2 toxin contamination level in food sample was assayed using an ELISA kit. The selenium levels of patients and controls were 42.0 ± 19.8 and 56.06 ± 22.4 µg/L, respectively. The serum selenium level in controls was higher than that in patients, but there was no significant difference, and the serum selenium level both in patients and controls in Tibet was lower than the normal range. The results of the dietary survey showed that the number of respondents who consumed butter tea was large; 46.67% of patients indicated that they drank buttered tea every day, which was significantly higher than in controls. The contents of T-2 toxin in Zanba powder, milk residue, hulless barley and drinking water samples were below the detection limit (0.05 µg/kg); this result was labeled Tr. Unexpectedly, the contents of T-2 toxin in brick tea were higher, with average levels of 424 ± 56 µg/kg in Detong village and 396 ± 24 µg/kg in Langcuo village. For the first time, we report the presence of an extremely high concentration of T-2 toxin in brick tea of Tibet.

Asunto(s)

RESUMEN

BACKGROUND: Further stratification of the risk of recurrence of clear-cell renal cell carcinoma (ccRCC) with venous tumor thrombus (VTT) will facilitate selection of candidates for adjuvant therapy. OBJECTIVE: To assess the impact of tumor grade discrepancy (GD) between the primary tumor (PT) and VTT in nonmetastatic ccRCC on disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective analysis of a multi-institutional nationwide data set for patients with pT3N0M0 ccRCC who underwent radical nephrectomy and thrombectomy. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: Pathology slides were centrally reviewed. GD, a bidirectional variable (upgrading or downgrading), was numerically defined as the VTT grade minus the PT grade. Multivariable models were built to predict DFS, OS, and CSS. RESULTS AND LIMITATIONS: We analyzed data for 604 patients with median follow-up of 42 mo (excluding events). Tumor GD between VTT and PT was observed for 47% (285/604) of the patients and was an independent risk factor with incremental value in predicting the outcomes of interest (all p < 0.05). Incorporation of tumor GD significantly improved the performance of the ECOG-ACRIN 2805 (ASSURE) model. A GD-based model (PT grade, GD, pT stage, PT sarcomatoid features, fat invasion, and VTT consistency) had a c index of 0.72 for DFS. The hazard ratios were 8.0 for GD = +2 (p < 0.001), 1.9 for GD = +1 (p < 0.001), 0.57 for GD = -1 (p = 0.001), and 0.22 for GD = -2 (p = 0.003) versus GD = 0 as the reference. According to model-converted risk scores, DFS, OS, and CSS significantly differed between subgroups with low, intermediate, and high risk (all p < 0.001). CONCLUSIONS: Routine reporting of VTT upgrading or downgrading in relation to the PT and use of our GD-based nomograms can facilitate more informed treatment decisions by tailoring strategies to an individual patient's risk of progression. PATIENT SUMMARY: We developed a tool to improve patient counseling and guide decision-making on other therapies in addition to surgery for patients with the clear-cell type of kidney cancer and tumor invasion of a vein.

Asunto(s)

RESUMEN

This study aims to determine the association of pregnancy cholesterol metabolism markers with gestational diabetes mellitus (GDM) risk. We performed a nested case-control study in the Tongji Birth Cohort. GDM was diagnosed according to the 75 g 2 h oral glucose tolerance test (OGTT) at 24-28 gestational weeks. Nine cholesterol metabolism markers were detected using gas chromatography-mass spectrometry. Conditional logistic regression models were conducted. A total of 444 pregnant women were matched in a 1:2 ratio. The cholestanolTC and ß-sitosterolTC in cholesterol absorption markers presented negative associations with the risks of GDM (adjusted OR: 0.77, 95% CI: 0.61-0.96; adjusted OR: 0.80, 95% CI: 0.64-1.00). The desmosterolTC in cholesterol synthesis markers were positively associated with the risks of GDM (adjusted OR: 1.25, 95% CI: 1.00-1.56), similar in the ratios of cholesterol synthesis to absorption markers. After adjustment for insulin or HOMA-IR, these effects were reduced. In conclusion, higher cholesterol synthesis and lower cholesterol absorption marker levels in the first pregnancy are associated with a higher risk of GDM, and insulin resistance may play a vital role in this association.

