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[This corrects the article DOI: 10.1371/journal.pone.0083132.].

BackgroundTo systematically review and perform a meta-analysis on the predictive value of the primary Gleason grade (PGG) at the positive surgical margin (PSM), length of PSM, number of PSMs, and pathological stage of the primary tumor on biochemical recurrence (BCR) in patients with prostate cancer (PCa) after radical prostatectomy (RP).MethodsA systematic literature search was performed using electronic databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, from January 1, 2005, to October 1, 2023. The protocol was pre-registered in PROSPERO. Subgroup analyses were performed according to the different treatments and study outcomes. Pooled hazard ratios with 95% confidence intervals were extracted from multivariate analyses, and a fixed or random effect model was used to pool the estimates. Subgroup analyses were performed to explore the reasons for the heterogeneity.ResultsThirty-one studies that included 50,028 patients with PCa were eligible for this meta-analysis. The results showed that, compared to PGG3, PGG4/5 was associated with a significantly increased risk of BCR. Compared with PSM ≤3 mm, PSM ≥3 mm was associated with a significantly increased risk of BCR. Compared with unifocal PSM, multifocal PSM (mF-PSM) was associated with a significantly increased risk of BCR. In addition, pT >2 was associated with a significantly increased risk of BCR compared to pT2. Notably, the findings were found to be reliable based on the sensitivity and subgroup analyses.ConclusionsPGG at the PSM, length of PSM, number of PSMs, and pathological stage of the primary tumor in patients with PCa were found to be associated with a significantly increased risk of BCR. Thus, patients with these factors should be treated differently in terms of receiving adjunct treatment and more frequent monitoring. Large-scale, well-designed prospective studies with longer follow-up periods are needed to validate the efficacy of these risk factors and their effects on patient responses to adjuvant and salvage therapies and other oncological outcomes.

The efficacy of rosuvastatin in reducing allergic inflammation has been established. However, its potential to reduce airway remodeling has yet to be explored. This study aimed to evaluate the efficacy of rosuvastatin in reducing airway inflammation and remodeling in a mouse model of chronic allergic asthma induced by sensitization and challenge with OVA. Histology of the lung tissue and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) showed a marked decrease in airway inflammation and remodeling in mice treated with rosuvastatin, as evidenced by a decrease in goblet cell hyperplasia, collagen deposition, and smooth muscle hypertrophy. Furthermore, levels of inflammatory cytokines, angiogenesis-related factors, and OVA-specific IgE in BALF, plasma, and serum were all reduced upon treatment with rosuvastatin. Western blotting was employed to detect AMPK expression, while immunohistochemistry staining was used to observe the expression of remodeling signaling proteins such as α-SMA, TGF-β, MMP-9, and p-AMPKα in the lungs. It was found that the activity of 5'-adenosine monophosphate-activated protein kinase alpha (AMPKα) was significantly lower in the lungs of OVA-induced asthmatic mice compared to Control mice. However, the administration of rosuvastatin increased the ratio of phosphorylated AMPK to total AMPKα, thus inhibiting the formation of new blood vessels, as indicated by CD31-positive staining mainly in the sub-epithelial region. These results indicate that rosuvastatin can effectively reduce airway inflammation and remodeling in mice with chronic allergic asthma caused by OVA, likely due to the reactivation of AMPKα and a decrease in angiogenesis.

Increasing yield is an important goal of barley breeding. In this study, 54 papers published from 2001-2022 on QTL mapping for yield and yield-related traits in barley were collected, which contained 1080 QTLs mapped to the barley high-density consensus map for QTL meta-analysis. These initial QTLs were integrated into 85 meta-QTLs (MQTL) with a mean confidence interval (CI) of 2.76 cM, which was 7.86-fold narrower than the CI of the initial QTL. Among these 85 MQTLs, 68 MQTLs were validated in GWAS studies, and 25 breeder's MQTLs were screened from them. Seventeen barley orthologs of yield-related genes in rice and maize were identified within the hcMQTL region based on comparative genomics strategy and were presumed to be reliable candidates for controlling yield-related traits. The results of this study provide useful information for molecular marker-assisted breeding and candidate gene mining of yield-related traits in barley.

BackgroundAs a leading cause of mortality and long-term disability, acute ischemic stroke can produce far-reaching pathophysiological consequences. Accumulating evidence has demonstrated abnormalities in the lower motor system following stroke, while the existence of Transsynaptic degeneration of contralateral spinal cord ventral horn (VH) neurons is still debated.MethodsUsing a rat model of acute ischemic stroke, we analyzed spinal cord VH neuron counts contralaterally and ipsilaterally after stroke with immunofluorescence staining. Furthermore, we estimated the overall lower motor unit abnormalities after stroke by simultaneously measuring the modified neurological severity score (mNSS), compound muscle action potential (CMAP) amplitude, repetitive nerve stimulation (RNS), spinal cord VH neuron counts, and the corresponding muscle fiber morphology. The activation status of microglia and extracellular signal-regulated kinase 1/2 (ERK 1/2) in the spinal cord VH was also assessed.ResultsAt 7 days after stroke, the contralateral CMAP amplitudes declined to a nadir indicating lower motor function damage, and significant muscle disuse atrophy was observed on the same side; meanwhile, the VH neurons remained intact. At 14 days after focal stroke, lower motor function recovered with alleviated muscle disuse atrophy, while transsynaptic degeneration occurred on the contralateral side with elevated activation of ERK 1/2, along with the occurrence of neurogenic muscle atrophy. No apparent decrement of CMAP amplitude was observed with RNS during the whole experimental process.ConclusionsThis study offered an overview of changes in the lower motor system in experimental ischemic rats. We demonstrated that transsynaptic degeneration of contralateral VH neurons occurred when lower motor function significantly recovered, which indicated the minor role of transsynaptic degeneration in lower motor dysfunction during the acute and subacute phases of focal ischemic stroke.

The Yangtze River Delta urban agglomeration (YRDUA) is China's most representative region with remarkable economic development vitality. The purpose of this study is to provide valuable data analysis to actively respond to the population aging in China. We mainly focus on the spatial and temporal evolution of population aging in YRDUA from 2000 to 2020 using city-level population data. This study constructs a multi-dimensional index system to measure population aging including population aging degree, speed, and density. It finds out: (1) the elderly population rate (EPR), the elder-child ratio (ECR), and the elderly dependency ratio (EDR) in the YRDUA area are gradually increasing from 2000 to 2020. In addition, the trends of these indicators in various cities and regions are relatively consistent. All 27 cities in YRDUA entered an aging society, from the primary to the moderate aging stage from 2000 to 2010 and from the moderate to the hyper aging stage from 2010 to 2020. (2) the absolute and relative growth rate of EPR is increasing from 2000 to 2020. However, the absolute and relative growth rate of ECR is increasing from 2000 to 2010 and then decreasing from 2010 to 2020. These results indicate that the two-child policy adopted by the Chinese government plays a positive role. (3) the density level of the elderly population in the YRDUA evolved from low in 2000 to middle in 2010 and then to high in 2020. (4) There are remarkable differences in the process of population aging among three provinces and one city. The contribution of this study is mainly reflected in two aspects: firstly, it constructs a multi-dimensional index system to measure population aging; secondly, using this multi-dimensional index system, it systematically observes the spatial and temporal evolution of population aging from 2000 to 2020 in the Yangtze River Delta Urban Agglomeration.

