Pramipexole improves depression-like behavior in diabetes mellitus with depression rats by inhibiting NLRP3 inflammasome-mediated neuroinflammation and preventing impaired neuroplasticity.

BACKGROUND: Diabetes mellitus (DM) is frequently associated with the occurrence and development of depression, and the co-occurrence of diabetes mellitus with depression (DD) may further reduce patients' quality of life. Recent research indicates that dopamine receptors (DRs) play a crucial role in immune and metabolic regulation. Pramipexole (PPX), a D2/3R agonist, has demonstrated promising neuroprotective and immunomodulatory effects. Nevertheless, the therapeutic effects and mechanisms of action of PPX on DM-induced depression are not clear at present. METHODS: Depression, DM, and DD were induced in a rat model through a combination of a high-fat diet (HFD) supplemented with streptozotocin (STZ) and chronic unpredictable mild stress (CUMS) combined with solitary cage rearing. The pathogenesis of DD and the neuroprotective effects of DRs agonists were investigated using behavioral assays, enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin (HE) staining, Nissl staining, Western blotting (WB) and immunofluorescence (IF). RESULTS: DD rats exhibited more severe dopaminergic, neuroinflammatory, and neuroplastic impairments and more pronounced depressive behaviors than rats with depression alone or DM. Our findings suggest that DRs agonists have significant therapeutic effects on DD rats and that PPX improved neuroplasticity and decreased neuroinflammation in the hippocampus of DD rats while also promoting DG cell growth and differentiation, ultimately mitigating depression-like behaviors. LIMITATION: Our study is based on a rat model. Further evidence is needed to determine whether the therapeutic effects of PPX apply to patients suffering from DD. CONCLUSIONS: Neuroinflammation mediated by damage to the dopaminergic system is one of the key pathogenic mechanisms of DD. We provide evidence that PPX has a neuroprotective effect on the hippocampus in DD rats and the mechanism may involve the inhibition of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation by DRs to attenuate the neuroinflammatory response and neuroplasticity damage.

RNA-Seq-Based WGCNA and Association Analysis Reveal the Key Regulatory Module and Genes Responding to Salt Stress in Wheat Roots.

Soil salinization is the main abiotic stressor faced by crops. An improved understanding of the transcriptional response to salt stress in roots, the organ directly exposed to a high salinity environment, can inform breeding strategies to enhance tolerance and increase crop yield. Here, RNA-sequencing was performed on the roots of salt-tolerant wheat breeding line CH7034 at 0, 1, 6, 24, and 48 h after NaCl treatment. Based on transcriptome data, a weighted gene co-expression network analysis (WGCNA) was constructed, and five gene co-expression modules were obtained, of which the blue module was correlated with the time course of salt stress at 1 and 48 h. Two GO terms containing 249 differentially expressed genes (DEGs) related to osmotic stress response and salt-stress response were enriched in the blue module. These DEGs were subsequently used for association analysis with a set of wheat germplasm resources, and the results showed that four genes, namely a Walls Are Thin 1-related gene (TaWAT), an aquaporin gene (TaAQP), a glutathione S-transfer gene (TaGST), and a zinc finger gene (TaZFP), were associated with the root salt-tolerance phenotype. Using the four candidate genes as hub genes, a co-expression network was constructed with another 20 DEGs with edge weights greater than 0.6. The network showed that TaWAT and TaAQP were mainly co-expressed with fifteen interacting DEGs 1 h after salt treatment, while TaGST and TaZFP were mainly co-expressed with five interacting DEGs 48 h after salt treatment. This study provides key modules and candidate genes for understanding the salt-stress response mechanism in wheat roots.

An Anti-Jamming Method against Interrupted Sampling Repeater Jamming Based on Compressed Sensing.

