Systematic analysis of various RNA transcripts and construction of biological regulatory networks at the post-transcriptional level for chronic obstructive pulmonary disease.

BACKGROUND: Although chronic inflammation, oxidative stress, airway remodeling, and protease-antiprotease imbalance have been implicated in chronic obstructive pulmonary disease (COPD), the exact pathogenesis is still obscure. Gene transcription and post-transcriptional regulation have been taken into account as key regulators of COPD occurrence and development. Identifying the hub genes and constructing biological regulatory networks at the post-transcriptional level will help extend current knowledge on COPD pathogenesis and develop potential drugs. METHODS: All lung tissues from non-smokers (n = 6), smokers without COPD (smokers, n = 7), and smokers with COPD (COPD, n = 7) were collected to detect messenger RNA (mRNA), microRNA (miRNA), circular RNA (circRNA), and long non-coding RNA (lncRNA) expression and identify the hub genes. Biological regulatory networks were constructed at the post-transcriptional level, including the RNA-binding protein (RBP)-hub gene interaction network and the competitive endogenous RNA (ceRNA) network. In addition, we assessed the composition and abundance of immune cells in COPD lung tissue and predicted potential therapeutic drugs for COPD. Finally, the hub genes were confirmed at both the RNA and protein levels. RESULTS: Among the 20 participants, a total of 121169 mRNA transcripts, 1871 miRNA transcripts, 4244 circRNA transcripts, and 122130 lncRNA transcripts were detected. There were differences in the expression of 1561 mRNAs, 48 miRNAs, 33 circRNAs, and 545 lncRNAs between smokers and non-smokers, as well as 1289 mRNAs, 69 miRNAs, 32 circRNAs, and 433 lncRNAs between smokers and COPD patients. 18 hub genes were identified in COPD. TGF-ß signaling and Wnt/ß-catenin signaling may be involved in the development of COPD. Furthermore, the circRNA/lncRNA-miRNA-mRNA ceRNA networks and the RBP-hub gene interaction network were also constructed. Analysis of the immune cell infiltration level revealed that M2 macrophages and activated NK cells were increased in COPD lung tissues. Finally, we identified that the ITK inhibitor and oxybutynin chloride may be effective in treating COPD. CONCLUSIONS: We identified several novel hub genes involved in COPD pathogenesis. TGF-ß signaling and Wnt/ß-catenin signaling were the most dysregulated pathways in COPD patients. Our study constructed post-transcriptional biological regulatory networks and predicted small-molecule drugs for the treatment of COPD, which enhanced the existing understanding of COPD pathogenesis and suggested an innovative direction for the therapeutic intervention of the disease.

Synergistic Promotion of Photocatalytic Degradation of Methyl Orange by Fluorine- and Silicon-Doped TiO2/AC Composite Material.

The direct or indirect discharge of organic pollutants causes serious environmental problems and endangers human health. The high electron-hole recombination rate greatly limits the catalytic efficiency of traditional TiO2-based catalysts. Therefore, starting from low-cost activated carbon (AC), a photocatalyst (F-Si-TiO2/AC) comprising fluorine (F)- and silicon (Si)-doped TiO2 loaded on AC has been developed. F-Si-TiO2/AC has a porous structure. TiO2 nanoparticles were uniformly fixed on the surface or pores of AC, producing many catalytic sites. The band gap of F-Si-TiO2/AC is only 2.7 eV. In addition, F-Si-TiO2/AC exhibits an excellent adsorption capacity toward methyl orange (MO) (57%) in the dark after 60 min. Under the optimal preparation conditions, F-Si-TiO2/AC showed a significant photodegradation performance toward MO, reaching 97.7% after irradiation with visible light for 70 min. Even under the action of different anions and cations, its degradation efficiency is the lowest, at 64.0%, which has good prospects for practical application. At the same time, F-Si-TiO2/AC has long-term, stable, practical application potential and can be easily recovered from the solution. Therefore, this work provides new insights for the fabrication of low-cost, porous, activated, carbon-based photocatalysts, which can be used as high-performance photocatalysts for the degradation of organic pollutants.

