The CD2v protein of African swine fever virus inhibits macrophage migration and inflammatory cytokines expression by downregulating EGR1 expression through dampening ERK1/2 activity.

African swine fever virus (ASFV) is a highly contagious and deadly virus that leads to high mortality rates in domestic swine populations. Although the envelope protein CD2v of ASFV has been implicated in immunomodulation, the molecular mechanisms underlying CD2v-mediated immunoregulation remain unclear. In this study, we generated a stable CD2v-expressing porcine macrophage (PAM-CD2v) line and investigated the CD2v-dependent transcriptomic landscape using RNA-seq. GO terms enrichment analysis and gene set enrichment analysis revealed that CD2v predominantly affected the organization and assembly process of the extracellular matrix. Wound healing and Transwell assays showed that CD2v inhibited swine macrophage migration. Further investigation revealed a significant decrease in the expression of transcription factor early growth response 1 (EGR1) through inhibiting the activity of extracellular signal-regulated kinase 1 and 2 (ERK1/2). Notably, EGR1 knockout in swine macrophages restricted cell migration, whereas EGR1 overexpression in PAM-CD2v restored the ability of macrophage migration, suggesting that CD2v inhibits swine macrophage motility by downregulating EGR1 expression. Furthermore, we performed chromatin immunoprecipitation and sequencing for EGR1 and the histone mark H3K27 acetylation (H3K27ac), and we found that EGR1 co-localized with the activated histone modification H3K27ac neighboring the transcriptional start sites. Further analysis indicated that EGR1 and H3K27ac co-occupy the promoter regions of cell locomotion-related genes. Finally, by treating various derivatives of swine macrophages with lipopolysaccharides, we showed that depletion of EGR1 decreased the expression of inflammatory cytokines including TNFα, IL1α, IL1ß, IL6, and IL8, which play essential roles in inflammation and host immune response. Collectively, our results provide new insights into the immunomodulatory mechanism of ASFV CD2v.

Event-Based Atmospheric Precipitation Uncovers Significant Even and Odd Hg Isotope Anomalies Associated with the Circumpolar Vortex.

The determination of the mass-independent fractionation of even Hg isotopes (even-MIF, Δ200Hg) in atmospheric samples adds another intriguing feature to the Hg isotope system. Despite our lack of sufficient experimental verification and the momentary absence of a valid mechanism to explain its occurrence, even-MIF could be instrumental in understanding the cycle and deposition of atmospheric Hg. In contrast to slightly positive Δ200Hg values (<0.30‰) frequently observed in most atmospheric samples, large Δ200Hg values (up to 1.24‰) determined in precipitation from Peterborough (Ontario, Canada) stand out and could provide valuable information for the origin of the even-MIF mystery. We now report a systematic analysis of high-resolution rainfall and snowfall samples collected in winter during cold weather at Peterborough, Canada. Dissolved and particulate Hg both displayed large variations of odd-MIF (from -0.93‰ to 2.02‰ for Δ199Hg), which may result from long-range transportation, as the negative odd-MIF in particulate Hg is likely a result of long-distance transport of arctic atmospheric Hg(II). Dissolved Hg revealed significant even-MIF values (from 0.25‰ to 1.19‰ for Δ200Hg) and a negative relationship between Δ200Hg and Δ204Hg, which provide further evidence for the previously proposed conceptual model of Δ200Hg. Disconnected odd-MIF and even-MIF trends were detected in sequentially collected precipitation samples, which further suggests different sources or mechanisms for Δ199Hg and Δ200Hg. Particularly, the high Δ200Hg values highlight the transport of stratospheric Hg through a polar vortex to the sampling region, stimulating further systematic investigation. The new Δ200Hg data for particulate Hg add to existing information on atmospheric Hg(II) worldwide, suggesting a global distribution of Hg characterized by even-MIF in the atmosphere, and further constrain the model of atmospheric Hg deposition.

Coprecipitation of Mercury from Natural Iodine-Containing Seawater for Accurate Isotope Measurement.