Asunto(s)

RESUMEN

The prevalence and disease burden of urolithiasis has increased substantially worldwide in the last decade, and intraluminal holmium laser lithotripsy has become the primary treatment method. However, inappropriate laser energy settings increase the risk of perioperative complications, largely due to the lack of intraoperative information on the stone composition, which determines the stone melting point. To address this issue, we developed a fiber-based fluorescence spectrometry method that detects and classifies the autofluorescence spectral fingerprints of urinary stones into three categories: calcium oxalate, uric acid, and struvite. By applying the support vector machine (SVM), the prediction accuracy achieved 90.28 % and 96.70% for classifying calcium stones versus non-calcium stones and uric acid versus struvite, respectively. High accuracy and specificity were achieved for a wide range of working distances and angles between the fiber tip and stone surface in an emulated intraoperative ambient. Our work establishes the methodological basis for engineering a clinical device that achieves real-time, in situ classification of urinary stones for optimizing the laser ablation parameters and reducing perioperative complications in lithotripsy.

Asunto(s)

RESUMEN

There is still controversy about optimal dietary iodine intake as the Universal Salt Iodization policy enforcement in China. A modified iodine balance study was thus conducted to explore the suitable iodine intake in Chinese adult males using the iodine overflow hypothesis. In this study, thirty-eight apparently healthy males (19·1 (sd 0·6) years) were recruited and provided with designed diets. After the 14-d iodine depletion, daily iodine intake gradually increased in the 30-d iodine supplementation, consisting of six stages and each of 5 d. All foods and excreta (urine, faeces) were collected to examine daily iodine intake, iodine excretion and the changes of iodine increment in relation to those values at stage 1. The dose-response associations of iodine intake increment with excretion increment were fitted by the mixed effects models, as well as with retention increment. Daily iodine intake and excretion were 16·3 and 54·3 µg/d at stage 1, and iodine intake increment increased from 11·2 µg/d at stage 2 to 118·0 µg/d at stage 6, while excretion increment elevated from 21·5 to 95·0 µg/d. A zero iodine balance was dynamically achieved as 48·0 µg/d of iodine intake. The estimated average requirement and recommended nutrient intake were severally 48·0 and 67·2 µg/d, which could be corresponded to a daily iodine intake of 0·74 and 1·04 µg/kg per d. The results of our study indicate that roughly half of current iodine intakes recommendation could be enough in Chinese adult males, which would be beneficial for the revision of dietary reference intakes.

Asunto(s)

RESUMEN

PURPOSE: We re-explored the basal iodine requirement based on healthy Chinese female and a new iodine overflow theory was proposed for iodine balance study. METHODS: Thirty-six Chinese healthy female adults (age 20.7 ± 1.1) were recruited for this study, which included 40 days low iodine depletion period and six stages of 30 days supplementation period. Uniform diets with low iodine were provided and the content of iodine in the diet was regulated by dairy products. The total iodine intake from food and the total iodine excretion through 24-h urine and staged feces were completely gathered and monitored. The incremental (Δ) intake and excretion over the range were calculated. RESULTS: The iodine intake and excretion were 13.6 µg/day and 48.6 µg/day at the first stage, respectively. The incremental iodine intakes and excretions were 21.1 µg/day to 120.3 µg/day and 25.8 µg/day to 105.4 µg/day for the supplementation stages, respectively. According to the 'iodine overflow theory', the zero iodine balance (Δ iodine intake = Δ iodine excretion) derived from a mixed effect model indicated a mean iodine intake of 52.2 µg/d (1.0 µg/d kg). The RNI for iodine to healthy Chinese female adult was 73.1 µg/d (1.4 µg/d kg). CONCLUSION: A daily iodine intake of 52.2 µg/d may meet the basal iodine requirement for healthy Chinese female adults, and Chinese female may need more than 20% iodine intake than male based on the 'iodine overflow theory'. The trial was registered at the Chinese Clinical Trial Registry in May 2018 (No: ChiCTR1800016184).

