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Abstract Background Iron deficiency (ID) impairs patient physical activity, recognition and life quality, which is difficult to perceive but should not be underestimated. Worldwide efforts have been made to lower ID burden, however, whether it decreased equally in different regions and sexes is unclear. This study is to examine regional and sex inequalities in global ID from 1990 to 2017. Methods We conducted a longitudinal, comparative burden-of-disease study. Disability-adjusted life-years (DALYs) of ID were obtained from Global Burden of Disease Report 2017. Human Development Index (HDI) data were obtained from Human Development Report 2017. Gini coefficient and the concentration index were calculated to assess the equities in global burden of ID. Results A downward trend of global ID burden (from 569.3 (95% Uncertainty Interval [UI]: 387.8–815.6) to 403.0 (95% UI: 272.4–586.6), p

Abstract At-home sampling is key to large scale seroprevalence studies. Dried blood spot (DBS) self-sampling removes the need for medical personnel for specimen collection but facilitates specimen referral to an appropriately accredited laboratory for accurate sample analysis. To establish a highly sensitive and specific antibody assay that would facilitate self-sampling for prevalence and vaccine-response studies. Paired sera and DBS eluates collected from 439 sero-positive, 382 sero-negative individuals and DBS from 34 vaccine recipients were assayed by capture ELISAs for IgG and IgM antibody to SARS-CoV-2. IgG and IgM combined on DBS eluates achieved a diagnostic sensitivity of 97.9% (95%CI 96.6 to 99.3) and a specificity of 99.2% (95% CI 98.4 to 100) compared to serum, displaying limits of detection equivalent to 23 and 10 WHO IU/ml, respectively. A strong correlation (r = 0.81) was observed between serum and DBS reactivities. Reactivity remained stable with samples deliberately rendered inadequate, (p = 0.234) and when samples were accidentally damaged or ‘invalid’. All vaccine recipients were sero-positive. This assay provides a secure method for self-sampling by DBS with a sensitivity comparable to serum. The feasibility of DBS testing in sero-prevalence studies and in monitoring post-vaccine responses was confirmed, offering a robust and reliable tool for serological monitoring at a population level.

Hall sensors have a relatively low withstand voltage but have been used at the neutral point of transformers to monitor geomagnetically induced currents (GICs). However, when introduced into monitoring devices via sensor wiring, high voltages at the transformer neutral point can lead to damage to electronic components and increase the risk of serious power grid accidents. For monitoring GICs from the neutral point of the transformer, this paper proposes a transformer GIC monitoring method based on high-voltage wire equipotentials and a transformer GIC power (GIC-Q) algorithm based on the proportional coefficient K value method. A transformer monitoring device based on the proposed methods was tested at a 500 kV substation in China. In addition, we verified the accuracy of the proposed method and validity of the monitoring data produced using geomagnetic disturbance data with a Kp-index of 4 from the Man Zhouli Geomagnetic Observatory Station.

Graph convolutional neural networks have received a lot of attention in various tasks dealing with graph data by aggregating information from neighboring nodes and passing node information. Many recent studies have looked at the impact of topological features on node classification tasks by altering aggregation based on degree values or incorporating topological data analysis into graph convolutional neural networks; however, graph data itself has many topological characteristics in complex networks. In most circumstances, the graph’s topological characteristics reveal the nodes’ similarity and facilitate the node classification task. This paper proposes a topological structure feature extraction method based on the concept of complex topological characteristics, which can obtain deeper topological features in the graph structure and use node features to obtain feature information that is more important for classification from both feature spaces. Evidence from experimental studies has established that the topological structure obtained by the method in this paper can be used as input to the GCN,and good results can be achieved on the classification task even without any external information on the nodes. In the graph dataset of connected topologies, the method exhibits a very large increase in accuracy and macro F1-score when compared to the state-of-the-art baseline model after mixing the node features.

Summary: Background: Although chronic kidney disease (CKD) is associated with high multimorbidity, polypharmacy, morbidity and mortality, existing classification systems (mild to severe, usually based on estimated glomerular filtration rate, proteinuria or urine albumin-creatinine ratio) and risk prediction models largely ignore the complexity of CKD, its risk factors and its outcomes. Improved subtype definition could improve prediction of outcomes and inform effective interventions. Methods: We analysed individuals ≥18 years with incident and prevalent CKD (n = 350,067 and 195,422 respectively) from a population-based electronic health record resource (2006–2020; Clinical Practice Research Datalink, CPRD). We included factors (n = 264 with 2670 derived variables), e.g. demography, history, examination, blood laboratory values and medications. Using a published framework, we identified subtypes through seven unsupervised machine learning (ML) methods (K-means, Diana, HC, Fanny, PAM, Clara, Model-based) with 66 (of 2670) variables in each dataset. We evaluated subtypes for: (i) internal validity (within dataset, across methods); (ii) prognostic validity (predictive accuracy for 5-year all-cause mortality and admissions); and (iii) medications (new and existing by British National Formulary chapter). Findings: After identifying five clusters across seven approaches, we labelled CKD subtypes: 1. Early-onset, 2. Late-onset, 3. Cancer, 4. Metabolic, and 5. Cardiometabolic. Internal validity: We trained a high performing model (using XGBoost) that could predict disease subtypes with 95% accuracy for incident and prevalent CKD (Sensitivity: 0.81–0.98, F1 score:0.84–0.97). Prognostic validity: 5-year all-cause mortality, hospital admissions, and incidence of new chronic diseases differed across CKD subtypes. The 5-year risk of mortality and admissions in the overall incident CKD population were highest in cardiometabolic subtype: 43.3% (42.3–42.8%) and 29.5% (29.1–30.0%), respectively, and lowest in the early-onset subtype: 5.7% (5.5–5.9%) and 18.7% (18.4–19.1%). Medications: Across CKD subtypes, the distribution of prescription medication classes at baseline varied, with highest medication burden in cardiometabolic and metabolic subtypes, and higher burden in prevalent than incident CKD. Interpretation: In the largest CKD study using ML, to-date, we identified five distinct subtypes in individuals with incident and prevalent CKD. These subtypes have relevance to study of aetiology, therapeutics and risk prediction. Funding: AstraZeneca UK Ltd, Health Data Research UK.

Vibrio cholerae serogroup O1 (V. cholerae O1) is closely associated with cholera epidemics and has two main immunologically distinguishable serotypes, Ogawa and Inaba. Isolates serotype as Ogawa if the O-antigen polysaccharide (O-PS) is methylated or as Inaba if the O-PS is not methylated. This methylation is mediated by a methyltransferase encoded by the rfbT gene, and the mutation and low expression of rfbT results in serotype switch from Ogawa to Inaba. Previously, we have shown that cAMP receptor protein (CRP) activates rfbT. In this study, we demonstrated that histone-like nucleoid structuring protein (H-NS) is directly involved in the transcriptional repression of rfbT. This finding is supported by the analyses of rfbT mRNA level, rfbT-lux reporter fusions, electrophoretic mobility shift assay (EMSA), and DNase I footprinting assay. The rfbT mRNA abundances were significantly increased by deleting hns rather than fis which also preferentially associates with AT-rich sequences. A single-copy chromosomal complement of hns partly restored the down-regulation of rfbT. Analysis of rfbT-lux reporter fusions validated the transcriptional repression of hns. Subsequent EMSA and DNase I footprinting assay confirmed the direct binding of H-NS to rfbT promoter and mapped the exact binding site which was further verified by site-directed mutagenesis and promoter functional analysis. Furthermore, we found that in hns deletion mutant, CRP is no longer required for transcriptionally activating rfbT, suggesting that CRP functions as a dedicated transcription factor to relieve H-NS repression at rfbT. Together, this study expanded our understanding of the genetic regulatory mechanism of serotype conversion by global regulators in V. cholerae O1.

