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BackgroundUrinary incontinence (UI) might be linked to suicidal ideation, but we do not yet have all the relevant details. This study aimed to dig deeper into the connection between UI and suicidal ideation using data from the National Health and Nutrition Examination Survey (NHANES).MethodsWe examined 31,891 participants aged ≥ 20 years from NHANES 2005-2018 who provided complete information. We used standardized surveys to check for UI and signs of suicidal ideation. To better understand this relationship, we used statistical tools such as multivariable logistic regression, subgroup analysis, and sensitivity analyses.ResultsAmong the 31,891 participants, 28.9% reported UI and 10.7% reported suicidal ideation. Those with UI exhibited a significantly greater incidence of suicidal ideation (15.5%) than did those without UI (8.8%, P < 0.001). After adjusting for various factors, including age, sex, marital status, socioeconomic status, educational level, lifestyle factors, and chronic comorbidities, UI remained significantly associated with suicidal ideation (OR:1.54, 95% CI = 1.39-1.7, P < 0.001). Among all types of UI, MUI participants were more likely to experience suicidal ideation. Compared with no UI, higher odds of suicidal ideation suffered from MUI (OR:2.11, 95%CI:1.83-2.44, P < 0.001), SUI (OR:1.4, 95%CI:1.19-1.65, P < 0.001), UUI(OR:1.37,95%CI:1.16-1.62, P < 0.001) after full adjustment. With the exception of individuals living with a partner, the remaining subgroups exhibited a positive correlation between urinary incontinence and suicidal ideation, considering that factors such as age, sex, and prevalent comorbidities such as hypertension, depression, and diabetes did not reveal any statistically significant interactions (all P > 0.05). Sensitivity analyses, incorporating imputed missing covariates, did not substantially alter the results (OR: 1.53, 95% CI: 1.4-1.68, P < 0.001).ConclusionUrinary incontinence may correlate with increased suicidal ideation risk, priority screening for suicidal ideation and timely intervention are essential for individuals with urinary incontinence, but prospective studies are needed to verify the results.

BackgroundRecent studies have shown that obesity may contribute to the pathogenesis of benign prostatic hyperplasia (BPH). However, the mechanism of this pathogenesis is not fully understood.MethodsA prospective case-control study was conducted with 30 obese and 30 nonobese patients with BPH. Prostate tissues were collected and analyzed using ultra performance liquid chromatography ion mobility coupled with quadrupole time-of-flight mass spectrometry (UPLC-IMS-Q-TOF).ResultsA total of 17 differential metabolites (3 upregulated and 14 downregulated) were identified between the obese and nonobese patients with BPH. Topological pathway analysis indicated that glycerophospholipid (GP) metabolism was the most important metabolic pathway involved in BPH pathogenesis. Seven metabolites were enriched in the GP metabolic pathway. lysoPC (P16:0/0:0), PE (20:0/20:0), PE (24:1(15Z)/18:0), PC (24:1(15Z)/14:0), PC (15:0/24:0), PE (24:0/18:0), and PC (16:0/18:3(9Z,12Z,15Z)) were all significantly downregulated in the obesity group, and the area under the curve (AUC) of LysoPC (P-16:0/0/0:0) was 0.9922. The inclusion of the seven differential metabolites in a joint prediction model had an AUC of 0.9956. Thus, both LysoPC (P-16:0/0/0:0) alone and the joint prediction model demonstrated good predictive ability for obesity-induced BPH mechanisms.ConclusionsIn conclusion, obese patients with BPH had a unique metabolic profile, and alterations in PE and PC in these patients be associated with the development and progression of BPH.

Underground reservoir technology for coal mines can realize the coordinated development of coal exploitation and water protection in water-shortage-prone areas. The seepage effect of the floor seriously affects the safety of underground reservoirs under the action of mining damage and seepage pressure. Focusing on the problem of floor seepage in underground reservoirs, a spatial mechanical model of underground reservoirs was established. The main factors affecting the seepage of the surrounding rock were studied. The seepage pressure law in different stages of spatial structure evolution of overlying strata was explored. The results showed that pressure change was the main factor affecting the stability of a reservoir's surrounding rock. The pore space between the broken and fractured rock in the water-flowing fractured zone was the main water storage space, which was directly related to the development of a breaking arch. According to the spatial structure evolution process of the overlying strata, the water storage state of an underground reservoir was divided into two stages and three situations. The seepage pressure was mainly affected by the water pressure and the overlying strata weight. The water pressure was affected by the reservoir head height, and the overlying strata weight was mainly affected by the overlying strata thickness.

Spatio-temporal evolution laws of storage coefficient and contact network of crushed rock are of great significance for the construction and utilization of underground reservoirs in coal mines. Based on discrete element method and irregular rigid block model, spatio-temporal evolution laws of storage coefficient and contact network of crushed rock under different overburden stresses are investigated and the following main conclusions are obtained: (1) The average storage coefficient and the storage coefficient at different vertical heights of the crushed rock packing system decrease exponentially as the overburden stress increases. When the overburden stress ranges from 0 to 20 MPa, the average storage coefficient decreases by 48.947%. (2) The average void radius and throat radius of water storage space decrease exponentially as the overburden stress increases. The increase in overburden stress leads to the transformation of large voids into smaller voids, causing a gradual decrease in void connectivity and a tendency towards irregular void shapes. (3) With the increase of overburden stress, the number of strong contacts in the packing system of crushed rock increases and gradually expands from the top to the bottom. The average contact force of crushed rock increases exponentially, while the coordination number increases linearly. (4) As the overburden stress increases, the majority of contact directions are concentrated within the ±30° range in the loading direction. This increase results in an enhancement of the anisotropy of the packing system structure of crushed rock.