Both the number of dust explosion accidents and the resulting number of casualties have increased dramatically in recent years. To reduce this risk of dust explosions, we use the functional resonance analysis method (FRAM) to analyze the cause of the dust explosion accident at the Kunshan factory and propose barrier measures to prevent such accidents. The functional units that changed in the production system during the accident and how these functional units coupled to eventually cause the dust explosion were examined and explained. In addition, barrier measures were developed for functional units that changed during production and emergency systems defined to block the propagation of changes between functions and prevent resonance. Through case study, the identification of key functional parameters in both triggering the initial explosion and in then allowing its spread are key to define barriers to prevent a recurrence of such an event. FRAM uses system function coupling instead of traditional linear causality to explain the accident process, and develops barrier measures for changing function units, providing a novel thinking strategy and method for the analysis of accidents and their prevention.

The ultrasonic characteristics of the coal and rock bodies around boreholes during failure are closely related to the crack propagation law. To investigate the ultrasonic characteristics and crack propagation law of coal and rock bodies around boreholes, different grouting samples with boreholes were taken to carry out ultrasonic test during progressive failure. The ultrasonic amplitude, velocity and attenuation coefficient of the samples were analyzed. According to the ultrasonic time difference formula, the equivalent crack width of the sample during the failure process is calculated. The influence of grouting material on the crack propagation law is quantitatively analyzed. The results show that: (1) The peak stress, elastic energy at the peak, ultrasonic parameters and crack propagation of the coal and rock bodies around boreholes show obvious differences influenced by the strength of the grouting material. (2) During the loading process, the arrival time of the first wave of the sample with holes is 5μs later than that of the grouting sample, and the ultrasonic energy attenuates fastest in the time domain, and the coda wave is not developed. (3) During the progressive failure, the ultrasonic velocity and attenuation coefficient of all show three stages of stability(0~0.6σp), slow change(0.6σp~0.8σp) and rapid change(0.8σp~1.0σp). According to the "sudden decrease" of velocity and the "sudden increase" of attenuation coefficient to judge the crack propagation of sample. (4) The equivalent crack width of the sample increases exponentially with the increase of stress level. At the time of reaching the peak stress, the equivalent crack width of SH-BH increases about 0.027mm~0.032mm, SH-PU about 0.01mm~0.014mm, and SH-CEM about 0.002mm~0.006mm.

Evolutionary polynomial regression (EPR) is a data mining tool that has been widely used in solving various geotechnical engineering problems. The fitness function is the core of EPR. However, overfitting may still occur in EPR, and this issue may cause the testing dataset not to perform effectively. Improvement of the EPR fitness function through L1 and L2 regularization methods is critical to avoid overfitting and enhance good generalization. First, the appropriate values of the regularization parameter λ of the L1 regularization method (L1RM) and L2 regularization method (L2RM) are determined by comparing the test data sets. Then, the EPR with a classical fitness function is compared with that of L1 or L2 regularization methods to evaluate their abilities in developing regression and producing accurate predictions. The results show that the fitness function combined with the regularization method could improve the EPR. However, L1RM performs better in prediction than L2RM. Improvement of EPR using L1RM could solve problems associated with construction constitutive models or could be used for prediction in geotechnical engineering.

Based on the perspective of ecology and innovation management, this paper selects seven elements from two aspects, innovation subject and innovation environment, to construct the evaluation index system for the health of pharmaceutical innovation ecological rainforest in Zhejiang from 2011 to 2019, together with the entropy weighted TOPSIS method and the obstacle factor diagnosis model. We find that the health of the pharmaceutical industry in Zhejiang can be measured as three stages: stagnation period, recovery period and development period. There is a relative balance between the development of innovation subject and innovation environment. The resilience of innovation subjects, followed by economic and cultural environment, is the key factor hindering the innovation of pharmaceutical industry in Zhejiang. Finally, we propose four countermeasures, including "deploying high-level service chains, broadening investment and financing channels for enterprises, building a reservoir of global talents, and creating an inclusive and open soft environment".

BackgroundThe aim of this study is to evaluate analgesic efficacy of pericapsular nerve group (PENG) block in patients with intertrochanteric femur fracture (IFF).MethodsThis double-blinded randomized controlled trial in patients with IFF scheduled for proximal femoral nail antirotation (PFNA) between December 2020 and November 2021. The primary outcome was VAS scores during exercising at 6 h after surgery; secondary outcomes were pain during exercising and rest, intraoperative dose of remifentanil, cumulative dose of postoperative fentanyl, postoperative analgesia satisfaction scores, and ratio of quadriceps weakness.ResultsA total of 50 patients were randomly divided into PENG block group (n = 25) or fascia iliaca compartment block (FICB) group (n = 25). Exercising VAS scores at 6 h after surgery were significantly lower in PENG block group than that in FICB group (2 (2, 4) vs. 6 (4, 7), P < 0.001). The intraoperative dose of remifentanil and cumulative dose of postoperative fentanyl by patient-controlled intravenous analgesia within 24 h after surgery in PENG block group were significantly lower than in FICB group (both P < 0.001). Postoperative analgesia satisfaction scores in PENG block group were significantly higher than those in FICB group (P = 0.016). The ratio of quadriceps weakness at 6 h after surgery was significantly higher in FICB group than PENG block group (48% vs. 0%, P < 0.001).ConclusionsCompared to FICB, ultrasound-guided PENG block may provide better postoperative pain relief in patients with IFF, with less pronounced quadriceps weakness.

[This corrects the article DOI: 10.1371/journal.pone.0166177.].

Objective Heart failure (HF) and atrial fibrillation (AF) are often coexisting. They have common risk factors and pathophysiologic mechanisms. Sacubitril/valsartan has shown efficacy and tolerability in patients with HF. Thus, the study was performed to evaluate the impact of sacubitril/valsartan on AF occurrence in patients with HF. Methods The Embase and PubMed were searched from their inception date to June 2021 for all relevant randomized controlled trials (RCTs) evaluating the efficacy of sacubitril/valsartan in HF. The outcome of interest was the AF occurrence during the follow-up. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Results Six trials involving a total of 15,512 patients were included (7,750 randomized to sacubitril/valsartan and 7,762 to control). All trials were randomized, double-blind, and active-control. There was no significant difference in the prevention of AF occurrence between the sacubitril/valsartan group and the control group (enalapril or valsartan) in patients with HF (RR 1.07, 95%CI 0.95 to 1.19; I2 4%). Conclusions Sacubitril/valsartan was similar to either enalapril or valsartan in preventing the occurrence of AF in patients with HF.

In order to investigate the compaction and re-crushing characteristics of crushed coal gangue with different gradation, the compaction fractal test was carried out for crushed coal gangue with different Talbol power index n. The compaction deformation parameters such as displacement, stress-strain were analyzed according to the test results. And according to the test results, the compaction deformation relationship of the lateral limit crushed coal rock body considering the gradation is obtained. The test results show that: the crushing of coal rock particles exists in almost the whole compaction process of the crushed coal rock body, and the crushing of coal rock particles has a non-negligible influence on the deformation of the whole crushed rock body; the structural stability of large-size coal rock particles is not as good as that of small-size coal rock particles, and the large-size coal rock is more likely to be crushed under the same stress conditions; the distribution coefficient r of the crushed coal rock body decreases with the increase of axial stress; and before the Before the axial stress reaches 8 MPa, the distribution coefficient r of crushed rock samples tends to increase with n in general, and after reaching 8 MPa and later, the distribution coefficient r of crushed rock samples tends to decrease with n in general; the difference value of particle crushing increases with the increase of axial stress, and the weight value of particle crushing decreases with the increase of axial stress, and the changes of both are non-linear; according to the stress recovery in the compaction process of crushed coal rock body The compaction deformation model of the crushed coal rock body is constructed according to the crushing characteristics of coal rock particles in the stage of compaction, which effectively combines its fine action mechanism with macroscopic physical phenomena in a simple form and has certain practical engineering significance.