The gamma-ray burst GRB 221009A, known as the “brightest of all time,” is the closest energetic burst detected so far, with an energy of E _γ _,iso ∼ 10 ^55 erg. This study aims to assess its compatibility with known GRB energy and luminosity distributions. Our analysis indicates that the energy/luminosity function of GRBs is consistent across various redshift intervals, and that the inclusion of GRB 221009A does not significantly impact the function at low redshifts. Additionally, our evaluation of the best-fitting result of the entire GRB sample suggests that the expected number of GRBs with energy greater than 10 ^55 erg at a low redshift is 0.2, so that the emergence of GRB 221009A is consistent with expected energy/luminosity functions within ∼2 σ Poisson fluctuation error, still adhering to the principles of small number statistics. Furthermore, we find that GRB 221009A and other energetic bursts, defined as E _γ _,iso ≳ 10 ^54 erg, exhibit no significant differences in terms of distributions of T _90 , minimum timescale, Amati relation, E _γ _,iso – E _X,iso relation, L _γ _,iso –Γ _0 relation, E _γ _,iso –Γ _0 relation, L _γ _,iso – E _p,i –Γ _0 relation, and host galaxy properties, compared to normal long GRBs. This suggests that energetic GRBs (including GRB 221009A) and other long GRBs likely have similar progenitor systems and undergo similar energy dissipation and radiation processes. The generation of energetic GRBs may be due to more extreme central engine properties or, more likely, a rarer viewing configuration of a quasi-universal structured jet.

Power load forecasting has gained considerable research interest in recent years. The power load is vulnerable to randomness and uncertainty during power grid operations. Therefore, it is crucial to effectively predict the electric load and improve the accuracy of the prediction. This study proposes a novel power load forecasting method based on an improved long short-term memory (LSTM) neural network. Thus, an long short-term memory neural network model is established for power load forecasting, which supports variable-length inputs and outputs. The conventional convolutional neural network (CNN) and recurrent neural network (RNN) cannot reflect the sequence dependence between the output labels. Therefore, the LSTM-Seq2Seq prediction model was established by combining the sequence-to-sequence (Seq2Seq) structure with that of the long short-term memory model to improve the prediction accuracy. Four prediction models, i.e., long short-term memory, deep belief network (DBN), support vector machine (SVM), and LSTM-Seq2Seq, were simulated and tested on two different datasets. The results demonstrated the effectiveness of the proposed LSTM-Seq2Seq method. In the future, this model can be extended to more prediction application scenarios.

Rapid urbanization leads to changes in ecosystem services and may exacerbate ecological risks. Clarifying the relationship between these two factors in a specific context is essential to explore the integrated management model and achieve sustainable regional development. However, previous studies mainly lack an integrated analysis, fail to clearly explain the mechanism of ecosystem change, and can neither support landscape ecological security construction nor spatial planning and management. This study, using the urban agglomeration on the northern slope of the Tianshan Mountains (UANSTM) as an example, applied multi-source data from 2010 to 2020, investigated the changes and relationships between ecological risks and ecosystem services, and proposes an assessment framework. The total ecosystem services (TES) of the studied agglomeration showed a decreasing trend, with an overall loss of 0.43%. Corresponding to the decrease of ecosystem services, the ecological risk was higher in the south and north of the UANSTM and lower in the northwestern, central, and eastern regions. The proportion of ecological high-risk areas was expanding. The key to the relationship between ecological risks and ecosystem services is the change in hydrological conditions. Therefore, we suggest that the UANSTM actively transforms the development and use mode of water resources and coordinates their allocation, aiming to reduce regional ecological risks and optimize the pattern of ecosystem services.

Objective:To analyze the risk factors of delayed encephalopathy in patients with acute carbon monoxide poisoning (DEACMP) and to investigate the clinical significance and clinical value.Methods:The baseline data from 68 patients admitted in the 981st Hospital of Chinese People’s Liberation Army Joint Logistics Support Force were collected, including sex, age, Glasgow Coma Scale (GCS), history of smoking/drinking, history of DEACMP. Laboratory examination records including cranial CT/MRI, cervical vascular color ultrasonography, cardiac color ultrasonography, blood biochemical markers, blood routine, and blood coagulation function were also collected. Additionally, patients were followed-up visited at 1 month and 6 months. Patients were divided into either the DEACMP group or the NDEACMP group according to the occurrence of DEACMP. The risk factors of DEACMP were identified by univariate and logistic regression analyses. The area under the curve (AUC), sensitivity, and specificity of each index were compared by the receiver operating characteristic (ROC) curve.Results:Among the 68 patients, 13 patients suffered from DEACMP with an incidence of 19.1%. Univariate analysis indicated that there were statistically significant differences in patients’ age, blood glucose, blood glucose/potassium, GCS scores, abnormal cranial CT/MRI, and coma time more than 4 h (P B, SE, Wald, df, P, Exp (B) of GCS score were -0.489, 0.208, 5.55, 1, 0.018 and 0.634, respectively. Overall, GCS score is correlated with DEACMP’s occurrence. ROC curve analysis showed that the sensitivity, specificity, and the AUC of GCS scores were 0.769, 0.873 and 0.843, respectively. The AUC of the indices in descending order are: GCS score, blood glucose, blood glucose/potassium and age.Conclusion:GCS score, blood glucose, blood glucose/potassium, and age are useful predictive factors for the occurrence of DEACMP. Among these, GCS score is the most significant predictive factor.

Abstract Background Observational studies suggest interconnections between thyroid status, metabolism, and risk of coronary artery disease (CAD), but causality remains to be proven. The present study aimed to investigate the potential causal relationship between thyroid status and cardiovascular disease and to characterize the metabolomic profile associated with thyroid status. Methods Multi-cohort two-sample Mendelian randomization (MR) was performed utilizing genome-wide significant variants as instruments for standardized thyrotropin (TSH) and free thyroxine (fT4) within the reference range. Associations between TSH and fT4 and metabolic profile were investigated in a two-stage manner: associations between TSH and fT4 and the full panel of 161 metabolomic markers were first assessed hypothesis-free, then directional consistency was assessed through Mendelian randomization, another metabolic profile platform, and in individuals with biochemically defined thyroid dysfunction. Results Circulating TSH was associated with 52/161 metabolomic markers, and fT4 levels were associated with 21/161 metabolomic markers among 9432 euthyroid individuals (median age varied from 23.0 to 75.4 years, 54.5% women). Positive associations between circulating TSH levels and concentrations of very low-density lipoprotein subclasses and components, triglycerides, and triglyceride content of lipoproteins were directionally consistent across the multivariable regression, MR, metabolomic platforms, and for individuals with hypo- and hyperthyroidism. Associations with fT4 levels inversely reflected those observed with TSH. Among 91,810 CAD cases and 656,091 controls of European ancestry, per 1-SD increase of genetically determined TSH concentration risk of CAD increased slightly, but not significantly, with an OR of 1.03 (95% CI 0.99–1.07; p value 0.16), whereas higher genetically determined fT4 levels were not associated with CAD risk (OR 1.00 per SD increase of fT4; 95% CI 0.96–1.04; p value 0.59). Conclusions Lower thyroid status leads to an unfavorable lipid profile and a somewhat increased cardiovascular disease risk.