BackgroundNitrous oxide (N2O) with rapid analgesic effect is often used to relieve pain induced by diagnostic procedures. This review was conducted to evaluate the efficacy and safety of N2O in patients undergoing puncture biopsy.MethodsWe systematically searched PubMed, Embase, the Cochrane Library, Web of Science, Scopus and the ClinicalTrials.gov up to March, 2022. Randomized controlled trials (RCTs) were included if they investigated the effect of N2O in adults undergoing puncture biopsy. The primary outcome was pain score. Secondary outcomes included anxiety score, patient satisfaction and side effects.ResultsTwelve RCTs with 1070 patients were included in the qualitative review, of which eleven RCTs were included in the meta-analysis. Pooled analysis suggested that compared with the controls (placebo, lidocaine and midazolam), N2O had better analgesic effect (MD -1.12, 95% CI -2.12 to -0.13, P = 0.03; I2 = 94%). In addition, N2O significantly alleviated patient anxiety (MD = -1.79, 95% CI -2.41 to -1.18, PConclusionThe present review suggested that N2O might be effective for pain management in patients undergoing puncture biopsy.

The pathophysiology underlying olfactory dysfunction is still poorly understood, and more efficient biomolecular tools are necessary to explore this aspect. Immunohistochemistry (IHC) on cross sections is one of the major tools to study the olfactory epithelium (OE), but does not allow reliable counting of olfactory sensory neurons (OSNs) or cartography of the OE. In this study, we want to present an easy immunostaining technique to compensate for these defects of IHC. Using the rat model, we first validated and pre-screened the key OSN markers by IHC on cross sections of the OE. Tuj-1, OMP, DCX, PGP9.5, and N-cadherin were selected for immunostaining on flat-mounted OE because of their staining of OSN dendrites. A simple technique for immunostaining on flat-mounted septal OE was developed: fixation of the isolated septum mucosa in 0.5% paraformaldehyde (PFA) preceded by pretreatment of the rat head in 1% PFA for 1 hour. This technique allowed us to correctly reveal the olfactory areas using all the 5 selected markers on septum mucosa. By combining the mature OSN marker (OMP) and an immature OSN marker (Tuj-1), we quantified the mature (OMP+, Tuj-1-), immature (OMP-, Tuj-1+), transitory (OMP+, Tuj-1+) and total OSN density on septal OE. They were respectively 42080 ± 11820, 49384 ± 7134, 14448 ± 5865 and 105912 ± 13899 cells per mm2 (mean ± SD). Finally, the same immunostaining technique described above was performed with Tuj-1 for OE cartography on ethmoid turbinates without flat-mount.

Background: Recent studies have shown that obesity may contribute to the pathogenesis of benign prostatic hyperplasia (BPH). However, the mechanism of this pathogenesis is not fully understood. Methods: A prospective case–control study was conducted with 30 obese and 30 nonobese patients with BPH. Prostate tissues were collected and analyzed using ultra performance liquid chromatography ion mobility coupled with quadrupole time-of-flight mass spectrometry (UPLC-IMS-Q-TOF). Results: A total of 17 differential metabolites (3 upregulated and 14 downregulated) were identified between the obese and nonobese patients with BPH. Topological pathway analysis indicated that glycerophospholipid (GP) metabolism was the most important metabolic pathway involved in BPH pathogenesis. Seven metabolites were enriched in the GP metabolic pathway. lysoPC (P16:0/0:0), PE (20:0/20:0), PE (24:1(15Z)/18:0), PC (24:1(15Z)/14:0), PC (15:0/24:0), PE (24:0/18:0), and PC (16:0/18:3(9Z,12Z,15Z)) were all significantly downregulated in the obesity group, and the area under the curve (AUC) of LysoPC (P-16:0/0/0:0) was 0.9922. The inclusion of the seven differential metabolites in a joint prediction model had an AUC of 0.9956. Thus, both LysoPC (P-16:0/0/0:0) alone and the joint prediction model demonstrated good predictive ability for obesity-induced BPH mechanisms. Conclusions: In conclusion, obese patients with BPH had a unique metabolic profile, and alterations in PE and PC in these patients be associated with the development and progression of BPH. [ABSTRACT FROM AUTHOR]

Osteoclasts are the only multinucleated cells in vivo responsible for bone resorption and are vital for regulating bone remodeling and maintaining bone mass. The RAW264.7 cell line is widely used to study osteoclastic differentiation and biological molecular mechanism. However, protocols for inducing osteoclast formation in RAW264.7 cells vary considerably between laboratories, hindering the replication of results. Therefore, we tested the influence of culture conditions on osteoclast differentiation, including cell density and receptor activator of nuclear factor kappa-B ligand (RANKL) concentrations with or without macrophage colony-stimulating factors (M-CSF). Tartrate-resistant acid phosphatase (TRAP) staining was used to detect the morphology of osteoclasts. qPCR was used to detect gene expression of osteoclast-specific gene marker cathepsin K (CTSK), osteoclast transcription factors c-Fos and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1). The bone resorption function was evaluated by a scanning electron microscope (SEM). RANKL treatment increased multinucleated osteoclasts formation and increased CTSK, c-Fos and NFATc1 gene expression. Compared with RANKL treatment, M-CSF significantly decreased multinucleated osteoclasts formation, reduced CTSK gene expression and had little effect on c-Fos and NFATc1 gene expression. Concerning bone resorption activity, RANKL treatment increased bone resorption pits on bovine bone slices. Significantly higher levels of osteoclastogenesis were observed with RAW264.7-cell density of 2×104 cells/well in 24-well plates. Our results suggest that the addition of 50 ng/ml M-CSF has no positive effect on osteoclastogenesis. RANKL treatment and cell density contribute to osteoclast formation, and the optimal conditions are beneficial when exploring osteoclast function and mechanism.