Interrupted sampling repeater jamming (ISRJ) is an attracted coherent jamming method to inverse synthetic aperture radar (ISAR) in the past decades. By means of different jamming parameters settings, realistic dense false targets can be formed around the true target. This paper proposed an adaptive anti-jamming method against ISRJ by adjusting the number of measurements based on compressed sensing (CS). The jamming signal is energy concentrated and segmented sparse in the frequency domain. The measurements number of the reconstructed target signal and the jamming signal is different. According to the restricted isometry property (RIP) condition of CS theory, signal reconstructing performance depends on the number of measurements that varies with the sparsity of the vector. Thus, the jamming signal is suppressed, and the true target signal is retained by altering the measurements number of echo signals. Besides, the two-dimensional (2D) anti-jamming method is derived in detail. The anti-jamming effect is analyzed with different signal-to-noise ratios (SNR), sampling rates, and jam-to-signal ratios (JSR). Simulations prove the effectiveness of the proposed anti-jamming method.

Study of the biomechanical mechanisms of benign paroxysmal positional vertigo.

From a biomechanical point of view, the process of Benign paroxysmal positional vertigo (BPPV) includes 2 fluid¯solid coupling effects: the interaction between particles and endolymph and the interaction between endolymph and cupula. The interaction between the canaliths and the wall would affect the coupling effects. This study aimed to investigate the entire process of cupula motion caused by canaliths motion and the influence of canalith particles composition. A biomechanical numerical model was established to simulate the canalith falling process and study the influence of canalith diameter, number, and initial falling position on cupula movement. Simultaneously, the relationship between cupula displacement and the nystagmus signal was analyzed in BPPV patients. The results revealed that the particle velocity was proportional to the particle diameter. The pressure difference between the two sides of the cupula was directly proportional to the canalith diameter and number. The degree of vertigo was positively related to the slow angular velocity of the nystagmus and, therefore, reflected canalith number and diameter. The BPPV latent period and vertigo duration were inversely related to particle diameter. Thus, the number of particles, particle radius, and initial falling position affected cupula movement, which was reflected in the nystagmus.

The biomechanical characteristics of human vestibular aqueduct: a numerical-based model construction and simulation.

Vestibular aqueduct is a precise structure embedded in the temporal bone and plays a key role in the physiological function of inner ear by maintaining the endolymphatic circulation and buffering the impact from intracranial pressure. Although the alterations on the morphology or volume of vestibular aqueduct result in variety of diseases, the approaches of evaluating the condition of vestibular aqueduct are still unsatisfing because the pathological sections utilized for the 3D construction model most likely undergoes morphological changes. In this study, the vestibular aqueduct images obtained by CT scanning were processed by finite element method to construct the 3D model. To assess if this numerical model reflects the actual biomechanical properties of vestibular aqueduct, the fluid-solid coupling calculation was applied to simulate the endolymphatic flow in the vestibular aqueduct. By measuring the dynamics of endolymphatic flow, and the pressure and displacement on round membrane under external pressure, we found the numerical 3D model recapitulated the biomechanical characteristics of the real vestibular aqueduct. In summary, our approach of 3D model construction for vestibular aqueduct will provide a powerful method for the research of vestibular aqueduct-related diseases.

Low extracellular lysyl oxidase expression is associated with poor prognosis in patients with prostate cancer.

Remodeling of the extracellular matrix (ECM), which is induced by lysyl oxidase (LOX), has been demonstrated to accompany tumor progression; however, the association between LOX expression levels and the malignant behavior of prostate cancer (Pca) remains unclear. The present study aimed to analyze the tumor-associated expression profile of LOX in patients with Pca and to evaluate its potential prognostic value. In the form of a retrospective study, the expression patterns of LOX and collagen I were analyzed in patients with benign prostate hyperplasia and Pca by immunohistochemical examination. The results demonstrated that, with the initiation and progression of Pca, the expression levels of LOX and collagen I were closely associated with Gleason score and tumor stage. In addition, although LOX was expressed in cancer and non-cancer tissues, the differential expression pattern observed in the ECM of Pca cells may indicate that LOX is an important molecule that affects the progression of this disease. Therefore, LOX expression level in the ECM may function as an independent predictor of Pca.

Impact of nasal septal perforations of varying sizes and locations on the warming function of the nasal cavity: A computational fluid-dynamics analysis of 5 cases.