[Critical quality attribute characterization of big brand TCM: taste formulation optimization strategy and application of Xiaoer Ganmao Oral Liquid based on taste quality attribute].

The taste is the quality attribute for the development and production of traditional Chinese medicine(TCM). To improve the medication compliance of the big brand TCM, Xiaoer Ganmao Oral Liquid, a correlation model between the electronic tongue sensor signal value and human sensory evaluation score was established, and an optimization strategy of taste improvement for Xiaoer Ganmao Oral Liquid was developed with the key techniques of statistical experimental design. Based on the above model, the optimal formulation was determined as follows: aspartame content of 1-2 mg·mL~(-1), acesulfame-K content of 1.5-3 mg·mL~(-1), and steviol glycoside content of 1-2 mg·mL~(-1). Furthermore, the optimal formulation was verified by human sensory evaluation. Therefore, the taste of Xiaoer Ganmao Oral Liquid was improved. Taking Xiaoer Ganmao Oral Liquid as an example, the present study developed the taste formulation optimization method based on the correlation between the electronic tongue and human sensory evaluation, which is expected to provide an important reference to improve the taste of oral liquid of TCM.

Family with sequence similarity 13 member A mediates TGF-ß1-induced EMT in small airway epithelium of patients with chronic obstructive pulmonary disease.

BACKGROUND: To explore the role of family with sequence similarity 13 member A (FAM13A) in TGF-ß1-induced EMT in the small airway epithelium of patients with chronic obstructive pulmonary disease (COPD). METHODS: Small airway wall thickness and protein levels of airway remodeling markers, EMT markers, TGF-ß1, and FAM13A were measured in lung tissue samples from COPD and non-COPD patients. The correlations of FAM13A expression with COPD severity and EMT marker expression were evaluated. Gain- and loss-of-function assays were performed to explore the functions of FAM13A in cell proliferation, motility, and TGF-ß1-induced EMT marker alterations in human bronchial epithelial cell line BEAS-2B. RESULTS: Independent of smoking status, lung tissue samples from COPD patients exhibited significantly increased small airway thickness and collagen fiber deposition, along with enhanced protein levels of remodeling markers (collagen I, fibronectin, and MMP-9), mesenchymal markers (α-SMA, vimentin, and N-cadherin), TGF-ß1, and FAM13A, compared with those from non-COPD patients. FAM13A expression negatively correlated with FEV1% and PO2 in COPD patients. In small airway epithelium, FAM13A expression negatively correlated with E-cadherin protein levels and positively correlated with vimentin protein levels. In BEAS-2B cells, TGF-ß1 dose-dependently upregulated FAM13A protein levels. FAM13A overexpression significantly promoted cell proliferation and motility in BEAS-2B cells, whereas FAM13A silencing showed contrasting results. Furthermore, FAM13A knockdown partially reversed TGF-ß1-induced EMT marker protein alterations in BEAS-2B cells. CONCLUSIONS: FAM13A upregulation is associated with TGF-ß1-induced EMT in the small airway epithelium of COPD patients independent of smoking status, serving as a potential therapeutic target for anti-EMT therapy in COPD.

System optimisation quantitative model of on-line NIR: a case of Glycyrrhiza uralensis Fisch extraction process.

INTRODUCTION: The on-line analysis of active pharmaceutical ingredients (APIs) during the extraction process in herbal medicine is a challenge. Establishing a reliable and robust model is a critical procedure for the industrial application of on-line near-infrared (NIR) technology. OBJECTIVE: To evaluate the advantages of on-line NIR model development using system optimisation strategy, Glycyrrhiza uralensis Fisch was used as a case. The content of liquiritin and glycyrrhizic acid was monitored during pilot scale extraction process of Glycyrrhiza uralensis Fisch in three batches. METHODS: High-performance liquid chromatography (HPLC) was used as reference method for content determination of liquiritin and glycyrrhizic acid. The quantitative models of on-line NIR were developed by system optimisation of processing trajectory. For comparison, the models were simultaneously developed by stepwise optimisation. Moreover, the modelling parameters obtained through system optimisation and stepwise optimisation were reused in three batches. Root mean square error of prediction (RMSEP) and residual predictive deviation (RPD) were used to assess the model quality. RESULTS: The average values of RMSEP and RPD of systematic model for liquiritin in three batches were 0.0361, 4.1525 (first batch), 0.0348, 4.7286 (second batch) and 0.0311, 4.9686 (third batch), respectively. In addition, the modelling parameters of systematic model for glycyrrhizic acid in three batches were same, and the average values of RMSEP and RPD were 0.0665 and 5.2751, respectively. The predictive performance and robustness of systematic models for the three batches were better than the comparison models. CONCLUSION: The work demonstrated that system optimisation quantitative model of on-line NIR could be used to determine the contents of liquiritin and glycyrrhizic acid during Glycyrrhiza uralensis Fisch extraction process.