Asunto(s)

RESUMEN

The ventrolateral periaqueductal gray (VLPAG) is thought to be the main PAG column for bladder control. PAG neurons (especially VLPAG neurons) and neurons in the pontine micturition center (PMC) innervating the bladder detrusor have anatomical and functional synaptic connections. The prevailing viewpoint on neural control of the bladder is that PAG neurons receive information on the decision to void made by upstream brain regions, and consequently activate the PMC through their direct projections to initiate urination reflex. However, the exact location of the PMC-projecting VLPAG neurons, their activity in response to urination, and their whole-brain inputs remain unclear. Here, we identified the distribution of VLPAG neurons that may participate in control of the bladder or project to the PMC through retrograde neural tracing. Population Ca2+ signals of PMC-projecting VLPAG neurons highly correlated with bladder contractions and urination as shown by in vivo recording in freely moving animals. Using a RV-based retrograde trans-synaptic tracing strategy, morphological results showed that urination-related PMC-projecting VLPAG neurons received dense inputs from multiple urination-related higher brain areas, such as the medial preoptic area, medial prefrontal cortex, and lateral hypothalamus. Thus, our findings reveal a novel insight into the VLPAG for control of bladder function and provide a potential therapeutic midbrain node for neurogenic bladder dysfunction.

RESUMEN

Soil denitrification is an important process in the emission of N2O, an atmospheric greenhouse gas. Environmental factors of different vegetation types are largely heterogeneous, which may directly or indirectly affect N2O fluxes. Through high-throughput sequencing of the nitrite reductase gene nirS, this study investigated the influence of vegetation type on the structure and diversity of denitrifying microbial communities in Qinghai Lake wetlands, China. The results showed that among the four vegetation types in the Qinghai Lake wetlands, Carex rigescens (CR) had the highest species richness index, and Leymus secalinus (LS) had the lowest species richness index. Species evenness followed the opposite trend. Proteobacteria were the main denitrifying bacterial phylum in the wetland soil of Qinghai Lake. There were 40 differential bacterial flora at different levels in the four vegetation types, most of which belonged to Proteobacteria. Magnetospirillum is a bacterium that differed significantly across the four vegetation types, and it was one of the main denitrifying taxa based on relative abundance in the LS vegetation type. Soil pH was the most important regulating factor of nirS-type denitrifying microbial community in Qinghai Lake wetland. In summary, the succession of vegetation types in the Qinghai Lake Wetlands changes the soil microenvironment and significantly affects the community structure and diversity of the denitrifying microbial communities. The large-area growth of CR might even increase the emission of nitrous oxide. This study can serve as a reference for further exploration of the N2O emission mechanism in the unique habitats of alpine wetlands.

Asunto(s)

RESUMEN

The sensory responses of cortical neuronal populations following training have been extensively studied. However, the spike firing properties of individual cortical neurons following training remain unknown. Here, we have combined two-photon Ca2+ imaging and single-cell electrophysiology in awake behaving mice following auditory associative training. We find a sparse set (~5%) of layer 2/3 neurons in the primary auditory cortex, each of which reliably exhibits high-rate prolonged burst firing responses to the trained sound. Such bursts are largely absent in the auditory cortex of untrained mice. Strikingly, in mice trained with different multitone chords, we discover distinct subsets of neurons that exhibit bursting responses specifically to a chord but neither to any constituent tone nor to the other chord. Thus, our results demonstrate an integrated representation of learned complex sounds in a small subset of cortical neurons.