Oceans play a key role in the global mercury (Hg) cycle, but studies on Hg isotopes in seawater are rare due to the extremely low Hg concentration and the lack of a good preconcentration method. Here, we introduce a new coprecipitation method for separating and preconcentrating Hg from seawater for accurate isotope measurement. The coprecipitation was achieved by sequential addition of 0.5 mL of 0.5 M CuSO4, 1 mL of 0.5 M Na2S, and 1 mL of 0.5 M CuSO4 reagents, which allowed for quantitatively precipitating Hg from up to 10 L of seawater. The protocol was validated by testing synthetic solutions with varying Hg and iodide (I-) concentrations and by comparing the reaction times of various reagents added. The method resulted in a quantitative recovery of 98 ± 12% (n = 32, two standard deviations, 2 SD) and a relatively low procedure blank (103 pg of Hg, n = 8). The precipitates were filtrated and analyzed for Hg isotopes. Repeated measurements of synthetic seawaters spiked with certificated standard materials (NIST 3133 and 3177) using the entire method gave identical Hg isotope ratios with near-quantitative Hg recovery, indicating no isotope fractionation during preconcentration. A total of six nearshore seawater samples from the Yellow Sea and the Bohai Sea (China) were analyzed using the coprecipitation method. The data showed a large fractionation of Hg isotopes and revealed the possible impact of both atmospheric and anthropogenic inputs to the coastal seawater Hg budget, implying the potential application of this method in studying marine Hg systematics and global Hg cycling.

Mercury isotope compositions in large anthropogenically impacted Pearl River, South China.

Rivers integrate natural and anthropogenic mercury (Hg), and are important vectors of terrestrial Hg to the oceans. Here, we report the total Hg concentration and Hg isotope compositions of dissolved load in the Pearl River, the second largest river in China, in order to understand the processes and sources affecting Hg systematics in large anthropogenically-impacted river water. The dissolved Hg showed a concentration varying from 0.45 to 2.44 ng/L, within the range reported for natural background lake and river waters. All river water samples showed significantly negative δ202Hg (-2.89‰ to -0.57‰), slightly positive Δ200Hg (-0.05‰ to 0.52‰), and mostly positive Δ199Hg (0.10‰ to 0.57‰), except for three extremely negative values (-2.25‰ to -0.76‰). Combined with other geochemical parameters, we suggest that the influence of in-river processes, such as sorption and reduction, on the Hg isotope compositions is very limited, and the dissolved Hg in the Pearl River mainly comes from atmospheric precipitation and surface soil weathering. Although the whole river basin is largely affected by urban, industrial and mining activities, unlike other heavy metals, their direct contributions to dissolved Hg seem limited. It is worth noting that the three samples with very negative Δ199Hg values (down to -2.25‰) are derived from special source which attribute to the input of Hg released from the local incineration of electronic wastes. This study demonstrates that isotope approach is a powerful tool for tracing sources and pathways of Hg in large complex river systems.

Photoreduction and origin of dissolved and particulate mercury in cloud water: Insights from stable mercury isotopes.

The photoreduction of mercury (Hg) in clouds is crucial for determining global Hg cycling. The recently-developed isotope approach provides new insight into the fate of atmospheric Hg, however, limited data have been reported on the dynamics of Hg isotopes in clouds. This study presented the isotopic compositions of dissolved mercury (DHg) and particulate mercury (PHg) in cloud water collected at Mt. Tai (1545 m a.s.l.) in eastern China during summer 2021. Both DHg and PHg exhibited positive mass-independent fractionation of odd isotopes (odd-MIF, denoted as Δ199Hg), with averaged Δ199Hg values of 0.83 ± 0.34‰ and 0.20 ± 0.11‰, respectively. This high odd-MIF likely resulted from aqueous photoreduction in clouds, with DHg being more susceptible to photolysis than PHg. Our findings indicated that the photoreduction was promoted by sunlight and influenced by the chemical compositions of cloud water that controlled the Hg(II) speciation. The isotope mixing model estimation revealed that particulate-bound Hg and reactive gaseous Hg constituted the principal sources of Hg in cloud water, accounting for 55% to 99% of the total, while gaseous element Hg also made a notable contribution. Additionally, cloud water samples with faster reduction rates of Hg(II) were located outside of the isotope mixing models, which indicated an enhanced photoreduction process in cloud water.

Oxidative potential of heavy-metal contaminated soil reflects its ecological risk on earthworm.