[Critical quality attribute assessment of big brand traditional Chinese medicine: modular identification of Tongren Niuhuang Qingxin Pills based on efficacy with chemical properties].

Identification of critical quality attribute(CQA) is crucial in quality control of Tongren Niuhuang Qingxin Pills(TRNHQXP). In this study, 661 active components in TRNHQXP were selected by liquid chromatography-mass spectrometry(LC-MS) and network pharmacology based on reported data and TCMSP, BATMAN-TCM, and TCMID databases, as well as mass spectrometry data, and 1 413 targets of the active components were obtained through SwissTargetPrediction. The 152 potential targets obtained from the intersection of predicted targets with 456 stroke targets underwent functional enrichment analysis by Metascape. The 27 Chinese medicinals in TRNHQXP were divided into four sets according to efficacies. Thirty-seven key targets in the blood-activating and stasis-resolving set and 41 in the tonifying set were screened out. On the basis of these potential key targets, 137 potential key CQA of TRNHQXP for stroke were reversely predicted. This study revealed the possible mechanism of TRNHQXP in treating stroke and established a modular identification method for the potential CQA of big brand traditional Chinese medicine(TCM) based on efficacies and chemical properties. Consequently, the CQA of TRNHQXP were identified by this method, which has provided a reference for the following experimental studies of CQA.

[Criticalquality attribute assessment of big brand traditional Chinese medicine: visualization method for quality control of Ginkgo Leaves Tablets based on spatial distribution uniformity].

Spatial distribution uniformity is the critical quality attribute(CQA) of Ginkgo Leaves Tablets, a variety of big brand traditional Chinese medicine. The evaluation of the spatial distribution uniformity of active pharmaceutical ingredients(APIs) in Ginkgo Leaves Tablets is important in ensuring their stable and controllable quality. In this study, hyperspectral imaging technology was used to construct the spatial distribution map of API concentration based on three prediction models, further to realize the visualization research on the spatial distribution uniformity of Ginkgo Leaves Tablets. The region of interest(ROI) was selected from each Ginkgo Leaves Tablet, with length and width of 50 pixels, and a total of 2 500 pixels. Each pixel had 288 spectral channels, and the number of content prediction data could reach 1×10~5 for a single sample. The results of the three models showed that the Partial Least Squares(PLS) model had the highest prediction accuracy, with calibration set determination coefficient R_(pre)~2 of 0.987, prediction set determination coefficient R_(pre)~2 of 0.942, root mean square error of calibration(RMSEC) of 0.160%, and root mean square error of prediction(RMSEP) of 0.588%. The classical least-squares(CLS) model had a greater prediction error, with the RMSEP of 0.867%. Multivariate Curve Resolution-Alternating Least Square(MCR-ALS) model showed the worst predictive ability among the three models, and it couldn't realize content prediction. Based on the prediction results of PLS and CLS models, the spatial distribution map of APIs concentration was obtained through three-dimensional data reconstruction. Furthermore, histogram method was used to evaluate the spatial distribution uniformity of API. The data showed that the spatial distribution of APIs in Ginkgo Leaves Tablets was relatively uniform. The study explored the feasibility of visualization of spatial distribution of Ginkgo Leaves Tablets based on three models. The results showed that PLS model had the highest prediction accuracy, and MCR-ALS model had the lowest prediction accuracy. The research results could provide a new strategy for the visualization method of quality control of Ginkgo Leaves Tablets.

