Revealing the Interaction Mechanism between Mycobacterium tuberculosis GyrB and Novobiocin, SPR719 through Binding Thermodynamics and Dissociation Kinetics Analysis.

With the rapid emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb), various levels of resistance against existing anti-tuberculosis (TB) drugs have developed. Consequently, the identification of new anti-TB targets and drugs is critically urgent. DNA gyrase subunit B (GyrB) has been identified as a potential anti-TB target, with novobiocin and SPR719 proposed as inhibitors targeting GyrB. Therefore, elucidating the molecular interactions between GyrB and its inhibitors is crucial for the discovery and design of efficient GyrB inhibitors for combating multidrug-resistant TB. In this study, we revealed the detailed binding mechanisms and dissociation processes of the representative inhibitors, novobiocin and SPR719, with GyrB using classical molecular dynamics (MD) simulations, tau-random acceleration molecular dynamics (τ-RAMD) simulations, and steered molecular dynamics (SMD) simulations. Our simulation results demonstrate that both electrostatic and van der Waals interactions contribute favorably to the inhibitors' binding to GyrB, with Asn52, Asp79, Arg82, Lys108, Tyr114, and Arg141 being key residues for the inhibitors' attachment to GyrB. The τ-RAMD simulations indicate that the inhibitors primarily dissociate from the ATP channel. The SMD simulation results reveal that both inhibitors follow a similar dissociation mechanism, requiring the overcoming of hydrophobic interactions and hydrogen bonding interactions formed with the ATP active site. The binding and dissociation mechanisms of GyrB with inhibitors novobiocin and SPR719 obtained in our work will provide new insights for the development of promising GyrB inhibitors.

Genome-wide chromatin accessibility landscape and dynamics of transcription factor networks during ovule and fiber development in cotton.

BACKGROUND: The development of cotton fiber is regulated by the orchestrated binding of regulatory proteins to cis-regulatory elements associated with developmental genes. The cis-trans regulatory dynamics occurred throughout the course of cotton fiber development are elusive. Here we generated genome-wide high-resolution DNase I hypersensitive sites (DHSs) maps to understand the regulatory mechanisms of cotton ovule and fiber development. RESULTS: We generated DNase I hypersensitive site (DHS) profiles from cotton ovules at 0 and 3 days post anthesis (DPA) and fibers at 8, 12, 15, and 18 DPA. We obtained a total of 1185 million reads and identified a total of 199,351 DHSs through ~ 30% unique mapping reads. It should be noted that more than half of DNase-seq reads mapped multiple genome locations and were not analyzed in order to achieve a high specificity of peak profile and to avoid bias from repetitive genomic regions. Distinct chromatin accessibilities were observed in the ovules (0 and 3 DPA) compared to the fiber elongation stages (8, 12, 15, and 18 DPA). Besides, the chromatin accessibility during ovules was particularly elevated in genomic regions enriched with transposable elements (TEs) and genes in TE-enriched regions were involved in ovule cell division. We analyzed cis-regulatory modules and revealed the influence of hormones on fiber development from the regulatory divergence of transcription factor (TF) motifs. Finally, we constructed a reliable regulatory network of TFs related to ovule and fiber development based on chromatin accessibility and gene co-expression network. From this network, we discovered a novel TF, WRKY46, which may shape fiber development by regulating the lignin content. CONCLUSIONS: Our results not only reveal the contribution of TEs in fiber development, but also predict and validate the TFs related to fiber development, which will benefit the research of cotton fiber molecular breeding.

Smoke exposure levels prediction following laboratory combustion of Pinus koraiensis plantation surface fuel.

