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.

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.

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.

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.

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.

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.

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.

[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.

Effects of interplay between disorder and anharmonicity on heat conduction.

Heat conduction through a disordered Fermi-Pasta-Ulam-ß (DFPU-ß) chain is studied. The presence of disorder makes the heat current behave significantly different from that of the ordered Fermi-Pasta-Ulam-ß (FPU-ß) chain. Thanks to the interplay between disorder and anharmonicity, a nonmonotonic-monotonic transition occurs when the disorder strength increases. That is, a peak for the heat current emerges for weak disorder; however, monotonic increasing of the heat current shows up for strong disorder. This can be understood based on the competition between two effects of anharmonicity on phonons, namely, delocalization and phonon-phonon scattering, which is shown by the spectral decomposition of heat current.

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.

[Application value of lung ultrasound in the diagnosis and severity assessment of ventilator-associated pneumonia].

OBJECTIVE: To explore the value of bedside lung ultrasound in the early diagnosis and severity assessment of ventilator-associated pneumonia (VAP). METHODS: A prospective observational study was conducted in 60 patients with VAP (VAP group) and 62 patients without VAP (control group) who were admitted to department of intensive care unit of General Hospital of Ningxia Medical University from September 2018 to July 2020. The gender, age and underlying diseases of non-VAP group were matched with VAP group. The general clinical data such as gender, age, underlying diseases, department source of the patient, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score were recorded. The body temperature, white blood cell count (WBC), procalcitonin (PCT), oxygenation index (PaO2/FiO2), alveolar artery oxygen differential pressure (PA-aDO2) were recorded. During mechanical ventilation, the patient's body temperature, WBC, sputum characteristics, and the change of the lung ultrasound were dynamically observed. With or without dynamic air bronchogram, lung ultrasound was considered to be positive as long as there were small subpleural consolidation or tissue-like sign. Ventilator-associated pneumonia lung ultrasound score (VPLUS) and lung ultrasound score (LUSS) were performed, and chest CT scan was completed on the same day. Use positive chest CT scan as the standard to evaluate the diagnostic efficacy of lung ultrasound, VPLUS score, and the combination of the two with PCT for VAP. LUSS was used to assess the severity of disease in patients with VAP. The correlation between LUSS and PaO2/FiO2, PA-aDO2, APACHE II score and SOFA score were analyzed. RESULTS: (1) General information: compared with non-VAP group, VAP group had more emergency surgery patients [51.7% (31/60) vs. 33.9% (21/62), P = 0.047], APACHE II score and SOFA score were significantly higher (APACHE II score: 15.4±5.7 vs. 13.4±3.4, P = 0.021; SOFA score: 8.8±4.2 vs. 6.3±3.3, P < 0.001), body temperature tended to rise (centigrade: 38.3±0.8 vs. 38.0±0.9, P = 0.054), more patients had airway purulent secretions [65.0% (39/60) vs. 41.9% (26/62), P = 0.011], and mechanical ventilation time and length of ICU stay were longer [mechanical ventilation time (days): 10.5 (6.6, 15.0) vs. 4.3 (3.0, 6.0), P < 0.001; length of ICU stay (days): 14.8 (9.0, 18.0) vs. 6.0 (4.0, 9.1), P < 0.001], 28-day mortality rate was higher [31.7% (19/60) vs. 9.7% (6/62), P = 0.003]. (2) Diagnostic efficacy evaluation: when lung ultrasound was positive, VPLUS ≥ 3 and PCT > 0.5 µg/L were used separately for the diagnosis of VAP, the sensitivity was 73.3%, 75.0%, 61.7%, respectively; the specificity was 80.6%, 58.1% and 59.7%, respectively; the 95% confidence interval (95%CI) was 0.685-0.842, 0.574-0.748, 0.514-0.694, respectively,all P < 0.05, positive lung ultrasound had good sensitivity and specificity. When positive lung ultrasound or VPLUS ≥ 3 were combined with PCT > 0.5 µg/L for tandem test, the specificity of VAP diagnosis was increased to 95.2% and 83.9%, respectively; but the specificity of VAP diagnosis of positive lung ultrasound combined with PCT > 0.5 µg/L was higher than VPLUS ≥ 3 combined with PCT > 0.5 µg/L (95.2% vs. 83.9%, P < 0.05). (3) Correlation analysis: LUSS showed a significant positive correlation with APACHE II and SOFA score (r values were 0.407, 0.399, P values were 0.001, 0.002, respectively), LUSS had no relation with PaO2/FiO2 and PA-aDO2 (r values were 0.189, -0.064, P values were 0.629, 0.149, respectively). CONCLUSIONS: Lung ultrasound can early detect VAP , and its diagnostic specificity is significantly improved when combined with PCT > 0.5 µg/L. LUSS is closely related to the severity of disease in VAP patients, therefore, lung ultrasound may be an effective method for early diagnosis and efficacy evaluation of VAP patients.

The potential diagnostic value of extracellular vesicle miRNA for human non-small cell lung cancer: a systematic review and meta-analysis.