[Critical quality attribute assessment of big brand traditional Chinese medicine: quality control method of Huangjing Zanyu Capsules based on chemical properties of characteristic components].

The chemical properties of characteristic components are significant to the manufacturing quality control of big brand traditional Chinese medicine. In this study, the Huangjing Zanyu Capsules were used as the research carrier to determine the content of five characteristic components including icraiin, emodin, schisandrin A, 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside, and osthole simultaneously by high-performance liquid chromatography(HPLC). The results showed that the chemical properties of five cha-racteristic components had a good linear relationship(r>0.999 9) within the quantitative range; the relative standard deviations(RSD) was 0.11%-2.0% and 0.25%-2.8% respectively for intra-day and inter-day precision; the RSD of repeatability was 1.8%-2.6%; the RSD of stability within 48 hours was 0.19%-2.8%, and the average recovery rate was 95.52%-100.1%, all meeting the requirements of pharmaceutical quantitative analysis. Additionally, the interval estimation method was used to directly reflect the distribution of samples with abnormal chemical properties of characteristic components, and the results showed ten samples were detected beyound the 95% control line of confidence level. Multivariate statistical process control(MSPC) method was used to monitor the abnormal samples of Huangjing Zanyu Capsules collectively, and the results showed that two samples were beyond the 95% control line of Hotelling's T~2 and three samples beyond the 95% control line of squared prediction error(SPE), indicating consistent quality control of Huangjing Zanyu Capsules. In conclusion, the proposed method is not only accurate and efficient but also a compensation for the traditional single-component quality control method, providing a scientific basis for the quality control in manufacturing process of Huangjing Zanyu Capsules. Furthermore, it could also serve as a reference method for the quality control in manufacturing big brand traditional Chinese medicine.

SULT2B1b promotes epithelial-mesenchymal transition through activation of the ß-catenin/MMP7 pathway in hepatocytes.

Epithelial-mesenchymal transition (EMT) occurs in the progression of liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The hydroxysteroid sulfotransferase 2B1b (SULT2B1b) promotes the proliferation of hepatocarcinoma cells both in vitro and in vivo. However, the correlation between SULT2B1b and the EMT in hepatocytes has not yet been addressed. The present study demonstrated that the SULT2B1b overexpression promoted the EMT process in mouse primary hepatocytes in the absence or presence of TGF-ß1 treatment. Moreover, SULT2B1b interference suppressed the EMT and attenuated the migration and invasion abilities of human hepatocarcinoma BEL-7402 cells by inhibiting the activation of the ß-catenin/MMP-7 pathway. In summary, SULT2B1b enhanced the EMT of hepatocytes and promoted the migration and invasion abilities of BEL-7402 cells by activing the ß-catenin/MMP-7 pathway. Therefore, inhibition of SULT2B1b has therapeutic potential for the treatment of HCC.

Down-regulation of long non-coding RNA SNHG14 protects against acute lung injury induced by lipopolysaccharide through microRNA-34c-3p-dependent inhibition of WISP1.

BACKGROUND: Accumulating evidence has shown the important roles of long non-coding RNAs (lncRNAs) in acute lung injury (ALI). This study aimed to investigate the potential role of lncRNA small nucleolar RNA host gene 14 (SNHG14) in lipopolysaccharides (LPS)-induced ALI. METHODS: Expression of SNHG14, microRNA-34c-3p (miR-34c-3p) and Wnt1 inducible signaling pathway protein 1 (WISP1) in LPS-exposed mouse alveolar macrophages (MH-S) and lung tissues from mice with LPS-induced ALI was determined by reverse transcription quantitative polymerase chain reaction. The interactions among SNHG14, miR-34c-3p and WISP1 were analyzed by dual-luciferase reporter and RIP assays. Using gain-of-function or loss-of-function approaches, the contents of proinflammatory proteins were determined and MH-S cell viability was assessed to evaluate the in vitro functions of SNHG14, miR-34c-3p and WISP1, and wet/dry weight ratio and proinflammatory proteins in lung tissues were determined to assess their in vivo effects. RESULTS: SNHG14 and WISP1 expression was increased, while miR-34c-3p was decreased in ALI models. SNHG14 bound to miR-34c-3p, resulting in impaired miR-34c-3p-dependent down-regulation of WISP1. Both SNHG14 silencing and miR-34c-3p over-expression reduced the levels of proinflammatory proteins IL-18, IL-1ß, TNF-α and IL-6 and inhibited MH-S cell viability. SNHG14 silencing or miR-34c-3p over-expression decreased the wet/dry weight ratio in lung tissues from ALI mice. The reductions induced by SNHG14 silencing or miR-34c-3p over-expression were rescued by WISP1 over-expression. CONCLUSION: This study demonstrated that lncRNA SNHG14 silencing alleviated inflammation in LPS-induced ALI through miR-34c-3p-mediated inhibition of WISP1. Our findings suggest that lncRNA SNHG14 may serve as a therapeutic target for ALI.