The bioconvection flow of tiny fluid conveying the nanoparticles has been investigated between two concentric cylinders. The contribution of Lorenz force is also focused to inspect the bioconvection thermal transport of tiny particles. The tiny particles are assumed to flow between two concentric cylinders of different radii. The first cylinder remains at rest while flow is induced due to second cylinder which rotates with uniform velocity. Furthermore, the movement of tiny particles follows the principle of thermophoresis and Brownian motion as a part of thermal and mass gradient. Similarly, the gyro-tactic microorganisms swim in the nanofluid as a response to the density gradient and constitute bio-convection. The problem is modeled by using the certain laws. The numerical outcomes are computed by using RKF -45 method. The graphical simulations are performed for flow parameters with specific range like 1≤Re≤5, 1≤Ha≤5, 0.5≤Nt≤2.5, 1≤Nb≤3, 0.2≤Sc≤1.8, 0.2≤Pe≤1.0 and 0.2≤Ω≤1.0. It is observed that the flow velocity decreases with the increase in the Hartmann number that signifies the magnetic field. This outcome indicates that the flow velocity can be controlled externally through the magnetic field. Also, the increase in the Schmidt numbers increases the nanoparticle concentration and the motile density.

To improve the prediction accuracy of temperature and humidity in typical Chinese solar greenhouses, this paper proposed a new longwave/shortwave radiation modeling method using bond graph. This model takes into account sun position, useful incoming solar radiation model, sky longwave radiation model, inside longwave, and shortwave radiation model. The approach solves the problems caused by underestimating the effects of longwave radiation on night temperature and relative humidity. The study found that after a period of t = 7.5 h, with the increase of sun altitude angle, the internal temperature was significantly affected by the temperature rise of outside environment on sunny day. The sun altitude angle gradually falls over a period of t = 12.5 h (beginning at 12.30 p.m.). The decline in night temperature steadily slowed after a period of t = 20.5 h. On the other hand, the temperature variation has a multi-peak distribution and the warming rate of the CSG slows down on cloudy days. Furthermore, a good agreement between the experimental and simulation data were obtained, with a maximum temperature deviation of 2°C and maximum humidity deviation of 5%. The developed model is a universal and valuable approach that can be used for greenhouse climate simulation. Furthermore, it can be used as a support system during decision-making processes to help manage Chinese solar greenhouses more efficiently, which provides several control perspectives on the low-energy greenhouse in the future. This work has also provided several control perspectives on the low energy greenhouse in the future.

Avian lymphoid leukosis-like (LL-like) lymphoma has been observed in some experimental and commercial lines of chickens that are free of exogenous avian leukosis virus. Reported cases of avian lymphoid leukosis-like lymphoma incidences in the susceptible chickens are relatively low, but the apathogenic subgroup E avian leukosis virus (ALV-E) and the Marek's disease vaccine, SB-1, significantly escalate the disease incidence in the susceptible chickens. However, the underlying mechanism of tumorigenesis is poorly understood. In this study, we bioinformatically analyzed the deep RNA sequences of 6 lymphoid leukosis-like lymphoma samples, collected from susceptible chickens post both ALV-E and SB-1 inoculation, and identified a total of 1,692 novel long non-coding RNAs (lncRNAs). Thirty-nine of those novel lncRNAs were detected with altered expression in the LL-like tumors. In addition, 13 lncRNAs whose neighboring genes also showed differentially expression and 2 conserved novel lncRNAs, XLOC_001407 and XLOC_022595, may have previously un-appreciated roles in tumor development in human. Furthermore, 14 lncRNAs, especially XLOC_004542, exhibited strong potential as competing endogenous RNAs via sponging miRNAs. The analysis also showed that ALV subgroup E viral gene Gag/Gag-pol and the MD vaccine SB-1 viral gene R-LORF1 and ORF413 were particularly detectable in the LL-like tumor samples. In addition, we discovered 982 novel lncRNAs that were absent in the current annotation of chicken genome and 39 of them were aberrantly expressed in the tumors. This is the first time that lncRNA signature is identified in avian lymphoid leukosis-like lymphoma and suggests the epigenetic factor, lncRNA, is involved with the avian lymphoid leukosis-like lymphoma formation and development in susceptible chickens. Further studies to elucidate the genetic and epigenetic mechanisms underlying the avian lymphoid leukosis-like lymphoma is indeed warranted.

ObjectiveTo examine the association of physical activities (PA) with diabetic retinopathy (DR) progression based on a 10-year follow-up of a large cohort of working-aged diabetic populations in Australia.MethodsNine thousand and eighteen working-aged diabetic patients were enrolled from the baseline of the 45 and Up Study from New South Wales, Australia. Self-reported PA collected by questionnaire at baseline in 2006 was graded into low (ResultsIn the fully adjusted model, higher PA level was significantly associated with a lower risk of RPC incident (Cox-regression, p-value for trend = 0.002; medium vs. low, hazard ratio (HR) = 0.78, 95% Confidence Interval (CI): 0.61-0.98; high vs. low, HR = 0.61, 95%CI: 0.36-0.84. In addition, gender, body mass index, insulin treatment, family history of diabetes, history of cardiovascular disease were significant effect modifiers for the association between PA and RPC.ConclusionsHigher PA level was independently associated with a lower risk of DR progression among working-aged diabetic populations in this large cohort study.

As a type of flexible impermeable material, a PVC geomembrane must be cooperatively used with cushion materials. The contact interface between a PVC geomembrane and cushion easily loses stability. In this present paper, we analyzed the shear models and parameters of the interface to study the stability. Two different cushion materials were used: the common extrusion sidewall and non-fines concrete. To simulate real working conditions, flexible silicone cushions were added under the loading plates to simulate hydraulic pressure loading, and the loading effect of flexible silicone cushions was demonstrated by measuring the actual contact areas under different normal pressures between the geomembrane and cushion using the thin-film pressure sensor. According to elastomer shear stress, there are two main types of shear stress between the PVC geomembrane and the cushion: viscous shear stress and hysteresis shear stress. The viscous shear stress between the geomembrane and the cement grout was measured using a dry, smooth concrete sample, then the precise formula parameters of the viscous shear stress and viscous friction coefficient were obtained. The hysteresis shear stress between the geomembrane and the cushion was calculated by subtracting the viscous shear stress from the total shear stress. The formula parameters of the hysteresis shear stress and hysteresis friction coefficient were calculated. The three-dimensional box-counting dimensions of the cushion surface were calculated, and the formula parameters of the hysteresis friction were positively correlated with the three-dimensional box dimensions.