The ecological risk of heavy metal-contaminated soil is usually evaluated by its oxidative stress on terrestrial animals, which are vulnerable to the impact of individual differences of animals and environmental conditions. Oxidative potential (OP) is the potential of particles to induce the formation of reactive oxygen species (ROS). In this study, OP of the in situ contaminated soils collected from an industrial site (i.e., 64.5-7783 mg/kg of Cu, 54.9-397 mg/kg of Pb, 278-2085 mg/kg of Zn and 0.615-121 mg/kg of Cd) were measured as 38.0-60.1 pmol/min/mg, and the water extractable Cu, Pb, Zn, and Cd in soils have been proved to contribute 89%-98% to OP. Oxidative stress in earthworms (Eisenia fetida) caused by the industrial contaminated soils can be reflected by the biomarkers such as 8-hydroxy-2'-deoxyguanosine, metallothionein, and antioxidant enzymes, and a negative correlation presents between the comprehensive biomarker response index and the OP of soils (r = -0.979, p < 0.01). This is the first time to propose a dose-response relationship between OP and oxidative stress. Metabolomic analysis also verified that the regulation of four ROS-related metabolites (i.e., l-pipecolate, 1-methylhistidine, 5-methoxytryptamine, and xanthosine) in earthworms treated with contaminated soil were directly correlated with OP values. These results indicate that OP can be used as an indicator for ecological risk assessment of heavy metal-contaminated soil, which provides a fast, stable and easily testable chemical method.

An Improved Glottal Flow Model Based on Seq2Seq LSTM for Simulation of Vocal Fold Vibration.

OBJECTIVES: An improved data-driven glottal flow model for fluid-structure interaction (FSI) simulation of the vocal fold vibration is proposed in this paper. This model aims to improve the prediction performance of the previously developed deep neural network (DNN) based empirical flow model (EFM)1 on accuracy and efficiency. METHODS: A Seq2Seq long short-term memory (LSTM) network is employed in the present model to infer the flow rate and pressure distribution from the subglottal pressure and cross-section area distribution of the glottis. The training data is collected from the generalized glottal shape library generated in Zhang et al.1 RESULTS AND CONCLUSIONS: Compared to the EFM, the present model not only discards the time-consuming optimization process, but also drastically reduces the errors, therefore the prediction performance can be greatly improved. The present model is evaluated by coupling with a solid dynamics solver for FSI simulation, and the results demonstrate a great improvement on accuracy and efficiency.

Source apportionment of soil heavy metals: A new quantitative framework coupling receptor model and stable isotopic ratios.

Tracing the source of heavy metals in soils is crucial for reversing the worrisome situation of heavy metal contamination. In this study, the origins of heavy metal pollution in soil were examined in a primary electronic waste treatment and disposal hub in China, using a synergistic source apportionment framework consisting of the positive matrix factorization (PMF) model and the Bayesian stable-isotope analysis mixing model (MixSIAR). Industrial activity is significant to heavy metal contamination in both industrial park and farmland soils, however, the contribution varied through PMF model (industrial park, 64.2%; farmland, 35.6%). In the industrial park, Pb was identified as the major pollutant in the soils, and the local children suffered from noncarcinogenic risks. Moreover, the contribution of Pb contamination sources were allocated more accurately (electronic waste dismantling, 25.1%; industrial production, 23.7%; vehicle exhaust from leaded gasoline, 9.1%; vehicle exhaust from unleaded gasoline, 20.2%; natural process, 21.9%) using MixSIAR for the first time. The main soil contaminants in surrounding farmland were Cd, Cu, and Zn. The variations in heavy metal pollution sources in soils were found to be associated with local policies and regulations, such as the phasing out of leaded gasoline and the conversion of industrial park from electronic waste demolition switched to production and storage. The identification of the source of heavy metals in soil will support targeted reduction of the associated emissions, which can immediately help alleviating soil contamination and control human health risks.

Long-Term Expansion of Porcine Intestinal Organoids Serves as an in vitro Model for Swine Enteric Coronavirus Infection.

A reliable and reproducible model in vitro for swine enteric coronaviruses infection would be intestinal models that support virus replication and can be long-term cultured and manipulated experimentally. Here, we designed a robust long-term culture system for porcine intestinal organoids from the intestinal crypt or single LGR5+ stem cell by combining previously defined insights into the growth requirements of the intestinal epithelium of humans. We showed that long-term cultured swine intestinal organoids were expanded in vitro for more than 6 months and maintained the potential to differentiate into different types of cells. These organoids were successfully infected with porcine enteric coronavirus, including porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV), and were capable of supporting virus replication and progeny release. RNA-seq analysis showed robust induction of transcripts associated with antiviral signaling in response to enteric coronavirus infection, including hundreds of interferon-stimulated genes and cytokines. Moreover, gene set enrichment analysis indicated that PEDV infection could suppress the immune response in organoids. This 3D intestinal organoid model offers a long-term, renewable resource for investigating porcine intestinal infections with various pathogens.