BackgroundStudies suggested that the association between depression and diabetic nephropathy may be bi-directional, but this hypothesis remains investigating. In this meta-analysis, the bi-directional relationship between depression and diabetic nephropathy was investigated.MethodsA search for the publications on depression and diabetic nephropathy in the databases of PubMed, Web of science, and Embase from the earliest available to August 2022 was conducted. Two sets of pooled risk estimates were calculated using random effects models: diabetic nephropathy predicting depression and depression predicting diabetic nephropathy. Cross-sectional studies were assessed using Agency for Healthcare Research and Quality (AHRQ), cohort and case-control studies were assessed using Newcastle-Ottawa Scale (NOS).ResultOf the 974,121 patients in 30 clinical studies, 24 studies met eligibility for diabetic nephropathy predicting onset of depression, representing 28,438 incident cases. The other 6 studies met criteria for depression predicting onset of diabetic nephropathy, representing 945,683 incident cases. The pooled odds ratio (OR) of diabetic nephropathy predicting depression was 1.46 (95% CI 1.27-1.67). The OR of depression predicting diabetic nephropathy was 1.22 (95% CI 1.13-1.31).ConclusionThis meta-analysis shows that the relationship between depression and diabetic nephropathy may be bidirectional. Diabetic nephropathy may be a predictor of depression, and depression may also be an indicator of diabetic nephropathy. The mechanisms underlying the bidirectional relationship need to be further investigated and interventions of the comorbidity of depression and diabetic nephropathy need be studied in clinical practice.

Keratoconus (KC) is a multifactorial progressive ectatic disorder characterized by local thinning of the cornea, leading to decreased visual acuity due to irregular astigmatism and opacities. Despite the evolution of advanced imaging methods, the exact etiology of KC remains unknown. Our aim was to investigate the involvement of corneal epithelium in the pathophysiology of the disease. Corneal epithelial samples were collected from 23 controls and from 2 cohorts of patients with KC: 22 undergoing corneal crosslinking (early KC) and 6 patients before penetrating keratoplasty (advanced KC). The expression of genes involved in the epidermal terminal differentiation program and of the oxidative stress pathway was assessed by real time PCR analysis. Presence of some of the differentially expressed transcripts was confirmed at protein level using immunofluorescence on controls and advanced KC additional corneal samples. We found statistically significant under-expression in early KC samples of some genes known to be involved in the mechanical resistance of the epidermis (KRT16, KRT14, SPRR1A, SPRR2A, SPRR3, TGM1 and TGM5) and in oxidative stress pathways (NRF2, HMOX1 and HMOX2), as compared to controls. In advanced KC samples, expression of SPRR2A and HMOX1 was reduced. Decreased expression of keratin (KRT)16 and KRT14 proteins was observed. Moreover, differential localization was noted for involucrin, another protein involved in the epidermis mechanical properties. Finally, we observed an immunofluorescence staining for the active form of NRF2 in control epithelia that was reduced in KC epithelia. These results suggest a defect in the mechanical resistance and the oxidative stress defense possibly mediated via the NRF2 pathway in the corneal keratoconic epithelium.

To better understand the effect of the size of hole defects on the mechanical properties of a rock mass, the two-dimensional particle flow discrete element code (PFC2D) is applied to establish rock mass models with single circular hole defects of different diameters. Uniaxial compressive strength (UCS) tests are conducted on each model by only taking the defect size (area) as a variable. This study analyzes each model's stress-strain, contact force chain, crack evolution, meso-damage and failure, and mechanical properties. The results showed that with the size enlargement of the circular hole defects, each model's UCS and elastic modulus gradually decrease, and the defect size is negatively correlated with the mechanical strength of the rock samples. The size of the hole defects affects the entire process of contact force chain and crack evolution. The larger the aperture dimension of the circular hole defects in each model, the greater the concentration degree of the contact force chain, the earlier the crack initiation, and the higher the degree of crack coalescence in the post-peak stage. The number of cracks decreases as the hole size increases, and the model is more prone to failure. Rock models' strength and failure characteristics with different numbers and arrangements of hole defects are discussed under the same defect area condition.

Insects change their stimulus-response through the perception of associating these stimuli with important survival events such as rewards, threats, and mates. Insects develop strong associations and relate them to their experiences through several behavioral procedures. Among the insects, Apis species, Apis mellifera ligustica are known for their outstanding ability to learn with tremendous economic importance. Apis mellifera ligustica has a strong cognitive ability and promising model species for investigating the neurobiological basis of remarkable olfactory learning abilities. Here we evaluated the olfactory learning ability of A. mellifera by using the proboscis extension reflex (PER) protocol. The brains of the learner and failed-learner bees were examined for comparative transcriptome analysis by RNA-Seq to explain the difference in the learning capacity. In this study, we used an appetitive olfactory learning paradigm in the same age of A. mellifera bees to examine the differential gene expression in the brain of the learner and failed-learner. Bees that respond in 2nd and 3rd trials or only responded to 3rd trials were defined as learned bees, failed-learner individuals were those bees that did not respond in all learning trials The results indicate that the learning ability of learner bees was significantly higher than failed-learner bees for 12 days. We obtained approximately 46.7 and 46.4 million clean reads from the learner bees failed-learner bees, respectively. Gene expression profile between learners’ bees and failed-learners bees identified 74 differentially expressed genes, 57 genes up-regulated in the brains of learners and 17 genes were down-regulated in the brains of the bees that fail to learn. The qRT-PCR validated the differently expressed genes. Transcriptome analyses revealed that specific genes in learner and failed-learner bees either down-regulated or up-regulated play a crucial role in brain development and learning behavior. Our finding suggests that down-regulated genes of the brain involved in the integumentary system, storage proteins, brain development, sensory processing, and neurodegenerative disorder may result in reduced olfactory discrimination and olfactory sensitivity in failed-learner bees. This study aims to contribute to a better understanding of the olfactory learning behavior and gene expression information, which opens the door for understanding of the molecular mechanism of olfactory learning behavior in honeybees.