Protective Effect of Hesperidin Against Sepsis-Induced Lung Injury by Inducing the Heat-Stable Protein 70 (Hsp70)/Toll-Like Receptor 4 (TLR4)/ Myeloid Differentiation Primary Response 88 (MyD88) Pathway.

BACKGROUND Sepsis-induced lung injury is associated with high mortality. The present investigation evaluated the protective effect of hesperidin against sepsis-induced lung injury and also postulates the possible mechanism of its action. MATERIAL AND METHODS Lung injury was induced by sepsis in all animals, in which sepsis was produced by cecal ligation and puncture (CLP). Animals were treated with hesperidin 10 and 20 mg/kg i.v. 30 min after the surgery. Oxygenation index and lung injury score were determined and levels of pro-inflammatory mediators and markers of oxidative stress were also estimated in the lung tissues. Moreover, expression of caspase-3, B-cell lymphoma (Bcl-2), Toll-like receptor 4 (TLR4), heat-stable protein 70 (Hsp70) and myeloid differentiation primary response 88 (MyD88) protein was estimated by Western blot assay and immunofluorescence assay. RESULTS Hesperidin attenuated the partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio and lung injury score in CLP-induced lung injury mice. There was a significant (p<0.01) decrease in the level of pro-inflammatory mediators in the lung tissue of CLP-induced lung injury mice. Moreover, markers of oxidative stress were attenuated in the hesperidin-treated group. Treatment with hesperidin attenuated the expression of caspase-3, Bcl-2, TLR4, Hsp70, and MyD88 protein in the lung tissue of CLP-induced lung injury mice. CONCLUSIONS Hesperidin protects against lung injury by attenuating the Hsp70/TLR4/MyD88 pathway in CLP-induced lung injury mice.

[Research of hospital preparations based on QbD concept: whole process optimization strategy of gynecological antipruritic lotion].

The stable quality of hospital preparations is the basis for their clinical efficacy. Gynecological antipruritic prescription is widely used in gynecology clinics of Chinese medicine hospitals. Therefore,in this study,the production process of gynecological antipruritic lotion was optimized based on the concept of quality by design( QbD). The production process of the gynecological antipruritic lotion was developed to ensure its process stability and reliable quality,and enhance its clinical applicability. With total amount of matrine and oxymatrine used as the critical quality attribute( CQA) of the production process,parameter levels were designed based on production practice of hospital preparations,and Plackett-Burman and Box-Behnken experiments were used to optimize the water extraction and alcohol precipitation process of antipruritic lotion based on CQA of intermediates and final product. The soaking time,the first extraction time,and the second extraction time were determined as the critical process parameters( CPPs) of the production process. The optimal preparation process was as follows: water volume of 8 times,soaking for 0. 5 h,extraction for 2 times,the first extraction for 30 min,the second extraction for 56 min,alcohol concentration of 50%,and alcohol precipitation for 3 h. Furthermore,the design space was established based on the binomial regress model between CPPs and CQA,so as to set the optimization target and risk range; and the control space was displayed by overlay plot. The results of three repeated experiments in the control space showed that the relative standard deviation( RSD) of CQA was 4. 70%,and the similarity of chromatogram for gynecological antipruritic lotion was 0. 978,0. 974,and 0. 998,respectively. The above results indicated that the operation in the control space can guarantee the quality and stability of gynecological antipruritic lotion,suitable for practical application.