PurposeTo introduce a modified frontalis muscle (FM) flap for use in FM flap advancement surgery and compare it with the conventional flap for correcting severe congenital ptosis.MethodsThis retrospective cohort study included 200 patients (278 eyes) with severe congenital ptosis treated with FM flap advancement at Tianjin Eye Hospital from April 2018 to October 2019. The patients were divided into two groups: 100 patients (138 eyes) in the conventional group and 100 patients (140 eyes) in the modified group. The success and complication rates were evaluated.ResultsThe final success rate was 77.5% (107/138) in the conventional group and 90.0% (126/140) in the modified group (p = 0.005). Undercorrection was observed in 31 eyes (22.5%) in the conventional group and 14 eyes (10%) in the modified group (p = 0.005). In the conventional group, angular deformity of the upper eyelid was observed in 29 eyes (21.0%), FM paralysis in 11 (8.0%), frontal hypoesthesia in 10 (7.2%), severe hematoma in 12 (8.7%), and exposure keratitis in 8 (5.8%); these complications were not observed in the modified group (p ConclusionCompared with the conventional FM flap, the modified FM flap in this study yielded a higher success rate with a clear field of vision, mild trauma, and few complications. This technique is simple and convenient for correcting severe congenital ptosis.

In Australian prisons approximately 20% of inmates are chronically infected with hepatitis C virus (HCV), providing an important population for targeted treatment and prevention. A dynamic mathematical model of HCV transmission was used to assess the impact of increasing direct-acting antiviral (DAA) treatment uptake on HCV incidence and prevalence in the prisons in New South Wales, Australia, and to assess the cost-effectiveness of alternate treatment strategies. We developed four separate models reflecting different average prison lengths of stay (LOS) of 2, 6, 24, and 36 months. Each model considered four DAA treatment coverage scenarios of 10% (status-quo), 25%, 50%, and 90% over 2016-2045. For each model and scenario, we estimated the lifetime burden of disease, costs and changes in quality-adjusted life years (QALYs) in prison and in the community during 2016-2075. Costs and QALYs were discounted 3.5% annually and adjusted to 2015 Australian dollars. Compared to treating 10% of infected prisoners, increasing DAA coverage to 25%, 50%, and 90% reduced HCV incidence in prisons by 9-33% (2-months LOS), 26-65% (6-months LOS), 37-70% (24-months LOS), and 35-65% (36-months LOS). DAA treatment was highly cost-effective among all LOS models at conservative willingness-to-pay thresholds. DAA therapy became increasingly cost-effective with increasing coverage. Compared to 10% treatment coverage, the incremental cost per QALY ranged from $497-$569 (2-months LOS), -$280-$323 (6-months LOS), -$432-$426 (24-months LOS), and -$245-$477 (36-months LOS). Treating more than 25% of HCV-infected prisoners with DAA therapy is highly cost-effective. This study shows that treating HCV-infected prisoners is highly cost-effective and should be a government priority for the global HCV elimination effort.

The increasing prevalence of carbapenem-resistant Acinetobacter baumannii (CRAB) caused nosocomial infections generate significant comorbidity and can cause death among patients. Current treatment options are limited. These infections pose great difficulties for infection control and clinical treatment. To identify the antimicrobial resistance, carbapenemases and genetic relatedness of Acinetobacter baumannii isolates from cerebrospinal fluid (CSF) and blood, a total of 50 nonrepetitive CSF isolates and 44 blood isolates were collected. The resistance phenotypes were determined, and polymerase chain reaction (PCR) was performed to examine the mechanisms of carbapenem resistance. Finally, multilocus sequence typing (MLST) was conducted to determine the genetic relatedness of these isolates. It was observed that 88 of the 94 collected isolates were resistant to imipenem or meropenem. Among them, the blaOXA-23 gene was the most prevalent carbapenemase gene, with an observed detection rate of 91.5% (86/94), followed by the blaOXA-24 gene with a 2.1% detection rate (2/94). Among all carbapenem-resistant Acinetobacter baumannii (CRAB) observations, isolates with the blaOXA-23 gene were resistant to both imipenem and meropenem. Interestingly, isolates positive for the blaOXA-24 gene but negative for the blaOXA-23 gene showed an imipenem-sensitive but meropenem-resistant phenotype. The MLST analysis identified 21 different sequence types (STs), with ST195, ST540 and ST208 most frequently detected (25.5%, 12.8% and 11.7%, respectively). 80 of the 94 isolates (85.1%) were clustered into CC92 which showed a carbapenem resistance phenotype (except AB13). Five novel STs were detected, and most of them belong to CRAB. In conclusion, these findings provide additional observations and epidemiological data of CSF and blood A. baumannii strains, which may improve future infection-control measures and aid in potential clinical treatments in hospitals and other clinical settings.

Drought stress in trees limits their growth, survival, and productivity and it negatively affects the afforestation survival rate. Our study focused on the molecular responses to drought stress in a coniferous species Larix olgensis A. Henry. Drought stress was simulated in one-year-old seedlings using 25% polyethylene glycol 6000. The drought stress response in these seedlings was assessed by analyzing select biochemical parameters, along with gene expression and metabolite profiles. The soluble protein content, peroxidase activity, and malondialdehyde content of L. olgensis were significantly changed during drought stress. Quantitative gene expression analysis identified a total of 8172 differentially expressed genes in seedlings processed after 24 h, 48 h, and 96 h of drought stress treatment. Compared with the gene expression profile of the untreated control, the number of up-regulated genes was higher than that of down-regulated genes, indicating that L. olgensis mainly responded to drought stress through positive regulation. Metabolite analysis of the control and stress-treated samples showed that under drought stress, the increased abundance of linoleic acid was the highest among up-regulated metabolites, which also included some saccharides. A combined analysis of the transcriptome and metabolome revealed that genes dominating the differential expression profile were involved in glutathione metabolism, galactose metabolism, and starch and sucrose metabolism. Moreover, the relative abundance of specific metabolites of these pathways was also altered. Thus, our results indicated that L. olgensis prevented free radical-induced damage through glutathione metabolism and responded to drought through sugar accumulation.

BackgroundThe safety of discontinuing oral anticoagulant (OAC) therapy after atrial fibrillation (AF) ablation remains controversial. A meta-analysis was performed to assess the safety and feasibility of discontinuing OAC therapy after successful AF ablation.MethodsPubMed and Embase were searched up to October 2020 for prospective cohort studies that reported the risk of thromboembolism (TE) after successful AF ablation in off-OAC and on-OAC groups. The primary outcome was the incidence of TE events. The Mantel-Haenszel method with random-effects modeling was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs).ResultsA total of 11,148 patients (7,160 in the off-OAC group and 3,988 in the on-OAC group) from 10 studies were included to meta-analysis. No significant difference in TE between both groups was observed (OR, 0.73; 95%CI, 0.51-1.05; I2 = 0.0%). The risk of major bleeding in off-OAC group was significantly lower compared to the on-OAC group (OR, 0.18; 95%CI, 0.07-0.51; I2 = 51.7%).ConclusionsOur study suggests that it may be safe to discontinue OAC therapy in patients after successful AF ablation. Additionally, an increased risk of major bleeding was observed in patients on OAC. However, the results of this meta-analysis should be interpreted with caution because of the heterogeneity among the included study designs. Large-scale and adequately powered randomized controlled trials are warranted to confirm these findings.