Astragali Radix (Huangqi) is an important herb medicine that is always processed into pieces for clinical use. Many operations need to be performed before use, among which drying of Astragali Radix (AR) pieces is a key step. Unfortunately, research on its drying mechanism is still limited. Low-field nuclear magnetic resonance (LF-NMR) and magnetic resonance imaging (MRI) techniques were applied to study the moisture state and distribution during drying. The content of bioactive components and texture changes were measured by HPLC and texture analyzer, respectively. The moisture content of the AR pieces decreased significantly during drying, and the time to reach the drying equilibrium were different at different temperatures. The time when at 70°C, 80°C, and 90°C reach complete drying are 180 min, 150 min and 120 min, respectively. 80°C was determined as the optimum drying temperature, and it was observed that the four flavonoids and astragaloside IV have some thermal stability in AR pieces. When dried at 80°C, although the total water content decreased, the free water content decreased from 99.38% to 15.49%, in contrast to the increase in bound water content from 0.62% to 84.51%. The texture parameters such as hardness changed to some extent, with the hardness rising most significantly from 686.23 g to 2656.67 g. Correlation analysis revealed some connection between moisture content and LF-NMR and texture analyzer parameters, but the springiness did not show a clear correlation with most parameters. This study shows that HPLC, LF-NMR, MRI, and texture analyzers provide a scientific basis for elucidating the drying principles of AR pieces. The method is useful and shows potential for extension and application; therefore, it can be easily extended to other natural herb medicines.

Donkey-hide gelatin is an important traditional Chinese medicine made from donkey skin. Despite decades of effort, identifying the animal materials (donkeys, horses, cattle and pigs) in donkey-hide gelatin remains challenging. In our study, we aimed to identify marker peptides of donkey-hide gelatin and its adulterants and develop a liquid chromatography-tandem mass spectrometry method to identify them. Theoretical marker peptides of four animals (donkeys, horses, cattle and pigs) were predicted and verified by proteomic experiments, and 12 species-specific marker peptides from donkey-hide gelatin and its adulterants were identified. One marker peptide for each gelatin was selected to develop the liquid chromatography-tandem mass spectrometry method. The applicability of the method was evaluated by investigating homemade mixed gelatin samples and commercial donkey-hide gelatin products. Using the liquid chromatography-tandem mass spectrometry method, the addition of cattle-hide gelatin and pig-hide gelatin to donkey-hide gelatin could be detected at a level of 0.1%. Horse-hide gelatin was detected when added at a level of 0.5%. Among 18 batches of donkey-hide gelatin products, nine were identified as authentic, and eight of the remaining samples were suspected to be adulterated with horse materials. These results provide both a practical method to control the quality of donkey-hide gelatin and a good reference for quality evaluations of other medicinal materials and foods containing protein components.

Regional cortical thickness alterations have been reported in many chronic inflammatory and painful conditions, including inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS), even though the mechanisms underlying such neuroplastic changes remain poorly understood. In order to better understand the mechanisms contributing to grey matter changes, the current study sought to identify the differences in regional alterations in cortical thickness between healthy controls and two chronic visceral pain syndromes, with and without chronic gut inflammation. 41 healthy controls, 11 IBS subjects with diarrhea, and 16 subjects with ulcerative colitis (UC) underwent high-resolution T1-weighted magnetization-prepared rapid acquisition gradient echo scans. Structural image preprocessing and cortical thickness analysis within the region of interests were performed by using the Laboratory of Neuroimaging Pipeline. Group differences were determined using the general linear model and linear contrast analysis. The two disease groups differed significantly in several cortical regions. UC subjects showed greater cortical thickness in anterior cingulate cortical subregions, and in primary somatosensory cortex compared with both IBS and healthy subjects. Compared with healthy subjects, UC subjects showed lower cortical thickness in orbitofrontal cortex and in mid and posterior insula, while IBS subjects showed lower cortical thickness in the anterior insula. Large effects of correlations between symptom duration and thickness in the orbitofrontal cortex and postcentral gyrus were only observed in UC subjects. The findings suggest that the mechanisms underlying the observed gray matter changes in UC subjects represent a consequence of peripheral inflammation, while in IBS subjects central mechanisms may play a primary role.

Underground reservoir technology for coal mines can realize the coordinated development of coal exploitation and water protection in water-shortage-prone areas. The seepage effect of the floor seriously affects the safety of underground reservoirs under the action of mining damage and seepage pressure. Focusing on the problem of floor seepage in underground reservoirs, a spatial mechanical model of underground reservoirs was established. The main factors affecting the seepage of the surrounding rock were studied. The seepage pressure law in different stages of spatial structure evolution of overlying strata was explored. The results showed that pressure change was the main factor affecting the stability of a reservoir's surrounding rock. The pore space between the broken and fractured rock in the water-flowing fractured zone was the main water storage space, which was directly related to the development of a breaking arch. According to the spatial structure evolution process of the overlying strata, the water storage state of an underground reservoir was divided into two stages and three situations. The seepage pressure was mainly affected by the water pressure and the overlying strata weight. The water pressure was affected by the reservoir head height, and the overlying strata weight was mainly affected by the overlying strata thickness. [ABSTRACT FROM AUTHOR]