[Correlation of severity classification of acute respiratory distress syndrome by the Berlin definition with extra vascular lung water index and pulmonary vascular permeability index].

OBJECTIVE: To explore the correlation of severity classification of acute respiratory distress syndrome (ARDS) by the Berlin definition with extra vascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI). METHODS: A total of 70 cases with ARDS at intensive care unit of our hospital from July 2012 to July 2014 were divided into three groups of mild (n = 20), moderate (n = 30) and severe (n = 20) according to the Berlin definition. The scores of acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) within 24 h of admission were recorded. And the values of EVLWI and PVPI of three groups from Day 1-4 were monitored by pulse indicator continuous cardiac output (PiCCO). Receiver operating characteristic (ROC) curve was drawn for these parameters and the area under curve was compared. Meanwhile blood gas was analyzed and oxygenation index (OI) calculated. And the correlations of EVLWI and PVPI with OI were analyzed. RESULTS: Comparisons of EVLWI, PVPI and OI were made for three groups at different timepoints: As the severity of ARDS aggravated, EVLWI and PVPI of three groups increased significantly at any timepoint while OI decreased sharply (P < 0.05). EVLWI and PVPI declined gradually from Day 1-4 in mild ARDS group (P < 0.05), PVPI declined dramatically (P < 0.05) while EVLWI showed no obvious change in moderate ARDS group (P > 0.05). There was no sharp decline of EVLWI or PVPI in severe ARDS group (P > 0.05). And OI increased significantly from Day 1-4 in three groups (P < 0.01). The area under ROC curve (AUC) for PVPI in evaluating the prognosis of three groups was 0.594, 0.643, 0.723 and 0.816 respectively. PVPI > 2.95 at Day 4 of admission was used as the best threshold value for judging prognosis. And the sensitivity was 70% and specificity 92%. OI had negative correlation with EVLWI and PVPI in three groups from Day 1-4 [(r = -0.685, P = 0.000) and (r = -0.631, P = 0.000)]. CONCLUSION: Both EVLWI and PVPI reflect adequately the severity of ARDS by the Berlin definition. And the dynamic trend of PVPI is superior to that of EVLWI.

[Investigation on the predictive value of the dynamic changes of EVLWI and PVPI on the prognosis of ARDS patients].

OBJECTIVE: To investigate the dynamic changes of extra vascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) on the prognosis of acute respiratory distress syndrome (ARDS), and predict the risk factors affecting prognosis of ARDS. METHODS: 70 patients meeting ARDS Berlin definition, who were admitted to the ICU from July 2012 to July 2014, were analyzed with a prospective method. The patients were divided into a survival group and a death group according to their survival situation in 28 days. EVLWI (EVLWI1-EVLWI4), PVPI (PVPI1-PVPI4), DeltaEVLWI (subtracting EVLWI day 4 from day 1), and DeltaPVPI (subtracting PVPI day 4 from day 1) of the two groups of patients from the 1st day to the 4th day were monitored by the pulse indicator continuous cardiac output (PiCCO). Parameters including the acute physiology and chronic health evaluation (APACHE II) score, sequential organ failure assessment (SOFA) score, EVLWI, PVPI, DeltaEVLWI, DeltaPVPI, oxygenation index (OI), CVP, the number of organ dysfunction were compared between the two groups. Univariate analysis and multivariate logistic regression were used to analyze the independent risk factors associated with prognosis. Receiver operating characteristic curve (ROC curve) was drawn to evaluate the prediction performance of those risk factors in the prognosis of ARDS. RESULTS: Comparison of EVLWI and PVPI between the survival group and the death group of ARDS patients at different time points: EVLWI and PVPI showed no statistical difference from the 1st day to the 2nd day after admission, but those two parameters in the death group were higher than those in the survival group form the 3rd day to the 4th day after admission (P<0.01). The comparison of the dynamic changes of EVLWI and PVPI within the two groups: the EVLWI and PVPI in the survival group declined gradually from 1st day to 4th day after treatment, but that changing trend in the death group showed no statistical difference. DeltaEVLWI and DeltaPVPI changes in the survival group were higher than in the death group (P<0.01). They were independent risk factors of patients 28-day prognosis (P<0.05). ROC curve and 28-day survival curve showed that the area under ROC curve of DeltaPVPI predicting prognosis of patients with ARDS was 0.812, when the optimal cut off value was 1.2, and the median survival period in DeltaPVPI>1.2 group was longer than that in the Delta PVPI≤1.2 group. CONCLUSIONS: The continuous dynamic observation of EVLWI and PVPI changes is better than that of a single detection. DeltaEVLWI and DeltaPVPI are independent risk factors and can be used as an auxiliary indicator for the prognosis of patients with ARDS.

