Genome-wide characterization of single-stranded DNA in rice.

Single-stranded DNA (ssDNA) is essential for various DNA-templated processes in both eukaryotes and prokaryotes. However, comprehensive characterizations of ssDNA still lag in plants compared to nonplant systems. Here, we conducted in situ S1-sequencing, with starting gDNA ranging from 5 µg to 250 ng, followed by comprehensive characterizations of ssDNA in rice (Oryza sativa L.). We found that ssDNA loci were substantially associated with a subset of non-B DNA structures and functional genomic loci. Subtypes of ssDNA loci had distinct epigenetic features. Importantly, ssDNA may act alone or partly coordinate with non-B DNA structures, functional genomic loci, or epigenetic marks to actively or repressively modulate gene transcription, which is genomic region dependent and associated with the distinct accumulation of RNA Pol II. Moreover, distinct types of ssDNA had differential impacts on the activities and evolution of transposable elements (TEs) (especially common or conserved TEs) in the rice genome. Our study showcases an antibody-independent technique for characterizing non-B DNA structures or functional genomic loci in plants. It lays the groundwork and fills a crucial gap for further exploration of ssDNA, non-B DNA structures, or functional genomic loci, thereby advancing our understanding of their biology in plants.

Bletilla striata polysaccharide alleviates chronic obstructive pulmonary disease via modulating gut microbiota and NR1H4 expression in mice.

Bletilla striata polysaccharide (BSP) is the main component of Bletilla striata and has been revealed to enhance immune responses. Chronic obstructive pulmonary disease (COPD) results from the chronic inhalation of toxic particles and gases, which initiates innate and adaptive immune responses in the lungs. This study aimed to evaluate whether the effects of BSP on COPD were related to the abundance of gut microbiota and explored the underlying mechanism. COPD mice were induced with cigarette smoke and human bronchial epithelial cells (HBEC) were subjected to cigarette smoke extract (CSE) for in vitro studies. BSP alleviated the inflammatory response and the inflammatory cell infiltration in lung tissues and promoted the recovery of respiratory function in COPD mice. BSP mitigated CSE-induced HBEC injury by repressing inflammation and oxidative stress. 16s rRNA sequencing revealed that BSP increased the abundance of Bacteroides intestinalis. Bacteroides intestinalis colonization enhanced the therapeutic effect of BSP in COPD mice by upregulating NR1H4 and its encoded protein FXR. Reduction of NR1H4 impaired the therapeutic impact of BSP and Bacteroides intestinalis in COPD. These data demonstrate that BSP inhibits COPD by upregulating NR1H4 through Bacteroides intestinalis, which underpins the application of BSP as a therapeutic agent for COPD.

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.

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.

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.

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.

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.

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.

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.

Suppression of magnetoresistance in PtSe2 microflakes with antidot arrays.

Suppression of magnetoresistance (MR) is meaningful for sensor applications to immure magnetic fields. Herein, we report the observation of suppressed MR in PtSe2 microflakes by introducing the antidot arrays (AAs). We have compared the magnetotransport properties of PtSe2 microflakes before and after milling of AAs. The enhanced resistivity and notable MR suppression were observed while the AAs are milled in the PtSe2 microflakes. Their physical mechanism has been ascribed to the enhanced electron scattering rate due to the additional electron-antidot interactions. This work gave an example to suppress MR in materials by introducing AAs, which may be useful for sensor applications in magnetic fields.

Metal-semiconductor transition of two-dimensional Mg2C monolayer induced by biaxial tensile strain.

Designing new two-dimensional (2D) materials with novel band topologies has continuously attracted intense interest in fundamental science and potential applications. Here, we report a unique 2D Mg2C monolayer featuring quasi-planar hexa-coordinate magnesium and hexa-coordinate carbon, which can be tuned from a metal to a semiconductor. The system has been studied using density functional theory, including electronic structure calculations and molecular dynamics simulations. In the freestanding state, the Mg2C monolayer behaves as a weak metal; however, by increasing the biaxial tensile strains, it can gradually be modulated to a gapless semimetal and then to a semiconductor. The Mg2C monolayer exhibits excellent dynamic and thermal stabilities and is also the global minimum of the 2D Mg2C system, implying the feasibility of its experimental synthesis. With unique band structures, the material may find applications in optoelectronics and electromechanics.