Background & aimsRegional reductions in gray matter (GM) have been reported in several chronic somatic and visceral pain conditions, including irritable bowel syndrome (IBS) and chronic pancreatitis. Reported GM reductions include insular and anterior cingulate cortices, even though subregions are generally not specified. The majority of published studies suffer from limited sample size, heterogeneity of populations, and lack of analyses for sex differences. We aimed to characterize regional changes in cortical thickness (CT) in a large number of well phenotyped IBS patients, taking into account the role of sex related differences.MethodsCortical GM thickness was determined in 266 subjects (90 IBS [70 predominantly premenopausal female] and 176 healthy controls (HC) [155 predominantly premenopausal female]) using the Laboratory of Neuro Imaging (LONI) Pipeline. A combined region of interest (ROI) and whole brain approach was used to detect any sub-regional and vertex-level differences after removing effects of age and total GM volume. Correlation analyses were performed on behavioral data.ResultsWhile IBS as a group did not show significant differences in CT compared to HCs, sex related differences were observed both within the IBS and the HC groups. When female IBS patients were compared to female HCs, whole brain analysis showed significant CT increase in somatosensory and primary motor cortex, as well as CT decrease in bilateral subgenual anterior cingulate cortex (sgACC). The ROI analysis showed significant regional CT decrease in bilateral subregions of insular cortex, while CT decrease in cingulate was limited to left sgACC, accounting for the effect of age and GM volume. Several measures of IBS symptom severity showed significant correlation with CT changes in female IBS patients.ConclusionsSignificant, sex related differences in CT are present in both HCs and in IBS patients. The biphasic neuroplastic changes in female IBS patients are related to symptom severity.

Schizonepetae Spica (SS), the dried spike of Schizonepeta tenuifolia Briq., is a traditional Chinese medicinal herb. According to the color of persistent calyx, SS is categorized into two classes: the yellowish-green-type and the brownish-type. Based on the chemometrics analysis of gas chromatography-mass spectrometry (GC-MS), a novel model of identifying and evaluating the quality of SS in different colors was constructed for the first time in this work. 20 batches SS samples of different colors were collected and used to extract essential oils. The average essential oils yield of SS in yellowish-green color was significantly higher than that of SS in brownish color from the same origin (p

The outbreak of SARS-CoV-2 began in December 2019 and rapidly became a pandemic. The present study investigated the significance of lymphopenia on disease severity. A total of 115 patients with confirmed COVID-19 from a tertiary hospital in Changsha, China, were enrolled. Clinical, laboratory, treatment and outcome data were gathered and compared between patients with and without lymphopenia. The median age was 42 years (1-75). Fifty-four patients (47.0%) of the 115 patients had lymphopenia on admission. More patients in the lymphopenia group had hypertension (30.8% vs. 10.0%, P = 0.006) and coronary heart disease (3.6% vs. 0%, P = 0.029) than in the nonlymphopenia group, and more patients with leukopenia (48.1% vs 14.8%, P

BackgroundHerpetic keratitis (HK) models using whole human corneas are essential for studying virus-host relationships, because of high species specificity and the role of interactions between corneal cell populations that cell culture cannot reproduce. Nevertheless, the two current corneal storage methods (hypothermia and organ culture (OC)) do not preserve corneas in good physiological condition, as they are characterized by epithelial abrasion, stromal oedema, and excessive endothelial mortality.MethodsTo rehabilitate human corneas intended for scientific use, we used an active storage machine (ASM) that restores two physiological parameters that are essential for corneal homeostasis: intraocular pressure and storage medium renewal (21mmHg and 2.6 μL/min, respectively). ASM storage regenerates a normal multilayer epithelium in 2 weeks. We infected six pairs of corneas unsuitable for graft by inoculating the epithelium with herpes simplex virus type 1 (HSV-1), and compared each ASM-stored cornea with the other cornea stored in the same medium using the conventional OC method.ResultsOnly corneas in the ASM developed a dendritic (n = 3) or geographic (n = 2) epithelial ulcer reproducing typical HSV-1-induced clinical lesions. Corneas in OC showed only extensive desquamations. None of the uninfected controls showed epithelial damage. Histology, immunohistochemistry, transmission electron microscopy and polymerase chain reaction on corneal tissue confirmed infection in all cases (excluding negative controls).ConclusionsThe ASM provides an innovative ex vivo model of HK in whole human cornea that reproduces typical epithelial lesions.

Macrophages play a pivotal role in the formation and development of atherosclerosis as a predominant inflammatory cell type present within atherosclerotic plaque. Promoting anti-atherosclerotic drug delivery into macrophages may provide a therapeutic potential on atherosclerotic plaque. In this study, we investigated whether membrane-permeabilized sonodynamic therapy (MP-SDT) enhances drug delivery into THP-1 macrophages. Images of confocal microscopy confirmed that the optimal plasma distribution of the sonosensitizer protoporphyrin IX (PpIX) was at 1 hour incubation. The non-lethal parameter of MP-SDT was determined by cell viability as measured by a CCK-8 assay. Bright field microscopy demonstrated plasma membrane deformation in response to MP-SDT. Using SYTOX Green, a model drug for cellular uptake, we found that MP-SDT significantly induced membrane permeabilization dependent on ultrasound intensity and exposure time. Using Fluo-3 AM, intracellular calcium elevation during MP-SDT was confirmed as a result of membrane permeabilization. Membrane perforation of MP-SDT-treated cells was observed by scanning electron microscopy and transmission electron microscopy. Moreover, MP-SDT-induced membrane permeabilization and perforation were remarkably prevented by scavenging reactive oxygen species (ROS) during MP-SDT. Furthermore, we assessed the therapeutic effect of MP-SDT in combination with anti-atherosclerotic drug atorvastatin. Our results showed that MP-SDT increased the therapeutic effect of atorvastatin on lipid-laden THP-1-derived foam cells, including decreasing lipid droplets, increasing the cholesterol efflux and the expression of PPARγ and ABCG1. In conclusion, MP-SDT might become a promising approach to facilitating the delivery of anti-atherosclerotic drugs into macrophages via membrane permeabilization.