Asunto(s)

RESUMEN

Adverse environmental conditions, such as salinity, cold, drought, heavy metals, and pathogens affect the yield and quality of Salvia miltiorrhiza, a well-known medicinal plant used for the treatment of cardiovascular and cerebrovascular diseases. Superoxide dismutase (SOD), a key enzyme of antioxidant system in plants, plays a vital role in protecting plants against various biotic and abiotic stresses via scavenging the reactive oxygen species produced by organisms. However, little is known about the SOD gene family in S. miltiorrhiza. In this study, eight SOD genes, including three Cu/Zn-SODs, two Fe-SODs and three Mn-SODs, were identified in the S. miltiorrhiza genome. Their gene structures, promoters, protein features, phylogenetic relationships, and expression profiles were comprehensively investigated. Gene structure analysis implied that most SmSODs have different introns/exons distrbution patterns. Many cis-elements related to different stress responses or plant hormones were found in the promoter of each SmSOD. Expression profile analysis indicated that SmSODs exhibited diverse responses to cold, salt, drought, heavy metal, and plant hormones. Additionally, 31 types of TFs regulating SmSODs were predicted and analyzed. These findings provided valuable information for further researches on the functions and applications of SmSODs in S. miltiorrhiza growth and adaptation to stress.

Asunto(s)

RESUMEN

Two-photon laser scanning microscopy has been extensively applied to study in vivo neuronal activity at cellular and subcellular resolutions in mammalian brains. However, the extent of such studies is typically confined to a single functional region of the brain. Here, we demonstrate a novel technique, termed the multiarea two-photon real-time in vivo explorer (MATRIEX), that allows the user to target multiple functional brain regions distributed within a zone of up to 12 mm in diameter, each with a field of view (FOV) of ~200 µm in diameter, thus performing two-photon Ca2+ imaging with single-cell resolution in all of the regions simultaneously. For example, we demonstrate real-time functional imaging of single-neuron activities in the primary visual cortex, primary motor cortex and hippocampal CA1 region of mice in both anesthetized and awake states. A unique advantage of the MATRIEX technique is the configuration of multiple microscopic FOVs that are distributed in three-dimensional space over macroscopic distances (>1 mm) both laterally and axially but that are imaged by a single conventional laser scanning device. In particular, the MATRIEX technique can be effectively implemented as an add-on optical module for an existing conventional single-beam-scanning two-photon microscope without requiring any modification to the microscope itself. Thus, the MATRIEX technique can be readily applied to substantially facilitate the exploration of multiarea neuronal activity in vivo for studies of brain-wide neural circuit function with single-cell resolution.

RESUMEN

Understanding the complex neural mechanisms controlling urinary bladder activity is an extremely important topic in both neuroscience and urology. Simultaneously recording of the bladder activity and neural activity in related brain regions will largely advance this field. However, such recording approach has long been restricted to anesthetized animals, whose bladder function and urodynamic properties are largely affected by anesthetics. In our recent report, we found that it is feasible to record bladder pressure (cystometry) and the related cortical neuron activity simultaneously in freely moving mice. Here, we aimed to demonstrate the use of this combined method in freely moving mice for recording the activity of the pontine micturition center (PMC), a more difficultly approachable small region deeply located in the brainstem and a more popularly studied hub for controlling bladder function. Interestingly, we found that the duration of urination events linearly correlated to the time course of neuronal activity in the PMC. We observed that the activities of PMC neurons highly correlated with spike-like increases in bladder pressure, reflecting bladder contractions. We also found that anesthesia evoked prominent changes in the dynamics of the Ca2+ signals in the PMC during the bladder contraction and even induced the dripping overflow incontinence due to suppression of the neural activity in the PMC. In addition, we described in details both the system for cystometry in freely moving mice and the protocols for how to perform this combined method. Therefore, this work provides a powerful approach that enables the simultaneous measurement of neuronal activity of the PMC or any other brain sites and bladder function in freely behaving mice. This approach offers a promising possibility to examine the neural mechanisms underlying neurogenic bladder dysfunction.

RESUMEN

Clinical observations indicate that the paramedian region of the thalamus is a critical node for controlling wakefulness. However, the specific nucleus and neural circuitry for this function remain unknown. Using in vivo fiber photometry or multichannel electrophysiological recordings in mice, we found that glutamatergic neurons of the paraventricular thalamus (PVT) exhibited high activities during wakefulness. Suppression of PVT neuronal activity caused a reduction in wakefulness, whereas activation of PVT neurons induced a transition from sleep to wakefulness and an acceleration of emergence from general anesthesia. Moreover, our findings indicate that the PVT-nucleus accumbens projections and hypocretin neurons in the lateral hypothalamus to PVT glutamatergic neurons' projections are the effector pathways for wakefulness control. These results demonstrate that the PVT is a key wakefulness-controlling nucleus in the thalamus.