Congenital disorder of glycosylation type Ia in a Chinese family: Function analysis of a novel PMM2 complex heterozygosis mutation.

Congenital disorder of glycosylation type Ia (CDG-Ia) is an autosomal recessive genetic disease caused by a mutation in the phosphomannomutase 2 (PMM2) gene. We have identified a 13-month-old boy who has been diagnosed with CDG-Ia. He displays several characteristic symptoms, including cerebellar hypoplasia, severe developmental retardation, hypothyroidism, impaired liver function, and abnormal serum ferritin levels. Through whole-exome sequencing, we discovered novel complex heterozygous mutations in the PMM2 gene, specifically the c.663C > G (p.F221L) mutation and loss of exon 2. Further analysis revealed that the enzymatic activity of the mutant PMM2 protein was significantly reduced by 44.97% (p < 0.05) compared to the wild-type protein.

A Comprehensive Review on Wastewater Nitrogen Removal and Its Recovery Processes.

Discharging large amounts of domestic and industrial wastewater drastically increases the reactive nitrogen content in aquatic ecosystems, which causes severe ecological stress and biodiversity loss. This paper reviews three common types of denitrification processes, including physical, chemical, and biological processes, and mainly focuses on the membrane technology for nitrogen recovery. The applicable conditions and effects of various treatment methods, as well as the advantages, disadvantages, and influencing factors of membrane technologies, are summarized. Finally, it is proposed that developing effective combinations of different treatment methods and researching new processes with high efficiency, economy, and energy savings, such as microbial fuel cells and anaerobic osmotic membrane bioreactors, are the research and development directions of wastewater treatment processes.

Integrative analysis of the expression profiles of whole coding and non-coding RNA transcriptomes and construction of the competing endogenous RNA networks for chronic obstructive pulmonary disease.

The pathogenesis of Chronic Obstructive Pulmonary Disease (COPD) is implicated in airway inflammation, oxidative stress, protease/anti-protease and emphysema. Abnormally expressed non-coding RNAs (ncRNAs) play a vital role in regulation of COPD occurrence and progression. The regulatory mechanisms of the circRNA/lncRNA-miRNA-mRNA (competing endogenous RNA, ceRNA) networks might facilitate our cognition of RNA interactions in COPD. This study aimed to identified novel RNA transcripts and constructed the potential ceRNA networks of COPD patients. Total transcriptome sequencing of the tissues from patients with COPD (COPD) (n = 7) and non-COPD control subjects (Normal) (n = 6) was performed, and the expression profiles of differentially expressed genes (DEGs), including mRNAs, lncRNAs, circRNAs, and miRNAs, were analyzed. The ceRNA network was established based on the miRcode and miRanda databases. Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA), and Gene set variation analysis (GSVA) were implemented for functional enrichment analysis of DEGs. Finally, CIBERSORTx was extracted to analyze the relevance between hub genes and various immune cells.The Starbase and JASPAR databases were used to construct hub-RNA binding proteins (RBPs) and lncRNA-transcription factor (TF) interaction networks. A total of 1,796 mRNAs, 2,207 lncRNAs, and 11 miRNAs showed differentially expression between the lung tissue samples from the normal and COPD groups. Based on these DEGs, lncRNA/circRNA-miRNA-mRNA ceRNA networks were constructed respectively. In addition, ten hub genes were identified. Among them, RPS11, RPL32, RPL5, and RPL27A were associated with the proliferation, differentiation, and apoptosis of the lung tissue. The biological function revealed that TNF-α via NF-kB and IL6/JAK/STAT3 signaling pathways were involved in COPD. Our research constructed the lncRNA/circRNA-miRNA-mRNA ceRNA networks, filtrated ten hub genes may regulate the TNF-α/NF-κB, IL6/JAK/STAT3 signally pathways, which indirectly elucidated the post-transcriptional regulation mechanism of COPD and lay the foundation for excavating the novel targets of diagnosis and treatment in COPD.