Powdery mildew is one of the most widespread diseases of wheat. The development and deployment of resistant varieties are one of the most economical and effective methods to manage this disease. Our previous study showed that the gene(s) at 2Mb in Chinese Spring (CS)-Aegilops biuncialis 2Mb disomic addition line TA7733 conferred a high level of resistance to powdery mildew of wheat. In this study, resistance spectrum of TA7733 was assayed by using 15 Blumeria graminis f. sp. tritici (Bgt) isolates prevalent in different regions of China. The result indicated that TA7733 was highly resistant to all tested Bgt isolates and the gene(s) on chromosome 2Mb conferred broad-spectrum resistance to powdery mildew. In order to characterize mechanism of powdery mildew resistance by identifying candidates R-genes derived from Ae. biuncialis chromosome 2Mb and develop 2Mb-specific molecular markers, we performed RNA-seq analysis on TA7733 and CS. In total we identified 7,278 unigenes that showed specific expression in TA7733 pre and post Bgt-infection when compared to CS. Of these 7,278 unigenes, 295 were annotated as putative resistance (R) genes. Comparatively analysis of R-gene sequences from TA7733 and CS and integration CS Ref Seq v1.0 were used to develop R-gene specific primers. Of 295 R-genes we identified 53 R-genes were specific to 2Mb and could be involved in powdery mildew resistance. Functional annotation of majority of the 53 R-genes encoded nucleotide binding leucine rich repeat (NLR) protein. The broad-spectrum resistance to powdery mildew in TA7733 and availability of 2Mb-derived putative candidate R-gene specific molecular markers identified in this study will lay foundations for transferring powdery mildew resistance from 2Mb to common wheat by inducing CS-Ae. biuncialis homoeologous recombination. Our study also provides useful candidates for further isolation and cloning of powdery mildew resistance gene(s) from Ae. biuncialis chromosome 2Mb.

Estradiol is an important sex steroid hormone that is involved in the regulation of crustacean ovarian development. However, the molecular regulatory mechanisms of estradiol on ovarian development are largely unknown. This study performed transcriptome sequencing of ovary, hepatopancreas, brain ganglion, eyestalk, and mandibular organ of crabs after estradiol treatment (0.1μg g-1 crab weight). A total of 23, 806 genes were annotated, and 316, 1300, 669, 142, 383 genes were expressed differently in ovary, hepatopancreas, brain ganglion, eyestalk, and mandibular organ respectively. Differentially expressed gene enrichment analysis revealed several crucial pathways including protein digestion and absorption, pancreatic secretion, insect hormone biosynthesis, drug metabolism-cytochrome P450 and signal transduction pathway. Through this study, some key genes in correlation with the ovarian development and nutrition metabolism were significantly affected by estradiol, such as vitelline membrane outer layer 1-like protein, heat shock protein 70, Wnt5, JHE-like carboxylesterase 1, cytochrome P302a1, crustacean hyperglycemic hormone, neuropeptide F2, trypsin, carboxypeptidase B, pancreatic triacylglycerol lipase-like, and lipid storage droplet protein. Moreover, RT-qPCR validation demonstrated that expression of transcripts related to ovarian development (vitelline membrane outer layer 1-like protein and cytochrome P302a1) and nutrition metabolism (trypsin, glucose dehydrogenase and lipid storage droplet protein) were significantly affected by estradiol treatment. This study not only has identified relevant genes and several pathways that are involved in estradiol regulation on ovarian development of P. trituberculatus, but also provided new insight into the understanding of the molecular function mechanisms of estradiol in crustacean.

China's universal medical insurance system (UMIS) is designed to promote social fairness through improving access to medical services and reducing out-of-pocket (OOP) costs for all Chinese. However, it is still not known whether UMIS has a significant impact on the accessibility of medical service supply and the affordability, as well as the seeking-care choice, of patients in China.Segmented time-series regression analysis, as a powerful statistical method of interrupted time series design, was used to estimate the changes in the quantity and quality of medical service supply before and after the implementation of UMIS. The rates of catastrophic payments and seeking-care choices for UMIS beneficiaries were selected to measure the affordability and medical service flow of patients after the implementation of UMIS.China's UMIS was established in 2008. After that, the trending increase of the expenditure of the UMIS was higher than that of increase in revenue compared to previous years. Up to 2014, the UMIS had covered 97.5% of the entire population in China. After introduction of the UMIS, there were significant increases in licensed physicians, nurses, and hospital beds per 1000 individuals. In addition, hospital outpatient visits and inpatient visits per year increased compared to the pre-UMIS period. The average fatality rate of inpatients in the overall hospital and general hospital and the average fatality rate due to acute myocardial infarction (AMI) in general hospitals was significantly decreased. In contrast, no significant and prospective changes were observed in rural physicians per 1000 individuals, inpatient visits and inpatient fatality rate in the community centers and township hospitals compared to the pre-UMIS period. After 2008, the rates of catastrophic payments for UMIS inpatients at different income levels were declining at three levels of hospitals. Whichever income level, the rate of catastrophic payments for inpatients of Urban Employee's Basic Medical Insurance was the lowest. For the low-income patients, a single hospitalization at a tertiary hospital can lead to catastrophic payments. It is needless to say what the economic burden could be if patients required multiple hospitalizations within a year. UMIS beneficiaries showed the intention of growth to seek hospitalization services in tertiary hospitals.Introduction of the UMIS contributed to an increase in available medical services and the use thereof, and a decrease in fatality rate. The affordability of UMIS beneficiaries for medical expenses was successfully ameliorated. The differences in patients' affordability are mainly manifested in different medical insurance schemes and different seeking-care choices. The ability of the poor patients covered by UMIS to resist catastrophic medical payments is still relatively weak. Therefore, the current UMIS should reform the insurance payment model to promote the integration of medical services and the formation of a tiered treatment system. UMIS also should establish supplementary medical insurance packages for the poor.

[This corrects the article DOI: 10.1371/journal.pone.0096283.].