Analysis of Chinese real estate market shifted from eco nomic fundamentals to non-fundamentals, but consensus conclusions are still rarely reached. This is because institutional perspectives and national subjects are still lacking. Based on critical realistic approach, this paper integrates a state–society relationship and institution provision, constructing an analytical framework for the role of state capacity in the institutional construction of the real estate market. In terms of the intervention of the state on actors in the Chinese real estate market, the central government influences local governments, interest groups, and society at large through its administrative, extracting, and market service capacities, respectively, forming a chain of interests that serves the state–society relationship.

With the rapid development of human society, people’s requirements for lighting are also increasing. The amount of energy consumed by lighting systems in buildings is increasing, but most current lighting systems are inefficient and provide insufficient light comfort. Therefore, this paper proposes an intelligent lighting control system based on a distributed architecture, incorporating a dynamic shading system for adjusting the interior lighting environment. The system comprises two subsystems: lighting and shading. The shading subsystem utilizes fuzzy control logic to control lighting based on the room’s temperature and illumination, thereby achieving rapid control with fewer calculations. The lighting subsystem employs a Deep Deterministic Policy Gradient (DDPG) algorithm to optimize the luminaire dimming problem based on room illuminance in order to maximize user convenience while achieving uniform illumination. This paper also includes the construction of a prototype box on which the system is evaluated in two distinct circumstances. The results of the tests demonstrate that the system functions properly, has stability and real-time performance, and can adapt to complex and variable outdoor environments. The maximum relative error between actual and expected illuminance is less than 10%, and the average relative error is less than 5% when achieving uniform illuminance.

This study aimed to investigate anemia treatment and other potential effects of two food-derived bioactive oligopeptide iron complexes on pregnant rats with iron deficiency anemia (IDA) and their offspring. Rats with IDA were established with a low iron diet and then mated. There were one control group and seven randomly assigned groups of pregnant rats with IDA: Control group [Control, 40 ppm ferrous sulfate (FeSO4)]; IDA model group (ID, 4 ppm FeSO4), three high-iron groups (H-FeSO4, 400 ppm FeSO4; MCOP-Fe, 400 ppm marine fish oligopeptide iron complex; WCOP-Fe, 400 ppm whey protein oligopeptide iron complex) and three low-iron groups (L-FeSO4, 40 ppm FeSO4; MOP-Fe, 40 ppm marine fish oligopeptide iron complex; WOP-Fe, 40 ppm whey protein oligopeptide iron complex). Rats in each group were fed the corresponding special diet during pregnancy until the day of delivery. After different doses of iron supplement, serum hemoglobin, iron, and ferritin levels in rats with IDA were significantly increased to normal levels (P < 0.05). Serum iron levels were significantly lower in two food-derived bioactive oligopeptide low-iron complex groups than in the low FeSO4 group (P

Summary: Obesity-prone or obesity-resistant phenotypes can exist in individuals who consume the same diet type. Brown adipose tissue functions to dissipate energy in response to cold exposure or overfeeding. Long noncoding RNAs play important roles in a wide range of biological processes. However, systematic examination of lncRNAs in phenotypically divergent mice has not yet been reported. Here, the lncRNA expression profiles in BAT of HFD-induced C57BL/6J mice were investigated by high-throughput RNA sequencing. Genes that play roles in thermogenesis and related pathways were identified. We found lncRNA (Gm44502) may play a thermogenic role in obesity resistance by interacting with six mRNAs. Our results also indicated that seven differentially expressed lncRNAs (4930528G23Rik, Gm39490, Gm5627, Gm15551, Gm16083, Gm36860, Gm42002) may play roles in reducing heat production in obesity susceptibility by interacting with seven differentially expressed mRNAs. The screened lncRNAs may participate in the pathogenesis of weight regulation and provide insight into obesity therapy.

The aim of this systematic review and meta-analysis was to evaluate the effects of probiotics and glucose-lowering drugs (thiazolidinedione [TZD], glucagon-like pep-tide-1 receptor agonists [GLP-1 RA], dipeptidyl peptidase IV inhibitors, and sodium glucose co-transporter 2 inhibitors [SGLT-2i]) in patients with type 2 diabetes from randomized con-trolled trials (RCTs). The PubMed, Web of science, Embase, and Cochrane Library databases were searched on the treatment effects of probiotics and glucose-lowering drugs on glycemia, lipids, and blood pressure metabolism published between Jan 2015 and April 2021. We performed meta-analyses using the random-effects model. We included 25 RCTs (2,843 participants). Overall, GLP-1RA, SGLT-2i, and TZD significantly reduce fasting blood sugar (FBS) and glycated hemoglobin (HbA1c), whereas GLP-1 RA increased the risk of hypoglycaemia. Multispecies probiotics decrease FBS, total cholesterol (TC), and systolic and diastolic blood pressure (SBP, DBP). Moreover, subgroup analyses indicated that participants aged >55 years, BMI ≥30 kg/m2, longer duration of intervention, and subjects from Eastern countries, showed significantly higher reduction in FBS and HbA1c, TC, TG and SBP. This meta-analysis revealed that including multiple probiotic rather than glucose-lowering drugs might be more beneficial regarding T2D prevention who suffering from simultaneously hyperglycemia, hypercholesterolemia, and hypertension.

A realistic and visible dynamic simulation platform can significantly facilitate research on underwater robots. This paper uses the Unreal Engine to generate a scene that resembles real ocean environments, before building a visual dynamic simulation platform in conjunction with the Air-Sim system. On this basis, the trajectory tracking of a biomimetic robotic fish is simulated and assessed. More specifically, we propose a particle swarm optimization algorithm-based control strategy to optimize the discrete linear quadratic regulator controller for the trajectory tracking problem, as well as tracking and controlling discrete trajectories with misaligned time series through introducing a dynamic time warping algorithm. Simulation analyses of the biomimetic robotic fish following a straight line, a circular curve without mutation, and a four-leaf clover curve with mutation are carried out. The obtained results verify the feasibility and effectiveness of the proposed control strategy.

Existing studies on rehabilitation robots are generally devoted to robot-assisted active rehabilitation training, which is conducive to facilitating muscle and nerve regeneration. However, human–robot interaction (HRI) requires imposing a limit on the workspace within which the robot operates, so as to ensure patient safety. A safe admittance boundary algorithm for a rehabilitation robot is proposed based on the space classification model which works by constructing a virtual boundary for the HRI workspace in the control layer. First, point cloud isodensification is performed for the workspaces within which the human body and the robot operate. Next, the nearest neighbor density is determined for the point cloud, and the space classification model is built on this basis. Finally, the space classification model is integrated with admittance control to derive the safe admittance boundary algorithm, which can be used for safety control. This algorithm is then subjected to space verification experiments and out–of–bounds experiments using a dynamic arm simulator (DAS). As indicated by the experimental results, when the side length of the voxel grid for voxel center filtering is set to 0.06 m, the accuracy of space definition is 98.40%. The average maximum response time for out–of–bounds behaviors is 165.62 ms. The safe admittance boundary algorithm can impose reasonable virtual constraints on the robot workspace, thereby improving HRI safety.