High concentrations of harmful gases released from forest fire will pose a short-term hazard to fire-fighters' cardiopulmonary function, even threaten their lives. In this study, laboratory experiments were conducted to examine the relationship between harmful gases concentrations and burning environment and fuel characteristics. In the experiments, fuel beds were created with controlled moisture contents and fuel loads; a wind tunnel device was used to conduct 144 trials, each with a specific wind speed. The easily predicted fire behavioral characteristics and the harmful gases concentrations such as CO, CO2, NOx, SO2 which were released during fuel combustion were measured and analyzed. The results showed that the influences of wind speed, fuel moisture content, and fuel load on the flame length are in accordance with the fundamental theory of forest combustion. The contributions by controled variables to the influence on the short-term exposure concentration of CO and CO2 can be ranked as fuel load > wind speed > fuel moisture. The R2 of the established linear model that was used to predict Mixed Exposure Ratio was 0.98. Our results can help protect the health and lives of forest fire-fighters and can be used by forest fire smoke management to guide fire suppression.

The Potential Diagnostic Biomarkers for the IgG Subclass in Coal Workers' Pneumoconiosis.

Evidence suggests that exposure to coal dust increases immunoglobulin concentration. However, there is a paucity of data reporting immunoglobulin G (IgG) subclass in coal workers' pneumoconiosis (CWP). Therefore, this study intended to evaluate potential diagnostic biomarkers for the disease. CWP patients, dust-exposed workers without pneumoconiosis (DEW), and matched healthy controls (HCs) presented to the General Hospital of Datong Coal Mining Group and Occupational Disease Prevention and Treatment Hospital of Datong Coal Mining Group between May 2019 and September 2019 were recruited. The serum immunoglobulin concentration was determined by the multiplex immunoassay technique. Totally, 104 CWP patients, 109 DEWs, and 74 HCs were enrolled. Serum levels of IgG1, IgG2, IgM, and IgA were elevated in CWPs compared with those in DEWs and HCs (P < 0.05). The order of diagnostic accuracy between CWPs and DEWs depicted by the receiver operating characteristic (ROC) curve was IgG2, IgM, IgG1, IgG3, and IgA. Significantly higher IgG1/IgG3 and IgG2/IgG3 ratios were observed in the CWP group than in DEW and HC groups. Based on the IgG2/IgG3 ratio, the area under the ROC curve between CWP and DEW was 0.785 (95% CI 0.723-0.838), with a sensitivity of 73.1% and a specificity of 73.4%. Our findings suggest that IgG1, IgG2, IgM, and IgA are higher in the CWPs than DEWs and HCs. The IgG2/IgG3 ratio provides a viable alternative for the diagnosis of CWP.

Effect of snow cover on water and heat transfer in alpine meadows in the source region of Yellow River.

Extreme snowfall events have been increasing in the Tibetan Plateau, causing greater variations in the snow cover conditions. However, the soil water-heat transfer under different snow conditions has rarely been characterized in detail. Here, by using the multi-source observation data of five years, we analyzed the influences of snow cover on water-heat transfer in alpine meadows of the source region of the Yellow River. The main findings are as follows: In the deep soil, the yearly warming rate from spring to summer was much faster than the cooling rate from autumn to winter, while in the shallow soil, conversely, the former was slower than the latter. Snow cover not only decreased the average soil temperature but also inhibited the occurrence of extremely low temperatures in the soil. The insulation effect of snow was mainly in the mid-frozen period. It was insufficient to balance out the heat lost by the high albedo during early and late frozen periods. In years with more snow, different depths of the soil featured similar thawing dates and plenty of soil voids due to small solid water content and high gravel content, together creating favorable conditions for the snowmelt infiltration, which passed through the frozen layer and infiltrated into the soil of 3.20 m or deeper. In years with less snow, the long-term freezing-thawing cycles aggravated the evaporation and loss of surface soil water in spring. Under different snow cover conditions, the difference in the sensible heat flux was much larger than the latent heat flux in winter and early spring. This study provides a refined physical image of soil water-heat transfer under extreme snow cover conditions in the Tibetan Plateau, which is expected to light the snow cover-frozen soil interaction in the mid-latitude and high-elevation areas.

Preparation and Performance Characterization of Exploding Foil Initiator Based on ODPA-ODA Polyimide Flyer.