OBJECTIVE:To compare dorsal penile nerve block (DPNB) and eutectic mixture of local anesthetics (EMLA) cream for pain relief in infants during circumcision. METHODS:We systematically searched Medline via PubMed, Embase, CNKI and the Cochrane Library Center Register to identify randomized controlled trials up to March 2018. Effect estimates were performed in random effect models. Mean neonate infant pain scale (NIPS) scores, incidence of hematoma, edema and erythema, mean heart rate were conducted to assessed the effect of analgesia. We found that the EMLA had significantly higher pain scores compared to DPNB (SMD = 3.72, 95% CI 1.27-6.17, P = 0.003). In DPNB group, the incidence of hematoma was significantly higher than EMLA group, OR = 0.03, 95% CI 0.00-0.24, P = 0.001. The analysis did not show any significant differences in mean heart rate and the risk of edema and erythema between EMLA and DPNB group (SMD = 21.71, 95% CI = -0.88-44.30, P = 0.06 & OR = 0.40, 95% CI 0.15-1.07, P = 0.07 & OR = 7.33, 95% CI 0.84-64.07, P = 0.07). CONCLUSION:Based on the pooled results from the included studies, we found that DPNB was significantly more effective in pain relief as indicated by mean NIPS score than EMLA in infants during circumcision. However, use of DPNB significantly increased the risk of hematoma.

Straw return plays an important role in reducing the use of chemical fertilizer, promoting soil carbon sequestration, thus maintaining soil fertility and alleviating environmental pollution. To examine the effects of straw return on soil bacterial communities, quantitative PCR and high-throughput sequencing approaches were used to analyze the bacterial abundance and community structures at the depths of 5-25 cm and 25-45 cm in the soils under six-year continuous straw return and removal treatments in Langfang, Hebei, the North China Plain. As a result, straw return had no effects on soil chemical properties, bacterial abundance, richness or diversity at both soil depths. In contrast, vertical distributions of available nitrogen and available potassium were affected. Similarly, straw return also changed the vertical distributions of Proteobacteria and Chloroflexi. Principal coordinate analysis based on weighted UniFrac distance matrix indicated a moderate separation of the bacterial community in the soil treated with straw return from that with straw removal at 5-25 cm depth, but they were not distinctly distinguished at 25-45 cm depth. T-test identified increased abundance of Candidatus Latescibacteria in the soil under straw return treatment at 5-25 cm depth but no differentially abundant phyla at 25-45 cm depth was found. These results suggested a selection effect from the six-year continuous straw return treatment and the soil bacterial communities were moderately changed.

Textual representations play an important role in the field of natural language processing (NLP). The efficiency of NLP tasks, such as text comprehension and information extraction, can be significantly improved with proper textual representations. As neural networks are gradually applied to learn the representation of words and phrases, fairly efficient models of learning short text representations have been developed, such as the continuous bag of words (CBOW) and skip-gram models, and they have been extensively employed in a variety of NLP tasks. Because of the complex structure generated by the longer text lengths, such as sentences, algorithms appropriate for learning short textual representations are not applicable for learning long textual representations. One method of learning long textual representations is the Long Short-Term Memory (LSTM) network, which is suitable for processing sequences. However, the standard LSTM does not adequately address the primary sentence structure (subject, predicate and object), which is an important factor for producing appropriate sentence representations. To resolve this issue, this paper proposes the dependency-based LSTM model (D-LSTM). The D-LSTM divides a sentence representation into two parts: a basic component and a supporting component. The D-LSTM uses a pre-trained dependency parser to obtain the primary sentence information and generate supporting components, and it also uses a standard LSTM model to generate the basic sentence components. A weight factor that can adjust the ratio of the basic and supporting components in a sentence is introduced to generate the sentence representation. Compared with the representation learned by the standard LSTM, the sentence representation learned by the D-LSTM contains a greater amount of useful information. The experimental results show that the D-LSTM is superior to the standard LSTM for sentences involving compositional knowledge (SICK) data.

Text representation can map text into a vector space for subsequent use in numerical calculations and processing tasks. Word embedding is an important component of text representation. Most existing word embedding models focus on writing and utilize context, weight, dependency, morphology, etc., to optimize the training. However, from the linguistic point of view, spoken language is a more direct expression of semantics; writing has meaning only as a recording of spoken language. Therefore, this paper proposes the concept of a pronunciation-enhanced word embedding model (PWE) that integrates speech information into training to fully apply the roles of both speech and writing to meaning. This paper uses the Chinese language, English language and Spanish language as examples and presents several models that integrate word pronunciation characteristics into word embedding. Word similarity and text classification experiments show that the PWE outperforms the baseline model that does not include speech information. Language is a storehouse of sound-images; therefore, the PWE can be applied to most languages.

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically relevant viral pathogens in pigs and causes substantial losses in the pig industry worldwide each year. At present, PRRSV vaccines do not effectively prevent and control this disease. Consequently, it is necessary to develop new antiviral strategies to compensate for the inefficacy of the available vaccines. Histone deacetylase 6 (HDAC6) is an important member of the histone deacetylase family that is responsible for regulating many important biological processes. Studies have shown that HDAC6 has anti-viral activities during the viral life cycle. However, whether HDAC6 overexpression enhances resistance to PRRSV in pigs remains unknown. In this study, we used a somatic cell cloning method to produce transgenic (TG) pigs that constitutively overexpress porcine HDAC6. These TG pigs showed germ line transmission with continued overexpression of HDAC6. In vitro, virus-challenged porcine alveolar macrophages (PAMs) overexpressed HDAC6, which suppressed viral gene expression and PRRSV production. In vivo, resistance to PRRSV in TG pigs was evaluated by direct or cohabitation mediated infection with a highly pathogenic PRRSV (HP-PRRSV) strain. Compared with non-TG (NTG) siblings, TG pigs showed a significantly lower viral load in the lungs and an extended survival time after infection with HP-PRRSV via intramuscular injection. In the cohabitation study, NTG pigs housed with challenged NTG pigs exhibited significantly worse clinical symptoms than the other three in-contact groups. These results collectively suggest that HDAC6 overexpression enhances resistance to PRRSV infection both in vitro and in vivo. Our findings suggest the potential involvement of HDAC6 in the response to PRRSV, which will facilitate the development of novel therapies for PRRSV.