Biophysical regulation of carbon fluxes over an alpine meadow ecosystem in the eastern Tibetan Plateau.

The eddy covariance method was used to measure net ecosystem CO2 exchange (NEE) between atmosphere and an alpine meadow ecosystem in the eastern Tibetan Plateau of China in 2010. Our results show that photosynthesis was reduced under low air temperature (T a), high vapor pressure deficit (VPD), and medium soil water content (SWC) conditions, when compared to that under other T a (i.e., medium and high), VPD (i.e., low and medium), and SWC (i.e., low and high) conditions. The apparent temperature sensitivity of ecosystem respiration (Q 10) declined with progressing phenology during the growing season and decreased with an increase of soil temperature (T s) during the non-growing season. Increased ecosystem respiration (R eco) was measured during spring soil thawing. By the path analysis, T a, T s, and VPD were the main control factors of CO2 exchange at 30-min scale in this alpine meadow. Integrated NEE, gross primary production (GPP), and R eco over the measured year were -156.4, 1164.3, and 1007.9 g C m(-2), respectively. Zoige alpine meadow was a medium carbon sink based on published data for grassland ecosystems.

Genetic variants in ADAM33 are associated with airway inflammation and lung function in COPD.

BACKGROUND: Genetic factors play a role in the development and severity of chronic obstructive pulmonary disease (COPD). The pathogenesis of COPD is a multifactorial process including an inflammatory cell profile. Recent studies revealed that single nucleotide polymorphisms (SNPs) within ADAM33 increased the susceptibility to COPD through changing the airway inflammatory process and lung function. METHODS: In this paper, we investigated associations of four polymorphisms (T1, T2, S2 and Q-1) of ADAM33 as well as their haplotypes with pulmonary function and airway inflammatory process in an East Asian population of patients with COPD. RESULTS: We found that T1, T2 and Q-1 were significantly associated with the changes of pulmonary function and components of cells in sputum of COPD, and T1 and Q-1 were significantly associated with cytokines and mediators of inflammation in airway of COPD in recessive models. 10 haplotypes were significantly associated with transfer factor of the lung for carbon monoxide in the disease state, 4 haplotypes were significantly associated with forced expiratory volume in one second, and other haplotypes were associated with airway inflammation. CONCLUSIONS: We confirmed for the first time that ADAM33 was involved in the pathogenesis of COPD by affecting airway inflammation and immune response in an East Asian population. Our results made the genetic background of COPD, a common and disabling disease, more apparent, which would supply genetic support for the study of the mechanism, classification and treatment for this disease.

USP22 promotes gefitinib resistance and inhibits ferroptosis in non-small cell lung cancer by deubiquitination of MDM2.

BACKGROUND: The emergence of chemoresistance markedly compromised the treatment efficiency of human cancer, including non-small cell lung cancer (NSCLC). In the present study, we aimed to explore the effects of ubiquitin-specific peptidase 22 (USP22) and murine double minute 2 (MDM2) in gefitinib resistance in NSCLC. METHODS: Immunohistochemistry (IHC) assay, quantitative real-time polymerase chain reaction (qRT-PCR) assay and western blot assay were carried out to determine the expression of USP22 and MDM2. Transwell assay and flow cytometry analysis were performed to evaluate cell migration and apoptosis. Cell Counting Kit-8 (CCK-8) assay was employed to assess gefitinib resistance. The phenomenon of ferroptosis was estimated by related commercial kits. The oxidized C11-BODIPY fluorescence intensity by C11-BODIPY staining. The relation between USP22 and MDM2 was analyzed by ubiquitination assay and co-immunoprecipitation (Co-IP) assay. RESULTS: USP22 was abnormally upregulated in NSCLC tissues and cells, and USP22 silencing markedly repressed NSCLC cell migration and facilitated apoptosis and ferroptosis. Moreover, our results indicated that ferroptosis could enhance the suppressive effect of gefitinib on NSCLC cells. Besides, USP22 overexpression enhanced gefitinib resistance and ferroptosis protection in NSCLC cells. Mechanically, USP22 stabilized MDM2 and regulated MDM2 expression through deubiquitination of MDM2. MDM2 deficiency partially restored the effects of USP22 on gefitinib resistance and ferroptosis in NSCLC cells. Of note, we validated the promotional effect of USP22 on gefitinib resistance in NSCLC in vivo through establishing the murine xenograft model. CONCLUSION: USP22/MDM2 promoted gefitinib resistance and inhibited ferroptosis in NSCLC, which might offer a novel strategy for overcoming gefitinib resistance in NSCLC.