Patients with a nasal septal perforation often exhibit symptoms associated with disturbed airflow, which can have an adverse effect on the warming function of the nasal cavity. The impact of this effect is not fully understood. The warming function is an important factor in the maintenance of nasal physiology. We conducted a study to investigate the impact of septal perforations of various sizes and locations on the warming function during inspiration in 5 patients-3 men and 2 women, aged 25 to 47 years. Three-dimensional computed tomography and computational fluid dynamics were used to model the flux of communication and temperature, and differences among patients were compared. All 5 patients exhibited an impairment of their nasal warming function. As the size of the perforation increased, the flux of communication increased and the warming function decreased. Perforations located in an anterior position were associated with greater damage to the warming function than those in a posterior position. In patients with a large or anteriorly located perforation, airflow temperature in the nasopharynx was decreased. Our findings suggest that septal perforations not only induce airflow disturbance, but they also impair the nasal warming function. Further analysis of warming function is necessary to better explore flow mechanisms in patients with structural abnormalities.

Numerical simulation of the role of the utriculo-endolymphatic valve in the rotation-sensing capabilities of semicircular canals.

The utriculo-endolymphatic valve (UEV) has an uncertain function, but its opening and closure have been predicted to maintain a constant endolymphatic pressure within the semicircular canals (SCCs) and the utricle of the inner ear. Here, the study׳s aim was to examine the role of the UEV in regulating the capabilities of the 3 SCCs in sensing angular acceleration by using the finite element method. The results of the developed model showed endolymphatic flow and cupula displacement patterns in good agreement with previous experiments. Moreover, the open valve was predicted to permit endolymph exchange between the 2 parts of the membranous labyrinth during head rotation and, in comparison to the closed valve, to result in a reinforced endolymph flow in the utricle and an enhanced or weakened cupula deflection. Further, the model predicted an increase in the size of the orifice would result in greater endolymph exchange and thereby to a greater impact on cupula deflection. The model findings suggest the UEV plays a crucial role in the preservation of inner ear sensory function.

Numerical study of the effects of bronchial structural abnormalities on respiratory flow distribution.

BACKGROUND: The anatomical configurations of respiratory tract would be directly associated with their ventilatory function. It is necessary to fully understand the association between airway configurations and their functions as well as the interactions between different airway segments. In this study, we developed a respiratory airway model to investigate the effects of bronchial structural abnormalities on flow distribution in the bronchi and upper airway. METHODS: Derived from computed tomography (CT) scanner data, three-dimensional (3D) finite element (FE) models of healthy human respiratory tracts were developed with anatomically realistic configurations, including the nasal cavity, oral cavity, pharynx, larynx, trachea, and partial bronchi. Abnormal bronchial configurations were built to correspond to four common bronchial diseases. Through numerical simulation, airway configurations of normal and abnormal bronchi were obtained, and flow patterns were compared between normal and abnormal respiratory tracts, as well as the effects of lower airway changes on flow distribution in the upper airway. RESULTS: The simulation results showed that during inspiration, abnormal bronchial structures can cause flow redistribution in each generation of bronchi and have significant effects on flow distribution in the daughter bronchi of abnormal segments, but no effect on flow distribution of the upper airway. During expiration, abnormal bronchus structures had a remarkable influence on flow distribution in the trachea, while there was no significant difference in flow distribution when airflow passed from the vocal cords and entered the laryngeal cavity. CONCLUSIONS: Therefore, abnormal bronchial structures can affect the downstream flow distribution and cause flow redistribution throughout the entire bronchial branches. During expiration, the configurations of the trachea and glottis can diminish the effects of abnormal bronchial structures on flow distribution.

[Study on the correlation between the ostia diameter changes and airflow characteristics in maxillary sinus].