[This corrects the article DOI: 10.1371/journal.pone.0168384.].

Plant leaves exhibit differentiated patterns of photosynthesis rates under diurnal light regulation. Maize leaves show a single-peak pattern without photoinhibition at midday when the light intensity is maximized. This mechanism contributes to highly efficient photosynthesis in maize leaves. To understand the molecular basis of this process, an isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomics analysis was performed to reveal the dynamic pattern of proteins related to photosynthetic reactions. Steady, single-peak and double-peak protein expression patterns were discovered in maize leaves, and antenna proteins in these leaves displayed a steady pattern. In contrast, the photosystem, carbon fixation and citrate pathways were highly controlled by diurnal light intensity. Most enzymes in the limiting steps of these pathways were major sites of regulation. Thus, maize leaves optimize photosynthesis and carbon fixation outside of light harvesting to adapt to the changes in diurnal light intensity at the protein level.

Flows (Qa) of arteriovenous fistula (AVF) impact the dialysis adequacy in hemodialysis (HD) patients. However, data for different access flow levels on outcomes related to long-term dialysis patients, especially in Chinese patients, are limited. Herein, we performed an ambispective, mono-centric cohort study investigating the association between the AVF flows and inflammation, cardiovascular events and deaths in Chinese hemodialysis patients bearing a radio-cephalic fistula (AVF) from 2009 to 2015. Twenty-three patients (35.9%) developed at least one episode of cardiovascular disease (CVD) in two years after AVF creation. AVF Qa, IL-6 and hsCRP were significantly higher in patients with CVD than in patients without CVD. Multi-factorial binary logistic regression analysis found that the independent and strongest risk factor for CVD in HD patients was serum IL-6, which showed a positive association with AVF Qa levels in patients. Therefore, the linkage between AVF Qa tertiles and adverse clinical outcomes (cardiovascular events and mortality) was examined over a median follow-up of five years. IL-6 was significantly increased in the high AVF Qa (>1027.13 ml/min) group. Patients with median AVF Qa showed the lowest morbidity and mortality of CVD according to the AVF Qa tertiles, whereas higher Qa was associated with a higher risk of CVD, and lower AVF Qa (600 ml/min ≤AVF Qa

In this paper, we develop a framework to model and analyze systems that are subject to dependent, competing degradation processes and random shocks. The degradation processes are described by stochastic differential equations, whereas transitions between the system discrete states are triggered by random shocks. The modeling is, then, based on Stochastic Hybrid Systems (SHS), whose state space is comprised of a continuous state determined by stochastic differential equations and a discrete state driven by stochastic transitions and reset maps. A set of differential equations are derived to characterize the conditional moments of the state variables. System reliability and its lower bounds are estimated from these conditional moments, using the First Order Second Moment (FOSM) method and Markov inequality, respectively. The developed framework is applied to model three dependent failure processes from literature and a comparison is made to Monte Carlo simulations. The results demonstrate that the developed framework is able to yield an accurate estimation of reliability with less computational costs compared to traditional Monte Carlo-based methods.

R-/S-2-(2-Hydroxypropanamido) benzoic acid (R-/S-HPABA), a marine-derived anti-inflammatory drug, however, the antiplatelet and antithrombotic effects have not been investigated. In this paper, the in vitro antiplatelet activities and in vivo antithrombotic effects of R-/S-HPABA were investigated, for the first time. The effects of R-/S-HPABA on platelet aggregation induced by adenosine diphosphate (ADP), collagen (COLL) and arachidonic acid (AA) were evaluated. In addition, the in vivo bleeding time, clotting time, collagen-epinephrine induced pulmonary thrombosis and common carotid artery thrombosis were also investigated in rats. R-/S-HPABA significantly inhibited ADP, COLL and AA induced platelet aggregation in rabbit platelet rich plasma in vitro compared with control group, to a degree similar to that of aspirin. Besides, R-/S-HPABA prolonged bleeding time and clotting time as well as increased the recovery rate obviously in pulmonary thrombosis. Moreover, the level of thromboxane B2 (TXB2) was decreased while the production of 6-keto-prostaglandin F1α (6-keto-PGF1α) was increased markedly by R-/S-HPABA. Furthermore, R-/S-HPABA reduced carotid artery thrombosis weight. These results illustrated that R-/S-HPABA could be a potent antiplatelet aggregation and antithrombotic agent.

Mulching management has been used in many places all over the world to improve agricultural sustainability. However, the cycling of carbon in the soil under applications of mulch on sloping arable land is not yet fully understood. A four-year field experiment was carried out in Xiaofuling watershed of Danjiangkou reservoir in China. The object was to evaluate the effects of the application of straw mulch (ST) and grass mulch (GT) on dynamic changes in soil organic carbon and its fractions. Results showed that mulch applied on the soil surface increased the contents of SOC and its active fractions in the soil. Compared to the control without cover (CK), ST and GT treatments increased the contents of SOC, LOC, DOC, POC and EOC by 14.73%, 16.5%, 22.5%, 41.5% and 21%, respectively, in the 0-40 cm soil layer, and by 17%, 14%, 19%, and 30%, respectively, in the 0-100 cm soil layer. The contents of organic carbon and its active fractions decreased with increasing soil depth in all of the treatments. SOC was accumulated in the period of December to the following March. The contents of soil DOC and LOC were high in January to March, while the contents of soil POC and EOC were high in June to September. The relative contents of soil organic carbon fractions were POC > EOC > LOC > DOC over the four years. Straw mulching had no significant effect on the changes in soil organic carbon active fractions during the different periods. Based on this long-term field experiment in Danjiangkou reservoir, we found that straw mulching had a significant effect on soil, increasing SOC content and stock in slopping arable land, and that live grass mulching was more effective than rice straw mulching. We discuss possible optimal periods for the implementation of mulching practices on sloping land.