CO2 adsorption is one of the promising CCS technologies, and activated coke is a solid adsorbent with excellent adsorption properties. In this study, activated coke was prepared by using bituminous coal and coconut shells activated with KOH or CaCl2 in a physically activated atmosphere and modified with ammonia. The effect of the active agent impregnation ratio on the physicochemical properties of activated coke was investigated by N2 adsorption isotherms, scanning electron microscopy (SEM) and Fourier transform infrared spectrometry (FTIR). The CO2 adsorption performance of activated coke was tested, and the effect of nitrogen-containing functional groups on CO2 adsorption was investigated by experiments and simulations. The results showed that the specific surface area of activated coke reached 629.81 m2/g at a KOH impregnation ratio of 0.5 and 610.66 m2/g at a CaCl2 impregnation ratio of 1. The maximum CO2 adsorption capacity of activated coke reached 71.70 mg/g and 90.99 mg/g for conventional power plant flue gas and oxy–fuel combustion flue gas, respectively. After ammonia modification, the CO2 adsorption capacity of activated coke was further increased. Simulations showed that pyrrole and pyrrole functional groups changed the polarity of graphene and established weak interactions with CO2.

Land use change has significant impacts on the regional and global environment; thus, in-depth research on the associated ecological risks is necessary for promoting ecological restoration and sustainable development. Xinjiang, China, is characterized by a fragile ecological environment, and this study aimed to predict the land use change in the region in 2030 under different scenarios, including natural development, ecological conservation, and urban development, by using the PLUS model based on land use data from 2000, 2010, and 2020. Based on the landscape structure of regional ecosystems, we developed a comprehensive ecological risk assessment framework by utilizing a combination of landscape disturbance index, vulnerability index, and loss index. This framework allowed us to evaluate the spatiotemporal patterns and variations of landscape ecological risks under different scenarios in 2030. The study results indicate the following: (1) During the period from 2000 to 2020, the primary landscape type in Xinjiang was unused land. However, significant changes were observed in the area of cultivated land, mainly due to the conversion of grassland and construction land. The expansion of construction land during the urbanization process resulted in a decline in ecological landscapes, such as grassland, thereby weakening the ecosystem’s stability. (2) Under different simulation scenarios, the urban development scenario primarily led to the conversion of unused land into construction land, which is beneficial for economic development. On the other hand, the ecological conservation scenario resulted in a modest increase in construction land and a transformation of unused land into forest and grassland, which aligns with the principles of sustainable development. (3) Different scenarios in 2030 result in varying degrees of changes in each landscape type in Xinjiang, with the spatial distribution characteristics of landscape ecological risks remaining similar to those observed in 2020. Notably, under the urban development scenario, the area of lowest and medium risk areas decreases significantly while the area of higher and highest risk areas increases substantially. Conversely, under the ecological conservation scenario, the area of the lowest risk areas experiences a more significant increase. (4) Overall, the spatial differences in the ecological risk of Xinjiang’s landscape are significant, with HH and LL clustering types predominating and presenting a polarization pattern. The distribution pattern is low in the north and high in the central and southern parts of the study area.

Losses, due to their non-Hermitian nature, are generally disregarded or even considered harmful when looking for non-trivial topological phases. Here, the authors experimentally demonstrate that higher-order topology can emerge as a result of introducing losses in an acoustic crystal.

Evolution of accretion disk and corona during outbursts in black hole binary systems is still unclear. Here, the authors show spectral analysis of MAXI J1820+070 and propose a scenario of a dynamical corona to explain the evolution of the reflection fraction observed by Insight-HXMT.

Vibrio fluvialis is an emerging enteric pathogen of increasing public health threat. Two quorum sensing (QS) systems, VfqI-VfqR and CqsA/LuxS-HapR, and two type VI secretion systems (T6SSs), VflT6SS1 and VflT6SS2, have been identified in V. fluvialis. Whether there exists any correlation between the two systems is unclear. In this study, we found that CqsA/LuxS-HapR circuit regulator LuxO represses while HapR activates VflT6SS2. The effect of LuxO is more pronounced at low cell density and is HapR-dependent. Deletion of hapR abolished Hcp expression and alleviated antibacterial virulence. However, these effects were rescued by HapR-expressing plasmid. Reporter fusion analyses showed that HapR is required for the promoter activities of VflT6SS2. Sequence inspection of the major cluster promoter revealed two potential Motif 1 HapR binding sites, and their bindings to HapR were confirmed by both electrophoretic mobility shift assay (EMSA) and DNase I footprinting assay. Meanwhile, two single Motif 2 sites were identified in tssD2_a (hcpA) and tssD2_b (hcpB) promoter regions of the orphan cluster which are less conserved and displayed lower affinities to HapR. Together, our study demonstrated that CqsA/LuxS-HapR QS manipulate VflT6SS2 in V. fluvialis, and this finding will enhance our understanding of possible crosstalk between T6SS and QS in microbes.

Abstract Background Osteonecrosis of the femoral head (ONFH) causes severe hip dysfunction. Left untreated, 80% of patients experience femoral head collapse, and 65–70% of patients require total hip arthroplasty (THA). Therefore, effective treatment is very important for ONFH. Objective To examine the effectiveness of fibula allografting for the treatment of early-stage ONFH Methods A systematic review was conducted by searching PubMed, EMBASE, and Web of Science databases using “avascular necrosis” or “ischemic necrosis” or “osteonecrosis” and “femoral head” and “fibula*,” and checking the references of primary articles and reviews. Two independent authors completed the study selection separately. We extracted the following details from each article: characteristics of the patients, clinical efficacy evaluation (Harris hip score [HSS], radiographic outcomes, the rate of conversation to total hip arthroplasty [THA], and adverse effects). Results A total of 213 articles were selected from PubMed (n = 45), EMBASE (n = 77), Web of Science (n = 203), and other sources (n = 10). After checking the articles, five articles were included in the final analysis. The average age of patients involved in this review was 34.48 years. The studies investigated fibula allografts to treat ONFH in 394 hips with a mean follow-up of 49.06 months. HHS was improved from 62.73 to 86.94. Radiographic progression was found in 33.66% of hips. The failure rate of head-saving surgery by THA was 14.5%. No patients had serious postoperative complications. Limitations The number of articles included in the study was small, and all studies were single-center studies. Most studies were retrospective with a low level of evidence. Surgical procedures were not identical with different follow-up times. Conclusion Although there are some limitations to our approach, this systematic review supports fibula allografting as a simple, effective treatment for early-stage ONFH, which presents less postoperative complications, and has a satisfactory clinical effect. We consider it to be worthy of promotion as a therapy for ONFH.