BackgroundEndogenous erythropoietin (EPO) concentrations vary widely in preterm infants and may be associated with perinatal risk factors and neurological outcomes. Erythropoietin is elevated in fetal hypoxia but is also a potential neuroprotectant.MethodsIn a prospective study of 27 infants ≤ 30 weeks gestation, serum erythropoietin concentrations were measured during the first month of life, on day 1 and weeks 1, 2, and 4, and related to perinatal risk factors and outcomes including retinopathy of prematurity and cerebral injury evaluated near term-equivalent post menstrual age using magnetic resonance imaging with quantitative scoring.ResultsLower birth weight was associated with higher EPO concentrations throughout the first 2 weeks of life (r = -0.6, p < 0.01). Higher day 1 and week 1 EPO concentrations were associated with lower Apgar score at 1 minute (r = - 0.5) and 5 minutes (r = -0.7), respectively (p < 0.01). Higher day 1 EPO concentrations and 2-week area under the curve were associated with increased risk (p = 0.01) and severity (r = 0.5, p < 0.02) of retinopathy of prematurity. Higher EPO concentrations at 2 weeks were associated with increased total brain injury score (r = 0.5, p < 0.05).ConclusionElevated endogenous erythropoietin concentrations in the first two weeks of life are associated with lower birth weight and increased risk of adverse outcomes.

Acute myeloid leukemia (AML) is as a highly aggressive and heterogeneous hematological malignancy. MiR-20a-5p has been reported to function as an oncogene or tumor suppressor in several tumors, but the clinical significance and regulatory mechanisms of miR-20a-5p in AML cells have not been fully understood. In this study, we found miR-20a-5p was significantly decreased in bone marrow from AML patients, compared with that in healthy controls. Moreover, decreased miR-20a-5p expression was correlated with risk status and poor survival prognosis in AML patients. Overexpression of miR-20a-5p suppressed cell proliferation, induced cell cycle G0/G1 phase arrest and apoptosis in two AML cell lines (THP-1 and U937) using CCK-8 assay and flow cytometry analysis. Moreover, miR-20a-5p overexpression attenuated tumor growth in vivo by performing tumor xenograft experiments. Luciferase reporter assay and western blot demonstrated that protein phosphatase 6 catalytic subunit (PPP6C) as a target gene of miR-20a-5p was negatively regulated by miR-20a-5p in AML cells. Furthermore, PPP6C knockdown imitated, while overexpression reversed the effects of miR-20a-5p overexpression on AML cell proliferation, cell cycle G1/S transition and apoptosis. Taken together, our findings demonstrate that miR-20a-5p/PPP6C represent a new therapeutic target for AML and a potential diagnostic marker for AML therapy.

In this study, the feasibility of classifying soybean frogeye leaf spot (FLS) is investigated. Leaf images and hyperspectral reflectance data of healthy and FLS diseased soybean leaves were acquired. First, image processing was used to classify FLS to create a reference for subsequent analysis of hyperspectral data. Then, dimensionality reduction methods of hyperspectral data were used to obtain the relevant information pertaining to FLS. Three single methods, namely spectral index (SI), principal component analysis (PCA), and competitive adaptive reweighted sampling (CARS), along with a PCA and SI combined method, were included. PCA was used to select the effective principal components (PCs), and evaluate SIs. Characteristic wavelengths (CWs) were selected using CARS. Finally, the full wavelengths, CWs, effective PCs, SIs, and significant SIs were divided into 14 datasets (DS1-DS14) and used as inputs to build the classification models. Models' performances were evaluated based on the classification accuracy for both the overall and individual classes. Our results suggest that the FLS comprised of five classes based on the proportion of total leaf surface covered with FLS. In the PCA and SI combination model, 5 PCs and 20 SIs with higher weight coefficient of each PC were extracted. For hyperspectral data, 20 CWs and 26 effective PCs were also selected. Out of the 14 datasets, the model input variables provided by five datasets (DS2, DS3, DS4, DS10, and DS11) were more superior than those of full wavelengths (DS1) both in support vector machine (SVM) and least squares support vector machine (LS-SVM) classifiers. The models developed using these five datasets achieved overall accuracies ranging from 91.8% to 94.5% in SVM, and 94.5% to 97.3% in LS-SVM. In addition, they improved the classification accuracies by 0.9% to 3.6% (SVM) and 0.9% to 3.7% (LS-SVM).

To date, there are few reports of the successful genetic transformation of larch and other conifers, mainly because it is difficult to transform and integrate exogenous genes. In this study, hybrid larch Larix kaempferi 3x Larix gmelinii 9 cones were collected on June 27, July 1, July 4, July 7 and July 16, 2017. Embryogenic callus induction was studied using a combination of different plant growth regulators and concentrations. The results showed that July 1 was the best stage; the highest induction rate was 10.83%, which cultured in BM medium (Button medium, which formula was listed in S1 Table) with 1.0 mg/L 2,4-D (2,4-dichlorophenoxyacetic acid) and 0.2 mg/L KT(kinetin). When cultured on a proliferation medium for 12 days, proliferation was the fastest, reaching 323.08%, which could also maintain the freshness and vitality. The suitable pre-culture medium for somatic embryogenesis was 1/4 BM medium containing 10 g/L inositol and 60 g/L sucrose. The combination of 45 mg/L ABA (abscisic acid) and 75 g/L PEG4000 (Polyethyene glycol 4000) could promote the number of somatic embryos, and reached the maximum, 210 140 per 1 g FW. The genetic transformation was carried out by the Agrobacterium-mediated transformation method with embryogenic callus cultured for 12 days. The results showed the optimal OD600 of the infection solution(suspension of A. tumefaciens) was 0.5, co-culture time was 2 days, and screening concentration of Hyg (hygromycin B) was 4 mg/L. In this study, the transformation rate of resistance callus was 32.1%. It provides a reference for low genetic transformation efficiency of larch at present. This study could be beneficial for the innovation and breeding of larch by genetic engineering and provides a certain basis for rapid propagation of excellent larch germplasm resources and genetic engineering breeding of larch and other conifers.

Recently, studies on competing endogenous RNA (ceRNA) networks have become prevalent, and circular RNAs (circRNAs) have crucial implications for the development and progression of carcinoma. However, studies relevant to metastatic prostate cancer (mPCa) are scant. This study aims to discover potential ceRNAs that may be related to the prognosis of mPCa. RNA-Seq data were obtained from the MiOncoCirc database and Gene Expression Omnibus (GEO). Differential expression patterns of RNAs were examined using R packages. Circular RNA Interactome, miRTarBase, miRDB and TargetScan were applied to predict the corresponding relation between circRNAs, miRNAs and mRNAs. The Gene Ontology (GO) annotations were performed to present related GO terms, and Gene Set Enrichment Analysis (GSEA) tools were applied for pathway annotations. Moreover, survival analysis was conducted for the hub genes. We found 820 circRNAs, 81 miRNAs and 179 mRNAs that were distinguishingly expressed between primary prostate cancer (PCa) and mPCa samples. A ceRNA network including 45 circRNAs, 24 miRNAs and 56 mRNAs was constructed. In addition, the protein-protein interaction (PPI) network was built, and 10 hub genes were selected by using the CytoHubba application. Among the 10 hub genes, survival analysis showed that ITGA1, LMOD1, MYH11, MYLK, SORBS1 and TGFBR3 were significantly connected with disease-free survival (DFS). The circRNA-mediated ceRNA network provides potential prognostic biomarkers for metastatic prostate cancer.