The exploding foil initiator (EFI) system has been extensively used in ignition and detonation sequences and proved to be of high safety and reliability. Polyimide is considered the ideal flyer material for EFI due to its excellent performance, including thermal stability, outstanding mechanical properties, high radiation resistance, and excellent dielectric properties. In this study, we prepared the EFI based on a polyimide (ODPA-ODA) flyer, which is spin-coated and solidified on patterned copper film in situ. The electric explosion test shows that the prepared EFI has good working performance, and the 4000 V working voltage drove the flyer to reach a maximum velocity of 5096 m/s. The polyimide morphology and chemical structure after the electric explosion was observed by microscope, SEM, XPS, and FTIR, which showed that the polyimide flyer underwent thermal deformation and complex chemical reactions during an electric explosion. A large number of polyimide bonds broke to form new carbonyl compounds, and the opening of aromatic rings was accompanied by the formation of aliphatic hydrocarbon chains. The morphology and chemical structure analysis after the electric explosion test will lay a foundation for us to further understand the working principle and evolution process of polyimide (ODPA-ODA) flyer.

FcεRI deficiency alleviates silica-induced pulmonary inflammation and fibrosis.

Silicosis is one of the most important occupational diseases worldwide, caused by inhalation of silica particles or free crystalline silicon dioxide. As a disease with high mortality, it has no effective treatment and new therapeutic targets are urgently needed. Recent studies have identified FCER1A, encoding α-subunit of the immunoglobulin E (IgE) receptor FcεRI, as a candidate gene involved in the biological pathways leading to respiratory symptoms. FcεRI is known to be important in allergic asthma, but its role in silicosis remains unclear. In this study, serum IgE concentrations and FcεRI expression were assessed in pneumoconiosis patients and silica-exposed mice. The role of FcεRI was explored in a silica-induced mouse model using wild-type and FcεRI-deficient mice. The results showed that serum IgE concentrations were significantly elevated in both pneumoconiosis patients and mice exposed to silica compared with controls. The mRNA and protein expression of FcεRI were also significantly increased in the lung tissue of patients and silica-exposed mice. FcεRI deficiency significantly attenuated the changes in lung function caused by silica exposure. Silica-induced elevations of IL-1ß, IL-6, and TNF-α were significantly attenuated in the lung tissue and bronchoalveolar lavage fluid (BALF) of FcεRI-deficient mice compared with wild-type controls. Additionally, FcεRI-deficient mice showed a significantly lower score of pulmonary fibrosis than wild-type mice following exposure to silica, with significantly lower hydroxyproline content and expression of fibrotic genes Col1a1 and Fn1. Immunofluorescent staining suggested FcεRI mainly on mast cells. Mast cell degranulation took place after silica exposure, as shown by increased serum histamine levels and ß-hexosaminidase activity, which were significantly reduced in FcεRI-deficient mice compared with wild-type controls. Together, these data showed that FcεRI deficiency had a significant protective effect against silica-induced pulmonary inflammation and fibrosis. Our findings provide new insights into the pathophysiological mechanisms of silica-induced pulmonary fibrosis and a potential target for the treatment of silicosis.

Effect of fire spread, flame characteristic, fire intensity on particulate matter 2.5 released from surface fuel combustion of Pinus koraiensis plantation- A laboratory simulation study.

PM2.5 is one of major pollutants emitted from forest fires. High PM2.5 concentration not only affects short-term human respiration health, but also poses a long-term threat to human cardiopulmonary functionality. Therefore, it is of great importance to quantitatively assess the PM2.5 released by forest combustion in forest fire studies. In this study we examine relationships between the PM2.5 concentration and environment and fuel characteristics laboratory experiments. In the experiments, fuel beds with controlled moisture contents and loads were first built; then 144 ignition experiments were conducted for various combinations of wind speeds using a wind tunnel device. Fire behavior characteristics and PM2.5 concentrations released from fuel combustion were measured and analyzed. The experimental results show that the relationship between fire characteristics, fire intensity and the influencing factors of wind speed, fuel moisture content, and fuel load can be explained by the fundamental theory of forest combustion. Although PM2.5 concentration rises with the increase of wind speed, the decrease of fuel moisture content, and the increase of fuel load, there appears to be a fuel load threshold for a given combination of wind speed and fuel moisture content that the increase of PM2.5 concentration decelerates quickly after the load passes the threshold value. After screening fire behavior characteristics that affect PM2.5 concentration, we found that fire line intensity and flame width are the ones with the strongest association with the concentration. With flame width as independent variable, we have built two regression models to predict PM2.5 and fire line intensity which are treated as dependent variable; the models have high accuracy with R2 = 0.92 for predicting PM2.5 and R2 = 0.97 for predicting fire line intensity. Study results can be used as reference to protect the health of forest fire fighters, and can be helpful for forest fire smoke management.