OBJECTIVE: To investigate the relationship between the maxillary sinus flow field, temperature field and the maxillary sinus ostium size, and to provide a reference for endoscopic surgery according to the maxillary sinus scope. METHODS: One case of adult female CT image data was obtained, and used to build a three-dimensional model of nasal cavity and maxillary sinus. Computational fluid dynamics method was used to study the airflow and temperature of the maxillary sinus, as well as the physiological function of the maxillary sinus. Simulation surgery by means of different maxillary sinus diameters (normal, 8 mm, 10 mm, 12 mm and 15 mm) was used to describe the maxillary sinus airflow and temperature change. RESULTS: It was found that by numerical simulation the airflow of maxillary sinus and nasal cavity showed lower speed (average speed 0.062 m/s) than that in the middle nasal meatus (average speed of 3.260 m/s), and the average temperature in the normal maxillary sinus was 34°C, which was higher than that in the middle nasal meatus (temperature 28.7°C). With the increase of the diameter of the maxillary sinus, the air temperature change was not obvious. CONCLUSIONS: The physiological function of the maxillary sinus can be studied through the numerical simulation. With the increase of the ostia diameter of maxillary sinus, the sinus temperature and ventilation is not affected. It provides a reference for quantification of clinical endoscopic maxillary sinus surgery.

Population data for 15 autosomal STR loci in the Miao ethnic minority from Guizhou Province, Southwest China.

Fifteen autosomal short tandem repeat (STR) loci were genotyped using the AmpFISTR Identifiler PCR Amplification kit from 505 unrelated healthy individuals of Miao ethnic minority living in the Guizhou Province, Southwest China. Also, the genetic distance between Miao and nine related populations was compared.

Numerical analysis of the relationship between nasal structure and its function.

The functions of the nasal cavity are closely related to its structure. In this study the three-dimensional finite element models were established based on the clinical data of twenty-four volunteers to study the influence of nasal structure on nasal functions of heating the inhaled airflow. Numerical simulations mainly concerning the airflow distribution and the airflow temperature are performed. The character of airflow heating process in these models is gained from the simulation results of these nasal cavities. The parameters describing the geometry of nasal cavity, such as the surface area of nasal airway and the volume of nasal cavity, are considered to be related to the nasal function of heating the inhaled airflow. The approximate function describing the relationship between the geometric parameters of the nasal airway and the nasal functions is gotten. This study can provide a numerical platform for studying some clinical problems and will contribute to the further research on the relationship between nasal structure and nasal functions.

Alterations in mechanical properties are associated with prostate cancer progression.

Cancer progression and metastasis have been shown to be accompanied by alterations in the mechanical properties of tissues, but the relationship between the mechanical properties and malignant behavior in prostate cancer (Pca) is less clear. The aims of this study were to detect the mechanical properties of benign prostatic hyperplasia (BPH) and Pca tissues on both the macro- and micro-scales, to explore the relationships between mechanical properties and malignant behavior and, finally, to identify the important molecules in the mechanotransduction signaling pathway. We demonstrated that the strain index of Pca tissue was significantly higher than that of BPH tissue on the macro-scale but the Young's modulus of the Pca tissues, especially in advanced Pca, was lower than that of BPH tissues on the micro-scale. These two seemingly contradictory results can be explained by the excessive proliferation of tumor cells (Ki-67) and the degradation of scaffold proteins (collagens). These data indicate that alterations of the macro- and micro-mechanical properties of Pca tissues with malignant behavior are contradictory. The mechanical properties of tissues might be useful as a new risk factor for malignancy and metastasis in Pca. Furthermore, collagens, matrix metalloproteinase, fibronectin, and integrins might be the important molecules in the mechanotransduction signaling pathway.

A biomechanical model of the inner ear: numerical simulation of the caloric test.

Whether two vertical semicircular canals can receive thermal stimuli remains controversial. This study examined the caloric response in the three semicircular canals to the clinical hot caloric test using the finite element method. The results of the developed model showed the horizontal canal (HC) cupula maximally deflected to the utricle side by approximately 3 µm during the hot supine test. The anterior canal cupula began to receive the caloric stimuli about 20 s after the HC cupula, and it maximally deflected to the canal side by 0.55 µm. The posterior canal cupula did not receive caloric stimuli until approximately 40 s after the HC cupula, and it maximally deflected to the canal side by 0.34 µm. Although the endolymph flow and the cupular deformation change with respect to the head position during the test, the supine test ensures the maximal caloric response in the HC, but no substantial improvement for the responses of the two vertical canals was observed. In conclusion, while the usual supine test is the optimum test for evaluating the functions of the inner ear, more irrigation time is needed in order to effectively clinically examine the vertical canals.

Impact of airflow communication between nasal cavities on nasal ventilation.