Objectives: The high prevalence of sleep disorders has greatly increased the demands for diagnosis and treatment; while the imbalance in geographical distribution of necessary medical resources coupled with lacking of specialist care expertise in China raise the challenges further. This study aims to explore the effectiveness of our proposed innovative PSGCloud system in providing or enhancing primary care institutions with sleep medicine service capabilities. We will introduce the entire study through a series of three research papers: this first one focuses on sleep structure and arousal analysis, and the other two ensuing papers will cover respiratory as well as limb movement issue, respectively. Methods: Firstly, the three Sleep Medical Centers involved in the study uploaded their respectively recorded polysomnography (PSG) data to the PSGCloud system. Secondly, the designated PSG technicians ran the cloud-integrated PSG scoring client of the PSGCloud to download and score PSG recordings, while the same technicians also used the standalone PSG systems built-in scoring software to score the data of the corresponding patient to generate two PSG monitoring reports, respectively. Finally, the two corresponding reports for each patient were compared and analyzed in respect of 20 parameters related to sleep structure and arousal analysis as per their differences, correlations, and agreements. Results: The dataset in this study included PSG recordings of 30 patients’ (17 male, 13 female, aged 40.8 ± 12.63 years, Body Mass Index 26.37 ± 4.34 kg/m2). For the parameters related to sleep structure, there was no significant difference between the two systems with regard to total sleep time, sleep efficiency, wake time after sleep onset, sleep latency, and so on. For the parameters concerning arousal, there was no statistically significant difference either. Significant correlations (all ICC > 0.8, and most ICC > 0.9, ICC stands for intra-class correlation) were found in parameters of the two systems. The Bland-Altman analysis showed positive agreements between the two systems. Conclusions: This study demonstrated clearly that the sleep scoring agent of our proposed PSGCloud system exhibited high agreement with that of the clinically recognized gold standard of the standalone PSG systems’ in terms of sleep structure and arousal analysis parameters within a limited sampling scope. And it would motivate the implementation of a large-scale validation study for the PSGCloud’s sleep care service delivery model.

High-redshift gamma-ray bursts (GRBs) are useful to probe the early Universe, but only a few candidates have been detected so far. Here, we report the optical and near-infrared observations of the afterglow of a relatively high-redshift event GRB 220101A, which was triggered on New Year’s Day of 2022, and therefore referred to as the “New Year’s burst.” With the optical spectra obtained by XL2.16/BFOSC and NOT/ALFOSC, we determine the redshift of the burst to be z = 4.615. We find that the optical afterglow of GRB 220101A is one of the most luminous ever detected. Based on our optical and near-infrared data, and combined with the X-ray observations, we perform a multiband fit with the Python package afterglowpy . The jet opening angle is constrained to ∼3.°4, which is consistent with the jet-break time at ∼0.7 day. We also determine the circumburst density of n _0 = 0.15 cm ^−3 and kinetic energy E _K,iso = 3.5 × 10 ^54 erg. In the prompt phase of the burst, we find a “mirror” feature in the lightcurve from 80 s to 120 s. The physical origin of such a mirror feature is unclear.

The formation of black hole–neutron star (BH–NS) or BH–BH systems may be accompanied by special supernova (SN) signals, due to the accretion feedback from the companion BH. The additional heating, which is mainly attributed to the Blandford–Payne mechanism, would disrupt the isotropic nature of the luminosity distribution on the surface of the SN ejecta, leading to the appearance of polarization. Here we develop a three-dimensional Monte Carlo polarization simulation code to conduct simulations for these special SNe. We find that the maximum polarization level of ∼2% occurs at the peak time of SN emission in the “close-binary” scenario, while in the “faraway-binary” case maximum polarization (i.e., ∼0.7%) is observed at a considerably later time than the peak of the SN. The magnitude of polarization is dependent on the degree of unevenness in the luminosity distribution and the angle between the line of sight and the equatorial direction. When considering the geometric distortion of SN ejecta at the same time, the magnitude of polarization may either increase (for a oblate ellipsoidal shape) or decrease (for a prolate ellipsoidal shape). The polarization signatures represent a promising auxiliary instrument to facilitate the identification of the companion-fed SNe. Moreover, comparing the event rate of these special SNe with the event rate density of LIGO-Virgo-detected BH–NS/BH systems could further help to distinguish the BH–NS/BH formation channel.

Recent observations indicate that hydrogen-poor superluminous supernovae (SLSNe-I) often display bumpy declining light curves. However, the cause of these undulations remains unclear. In this paper, we have improved the magnetar model, which includes flare activities. We present a systematic analysis of a well-observed SLSN-I sample with bumpy light curves in their late phase. These SLSNe-I were identified from multiple transient surveys, such as the Pan-STARRS1 Medium Deep Survey and the Zwicky Transient Facility. Our study provides a set of magnetar-powered model light curve fits for five SLSNe-I, which accurately reproduce the observed light curves using reasonable physical parameters. By extracting the essential characteristics of both the explosions and central engines, these fits provide valuable insights into investigating their potential association with gamma-ray burst engines. We found that the SLSN flares tend to be the dim and long extension of GRB flares in the peak luminosity versus peak time plane. Conducting large-scale, high-cadence surveys in the near future could enhance our comprehension of both SLSN undulating light curve properties and their potential relationship with GRBs by modeling their light curve characteristics.

Early optical observations of gamma-ray bursts can significantly contribute to the study of the central engine and physical processes therein. However, of the thousands observed so far, only a few have data at optical wavelengths in the first minutes after the onset of the prompt emission. Here we report on GRB 190106A, whose afterglow was observed in optical bands just 36 s after the Swift/BAT trigger, i.e., during the prompt emission phase. The early optical afterglow exhibits a bimodal structure followed by a normal decay, with a faster decay after ∼ T _0 + 1 day. We present optical photometric and spectroscopic observations of GRB 190106A. We derive the redshift via metal absorption lines from Xinglong 2.16 m/BFOSC spectroscopic observations. From the BFOSC spectrum, we measure z = 1.861 ± 0.002. The double-peak optical light curve is a significant feature predicted by the reverse-forward external-shock model. The shallow decay followed by a normal decay in both the X-ray and optical light curves is well explained with the standard forward-shock model with late-time energy injection. Therefore, GRB 190106A offers a case study for GRB emission from both reverse and forward shocks.

In the second work of this series, we explore the optimal search strategy for serendipitous and gravitational-wave-triggered target-of-opportunity (ToO) observations of kilonovae and optical short-duration gamma-ray burst (sGRB) afterglows from binary neutron star (BNS) mergers, assuming that cosmological kilonovae are AT2017gfo-like (but with viewing-angle dependence) and that the properties of afterglows are consistent with those of cosmological sGRB afterglows. A one-day cadence serendipitous search strategy with an exposure time of ∼30 s can always achieve an optimal search strategy of kilonovae and afterglows for various survey projects. We show that the optimal detection rates of the kilonovae (afterglows) are ∼0.3/0.6/1/20 yr ^−1 (∼50/60/100/800 yr ^−1 ) for Zwicky the Transient Facility (ZTF)/Multi-channel Photometric Survey Telescope (Mephisto)/Wide Field Survey Telescope (WFST)/Large Synoptic Survey Telescope (LSST), respectively. A better search strategy for SiTian than the current design is to increase the exposure time. In principle, a fully built SiTian can detect ∼7(2000) yr ^−1 kilonovae (afterglows). Population properties of electromagnetic (EM) signals detected by serendipitous observations are studied in detail. For ToO observations, we predict that one can detect ∼11 yr ^−1 BNS gravitational wave (GW) events during the fourth observing run (O4) by considering an exact duty cycle of the third observing run. The median GW sky localization area is expected to be ∼10 deg ^2 for detectable BNS GW events. For O4, we predict that ZTF/Mephisto/WFST/LSST can detect ∼5/4/3/3 kilonovae (∼1/1/1/1 afterglows) per year, respectively. The GW detection rates, GW population properties, GW sky localizations, and optimistic ToO detection rates of detectable EM counterparts for BNS GW events at the Advanced Plus, LIGO Voyager, and ET&CE eras are detailedly simulated in this paper.