Conservation and Divergence of Phosphoenolpyruvate Carboxylase Gene Family in Cotton.

Phosphoenolpyruvate carboxylase (PEPC) is an important enzyme in plants, which regulates carbon flow through the TCA cycle and controls protein and oil biosynthesis. Although it is important, there is little research on PEPC in cotton, the most important fiber crop in the world. In this study, a total of 125 PEPCs were identified in 15 Gossypium genomes. All PEPC genes in cotton are divided into six groups and each group generally contains one PEPC member in each diploid cotton and two in each tetraploid cotton. This suggests that PEPC genes already existed in cotton before their divergence. There are additional PEPC sub-groups in other plant species, suggesting the different evolution and natural selection during different plant evolution. PEPC genes were independently evolved in each cotton sub-genome. During cotton domestication and evolution, certain PEPC genes were lost and new ones were born to face the new environmental changes and human being needs. The comprehensive analysis of collinearity events and selection pressure shows that genome-wide duplication and fragment duplication are the main methods for the expansion of the PEPC family, and they continue to undergo purification selection during the evolutionary process. PEPC genes were widely expressed with temporal and spatial patterns. The expression patterns of PEPC genes were similar in G. hirsutum and G. barbadense with a slight difference. PEPC2A and 2D were highly expressed in cotton reproductive tissues, including ovule and fiber at all tested developmental stages in both cultivated cottons. However, PEPC1A and 1D were dominantly expressed in vegetative tissues. Abiotic stress also induced the aberrant expression of PEPC genes, in which PEPC1 was induced by both chilling and salinity stresses while PEPC5 was induced by chilling and drought stresses. Each pair (A and D) of PEPC genes showed the similar response to cotton development and different abiotic stress, suggesting the similar function of these PEPCs no matter their origination from A or D sub-genome. However, some divergence was also observed among their origination, such as PEPC5D was induced but PEPC5A was inhibited in G. barbadense during drought treatment, suggesting that a different organized PEPC gene may evolve different functions during cotton evolution. During cotton polyploidization, the homologues genes may refunction and play different roles in different situations.

Inhibition of gasdermin D-dependent pyroptosis attenuates the progression of silica-induced pulmonary inflammation and fibrosis.

Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide, but the molecular basis underlying its development remains unclear. An accumulating body of evidence supports gasdermin D (GSDMD)-mediated pyroptosis as a key component in the development of various pulmonary diseases. However, there is little experimental evidence connecting silicosis and GSDMD-driven pyroptosis. In this work, we investigated the role of GSDMD-mediated pyroptosis in silicosis. Single-cell RNA sequencing of healthy and silicosis human and murine lung tissues indicated that GSDMD-induced pyroptosis in macrophages was relevant to silicosis progression. Through microscopy we then observed morphological alterations of pyroptosis in macrophages treated with silica. Measurement of interleukin-1ß release, lactic dehydrogenase activity, and real-time propidium iodide staining further revealed that silica induced pyroptosis of macrophages. Additionally, we verified that both canonical (caspase-1-mediated) and non-canonical (caspase-4/5/11-mediated) signaling pathways mediated silica-induced pyroptosis activation, in vivo and in vitro. Notably, Gsdmd knockout mice exhibited dramatically alleviated silicosis phenotypes, which highlighted the pivotal role of pyroptosis in this disease. Taken together, our results demonstrated that macrophages underwent GSDMD-dependent pyroptosis in silicosis and inhibition of this process could serve as a viable clinical strategy for mitigating silicosis.