EEG Characteristics Before and After Dexmedetomidine Treatment in Severe Patients: A Prospective Study.

Background. Bedside electroencephalography (EEG) can monitor the changes in brain function in critical patients. Light sedation is recommended in intensive care unit (ICU) patients, but sedation might confuse the EEG readings. There are few studies on the changes of EEG in severe patients with dexmedetomidine. This study aimed to explore the EEG characteristics before and after dexmedetomidine in severe patients in the ICU. Methods. This prospective study enrolled severe patients with sepsis who needed light sedation, we sedated the patients with dexmedetomidine. EEG was recorded for at least 60 min using a quantitative EEG (qEEG) bedside monitor. Amplitude-EEG (aEEG), relative spectral energy, alpha variation, and spectral entropy were recorded and compared before/after dexmedetomidine. Results. Sixty-three participants were enrolled. The relative spectral energy and alpha variation were not different before and after the use of dexmedetomidine (P > .05). The amplitude of the upper and lower boundaries in aEEG and spectral entropy were significantly lower after light sedation with dexmedetomidine compared with before (P < .05). When grouped according to the Glasgow Coma Scale (GCS), the amplitude of qEEG in participants with moderate GCS decreased significantly(P < .05), but not in mild or severe GCS. Conclusion. Relative spectral energy and alpha variation derived from qEEG could be used to evaluate the state of brain function even under light sedation with dexmedetomidine in severe patients during their ICU stay.

A Comprehensive Review on Forward Osmosis Water Treatment: Recent Advances and Prospects of Membranes and Draw Solutes.

Forward osmosis (FO) is an evolving membrane separation technology for water treatment and reclamation. However, FO water treatment technology is limited by factors such as concentration polarization, membrane fouling, and reverse solute flux. Therefore, it is of a great importance to prepare an efficient high-density porous membrane and to select an appropriate draw solute to reduce concentration polarization, membrane fouling, and reverse solute flux. This review aims to present a thorough evaluation of the advancement of different draw solutes and membranes with their effects on FO performance. NaCl is still widely used in a large number of studies, and several general draw solutes, such as organic-based and inorganic-based, are selected based on their osmotic pressure and water solubility. The selection criteria for reusable solutes, such as heat-recovered gaseous draw, magnetic field-recovered MNPs, and electrically or thermally-responsive hydrogel are primarily based on their industrial efficiency and energy requirements. CA membranes are resistant to chlorine degradation and are hydrophilic, while TFC/TFN exhibit a high inhibition of bio-adhesion and hydrolysis. AQPs are emerging membranes, due to proteins with complete retention capacity. Moreover, the development of the hybrid system combining FO with other energy or water treatment technologies is crucial to the sustainability of FO.

Progress in the Preparation and Modification of Zinc Ferrites Used for the Photocatalytic Degradation of Organic Pollutants.

Zinc ferrite is a type of photocatalytic material with high physicochemical stability, narrow band gap, high carrier separation efficiency, high porosity, and paramagnetism, which makes it easy to recover. Thus, zinc ferrite is widely used as a photocatalyst in water treatment. In this paper, the preparation principles as well as the advantages and disadvantages of typical methods used to prepare zinc ferrite including hydrothermal, co-precipitation, sol-gel, and other novel methods such as biosynthesis have been summarized. Modification methods such as elemental doping, composite formation, and morphological modification have been highlighted. Using these modification methods, the catalytic activity of zinc ferrite toward the photocatalytic degradation of organic pollutants in water has been enhanced. Biosynthesis is regarded as a promising preparation method that uses biological materials instead of chemical materials to achieve the large-scale preparation of zinc ferrite using low cost, energy efficient, and environmentally friendly processes. Meanwhile, the combination of multiple modification techniques to enhance the photocatalytic performance of zinc ferrite will be an important research trend in the future.