Felsic volcanism as a factor driving the end-Permian mass extinction.

The Siberian Traps large igneous province (STLIP) is commonly invoked as the primary driver of global environmental changes that triggered the end-Permian mass extinction (EPME). Here, we explore the contributions of coeval felsic volcanism to end-Permian environmental changes. We report evidence of extreme Cu enrichment in the EPME interval in South China. The enrichment is associated with an increase in the light Cu isotope, melt inclusions rich in copper and sulfides, and Hg concentration spikes. The Cu and Hg elemental and isotopic signatures can be linked to S-rich vapor produced by felsic volcanism. We use these previously unknown geochemical data to estimate volcanic SO2 injections and argue that this volcanism would have produced several degrees of rapid cooling before or coincident with the more protracted global warming. Large-scale eruptions near the South China block synchronous with the EPME strengthen the case that the STLIP may not have been the sole trigger.

Predicting underestimation of ductal carcinoma in situ: a comparison between radiomics and conventional approaches.

PURPOSE: We aimed to investigate the feasibility of predicting invasion carcinoma from ductal carcinoma in situ (DCIS) lesions diagnosed by preoperative core needle biopsy using radiomics signatures, clinical imaging characteristics, and breast imaging reporting and data system (BI-RADS) descriptors on mammography. METHODS: Retrospectively, we enrolled 362 DCIS patients diagnosed by core needle biopsy, 110 (30.4%) of which had invasive carcinoma confirmed by operation and pathology. We analyzed the images identified suspicious calcification from 250 subjects (161 pure DCIS and 89 DCIS with invasion). A total of 569 calcification radiomics signatures were extracted from microcalcification for each patient. We included a group of routine clinical imaging characteristics and BI-RADS descriptors for comparison purpose. Five feature selection and seven classification methods were evaluated in terms of their prediction performance. We compared the area under the receiver operating characteristic curve (AUC) averaged from tenfold cross-validation of different feature sets to identify the best combination of feature selection and classification methods. RESULTS: Optimal feature selection and classification methods were identified after evaluating various combinations of feature sets. The best performance was achieved using both radiomics and clinical imaging characteristics (AUC = 0.72) performing better than BI-RADS descriptors or radiomics, but was no significant difference with clinical imaging characteristics (AUC = 0.66). The most significant features found were morphology signatures, first-order statistics, asymmetry/mass prevalence, and nuclear grade. CONCLUSIONS: We found that the prediction model established using microcalcifications radiomics signatures and clinical imaging characteristics has the potential to identify an understaging of invasive breast cancer.

User Profiling in Elderly Healthcare Services in China: Scalper Detection.

Driven by the automation technologies and health informatics of Industry 4.0, hospitals in China have deployed a complete automation system/platform for healthcare services accessing. Without much more Internet knowledge, elderlies usually seek the third-party to assist them to get healthcare services from Web or APPs, it consequently results in an unexpected situation that scalpers could grab all healthcare services booking by unrighteous means in order to resell to elderlies for a much higher price. Moreover, it is hard for physicians to identify the scalpers due to the complexity, ad-hoc, and multiscenario nature of healthcare processes. In this paper, a novel method is proposed for the identification and creation of user groups of scalpers in mobile healthcare services. The approach utilizes and extends state of the art data analysis approaches in the event-logs of the mobile system to identify user groups. Based on the user groups, user profiles are extracted by identifying representative eventcases from hierarchical user-event clusters. A comprehensive evaluation is conducted in a selected test-set from the event-logs of a mobile healthcare APP. The result shows its accuracy and effectiveness in scalper detection in mobile healthcare APP. Further, a complete case study is deployed in a real word hospital to ensure its utility, efficacy, and reliability.

Sequential samples reveal significant variation of mercury isotope ratios during single rainfall events.