Pirfenidone ameliorates silica-induced lung inflammation and fibrosis in mice by inhibiting the secretion of interleukin-17A.

Silicosis is a global occupational disease characterized by lung dysfunction, pulmonary inflammation, and fibrosis, for which there is a lack of effective drugs. Pirfenidone has been shown to exert anti-inflammatory and anti-fibrotic properties in the lung. However, whether and how pirfenidone is effective against silicosis remains unknown. Here, we evaluated the efficacy of pirfenidone in the treatment of early and advanced silicosis in an experimental mouse model and explored its potential pharmacological mechanisms. We found that pirfenidone alleviated silica-induced lung dysfunction, secretion of inflammatory cytokines (TNF-α, IL-1ß, IL-6) and deposition of fibrotic proteins (collagen I and fibronectin) in both early and advanced silicosis models. Moreover, we observed that both 100 and 200 mg/kg pirfenidone can effectively treat early-stage silicosis, while 400 mg/kg was recommended for advanced silicosis. Mechanistically, antibody array and bioinformatic analysis showed that the pathways related to IL-17 secretion, including JAK-STAT pathway, Th17 differentiation, and IL-17 pathway, might be involved in the treatment of silicosis by pirfenidone. Further in vivo experiments confirmed that pirfenidone reduced the production of IL-17A induced by silica exposure via inhibiting STAT3 phosphorylation. Neutralizing IL-17A by anti-IL-17A antibody improved lung function and reduced pulmonary inflammation and fibrosis in silicosis animals. Collectively, our study has demonstrated that pirfenidone effectively ameliorated silica-induced lung dysfunction, pulmonary inflammation and fibrosis in mouse models by inhibiting the secretion of IL-17A.

Tetrandrine alleviates silicosis by inhibiting canonical and non-canonical NLRP3 inflammasome activation in lung macrophages.

Silicosis caused by inhalation of silica particles leads to more than ten thousand new occupational exposure-related deaths yearly. Exacerbating this issue, there are currently few drugs reported to effectively treat silicosis. Tetrandrine is the only drug approved for silicosis treatment in China, and despite more than decades of use, its efficacy and mechanisms of action remain largely unknown. Here, in this study, we established silicosis mouse models to investigate the effectiveness of tetrandrine of early and late therapeutic administration. To this end, we used multiple cardiopulmonary function test, as well as markers for inflammation and fibrosis. Moreover, using single cell RNA sequencing and transcriptomics of lung tissue and quantitative microarray analysis of serum from silicosis and control mice, our results provide a novel description of the target pathways for tetrandrine. Specifically, we found that tetrandrine attenuated silicosis by inhibiting both the canonical and non-canonical NLRP3 inflammasome pathways in lung macrophages. Taken together, our work showed that tetrandrine yielded promising results against silicosis-associated inflammation and fibrosis and further lied the groundwork for understanding its molecular targets. Our results also facilitated the wider adoption and development of tetrandirne, potentially accelerating a globally accepted therapeutic strategy for silicosis.

Identification of the Golden-2-like transcription factors gene family in Gossypium hirsutum.

BACKGROUND: Golden2-Like (GLK) transcription factors are a type of transcriptional regulator in plants. They play a pivotal role in the plant physiological activity process and abiotic stress response. METHODS: In this study, the potential function of GLK family genes in Gossypium hirsutum was studied based on genomic identification, phylogenetic analysis, chromosome mapping and cis-regulatory elements prediction. Gene expression of nine key genes were analyzed by qRT-PCR experiments. RESULTS: Herein, we identified a total of 146 GhGLK genes in Gossypium hirsutum, which were unevenly distributed on each of the chromosomes. There were significant differences in the number and location of genes between the At sub-genome and the Dt sub-genome. According to the phylogenetic analysis, they were divided into ten subgroups, each of which had very similar number and structure of exons and introns. Some cis-regulatory elements were identified through promoter analysis, including five types of elements related to abiotic stress response, five types of elements related to phytohormone and five types of elements involved in growth and development. Based on public transcriptome data analysis, we identified nine key GhGLKs involved in salt, cold, and drought stress. The qRT-PCR results showed that these genes had different expression patterns under these stress conditions, suggesting that GhGLK genes played an important role in abiotic stress response. This study laid a theoretical foundation for the screening and functional verification of genes related to stress resistance of GLK gene family in cotton.