BACKGROUND:Handwriting ability is related to many neuronal functions, such as visual-perceptual skills, orthographic coding, motor planning and execution, kinesthetic feedback and visual-motor coordination. To date, there is no specific assessment tool for to assess preschool children's handwriting ability in Mainland China. Our study aimed to develop a tool to assess the handwriting ability of children aged 5-6 years old in Mainland China and to analyze its reliability and validity. METHODS:The investigation comprised three phases: 1) original tool generation, 2) tool revision, 3) reliability analysis (i.e., interrater, test-retest) and validity analysis (i.e., content, criterion). RESULTS:The sample included a total of 482 children. The internal consistency (Cronbach alpha) was 0.74. The test-retest correlation coefficients ranged from 0.38 to 0.80. As expected, our data showed an improving trend in handwriting, and differences in respect to age and gender. When compared with the 'handwriting difficulty' group, each subtest score of children in the 'normal' group showed significant differences (p < 0.05). The correlation validity, compared with the visual-motor integration development test (VMI), was 0.17-0.52. CONCLUSION:The Handwriting Test for Preschool Children (HT-PRE), which is a newly developed handwriting screening tool for preschool children aged 5-6 years old in Mainland China, has displayed a very good internal consistency, acceptable test-retest reproducibility, and good criterion-based validity, and has also shown good application prospects for handwriting difficulty screening in a clinical setting.

Deep learning methods are being increasingly widely used in static malware detection field because they can summarize the feature of malware and its variants that have never appeared before. But similar to the picture recognition model, the static malware detection model based on deep learning is also vulnerable to the interference of adversarial samples. When the input feature vectors of the malware detection model is based on static features of Windows PE (Portable Executable, PE) file, the model is vulnerable to gradient-based attacks. Regarding the issue above, a method of adversarial sample generation is proposed, which can summarize the blind spots of the original detection model. However, the existing malware adversarial sample generation method is not universal and low in generation efficiency due to the need for human control and difficulty in maintaining a normal file format. In response to these problems, this paper proposes a novel method of automatic adversarial samples generation based on deep reinforcement learning. Firstly, a static PE malware detection model based on deep learning called DeepDetectNet is constructed, the original AUC of which can reach 0.989. Then, an adversarial sample generation model based on reinforcement learning called RLAttackNet is implemented, which generates malware samples that can bypass DeepDetectNet. Finally, when we re-input the adversarial samples into the previously trained DeepDetectNet, the original defects of DeepDetectNet can be reinforced. Experimental results show that the RLAttackNet proposed in this paper can generate about 19.13% of malware samples bypass DeepDetectNet. When DeepDetectNet is retrained with these adversarial samples, the AUC value improves from 0.989 to 0.996 and attack success rate has a significant drop, from 19.13% to 3.1%, compared with the original model.

The impact of damaged sidewalls at the joints between tubes on dam structures subjected to horizontal seepage is investigated. First, an experimental scheme is designed to test the mode and critical gradient of seepage failure of the soil in the damaged tubes. The effects of various overburden pressures (0, 5, 10, 20, and 30 kPa), hole radii(0.5, 1.0, 1.5, and 2 cm) and soil specimen properties were studied. The test phenomena and the changes in the pore water pressure were used to determine the seepage failure modes and the critical gradients under different conditions. Combined with the modified Terzaghi soil arching theory, a mathematical model was developed for the critical gradient for soil seepage failure. The model fitting curve was in good agreement with the laboratory test results. The critical gradient is independent of the overburden pressure and weakly dependent on the internal friction angle of the soil. The critical gradient increases with the cohesion. For fixed characteristic soil parameters, the critical gradient decreases at a gradually decreasing rate as the radius of the damaged hole increases.

The objective is to study the design method of roadway support and provide technical support for coal mining and other mining methods that need deep roadway excavation. Through literature review, the occurrence, development mechanism and influencing factors of surrounding loose rock zones of roadways are analyzed. A method of detecting is selected according to the characteristics of surrounding rock loosening. Knowledge of elastoplastic mechanics is used to theoretically study the failure mechanism of surrounding rock in deep re-mining roadways. Based on the artificial neural network prediction model (ANN), the surrounding rock is classified and a support network model of the decision system is constructed. After the design of roadway support, a sharp change of vault subsidence normally occurs within about 7 days after excavation, and the total subsidence is 14 mm. In the following month, deformation is slow, subsidence is small, and it is basically stable after one month. The curve of the vault subsidence rate shows that the vault subsidence rate is less than or equal to 1mm/d after 7 days. The convergence rate is also less than 1 mm/d after 7 days. There are two cave mouths AB and CD, and the convergence value of AB is 6.47mm, CD is 10.26mm: CD is slightly larger than AB, and it is close to stable one month later. It is essentially consistent with the time of vault settlement and stability, and the amount of deformation is approximately the same. This shows that, with the advance of the working face, the displacement of the surrounding rock in the section away from the working face will gradually decrease and the surrounding rock will be stable. The stability time of surrounding rock displacement of the portal section is the same as that of vault subsidence under the initial support, and the amount of deformation is approximately the same, indicating that the support parameters and construction methods are reasonable.

BackgroundBorder areas are at high risk of measles epidemics. This study aimed to evaluate the effectiveness of the implementation of the routine two-dose measles containing vaccine (MCV) program in border counties of Southwest China.MethodsData used in the study were derived from a cross-sectional survey among 1,467 children aged 8 to 84 months from five border counties of Yunnan Province, Southwest China in 2016. The participants were recruited using a multistage sampling method. Primary guardians of the children were interviewed to collect information on vaccination history, socio-economic status, and knowledge about immunization. Both coverage and timely coverage for the first (MCV1) and the second (MCV2) dose of MCV were calculated. The Kaplan-Meier method was performed to estimate the cumulative coverage of MCV, and Log-rank tests were adopted to compare the differences across counties and birth cohorts. Univariate and multivariate logistic regression models were used to investigate the predictors of delayed MCV1 vaccination.ResultsThe coverage for MCV1 and MCV2 were 97.5% and 93.4%, respectively. However, only 63.8% and 84.0% of the children received MCV1 or MCV2 on time. Significant differences in the cumulative coverage were detected across counties and birth cohorts. Results of the multivariate logistic regression analysis indicated that children whose primary guardian knew the schedule of MCV were less likely to receive MCV1 late (OR = 0.63, PConclusionsAlthough the coverage for MCV is high in border areas of Southwest China, the timeliness of MCV vaccination seems suboptimal. Tailored information from local health professionals may help to reduce untimely vaccination.

To improve the single-layer all-solid-state ion selective electrode' defects including poor conductivity of PVC sensitive membrane and interference of water layer between substrate electrode and sensitive membrane, a double-layer all-solid-state ion selective electrode with nanomaterial as the solid contact layer and conductive polymer as the ion sensitive membrane was developed. A gold nanoparticles solid contact layer and a nitrate-doped polypyrrole molecularly imprinted polymer membrane were prepared by electrodeposition. The optimal parameters obtained by electrochemical performance test were 2.5 mmol/L HAuCl4 electrolyte for solid contact layer and 1800s electrodeposition time for sensitive membrane. The new electrode exhibited a Nernstian response of -50.4 mV/decade and a low detection limit of 5.25×10-5mol/L. Potentiometric water layer test showed no water film formed between the gold nanoparticles solid contact layer and nitrate-doped polypyrrole molecularly imprinted polymer membrane. The contact angle between droplet and the surface of solid contact layer was 112.35° and showed good hydrophobic property. Furthermore, the developed electrode exhibited fast response, excellent potential stability and long lifetime. This electrode is suitable for the detection of nitrate concentration in water and liquid fertilizer.