OBJECTIVE: To investigate the impact of airflow communication between bilateral nostril sides on nasal ventilation. In addition, we try to validate the efficacy of the Draf III procedure from the aerodynamics perspective. METHODS: One health model and two disease models were constructed. These included 2 patients with nasal septum perforation and 1 patient who received the Draf III procedure. With the computational fluid dynamics method, indices such as airflow velocity and wall shear stress in the nasal cavity were detected and compared among the 3 subjects. RESULTS: The main pathway for airflow in the nasal cavity is the common meatus. Little airflow exchange occurred in the patient who underwent the Draf III procedure, and the wall shear stress around the communication site was as low as in the adjacent areas. However, when airflow communication occurred in the lower part of the nasal cavity, the airflow velocity and wall shear stress were obviously altered, and the ventilation function of the nasal cavity was impaired. CONCLUSION: Airflow communication in the upper part of the nasal cavity has little impact on nasal ventilation. Nonetheless, airflow communication occurring in the lower part of the nasal cavity disturbs the overall airflow distribution and a repair procedure is necessary.

Differentiated markers in undifferentiated cells: expression of smooth muscle contractile proteins in multipotent bone marrow mesenchymal stem cells.

In studying the differentiation of stem cells along smooth muscle lineage, smooth muscle cell (SMC) contractile proteins serve as markers for the relative state of maturation. Yet, recent evidence suggests that some SMC markers are probably expressed in multipotent mesenchymal stem cells (MSCs). Such a paradox necessitates investigations to re-examine their role as differentiated markers in MSCs. We tried to detect the expression of four widely used SMC markers including α-smooth muscle actin (α-SMA), h1-calponin, desmin and smooth muscle myosin heavy chain (SM-MHC), as well as the other isoforms of calponin family in resting MSCs. Then we used three different conditions to initiate MSCs differentiation along SMC lineage, and examined the alternation of SMC markers expression at both the transcript level and protein level. Desmin and h1-calponin are expressed in MSCs, in the presence or absence of SMC induction conditions. Moreover, MSCs are shown to express all known isoforms of calponin. Double-staining reveals that h1-calponin +/α-SMA - cells constitute the majority of resting MSCs. Under differentiated conditions, expression of SM-MHC was initiated and expression of α-SMA was promoted. The expression of SM-MHC and upregulation of α-SMA are relatively reliable indications of a mature smooth muscle phenotype in MSCs. Given that the cells are particularly rich in calponins expression, we postulate possible roles of these proteins in regulating cellular function by taking part in actin cytoskeleton and signaling. These findings imply that an extensive study of the cell physiology of MSCs should focus on the functional roles for these proteins, rather than simply regard them as differentiated markers.

[Nasal cavity computer fluid dynamics analysis on 60 healthy Chinese adults].

OBJECTIVES: To investigate the aerodynamics characteristics of nasal cavity in inspiration phase from 60 healthy Chinese people and provide the reference values for future computational fluid dynamics (CFD) research. METHODS: CFD was used for numerical simulation. The indices of main airflow passage, total nasal airway resistance, maximal velocity, maximal wall shear stress, nasal mucosa area, nasal volume and surface area-to-volume ratio were extracted from CFD analysis results. SPSS 16.0 software was used to analyze the data. RESULTS: The main airflow passage in nasal cavity was common meatus, the mean total nasal airway resistance was (0.211 ± 0.085) kPa·s·L(-1), the mean maximal velocity was (12.01 ± 2.79) m/s, the mean maximal wall shear stress was (2.50 ± 0.89) Pa, the mean nasal mucosa area was (161.2 ± 34.7) mm(2), the mean nasal volume was (31.7 ± 8.1) ml and the mean surface area-to-volume ratio was (0.58 ± 0.09) mm(-1). No significant difference was detected in aerodynamics indices between male and female people. CONCLUSIONS: The main airflow passage is located in common meatus. The nasal valve area is the key constrictive plane in nasal cavity. There are no gender differences of main airflow characteristics in nasal cavity. The normal ranges of aerodynamics indices could be used for reference values for future CFD research.

Aerodynamic investigation of the correlation between nasal septal deviation and chronic rhinosinusitis.