Changes in climate and snow cover and their synergistic influence on spring runoff in the source region of the Yellow River.

As an important runoff-producing area, the runoff variation in the source region of the Yellow River (SRYR) has critical importance for the whole basin in broad aspects. In recent decades, the climate in the SRYR has undergone drastic changes, which affected runoff across different time scales. Many studies have focused on runoff in the SRYR with a long-time series, and presented a discordant relationship between precipitation and runoff. However, differences in this relationship over different time scales are ignored. Here, by using multi-source observation data and correlation analysis, climate elasticity, and principal component analysis methods, we document the changes in climate and snow cover and their synergistic influence on spring runoff. When the 20-year period was innovatively adopted, the runoff and precipitation coincided well during last three periods (1960-2019). The yearly precipitation presented a bimodal pattern, with the most significant increase in late spring and early summer. A bimodal pattern also appeared in annual runoff, and the rate of increase was much greater than that of precipitation (2.51%/year vs 1.01%/year). The runoff during main increase period (particularly in April) showed a high correlation with the remote sensing snow depth from November to March, but a poor correlation with snow depth from meteorological stations. Climate warming in the SRYR was much more reflected in minimum surface temperature (0.235 °C/year) than in air temperature minimum (0.081 °C/year) in last 20 years. However, the principal component analysis shows that the effect of temperature on spring runoff was obviously less than that of snow cover. A 1% variation in snow depth in the SRYR from November to March caused a 0.43% variation in runoff in April, and a 1% variation in snow days caused a 0.82% variation in runoff. This study will bring to light for understanding the evolution mechanism of spring runoff in the SRYR.

Genome-wide identification of the MIOX gene family and their expression profile in cotton development and response to abiotic stress.

The enzyme myo-inositol oxygenase (MIOX) catalyzes the myo-inositol into glucuronic acid. In this study, 6 MIOX genes were identified from all of the three diploid cotton species (Gossypium arboretum, Gossypium herbaceum and Gossypium raimondii) and Gossypioides kirkii, 12 MIOX genes were identified from two domesticated tetraploid cottons Gossypium hirsutum, Gossypium barbadense, and 11 MIOX genes were identified from three wild tetraploid cottons Gossypium tomentosum, Gossypium mustelinum and Gossypium darwinii. The number of MIOX genes in tetraploid cotton genome is roughly twice that of diploid cotton genome. Members of MIOX family were classified into six groups based on the phylogenetic analysis. Integrated analysis of collinearity events and chromosome locations suggested that both whole genome duplication and segmental duplication events contributed to the expansion of MIOX genes during cotton evolution. The ratios of non-synonymous (Ka) and synonymous (Ks) substitution rates revealed that purifying selection was the main force driving the evolution of MIOX genes. Numerous cis-acting elements related to light responsive element, defense and stress responsive element were identified in the promoter of the MIOX genes. Expression analyses of MIOX genes based on RNA-seq data and quantitative real time PCR showed that MIOX genes within the same group shared similar expression patterns with each other. All of these results provide the foundation for further study of the biological functions of MIOX genes in cotton environmental adaptability.

Comparative Transcriptome Analyses Reveal a Transcriptional Landscape of Human Silicosis Lungs and Provide Potential Strategies for Silicosis Treatment.