In March of this year, COVID-19 was declared a pandemic, and it continues to threaten public health. This global health crisis imposes limitations on daily movements, which have deteriorated every sector in our society. Understanding public reactions to the virus and the non-pharmaceutical interventions should be of great help to fight COVID-19 in a strategic way. We aim to provide tangible evidence of the human mobility trends by comparing the day-by-day variations across the U.S. from January 2020 to early April 2020. Large-scale public mobility at an aggregated level is observed by leveraging mobile device location data and the measures related to social distancing. Our study captures spatial and temporal heterogeneity as well as the sociodemographic variations and teleworking trends regarding the pandemic propagation and the non-pharmaceutical mobility interventions. All metrics adapted capture decreased public movements after the national emergency declaration. The population staying home has increased in all states before the stay-at-home mandates implemented and becomes more stable after the order with a smaller range of fluctuation. The public had been taking active responses, voluntarily staying home more, to the in-state confirmed cases while the stay-at-home orders stabilize the variations. As the estimated teleworking rates also continue to incline throughout the study period, the teleworking trend can be another driving factor for the growing stay-at-home population. We confirm that there exists overall mobility heterogeneity between the income or population density groups. The study suggests that public mobility trends are in line with the government message urging to stay home. We anticipate our data-driven analysis offers integrated perspectives and serves as evidence to raise public awareness and, consequently, reinforce the importance of social distancing while assisting policymakers.

Gap-graded soils from mountain areas are often used as subgrade filling materials, but problems associated with the gap-graded soils such as large permeability, poor uniformity, and poor seepage stability have to be solved. This article proposes a new terminology "void filling ratio" to study the seepage internal stability of gap-graded soils as subgrade filling materials. Laboratory seepage tests were performed to investigate the effects of compaction degrees of coarse grains, void filling ratios, and clay contents on the internal stability. Laboratory model tests were also performed to verify the findings from the laboratory seepage tests. It was found that the internal stability increased with increase of the void filling ratios, confirmed by both laboratory seepage tests and slope model tests. The increases of both void filling ratio and the clay content were able to change the type of internal instability from piping to the transitional type of internal instability. In laboratory model tests, surface areas lost more fine particles than the deeper area did in the models, but when the void filling ratio was increased, the amount of lost fine particles was significantly reduced. Finally, it was confirmed that void filling ratio was able to effectively describe the internal stability of gap-graded soils subject to different levels of hydraulic gradient.

In this study, we investigated the changes in the distribution and regulation of endogenous hormones in Phyllostachys edulis 'Pachyloen' during bamboo shooting. Enzyme-linked immunosorbent assay was used to measure the mass fractions of indole-3-acetic acid (IAA), gibberellic acid (GA), zeatin riboside (ZR), and abscisic acid (ABA) in rhizomes, shoots, and maternal bamboo organs during shoot sprouting, shoot growth, and new-bamboo formation. Measurements were compared among bamboo parts and developmental periods. The overall mass fractions of IAA and ABA were significantly higher than those of ZR and GA, driven by differences among bamboo parts and developmental periods. The abundance of each endogenous hormone varied among bamboo parts and developmental periods. During bamboo shooting, ABA had the highest mass fraction in all bamboo parts sampled, followed by IAA, GA, and ZR. Among bamboo parts, rhizomes had more IAA, ZR, and GA than the other parts, but significantly less ABA. Winter shoots had higher ZR: IAA and GA: IAA ratios than rhizomes and maternal bamboo organs. During shoot growth, ABA was the most abundant hormone in rhizomes and maternal bamboo organs, followed by IAA, ZR, and GA. In contrast, IAA was the most abundant hormone in spring shoots, followed by ABA, ZR, and GA. Maternal bamboo organs had a significantly higher ZR: GA ratio, and significantly lower IAA: ABA, ZR: ABA, and GA: ABA ratios than rhizomes. Spring shoots had significantly higher IAA: ABA, ZR: ABA, and GA: ABA ratios than rhizomes and maternal bamboo organs; significantly higher ZR mass fractions, and ZR: GA and ZR: IAA ratios and significantly lower ABA mass fractions than rhizomes; and significantly higher GA: IAA ratio than maternal bamboo organs. During new-bamboo formation, ABA was the most abundant hormone in rhizomes, winter shoots, and maternal bamboo organs, followed by IAA, ZR, and GA. Maternal bamboo organs had significantly lower IAA mass fractions and significantly higher ABA mass fractions than rhizomes and new bamboo tissue. IAA and ABA abundances exhibited an inverse relationship in rhizomes and maternal bamboo organs. GA: ABA and GA: IAA ratios decreased gradually and other hormone ratios exhibited parabolic trends over the bamboo-shooting period, with the highest ratios observed in new bamboo tissues. Overall, the coordination or antagonism among endogenous hormones plays a key regulatory role in bamboo shoot growth. The formation of thick walls in P. edulis 'Pachyloen', one of its major traits, may be partially attributed to the relatively high IAA and ZR and low GA mass fractions.

Metacaspase (MC), which is discovered gene family with distant caspase homologs in plants, fungi, and protozoa, may be involved in programmed cell death (PCD) processes during plant development and respond abiotic and biotic stresses. To reveal the evolutionary relationship of MC gene family in Rosaceae genomes, we identified 8, 7, 8, 12, 12, and 23 MC genes in the genomes of Fragaria vesca, Prunus mume, Prunus persica, Pyrus communis, Pyrus bretschneideri and Malus domestica, respectively. Phylogenetic analysis suggested that the MC genes could be grouped into three clades: Type I*, Type I and Type II, which was supported by gene structure and conserved motif analysis. Microsynteny analysis revealed that MC genes present in the corresponding syntenic blocks of P. communis, P. bretschneideri and M. domestica, and further suggested that large-scale duplication events play an important role in the expansion of MC gene family members in these three genomes than other Rosaceae plants (F. vesca, P. mume and P. persica). RNA-seq data showed the specific expression patterns of PbMC genes in response to drought stress. The expression analysis of MC genes demonstrated that PbMC01 and PbMC03 were able to be detected in all four pear pollen tubes and seven fruit development stages. The current study highlighted the evolutionary relationship and duplication of the MC gene family in these six Rosaceae genomes and provided appropriate candidate genes for further studies in P. bretschneideri.

Sirtuin 5 (SIRT5) is a member of the NAD+-dependent sirtuin family of protein deacylase that catalyzes removal of post-translational modifications, such as succinylation, malonylation, and glutarylation on lysine residues. In light of the SIRT5's roles in regulating mitochondrion function, we show here that SIRT5 deficiency leads to suppression of mitochondrial NADH oxidation and inhibition of ATP synthase activity. As a result, SIRT5 deficiency decreases mitochondrial ATP production, increases AMP/ATP ratio, and subsequently activates AMP-activated protein kinase (AMPK) in cultured cells and mouse hearts under energy stress conditions. Moreover, Sirt5 knockout attenuates transverse aortic constriction (TAC)-induced cardiac hypertrophy and cardiac dysfunction in mice, which is associated with decreased ATP level, increased AMP/ATP ratio and enhanced AMPK activation. Our study thus uncovers an important role of SIRT5 in regulating cellular energy metabolism and AMPK activation in response to energy stress.