In this paper, we forecast the expected detection rates and redshift distributions of gravitationally lensed gravitational waves (GWs) from three different mass distributions of primordial black holes (PBHs) and two stellar formation models of astrophysical black holes (ABHs) in the context of the DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) and its smaller-scale version B-DECIGO. It suggests that DECIGO will be able to detect 10 ^4 –10 ^5 GW signals from such binary black holes each year and the event rate distributions for PBHs will differ from those for ABHs due to their different merger rate with respect to redshift. The large number of event rates makes 5–70 detections of lensed GW signals possible. After considering the gravitational lensing effect, the difference between the detection rates and distributions for PBHs and ABHs will be more significant. Therefore, this can be served as a complementary method to distinguish PBHs from ABHs.

GRB 221009A is a bright gamma-ray burst (GRB) with isotropic energy larger than 10 ^54 erg. Its fairly low redshift makes it a promising candidate for high-energy neutrino detection. However, a neutrino search for this GRB reported by the IceCube collaboration yielded a null result. In this paper, we utilize the upper limit from the IceCube observation to test different GRB prompt emission models. We find that, at least for this specific burst, the dissipative photosphere model could be ruled out in a large parameter space. The internal-shock model can survive only with a large bulk motion Lorentz factor Γ, where the most stringent and conservative constraints are Γ > ∼ 450 and Γ > ∼ 200, respectively. Also, the ratio of the total dissipated energy that goes into the protons and electrons ( ϵ _p / ϵ _e ) can be constrained with a given Γ. For Γ < 400, ϵ _p / ϵ _e < 10 is required. For the Internal-collision-induced Magnetic Reconnection and Turbulence (ICMART) model, the constraint from GRB 221009A is modest. Under the ICMART model, only for extreme situations when most dissipated energy deposit into protons and all accelerated protons are suitable for producing neutrinos, a slightly large bulk motion (Γ > ∼ 250) is required.

Recently, some gamma-ray bursts (GRBs) whose light curves consist of repeating emission episodes with similar temporal profiles have attracted extensive attention. They are proposed to be candidates of millilensing events, although smoking gun evidence is lacking, since there are no redshift measurements and no angular offset detections for any of these candidates. Here we show that without invoking gravitational lensing, the repeating light-curve properties of these GRBs could also be interpreted under the jet precession model, as long as the detectable period in every precession circle is less than the precession period, and the precession period is close to the jet emission duration. By fitting the gamma-ray light curves of these GRBs, we suggest that the jet precession angle for these bursts should be relatively small (e.g., θ _p < 5.°3), and the jet structure for these bursts are more likely Gaussian. The results suggest us to be careful when identifying millilensing GRBs. Multiband afterglow data and especially angular offset detections are essential to provide comprehensive justification for this identification.

Background: Repetitive transcranial magnetic stimulation (rTMS) has therapeutic effects on craving in methamphetamine (METH) use disorder (MUD). The chronic abuse of METH causes impairments in executive function, and improving executive function reduces relapse and improves treatment outcomes for drug use disorder. The purpose of this study was to determine whether executive function helped predict patients' responses to rTMS treatment.Methods: This study employed intermittent theta burst stimulation (iTBS) rTMS modalities and observed their therapeutic effects on executive function and craving in MUD patients. MUD patients from an isolated Drug Rehabilitation Institute in China were chosen and randomly allocated to the iTBS group and sham-stimulation group. All participants underwent the Behavior Rating Inventory of Executive Function - Adult Version Scale (BRIEF-A) and Visual Analog Scales (VAS) measurements. Sixty-five healthy adults matched to the general condition of MUD patients were also recruited as healthy controls.Findings: Patients with MUD had significantly worse executive function. iTBS groups had better treatment effects on the MUD group than the sham-stimulation group. Further Spearman rank correlation and stepwise multivariate regression analysis revealed that reduction rates of the total score of the BRIEF-A and subscale scores of the inhibition factor and working memory factor in the iTBS group positively correlated with improvements in craving. ROC curve analysis showed that working memory (AUC = 87.4%; 95% CI = 0.220, 0.631) and GEC (AUC = 0.761%; 95% CI = 0.209, 0.659) had predictive power to iTBS therapeutic efficacy. The cutoff values are 13.393 and 59.804, respectively.Conclusions: The iTBS rTMS had a better therapeutic effect on the executive function of patients with MUD, and the improved executive function had the potential to become a predictor for the efficacy of iTBS modality for MUD treatment.Clinical Trial Registration:ClinicalTrials.gov, identifier: ChiCTR2100046954.

ObjectivesThis study aimed to analyze the periodontal conditions of patients with obstructive sleep apnea (OSA) in relation to the salivary microbiome.Materials and MethodsIn total, 54 male adults (27 with OSA, 27 controls) completed this cross-sectional study. All participants were monitored by overnight polysomnography (PSG) and underwent full-mouth periodontal examination. Saliva samples were then collected, and the microbial 16S ribosomal RNA gene was sequenced. The data were analyzed to determine the microbial distribution and the community structure of the two groups.ResultsDemonstrated by alpha and beta diversity, the OSA group had a lower microbial richness and a lower observed species than the controls. There was no significant difference in the microbial species diversity or evenness between the OSA and the non-OSA groups. The OSA group had fewer operational taxonomic units (OTUs), and the distribution of microbiome showed that several gram-positive bacteria had higher abundance in the OSA group. As for periodontal pathogens, the relative abundance of Prevotella was significantly increased in the OSA group. No significant difference was observed in the relative abundance of other pathogens at either the genus or species level.ConclusionsThe salivary microbial community structure was altered in patients with OSA in terms of species richness and trans-habitat diversity, along with an increase in Prevotella, a specific periodontal pathogen. These findings might explain the high prevalence of periodontitis in OSA patients.

An experimental study was carried out on the ignition characteristics of the HAN/(Emim)(EtSO4) (hydroxylammonium nitrate and 1-ethyl-3-methyl-imidazolium ethyl sulfate) dual-mode ionic liquid monopropellant in chemical propulsion mode in model thrusters. Firstly, a model thruster with a detachable convergent nozzle was designed and fabricated. Secondly, catalytic ignition experiments at different flow rates were carried out in atmosphere and in high chamber pressure environment, respectively, using a model thruster, with and without the convergent nozzle. During the catalytic ignition process, measurement methods such as thermocouple, pressure sensor, and flue gas analyzer were employed to obtain the temperature at different depths of the catalytic bed, the pressure of the combustion chamber, and the concentration variations of gaseous products CO, CO2, CH4, SO2, NO, and NO2. Then the three characteristic stages of water evaporation, HAN decomposition, and (Emim)(EtSO4) combustion were analyzed at the initiation time, and the reaction characteristics in the process of the catalytic ignition were analyzed. In addition, the composition and concentration of the combustion products at equilibrium were theoretically calculated. The effects of temperature and pressure on the concentrations of five main gaseous products were studied. Finally, the exhaust gas of the three groups of catalytic ignition experiments under different pressure environments was separately collected and measured with gas chromatography (GC) when the experiments approached equilibrium, the result of which roughly agrees with the theoretical calculations. These results are of great significance for exploring the chemical propulsion of the dual-mode ionic liquid propellant and understanding its physical catalytic combustion mechanisms.