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.

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.

Transcriptional Landscape of Cotton Roots in Response to Salt Stress at Single-cell Resolution.

Increasing soil salinization has led to severe losses of plant yield and quality. Thus, it is urgent to investigate the molecular mechanism of the salt stress response. In this study, we took systematically analyzed cotton root response to salt stress by single-cell transcriptomics technology; 56,281 high-quality cells were totally obtained from 5-days-old lateral root tips of Gossypium arboreum under natural growth and different salt-treatment conditions. Ten cell types with an array of novel marker genes were synthetically identified and confirmed with in situ RNA hybridization, and some specific-type cells of pesudotime analysis also pointed out their potential differentiation trajectory. The prominent changes of cell numbers responding to salt stress were observed on outer epidermal and inner endodermic cells, which were significantly enriched in response to stress, amide biosynthetic process, glutathione metabolism, and glycolysis/gluconeogenesis. Other functional aggregations were concentrated on plant-type primary cell wall biogenesis, defense response, phenylpropanoid biosynthesis and metabolic pathways by analyzing the abundant differentially expressed genes (DEGs) identified from multiple comparisons. Some candidate DEGs related with transcription factors and plant hormones responding to salt stress were also identified, of which the function of Ga03G2153, an annotated auxin-responsive GH3.6, was confirmed by using virus-induced gene silencing (VIGS). The GaGH3.6-silenced plants presented severe stress-susceptive phenotype, and suffered more serious oxidative damages by detecting some physiological and biochemical indexes, indicating that GaGH3.6 might participate in salt tolerance in cotton through regulating oxidation-reduction process. For the first time, a transcriptional atlas of cotton roots under salt stress were characterized at a single-cell resolution, which explored the cellular heterogeneityand differentiation trajectory, providing valuable insights into the molecular mechanism underlying stress tolerance in plants.

[Clinical observation of home noninvasive positive pressure ventilation in hypercapnic patient with stable severe chronic obstructive pulmonary disease].