Silicosis is a fatal occupational lung disease which currently has no effective clinical cure. Recent studies examining the underlying mechanism of silicosis have primarily examined experimental models, which may not perfectly reflect the nature of human silicosis progression. A comprehensive profiling of the molecular changes in human silicosis lungs is urgently needed. Here, we conducted RNA sequencing (RNA-seq) on the lung tissues of 10 silicosis patients and 7 non-diseased donors. A total of 2,605 differentially expressed genes (DEGs) and critical pathway changes were identified in human silicosis lungs. Further, the DEGs in silicosis were compared with those in idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary diseases (COPD), to extend current knowledge about the disease mechanisms and develop potential drugs. This analysis revealed both common and specific regulations in silicosis, along with several critical genes (e.g., MUC5AC and FGF10), which are potential drug targets for silicosis treatment. Drugs including Plerixafor and Retinoic acid were predicted as potential candidates in treating silicosis. Overall, this study provides the first transcriptomic fingerprint of human silicosis lungs. The comparative transcriptome analyses comprehensively characterize pathological regulations resulting from silicosis, and provide valuable cues for silicosis treatment.

Analysis of Risk Factors for Thromboembolic Events in 88 Patients with COVID-19 Pneumonia in Wuhan, China: A Retrospective Descriptive Report.

BACKGROUND Since the outbreak of COVID-19 in December 2019, there have been 96 623 laboratory-confirmed cases and 4784 deaths by December 29 in China. We aimed to analyze the risk factors and the incidence of thrombosis from patients with confirmed COVID-19 pneumonia. MATERIAL AND METHODS Eighty-eight inpatients with confirmed COVID-19 pneumonia were reported (31 critical cases, 33 severe cases, and 24 common cases). The thrombosis risk factor assessment, laboratory results, ultrasonographic findings, and prognoses of these patients were analyzed, and compared among groups with different severity. RESULTS Nineteen of the 88 cases developed DVT (12 critical cases, 7 severe cases, and no common cases). In addition, among the 18 patients who died, 5 were diagnosed with DVT. Positive correlations were observed between the increase in D-dimer level (≥5 µg/mL) and the severity of COVID-19 pneumonia (r=0.679, P<0.01), and between the high Padua score (≥4) and the severity (r=0.799, P<0.01). In addition, the CRP and LDH levels on admission had positive correlations with the severity of illness (CRP: r=0.522, P<0.01; LDH: r=0.600, P<0.01). A negative correlation was observed between the lymphocyte count on admission and the severity of illness (r=-0.523, P<0.01). There was also a negative correlation between the lymphocyte count on admission and mortality in critical patients (r=-0.499, P<0.01). Univariable logistic regression analysis showed that the occurrence of DVT was positively correlated with disease severity (crude odds ratio: 3.643, 95% CI: 1.218-10.896, P<0.05). CONCLUSIONS Our report illustrates that critically or severely ill patients have an associated high D-dimer value and high Padua score, and illustrates that a low threshold to screen for DVT may help improve detection of thromboembolism in these groups of patients, especially in asymptomatic patients. Our results suggest that early administration of prophylactic anticoagulant would benefit the prognosis of critical patients with COVID-19 pneumonia and would likely reduce thromboembolic rates.

Profiling of H3K4me3 and H3K27me3 and Their Roles in Gene Subfunctionalization in Allotetraploid Cotton.

Cotton is an excellent model for studying crop polyploidization and domestication. Chromatin profiling helps to reveal how histone modifications are involved in controlling differential gene expression between A and D subgenomes in allotetraploid cotton. However, the detailed profiling and functional characterization of broad H3K4me3 and H3K27me3 are still understudied in cotton. In this study, we conducted H3K4me3- and H3K27me3-related ChIP-seq followed by comprehensively characterizing their roles in regulating gene transcription in cotton. We found that H3K4me3 and H3K27me3 exhibited active and repressive roles in regulating the expression of genes between A and D subgenomes, respectively. More importantly, H3K4me3 exhibited enrichment level-, position-, and distance-related impacts on expression levels of related genes. Distinct GO term enrichment occurred between A/D-specific and homeologous genes with broad H3K4me3 enrichment in promoters and gene bodies, suggesting that broad H3K4me3-marked genes might have some unique biological functions between A and D subgenome. An anticorrelation between H3K27me3 enrichment and expression levels of homeologous genes was more pronounced in the A subgenome relative to the D subgenome, reflecting distinct enrichment of H3K27me3 in homeologous genes between A and D subgenome. In addition, H3K4me3 and H3K27me3 marks can indirectly influence gene expression through regulatory networks with TF mediation. Thus, our study provides detailed insights into functions of H3K4me3 and H3K27me3 in regulating differential gene expression and subfunctionalization of homeologous genes, therefore serving as a driving force for polyploidization and domestication in cotton.