Background: This meta-analysis aimed to evaluate the diagnostic accuracy of extracellular vesicles (EV) miRNAs for non-small cell lung cancer (NSCLC).Methods: All eligible studies were searched in an online database. Stata 15.0, Meta-disc 14.0 and Review Manager 5.2 software packages were used to perform all statistical analysis.Results: The analysis included 16 articles and 70 studies. Pooled sensitivity (SEN) and specificity (SPE), positive predictive value and negative predictive value were 0.77 (95% CI: 0.72-0.80), 0.83 (95% CI: 0.78-0.86), 0.88 (95% CI: 0.86-0.90) and 0.63 (95% CI: 0.58-0.68), respectively. The overall diagnostic odds ratio (DOR) was 16 (95% CI: 11-21) and the area under the curve (AUC) was 0.86 (95% CI: 0.83-0.89). 3 EV miRNAs could identify metastatic NSCLC from healthy, and 10 distinguish early-stage NSCLC. The respective targets of EV miR-21, miR-210, and miR-1290 could activate PI3K/AKT-related pathway.Conclusion: EV miRNAs had high diagnostic accuracy (AUC = 0.86) for NSCLC, especially metastatic NSCLC (AUC = 0.90), and early-stage NSCLC (AUC = 0.88). Besides, multitudinous EV miRNAs combined showed higher diagnostic value than alone. EV miR-21, miR-210, and miR-1290 might be associated with PI3K/AKT-related pathway and the valuable diagnostic biomarkers for NSCLC.

Nucks1 gene polymorphism rs823114 is associated with the positive symptoms and neurocognitive function of patients with schizophrenia in parts of southern China.

Nuclear casein kinase and cyclin-dependent kinase substrate 1 (nucks1) are considered a potential susceptibility gene for certain neurological diseases, such as Parkinson's disease (PD). In our study, we genotyped three single nucleotide polymorphisms (SNPs) (rs4951261, rs823114 and rs951366) of the nucks1 gene in 774 schizophrenic patients and 819 healthy controls using the improved multiplex ligation detection reaction (imLDR) technique. Furthermore, we also studied the relationship between the above SNPs and the clinical psychiatric symptoms and neurocognitive function of the patients. Genotype distributions and allele frequencies of these SNPs showed no significant differences and were found between patients and healthy controls. However, in an analysis of the positive symptom score of rs823114 among male patients, we found that the score of the A/A genotype was lower than that of the G/A+G/G genotypes (P = 0.001, P(corr) = 0.003]. Additionally, we also found that among the female patients, G allele carriers with rs823114 had lower semantic fluency scores than subjects with the A/A genotype (P = 0.010, P(corr) = 0.030]. Our data show for the first time that rs823114 polymorphism of nucks1 may affect positive symptoms and neurocognitive function in patients with schizophrenia in parts of southern China.

[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.

miR-378d is Involved in the Regulation of Apoptosis and Autophagy of and E2 Secretion from Cultured Ovarian Granular Cells Treated by Sodium Fluoride.

Taking excessive sodium fluoride may cause female reproductive dysfunction, but underlying molecular mechanism is unclear. The ovarian granulosa cells are the key endocrine cells releasing reproductive hormones. The miRNAs in the granulosa cells play an important function in regulating reproduction. The aim of this study is to explore the role of miRNAs in granulosa cell apoptosis and autophagy, as well as estradiol (E2) release in response to excessive sodium fluoride. The ovarian granulosa cells (KGN cells) were treated in vitro by different concentrations of sodium fluoride (NaF) for 24 h. The level of estradiol (E2) in the incubation medium was measured by ELISA kits. The total RNA and protein were collected and purified from KGN cells. The expression of miRNAs was detected by the real-time PCR. The signal molecules involved in cell apoptosis and autophagy were detected by the real-time PCR and Western blotting. Six miRNAs in granulosa cells were significantly up- or downregulated by NaF and selected for real-time PCR analysis. The miR-378d was the most significantly upregulated one dose dependently by NaF. It was positively correlated to the extent of apoptosis but negatively correlated to the level of autophagy in KGN cells in response to NaF. In addition, miR-378d promoted E2 release in response to 1 and 2 mM NaF but reduced E2 release in response to 4 and 8 mM NaF treatments. It is concluded that expression of miR-378d in ovarian granulosa cells is negatively correlated to the autophagy and E2 release and positively correlated to cell apoptosis under the influence of NaF.

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.

Carbon monoxide attenuates LPS-induced myocardial dysfunction in rats by regulating the mitochondrial dynamic equilibrium.

Lipopolysaccharide (LPS) induces myocardial dysfunction by damaging the mitochondrial structure in cardiomyocytes. Since low levels of carbon monoxide can confer cytoprotective effects against end-organ damage from endotoxic shock, we tested whether treatment with carbon monoxide-releasing molecule-2 (CORM-2) could ameliorate LPS-induced myocardial dysfunction in rats by maintaining the dynamic equilibrium between the mitochondrial fusion and fission processes. Cardiac function, myocardial histopathology, myocardial enzymes, and changes in myocardial mitochondrial function and mitochondrial fusion-fission protein expression were assessed in rats. The mitochondrial structure and morphology were studied by electron microscopy, and the expression levels of key proteins involved in the mitochondrial dynamics were assessed by Western blot assay. Cardiac dysfunction and increased myocardial enzyme activity together with myocardial pathological damage, mitochondrial dysfunction, and impaired mitochondrial dynamics homeostasis were observed in the LPS-challenged septic rats. However, these observations were reversed by CORM-2, which effectively inhibited cardiac and mitochondrial damage in the LPS-challenged rats and improved the survival rate of the animals. In conclusion, CORM-2 regulates the LPS-induced imbalance of the dynamic mitochondrial fusion and fission processes, thereby effectively ameliorating the LPS-induced myocardial dysfunction and improving the survival of the rats.