OBJECTIVE: To evaluate the efficacy and safety of home noninvasive positive pressure ventilation (HNIPPV) in hypercapnic patients with stable severe chronic obstructive pulmonary disease (COPD). METHODS: Forty four patients (30 males and 14 females, mean age 68.5 years (range: 60 - 80)) were recruited from a total of 106 patients with arterial PaCO2 ≥ 55 mm Hg in Second Hospital Affiliated to Harbin Medical University from January 2009 to December 2010. Their clinical data were collected and analyzed. The patients in the HNIPPV group (n = 20) accepted tiotropium bromide, doxofylline tablets and HNIPPV treatment while those in the control group (n = 24) tiotropium bromide, doxofylline tablets and a low-flow inhalation of oxygen. The entire observation period was 6 months. The parameters before and after 6-month follow-up were compared, including lung function test, 6-min walking distance (6MWD), arterial blood gases (PaO2 and PaCO2), dyspnea grade, scores of emotional disorders and mean pulmonary artery pressure (mPAP). RESULTS: No significant difference existed in the baseline data between the HNIPPV and control groups. The forced expiratory volume in one second (FEV(1)), forced vital capacity (FVC), inspiratory capacity (IC), 6MWD, PaO2, PaCO2, dyspnea grade, hospitalization rate, anxiety scores, depression scores and mPAP showed no significant difference between the HNIPPV and control groups before treatment. However, at Month 6, the differences of IC, 6MWD, PaO2, PaCO2, dyspnea grade, anxiety scores, depression scores and mPAP in HNIPPV group ((1.80 ± 0.14) L, (266 ± 24) m, (62.6 ± 4.6) mm Hg, (46.8 ± 2.2) mm Hg, (2.2 ± 0.5), (6.5 ± 2.4), (6.0 ± 1.6), (33.8 ± 2.4) mm Hg) were statistically significant compared with the control group ((1.62 ± 0.14) L, (194 ± 23) m, (56.2 ± 3.8) mm Hg, (55.6 ± 3.0) mm Hg, (3.2 ± 0.6), (10.6 ± 2.8), (10.2 ± 2.4), (36.6 ± 2.4) mm Hg) (P values: 0.031, 0.018, 0.025, 0.026, 0.001, 0.013, 0.002, 0.014 respectively). FEV(1) and FVC in the HNIPPV group improved slightly but with no statistically significant difference (all P > 0.05). Two patients in the control group were taken to hospital because of acute exacerbation. And hospitalization rates increased in the control group. But no statistically significant difference existed between the HNIPPV and control groups (P > 0.05). The tolerance and compliance of HNIPPV in the HNIPPV group were better and the patients in the HNIPPV group had no pulmonary barotraumas. CONCLUSION: HNIPPV plus tiotropium bromide and doxofylline tablets is both effective and safe in the treatment of hypercapnic patient with stable severe COPD.

[The effect of marrow mesenchymal stem cell transplantation on pulmonary fibrosis in rats].

OBJECTIVE: To study the possible mechanisms of marrow mesenchymal stem cells (MSC) in therapy of bleomycin (BLM)-induced pulmonary fibrosis in rats. METHODS: Fifty-four female Wistar rats were randomly divided into a control group, a BLM group and a MSC group. The control group received intratracheal normal saline, the BLM group received intratracheal instillation of bleomycin, and the MSC group was injected with male rat MSC solution of 0.5 ml (2.5×10(6) cells) via the tail vein after intratracheal instillation of bleomycin. Six rats from each group were killed on day 7, 14 and 28 of the experiments. BrdU labeling rate was measured before MSC transplantation. Lung tissue specimens were obtained for pathological examination, hydroxyproline content measurement, and detection of the expression of type II alveolar cell (ATII) specific marker-pulmonary surfactant protein-C (SP-C) in BrdU labeled MSC using dual immunofluorescence method. RT-PCR method was used to detect SP-C mRNA expression in the lung tissue and the bone marrow at different stages. The bone marrow mobilization involved in repair of type II alveolar cells after lung injury was observed. RESULTS: The final concentration of BrdU labeled MSC at 48 h was 10 µmol/L, while the labeling efficiency was>98%, and the passage cells could be continuously labeled. In the MSC group, BrdU labeled MSCs with expression of SP-C were observed in all frozen sections of lung tissue at day 7, 14, and 28. By day 28, the lung fibrosis scores of the MSC group and the BLM group were (2.17 ± 0.26) and (2.83 ± 0.24), respectively, the lung tissue hydroxyproline contents were (138 ± 21) mg/g and (184 ± 19) mg/g, respectively, and the lung tissue SP-C mRNA expressions were (0.98 ± 0.15) and (0.59 ± 0.14), respectively. For both groups the SP-C mRNA expressions in the bone marrow at different stages were significantly increased as compared to the control group. CONCLUSIONS: Marrow mesenchymal stem cells could be transplanted into lung tissues of rats, and transformed into type II alveolar cells and was shown to prevent the development of pulmonary fibrosis. The damage-induced enhancement of host bone marrow mobilization was also involved in the repair process.