Mechanochemical treatment of phosphate rock is considered as an effective and ecologically clean way of treating the medium- and low-grade phosphorite which could be used as fertilizer instead of the high-grade phosphorite. In order to investigate the effects of different milling times on the mechanochemically activated phosphorite (lower total phosphorus content) by more efficient milling equipment with enhanced milling speed, phosphorus solubility in citric acid and structural characteristics of natural and mechanochemically activated phosphorite from Yichang, China were studied using scanning electron microscope, infrared spectroscopy and X-ray diffraction. Phosphorus solubility in citric acid increased proportionately with the milling time until 30 min (57.51%), but then gradually reached an equilibrium with the maximum (59.03%) in 50 min. These changes were mainly manifested in considerably reduced particle size, decreased crystallinity and increased structural defects of phosphorite due to substitution of PO43- with CO32- and the incorporation of OH-. With the incorporation of CO32- and OH-, the non-activated carbonate-fluorapatite (type B) was transformed into a mixture of carbonate-fluorapatite, hydroxyapatite, fluorocarbon hydroxyapatite and/or carbonate apatite, respectively during the process of mechanochemical activation. As a result of the structural and phase transformations after mechanochemical activation, phosphorus solubility remarkably increased.

As the root cause of illegal cyber activities, botnets are evolving continuously over the last two decades. Current researches on botnet command and control mechanism based on blockchain network suffer from high economic cost, single point of failure, and limited scalability. In this paper, we present DUSTBot, a novel P2P botnet model based on Bitcoin transactions to prepare for new cyber threats. Specifically, a covert, duplex, and low-cost command and control (C&C) channel in the Bitcoin network is presented in our work. DUSTBot uses the Bitcoin main network as the downstream channel while using the Bitcoin testnet as the upstream channel. Furthermore, the peer list exchange algorithm based on the Ethereum block hash proposed in this paper is effective against routing table poisoning attack and P2P botnet crawling. The robustness of DUSTBot against node removal is studied through constructing the botnet with a P2P simulator. We deploy the implementation of DUSTBot on cloud platforms to test its feasibility and performance. Moreover, the stealthiness of DUSTBot and the effectiveness of the proposed peer list exchange algorithm are evaluated. The results demonstrate the feasibility, performance, stealthiness, and robustness of DUSTBot. In the end, possible countermeasures are discussed to mitigate similar threats in the future.

As the location trajectory contains more spatial-temporal information about the user, it will be even dangerous for jeopardizing the privacy of the user. In order to cope with the correlation, an algorithm that utilizes the query division had been proposed. In this algorithm, random blocks of query context was used, so as the adversary was obfuscated and difficult to correlate the real result. However, this algorithm fails to dispose the size of each query block, as once same size blocks were obtained by the adversary continuously, so the adversary can regard them as blocks from the same query context, and then obtains the query context to correlate the discrete locations. In view of above conditions, in this paper we propose a fine granularity block division algorithm based on the conception of granularity measurement as well as granularity layer division, so with the help of collaborative users the location privacy of the user will be protected. In this algorithm, the query context will be divided into fine granularity size of information blocks that difficult to be distinguished with others, and then these blocks will be exchanged with other collaborative users to eliminate the difference in block size. In addition, as each block is divided into fine granularity size, the adversary will be difficult to correlate the discrete locations into location trajectory, so the location privacy will be protected. At last, through security analysis and experimental verification, this granularity indistinguishable algorithm is analyzed and verified at both theoretical and practical levels, which further demonstrate the superiority of the proposed algorithm compared with other similar algorithms.

BackgroundClinical outcomes of patients with end-stage kidney disease (ESKD) secondary to membranous nephropathy (MN) have not been well described. This study aimed to evaluate patient and/or allograft outcomes of dialysis or kidney transplantation in patients with ESKD secondary to MN.Material and methodsAll adult patients with ESKD commencing renal replacement therapy in Australia and New Zealand from January 1998 to December 2010 were extracted retrospectively from ANZDATA registry on 31st December 2013. Outcomes of MN were compared to other causes of ESKD. In a secondary analysis, outcomes of MN were compared to all patients with ESKD due to other forms of glomerulonephritis.ResultsOf 32,788 included patients, 417 (1.3%) had MN. Compared to other causes of ESKD, MN experienced lower mortality on dialysis (adjusted hazard ratio [aHR] 0.79, 95% CI 0.68-0.92, p = 0.002) and following kidney transplantation (aHR 0.57, 95% CI 0.33-0.97, p = 0.04), had a higher risk of death-censored kidney allograft failure (aHR 1.55, 95% CI: 1.00-2.41, p = 0.05) but comparable risk of overall kidney allograft failure (aHR 1.35, 95% CI 0.91-2.01, p = 0.13). Similar results were obtained using competing-risk regression analyses. MN patients were significantly more likely to receive a kidney transplant (aHR 1.38, 95% CI 1.16-1.63, pConclusionMN was associated with superior survival on dialysis and following kidney transplantation compared to patients with other causes of ESKD, and comparable patient survival compared to patients with other forms of glomerulonephritis. However, patients with MN exhibited a higher rate of death-censored allograft loss as a result of primary kidney disease recurrence.

The role of zinc (Zn2+), a modulator of N-methyl-D-aspartate (NMDA) receptors, in regulating long-term synaptic plasticity at hippocampal CA1 synapses is poorly understood. The effects of exogenous application of Zn2+ and of chelation of endogenous Zn2+ were examined on long-term potentiation (LTP) of stimulus-evoked synaptic transmission at Schaffer collateral (SCH) synapses in field CA1 of mouse hippocampal slices using whole-cell patch clamp and field recordings. Low micromolar concentrations of exogenous Zn2+ enhanced the induction of LTP, and this effect required activation of NMDA receptors containing NR2B subunits. Zn2+ elicited a selective increase in NMDA/NR2B fEPSPs, and removal of endogenous Zn2+ with high-affinity Zn2+ chelators robustly reduced the magnitude of stimulus-evoked LTP. Taken together, our data show that Zn2+ at physiological concentrations enhances activation of NMDA receptors containing NR2B subunits, and that this effect enhances the magnitude of LTP.

BACKGROUND:Based on published data, we aimed to quantitatively elucidate the possible genetic influence of rs17561 G/T and rs1800587 C/T polymorphisms of the IL1A (interleukin 1 alpha) gene in the susceptibility to several autoimmune diseases. METHODS:A series of meta-analyses were carried out. After database searching, we utilized our inclusion/exclusion criteria to screen and include the eligible studies. Passociation (P value of association test), Bonferroni-corrected Passociation value; false discovery rate (FDR)-corrected Passociation, ORs (odd ratios), and 95% CI (confidence interval) were generated to assess the magnitudes of genetic relationships. RESULTS:A total of 35 eligible articles were included. Pooled analysis data of both rs17561 G/T and rs1800587 C/T in the overall population indicated a negative association between cases of autoimmune diseases and negative controls (all Passociation>0.05, Bonferroni-corrected Passociation>0.05, FDR-corrected Passociation>0.05). Similar results were found in most subgroup analyses (all Passociation>0.05, Bonferroni-corrected Passociation>0.05, FDR-corrected Passociation>0.05), apart from the rs1800587 in the Graves' disease subgroup, which showed an increased risk in some cases, compared with controls, under the models of allele T vs. C, carrier T vs. C, CT+TT vs. CC, and CT vs. CC (all Passociation0.05, OR>1). CONCLUSION:Based on the available data, C/T genotype of the rs1800587 polymorphism within IL1A gene may be associated with an increased Graves' disease risk. We did not see evidence regarding a positive role for rs1800587 or rs17561 in the risk of other autoimmune diseases, such as systemic sclerosis or rheumatoid arthritis. These conclusions still merit further data support and molecular exploration.