OBJECTIVES/HYPOTHESIS: To compare the aerodynamic differences around ostiomeatal complex between the convex side and concave side in patients with concurrent nasal septal deviation and chronic rhinosinusitis, and to explore the potential correlation between nasal septal deviation and chronic rhinosinusitis occurrence from the perspective aerodynamics. STUDY DESIGN: Retrospective case series. METHODS: Fifty-six patients with concurrent nasal septal deviation and chronic rhinosinusitis were recruited. Nasal septal deviation was divided into mild, moderate, and severe deviations according to deviation angle. Using computational fluid dynamics, indices such as maximal velocity, maximal turbulence kinetic energy, maximal wall shear stress, and minimal temperature around the ostiomeatal complex were calculated and compared between the convex side and concave side, and among patients with varying severities of deflection. RESULTS: The proportion for mild, moderate, and severe deviations was 12.5%, 32.1%, and 55.4%, respectively. Significant differences for maximal velocity, maximal wall shear stress, maximal turbulence kinetic energy, and minimal temperature around the ostiomeatal complex between the convex side and concave side could be detected. No significant difference of aerodynamic characteristics around the osteomeatal complex could be detected with the increasing of deviation angles. The incidence for chronic rhinosinusitis in convex, concave, and bilateral sides was 16.1%, 25%, and 58.9%, respectively. CONCLUSIONS: From the aerodynamics perspective, both sides of nasal cavity have the potential to predispose the occurrence of chronic rhinosinusitis in patients with nasal septal deviation. The increased deviation angle did not aggravate aerodynamic disturbance around the osteomeatal complex. The contributing role of nasal septal deviation in the pathogenesis of chronic rhinosinusitis should not be emphasized in excess.

Airflow and temperature distribution inside the maxillary sinus: a computational fluid dynamics simulation.

CONCLUSION: The airflow velocity and flux in maxillary sinuses were much lower than those in the nasal cavity, and the temperature in maxillary sinuses was much higher than the temperature in the middle meatus. With the increase of maximum diameter of the ostium, the above indices changed little. OBJECTIVES: The purpose of the paper was to investigate, first, the flow and temperature distribution inside normal maxillary sinus in inspiration, and second, flow and temperature alteration with the increase of maximum ostium diameter. METHODS: Three-dimensional models with nasal cavities and bilateral maxillary sinuses were constructed for computational fluid dynamics analysis. Virtual surgeries were implemented for the maxillary ostium, the maximum diameters of which were 8, 10, 12, and 15 mm, respectively. The finite volume method was used for numerical simulation. The indices of velocity, pressure, vector, and temperature were processed and compared between models. RESULTS: The airflow velocity in maxillary sinuses (average velocity 0.062 m/s) was much lower than that in the middle meatus (average velocity 3.26 m/s). With the increase of ostium diameter, airflow characteristics distributed in the maxillary sinuses changed little. The normal temperature in the maxillary sinus remained almost constant at 34°C and changed little with the increase of ostium diameter.

Fluid-structure interaction modeling of upper airways before and after nasal surgery for obstructive sleep apnea.

Nasal obstruction frequently has been associated with obstructive sleep apnea (OSA). Although correction of an obstructed nasal airway is considered an important component in OSA treatment, the effect of nasal surgery on OSA remains controversial. Variation in airway anatomy between before and after nasal surgery may cause significant differences in airflow patterns within the upper airway. In this paper, anatomically accurate models of the interaction between upper airway and soft palate were developed from prenasal and post-nasal surgery multidetector computed tomography data of a patient with OSA and nasal obstruction. Computational modeling for inspiration and expiration was performed by using fluid-structure interaction method. The airflow characteristics such as velocity, turbulence intensity and pressure drop, and displacement distribution of soft palate are selected for comparison. Airway resistances significantly decrease after the nasal surgery, especially in the velopharynx region because of an enlarged pharyngeal cavity and a reduced upstream resistance. Meanwhile, the decreased aerodynamic force would result in a smaller displacement of soft palates, which would lead to slight impact of the soft palate motion on the airflow characteristics. The present results suggest that airflow distribution in the whole upper airway and soft palate motions have improved following nasal surgery.