To understand the characteristics of Vibrio isolates in aquatic environments in China and their public health significance, this study investigated water samples in six cities in China in 2020. A total of 88 sampling locations were included and Vibrio isolates were identified in 81 of them. A total of 143 Vibrio isolates belonging to 16 species were selected for characterization. The population structure of Vibrio species showed great differences among the six cities, indicating regional specificity. The presence of virulence genes was examined for the isolates (n = 78) of five pathogenic Vibrio species. All isolates except one (n = 77) contained at least one virulence gene and isolates belonging to the same species showed very similar virulence gene profiles. Then, 26 isolates from 12 species were examined by multilocus sequence typing and were assigned to 25 STs, of which 24 STs were new. Also, the presence of antibiotic-resistant genes was investigated for all 143 isolates and only three isolates were found to contain genes from aminoglycosides, phenicols, beta-lactams or the tetracycline family. Our results provide valuable insights into the Vibrio community in Chinese aquatic environments and can be applied as guidance for the environmental surveillance of the risk of Vibrio isolates.

Objective: To observe the changes in sleep characteristics and BDI scores in patients with short-term insomnia disorder (SID) using a longitudinal observational study.Methods: Fifty-four patients who met the criteria for SID of the International Classification of Sleep Disorders, third edition, were recruited. Depression levels were assessed using the Beck depression inventory (BDI) at enrollment and after 3 months of follow-up, respectively. Sleep characteristics were assessed by polysomnography.Results: After 3 months of follow-up, the group was divided into SID with increased BDI score (BDI >15) and SID with normal BDI score (BDI ≤ 15) according to the total BDI score of the second assessment. The differences in rapid eye movement (REM) sleep latency, REM sleep arousal index, and NREM sleep arousal index between the two groups were statistically significant. The total BDI score was positively correlated with REM and NREM sleep arousal index and negatively correlated with REM sleep latency, which were analyzed by Pearson correlation coefficient. Multiple linear regression was used to construct a regression model to predict the risk of depression in which the prediction accuracy reached 83.7%.Conclusion: REM sleep fragmentation is closely associated with future depressive status in patients with SID and is expected to become an index of estimating depression risk.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.

ObjectiveThis study compared the clinical efficacy and safety of argatroban and alteplase in the treatment of acute cerebral infarction.MethodsThis study retrospectively analyzed 131 patients admitted for acute cerebral infarction within 48 h of onset from 1 December 2018 to 1 May 2021. The patients were divided according to treatment (i.e., the argatroban and alteplase groups). The National Institutes of Health Stroke Scale (NIHSS) scores (before treatment, at 24 h, and at 3, 7, and 14 days), 14-day response rate, 3-month modified Rankin Scale score (mRS), activities of daily living (ADL) score, prognosis, and adverse events during treatment were compared.ResultsSixty-two and 69 patients were enrolled in the alteplase and argatroban groups, respectively, and both had comparable baseline data. The NIHSS scores of the alteplase group decreased significantly before and after treatment (24 h and at 3, 7, and 14 days), whereas those of the alteplase group decreased most rapidly after 24 h of administration. The argatroban group showed no significant changes in NIHSS score in the first 7 days after treatment until day 14, at which it significantly decreased. Statistically significant differences between the two groups were observed in four points (P vs. 65.2%; χ2 = 131; P = 0.001). The 3-month mRS, ADL and pre-treatment comparisons were statistically significant in the two groups (P P > 0.05). Furthermore, the outcomes at 3 months after treatment in both groups did not vary significantly (alteplase vs. argatroban: 48/62 vs. 51/69; χ2 = 0.217; P = 0.641). Adverse events during treatment included gingival bleeding (two patients), positive fecal occult blood (two patients), and minor intracranial blood ooze (one patient) in the alteplase group, whereas no adverse events (e.g., bleeding and shock) were noted in the argatroban group.ConclusionThe short-term efficacy of argatroban in improving neurological function in patients with acute cerebral infarction was significantly lower than that of alteplase. However, the long-term efficacy at 3 months of treatment was comparably significant to that of alteplase with fewer adverse events.

Staphylococcus spp., especially Staphylococcus aureus (S. aureus), is an important pathogen in hospital-acquired infection and food poisoning. Here, we developed a multienzyme isothermal rapid amplification combined with duplex quantitative PCR (duplex MIRA-qPCR) method, which can simultaneously detect the S. aureus species-specific conserved gene FMN-bgsfp and the Staphylococcus genus-specific conserved gene tuf. This assay enabled the amplification of DNA within 20 min at a constant temperature of 39 °C. Specificity analysis indicated that all nine common Staphylococcus species were positive and non-Staphylococcus spp. were negative for tuf gene, whereas S. aureus was positive, non-aureus Staphylococci species and non-Staphylococcus spp. were negative for FMN-bgsfp gene, suggesting that duplex MIRA-qPCR exhibited high specificity. Meanwhile, the sensitivity was tested and the limit of detection (LoD) was 3 × 102 CFU/mL. The coefficient variation values ranged from 0.13% to 2.09%, indicating that the assay had good repeatability. Furthermore, all the nine common Staphylococcus species (including S. aureus) could be detected from four kinds of simulated samples and the LoD of S. aureus was 8.56 × 103 CFU/mL. In conclusion, the duplex MIRA-qPCR has advantages of stronger specificity, lower detection threshold, shorter detection time, and simpler operation, which is an effective tool to detect S. aureus and non-aureus Staphylococci spp. infections rapidly.

The efficient utilization of energy in rich fuel detonation processes and the effective control method of soot are important topics in combustion research. In this paper, we numerically study the detonation wave behavior of acetylene–air systems in rich fuel condition by using a reduced reaction mechanism. The non-stiff terms of the governing equations are solved explicitly using the gas kinetic scheme, and the stiff terms are solved implicitly. Our results show that the acetylene pyrolysis is the dominant reaction process. The oxidation reaction is exploited to initiate the reaction induction process, providing the required energy to overcome the potential energy barrier. The secondary detonation structure is due to the stable interaction of the transverse waves and the combined action of the vinyl reaction system, thus effectively improve the energy release rate and providing a powerful solution for the fuel-rich high-energy release of advanced heat engines. The area of the unreacted pocket increases with the acetylene concentration, resulting in an irregular wave-front and detonation cell. The reflected shock wave impacting on the wall induces the secondary reaction of the detonation products. The concentration of polycyclic aromatic hydrocarbons decreases significantly and regenerates near the wall. Our approach provides an effective tool for controlling detonation soot and the preparation of carbon particles.

Vibrio parahaemolyticus, the leading cause of seafood-associated gastroenteritis worldwide, has a strong ability to form biofilms on surfaces. Quorum sensing (QS) is a process widely used by bacteria to communicate with each other and control gene expression via the secretion and detection of autoinducers. OpaR is the master QS regulator of V. parahaemolyticus operating under high cell density (HCD). OpaR regulation of V. parahaemolyticus biofilm formation has been reported, but the regulatory mechanisms are still not fully understood. bis-(3′-5′)-cyclic di-GMP (c-di-GMP) is an omnipresent intracellular second messenger that regulates diverse behaviors of bacteria including activation of biofilm formation. In this work, we showed that OpaR repressed biofilm formation and decreased the intracellular concentration of c-di-GMP in V. parahaemolyticus RIMD2210633. The OpaR box-like sequences were detected within the regulatory DNA regions of scrA, scrG, VP0117, VPA0198, VPA1176, VP0699, and VP2979, encoding a group of GGDEF and/or EAL-type proteins. The results of qPCR, LacZ fusion, EMSA, and DNase I footprinting assays demonstrated that OpaR bound to the upstream DNA regions of scrA, VP0117, VPA0198, VPA1176, and VP0699 to repress their transcription, whereas it positively and directly regulated the transcription of scrG and VP2979. Thus, transcriptional regulation of these genes by OpaR led directly to changes in the intracellular concentration of c-di-GMP. The direct association between QS and c-di-GMP metabolism in V. parahaemolyticus RIMD2210633 would be conducive to precise control of gene transcription and bacterial behaviors such as biofilm formation.