A novel pathophysiological classification of silicosis models provides some new insights into the progression of the disease.

Silicosis is caused by massive inhalation of silica-based particles, which leads to pulmonary inflammation, pulmonary fibrosis and lung dysfunction. Currently, the pathophysiological process of silicosis has not been well studied. Here, we defined the progression of silicosis as four stages by unsupervised clustering analysis: normal stage, inflammatory stage, progressive stage and fibrotic stage. Specifically, in normal stage, the lung function was normal, and no inflammation or fibrosis was detected in the lung tissue. Inflammatory stage showed a remarkable pulmonary inflammation but mild fibrosis and lung dysfunction. In progressive stage, significant lung dysfunction was observed, while pulmonary inflammation and fibrosis continued to deteriorate. Fibrotic stage revealed the most severe pulmonary fibrosis and lung dysfunction but no significant deterioration in inflammation. Since the common features were founded in both silicosis patients and rodents, we speculated that the pathophysiological processes of silicosis in patients might be similar to the rodents. Collectively, our new classification identified the process of silicosis, clarified the pathophysiological features of each stage, and provided some new insights for the progression of the disease.

LncRNA MIR210HG promotes proliferation and invasion of non-small cell lung cancer by upregulating methylation of CACNA2D2 promoter via binding to DNMT1.

Background: In recent years, a large number of studies have shown that differentially expressed lncRNAs are capable of promoting the occurrence and development of tumors by regulating cell proliferation and differentiation. However, the biological effects of lncRNAs in non-small cell lung cancer (NSCLC) are still needed to be further investigated. Methods: The differentially expressed lncRNAs in NSCLC tissues in the downloaded profiles from GEO database were analyzed and further verified in 100 pairs of NSCLC samples collected in our hospital. After identification of the target gene MIR210HG, the relationship between MIR210HG expression and clinical data of NSCLC patients was analyzed. Regulatory effects of MIR210HG on proliferation, migration, and invasion of NSCLC cells were detected by CCK-8, colony formation, and transwell assay, respectively. The binding condition of MIR210HG and DNA methyltransferase 1 (DNMT1) was detected by RNA binding protein immunoprecipitation. Subsequently, chromatin immunoprecipitation assay assessed the promoter binding of DNMT1 to CACNA2D2. Rescue experiments were conducted to assess whether CACNA2D2 can reverse the function of MIR210HG. Results: MIR210HG was highly expressed in NSCLC tissues not only in GSE30219 dataset but also in our collected NSCLC tissues. MIR210HG expression was correlated to tumor stage and lymph node metastasis of NSCLC patients. Besides, lower disease-free survival (DFS) and overall survival (OS) were found in NSCLC patients with high-level MIR210HG compared with those with low-level MIR210HG. Regression analysis indicated that MIR210HG was the independent risk factor for DFS and OS of NSCLC patients. In vitro experiments demonstrated that MIR210HG knockdown remarkably inhibited proliferation and migration of NSCLC cells. MIR210HG could recruit DNMT1, thereafter promoting methylation of CACNA2D2 promoter region. CACNA2D2 overexpression remarkably inhibited cell proliferation. Moreover, inhibited proliferation induced by MIR210HG knockdown was reversed by CACNA2D2 knockdown. Conclusion: MIR210HG can promote the tumorigenesis of NSCLC by inhibiting the expression of CACNA2D2. Our findings provide new therapeutic strategies for the future treatment of NSCLC.