Although the investigation of mercury (Hg) isotopes in precipitation has largely improved our knowledge of the source and transformation of Hg in the atmosphere, rainwater investigated in previous studies were integrated samples collected over an event and could obscure key information about the physiochemical transformation and deposition dynamics of Hg (and its isotopes) in short precipitation events. In this study, we investigated Hg isotopic composition of filtered (HgF) and particulate Hg (HgPM) in sequential rain samples from three single rainfall events in Guiyang, China. All samples showed a decrease of total Hg concentration, as well as HgF and HgPM with time in each rainfall event, and large variation of both mass-dependent fractionation (MDF) and mass-independent fractionation of odd Hg isotopes (odd-MIF) for both phases. Isotopic data indicated variable contributions of different sources triggered by the instant change of meteorological conditions, rather than internal atmospheric processes. The rapid response of MDF and odd-MIF of precipitation samples to the incense burning on the Tomb Sweeping Day implied that Hg isotopic composition was very sensitive to the momentary anthropogenic emission, which could have at least a regional short-lived effect and should be taken into account in future studies. Hg isotopes are a powerful tool for investigating both atmospheric transformation and instant deposition dynamic of Hg, and like stable H and O isotopes, could provide useful information about local or regional meteorological changes.

Chronic pain after soft-tissue injury of the cervical spine: trapezius muscle blood flow and electromyography at static loads and fatigue.

Microcirculation in the upper portion of the right and left trapezius muscles was measured percutaneously by laser-doppler flowmetry (LDF) during two 10-min-long series of alternating 1-min periods of static contraction and rest determined electromyographically (EMG). Twenty-five patients with pain persisting after a soft-tissue injury of the neck were studied. Pain assessments by using visual analogue scales and drawings showed 13 patients with predominantly unilateral and 12 with bilateral neck-shoulder pain, in some cases with arm pain and numbness. Mean age was 41 (23-58) and 39 (22-54) years and a female/male ratio 8:5 and 10:2, respectively. Stepwise increased contraction was induced by keeping straight arms at 30 degrees, 60 degrees, 90 degrees and 135 degrees of elevation, and repeated with a 1 kg (women) or 2 kg (men) hand loads. Signal processing was done on-line by using a 386SX computer. LDF and EMG values were normalized. Spectral shift of EMG mean power frequency (MPF) for fatigue was analyzed. Muscle blood flow on the "normal" side in the unilateral pain group showed an ordinary increase at increased angle of arm elevation, shoulder torque and EMG amplitude. On the painful side, during increased muscle tension and fatigue, the ability to increase blood flow appeared to be impaired, and there was no consistent increase in either side of the bilateral pain group. EMG amplitude showed a significant positive correlation to the angle of arm elevation and shoulder torque. The rms-EMG (root mean squared EMG) increase was lower in the painful side at high force contraction (non-normalized data).(ABSTRACT TRUNCATED AT 250 WORDS)

[Influence of the included angle between anterior aspects of S2 and S1 vertebral bodies on pelvic inlet imaging in mid-line sagittal plane].

OBJECTIVE: To analyze the influence of included angle between the anterior aspects of S2 and S vertebral bodies on pelvic inlet imaging in the pelvic midline sagittal plane. METHODS: Totally 58 axial pelvic CT scans were chosen as study objects including 43 males and 15 females,with an average age of 40.7 years old (ranged,18 to 68 years old). The angles between the anterior aspects of S2 and S1, vertebral bodies and the horizontal plane on midline sagittal CT reconstruction were measured to simulate the optimal S2 and S1 inlet angles. The included angle between the anterior aspects of S2 and S1 vertebral bodies was calculated by subtrocting the S1,inlet angle from the S2 inlet angle defined as a base number. Then, the impact of the calculated included angles on the pelvic inlet imaging was analyzed. Results:The S2 inlet angles averaged (30.5±6.5) degrees; the S inlet angles averaged (25.7±5.9) degrees. The difference between them was significant (t=3.35, P=0.001). Ten patients had zero angle between the anterior aspects of S2 and S1 vertebral bodies; 14 patients had negative angle, averaged-(8.9±8.1) degrees; 34 patients had positive angle,averaged (11.8+6.4) degrees. CONCLUSION: The difference of included angle between the anterior aspects of S2 and S1 vertebral bodies leads to the difference between S1 inlet view and S2 inlet view in most cases, complicating the pelvic inlet imaging,and affecting the reliability of the application of pelvic inlet view. Utilizing the angles measured on the preoperative midlihe sagittal CT reconstruction to obatin the patient-customized S1 and S2 inlet views could accurately guide the S1 and S2 iliosacral screw insertion.