Background: Excessive alcohol consumption is associated with damage to various organs, but its multi-organ effects have not been characterised across the usual range of alcohol drinking in a large general population sample. Methods: We assessed global effect sizes of alcohol consumption on quantitative magnetic resonance imaging phenotypic measures of the brain, heart, aorta, and liver of UK Biobank participants who reported drinking alcohol. Results: We found a monotonic association of higher alcohol consumption with lower normalised brain volume across the range of alcohol intakes (–1.7 × 10−3 ± 0.76 × 10−3 per doubling of alcohol consumption, p=3.0 × 10−14). Alcohol consumption was also associated directly with measures of left ventricular mass index and left ventricular and atrial volume indices. Liver fat increased by a mean of 0.15% per doubling of alcohol consumption. Conclusions: Our results imply that there is not a ‘safe threshold’ below which there are no toxic effects of alcohol. Current public health guidelines concerning alcohol consumption may need to be revisited. Funding: See acknowledgements.

Streptomycin is considered to be one of the effective antibiotics for the treatment of plague. In order to investigate the streptomycin resistance of Y. pestis in China, we evaluated streptomycin susceptibility of 536 Y. pestis strains in China in vitro using the minimal inhibitory concentration (MIC) and screened streptomycin resistance-associated genes (strA and strB) by PCR method. A clinical Y. pestis isolate (S19960127) exhibited high-level resistance to streptomycin (the MIC was 4,096 mg/L). The strain (biovar antiqua) was isolated from a pneumonic plague outbreak in 1996 in Tibet Autonomous Region, China, belonging to the Marmota himalayana Qinghai-Tibet Plateau plague focus. In contrast to previously reported streptomycin resistance mediated by conjugative plasmids, the genome sequencing and allelic replacement experiments demonstrated that an rpsL gene (ribosomal protein S12) mutation with substitution of amino-acid 43 (K43R) was responsible for the high-level resistance to streptomycin in strain S19960127, which is consistent with the mutation reported in some streptomycin-resistant Mycobacterium tuberculosis strains. Streptomycin is used as the first-line treatment against plague in many countries. The emergence of streptomycin resistance in Y. pestis represents a critical public health problem. So streptomycin susceptibility monitoring of Y. pestis isolates should not only include plasmid-mediated resistance but also include the ribosomal protein S12 gene (rpsL) mutation, especially when treatment failure is suspected due to antibiotic resistance.

Vibrio cholerae and Vibrio parahaemolyticus are common diarrheal pathogens of great public health concern. A multiplex TaqMan-based real-time PCR assay was developed on the BD MAX platform; this assay can simultaneously detect and differentiate V. cholerae and V. parahaemolyticus directly from human fecal specimens. The assay includes two reactions. One reaction, BDM-VC, targets the gene ompW, the cholera toxin (CT) coding gene ctxA, the O1 serogroup specific gene rfbN, and the O139 serogroup specific gene wbfR of V. cholerae. The other, BDM-VP, targets the gene toxR and the toxin coding genes tdh and trh of V. parahaemolyticus. In addition, each reaction contains a sample process control. When evaluated with spiked stool samples, the detection limit of the BD MAX assay was 195–780 CFU/ml for V. cholerae and 46–184 CFU/ml for V. parahaemolyticus, and the amplification efficiency of all genes was between 95 and 115%. The assay showed 100% analytical specificity, using 63 isolates. The BD MAX assay was evaluated for its performance compared with conventional real-time PCR after automated DNA extraction steps, using 164 retrospective stool samples. The overall percent agreement between the BD MAX assay and real-time PCR was ≥ 98.8%; the positive percent agreement was 85.7% for ompW, 100% for toxR/tdh, and lower (66.7%) for trh because of a false negative. This is the first report to evaluate the usage of the BD MAX open system in detection and differentiation of V. cholerae and V. parahaemolyticus directly from human samples.

Attached Vibrio cholerae biofilms are essential for environmental persistence and infectivity. The vps loci (vpsU, vpsA-K, and vpsL-Q) are required for mature biofilm formation and are responsible for the synthesis of exopolysaccharide. Transcription of vps genes is activated by the signaling molecule bis-(3′–5′)-cyclic di-GMP (c-di-GMP), whose metabolism is controlled by the proteins containing the GGDEF and/or EAL domains. The ferric uptake regulator (Fur) plays key roles in the transcription of many genes involved in iron metabolism and non-iron functions. However, roles for Fur in Vibrio biofilm production have not been documented. In this study, phenotypic assays demonstrated that Fur, independent of iron, decreases in vivo c-di-GMP levels and inhibits in vitro biofilm formation by Vibrio cholerae. The Fur box-like sequences were detected within the promoter-proximal DNA regions of vpsU, vpsA-K, vieSAB, and cdgD, suggesting that transcription of these genes may be under the direct control of Fur. Indeed, the results of luminescence, quantitative PCR (qPCR), electrophoretic mobility shift assay (EMSA), and DNase I footprinting assays demonstrated Fur to bind to the promoter-proximal DNA regions of vpsU, vpsA-K, and cdgD to repress their transcription. In contrast, Fur activates the transcription of vieSAB in a direct manner. The cdgD and vieSAB encode proteins with GGDEF and EAL domains, respectively. Thus, data presented here highlight a new physiological role for Fur wherein it acts as a repressor of V. cholerae biofilm formation mediated by decreasing the production of exopolysaccharide and the intracellular levels of c-di-GMP.

Cholera toxin (CT) and toxin coregulated pilus (TCP, TcpA is the major subunit) are two major virulence factors of Vibrio cholerae, both of which play critical roles in developing severe diarrhea in human. Expression of CT and TCP is under the tight control of the regulatory cascade known as the ToxR virulence regulon, which is composed of three regulators ToxR, TcpP, and ToxT. Besides, their expression is also regulated by the quorum sensing (QS) master regulator HapR and the regulatory protein Fur. Though transcription of tcpP, toxT, and/or tcpA are reported to be regulated by HapR and Fur, to date there are no studies to verify their direct regulations. In the present study, we showed that HapR directly repress the transcription of tcpP and tcpA by binding to their promoter regions, and possibly repress toxT transcription in an indirect manner. Fur directly activated the transcription of tcpP, toxT, and tcpA by binding to their promoters. Taking account of the sequential expression of hapR, fur, tcpP, toxT, and tcpA in the different growth phases of V. cholerae, we deduce that at the early mid-logarithmic growth phase, Fur binds to the promoters of tcpP, toxT, and tcpA to activate their transcription; while at the later mid-logarithmic growth phase, HapR can bind to the promoters of tcpP and tcpA to repress their transcription. Our study reveals the new recognition in the virulence regulatory pathways in V. cholerae and suggests the complicated and subtle regulation network with the growth density dependence.