Asunto(s)

RESUMEN

Urination (also called micturition) is thought to be regulated by a neural network that is distributed in both subcortical and cortical regions. Previously, urination-related neurons have been identified in subcortical structures such as the pontine micturition center (also known as Barrington's nucleus). However, the origin of the descending cortical pathway and how it interfaces with this subcortical circuit to permit voluntary initiation of urination remain elusive. Here we identified a small cluster of layer 5 neurons in the primary motor cortex whose activities tightly correlate with the onset of urination in freely behaving mice and increase dramatically during territorial marking. Optogenetically activating these neurons elicits contraction of the bladder and initiates urination, through their projections to the pontine micturition center, while silencing or ablating them impairs urination and causes retention of urine. Together these results reveal a novel cortical component upstream of the pontine micturition center that is critically involved in urination.

Asunto(s)

RESUMEN

The ability to remember and to navigate to safe places is necessary for survival. Place navigation is known to involve medial entorhinal cortex (MEC)-hippocampal connections. However, learning-dependent changes in neuronal activity in the distinct circuits remain unknown. Here, by using optic fiber photometry in freely behaving mice, we discovered the experience-dependent induction of a persistent-task-associated (PTA) activity. This PTA activity critically depends on learned visual cues and builds up selectively in the MEC layer II-dentate gyrus, but not in the MEC layer III-CA1 pathway, and its optogenetic suppression disrupts navigation to the target location. The findings suggest that the visual system, the MEC layer II, and the dentate gyrus are essential hubs of a memory circuit for visually guided navigation.

Asunto(s)

RESUMEN

In vivo two-photon Ca2+ imaging is a powerful tool for recording neuronal activities during perceptual tasks and has been increasingly applied to behaving animals for acute or chronic experiments. However, the auditory cortex is not easily accessible to imaging because of the abundant temporal muscles, arteries around the ears and their lateral locations. Here, we report a protocol for two-photon Ca2+ imaging in the auditory cortex of head-fixed behaving mice. By using a custom-made head fixation apparatus and a head-rotated fixation procedure, we achieved two-photon imaging and in combination with targeted cell-attached recordings of auditory cortical neurons in behaving mice. Using synthetic Ca2+ indicators, we recorded the Ca2+ transients at multiple scales, including neuronal populations, single neurons, dendrites and single spines, in auditory cortex during behavior. Furthermore, using genetically encoded Ca2+ indicators (GECIs), we monitored the neuronal dynamics over days throughout the process of associative learning. Therefore, we achieved two-photon functional imaging at multiple scales in auditory cortex of behaving mice, which extends the tool box for investigating the neural basis of audition-related behaviors.

Asunto(s)

RESUMEN

Locomotion involves complex neural activity throughout different cortical and subcortical networks. The primary motor cortex (M1) receives a variety of projections from different brain regions and is responsible for executing movements. The primary visual cortex (V1) receives external visual stimuli and plays an important role in guiding locomotion. Understanding how exactly the M1 and the V1 are involved in locomotion requires recording the neural activities in these areas in freely moving animals. Here, we used an optical fiber-based method for the real-time monitoring of neuronal population activities in freely moving mice. We combined the bulk loading of a synthetic Ca2+ indicator and the optical fiber-based Ca2+ recordings of neuronal activities. An optical fiber 200 µm in diameter can detect the coherent activity of a subpopulation of neurons. In layer 5 of the M1 and V1, we showed that population Ca2+ transients reliably occurred preceding the impending locomotion. Interestingly, the M1 Ca2+ transients started ~100 ms earlier than that in V1. Furthermore, the population Ca2+ transients were robustly correlated with head movements. Thus, our work provides a simple but efficient approach for monitoring the cortical Ca2+ activity of a local cluster of neurons during locomotion in freely moving animals.

Asunto(s)