Exogenous betaine enhances salt tolerance of Glycyrrhiza uralensis through multiple pathways.

BACKGROUND: Glycyrrhiza uralensis Fisch., a valuable medicinal plant, shows contrasting salt tolerance between seedlings and perennial individuals, and salt tolerance at seedling stage is very weak. Understanding this difference is crucial for optimizing cultivation practices and maximizing the plant's economic potential. Salt stress resistance at the seedling stage is the key to the cultivation of the plant using salinized land. This study investigated the physiological mechanism of the application of glycine betaine (0, 10, 20, 40, 80 mM) to seedling stages of G. uralensis under salt stress (160 mM NaCl). RESULTS: G. uralensis seedlings' growth was severely inhibited under NaCl stress conditions, but the addition of GB effectively mitigated its effects, with 20 mM GB had showing most significant alleviating effect. The application of 20 mM GB under NaCl stress conditions significantly increased total root length (80.38%), total root surface area (93.28%), and total root volume (175.61%), and significantly increased the GB content in its roots, stems, and leaves by 36.88%, 107.05%, and 21.63%, respectively. The activity of betaine aldehyde dehydrogenase 2 (BADH2) was increased by 74.10%, 249.38%, and 150.60%, respectively. The 20 mM GB-addition treatment significantly increased content of osmoregulatory substances (the contents of soluble protein, soluble sugar and proline increased by 7.05%, 70.52% and 661.06% in roots, and also increased by 30.74%, 47.11% and 26.88% in leaves, respectively.). Furthermore, it markedly enhanced the activity of antioxidant enzymes and the content of antioxidants (SOD, CAT, POD, APX and activities and ASA contents were elevated by 59.55%, 413.07%, 225.91%, 300.00% and 73.33% in the root, and increased by 877.51%, 359.89%, 199.15%, 144.35%, and 108.11% in leaves, respectively.), and obviously promoted salt secretion capacity of the leaves, which especially promoted the secretion of Na+ (1.37 times). CONCLUSIONS: In summary, the exogenous addition of GB significantly enhances the salt tolerance of G. uralensis seedlings, promoting osmoregulatory substances, antioxidant enzyme activities, excess salt discharge especially the significant promotion of the secretion of Na+Future studies should aim to elucidate the molecular mechanisms that operate when GB regulates saline stress tolerance.

Long-term outcome of uniport vs. multiport video-assisted thoracoscopic lobectomy for lung cancer.

This study aims to compare the perioperative outcomes and long-term survival of U-VATS lobectomy for NSCLC with multiportal VATS (M-VATS, involving two ports or more) lobectomy. A total of 339 patients who underwent intentional VATS lobectomy for lung cancer between 2012 and 2017 were included in the analysis. Perioperative outcomes and long-term survival were evaluated. Propensity score matching was utilized to minimize baseline characteristic differences between the two groups. Out of the total cases, 17 (5.01%) were converted to open thoracotomy. The conversion rates were 4.96% (7/141) in the U-VATS group and 5.05% (10/198) in the M-VATS group. A total of 322 consecutive patients underwent VATS lobectomy and mediastinal lymphadenectomy. After propensity matching, 106 pairs were obtained, consisting of 83 males and 129 females. Intraoperative bleeding volume, number of retrieved lymph nodes, explored nodal stations, drainage time and volume, and postoperative hospital stay were similar between the two groups. Both groups exhibited comparable morbidity and mortality rates. From the multivariable analysis, there was no significant difference observed in terms of overall survival (OS) and disease-free survival (DFS) between the two patient cohorts. U-VATS demonstrated comparable perioperative outcomes and long-term efficacy to M-VATS. However, further confirmation of these findings is required.

Metastasis-associated 1 localizes to the sarcomeric Z-disc and is implicated in skeletal muscle pathology.

Metastasis-associated 1 (MTA1), a subunit of the nucleosome remodeling and histone deacetylation (NuRD) corepressor complex, was reported to be expressed in the cytoplasm of skeletal muscles. However, the exact subcellular localization and the functional implications of MTA1 in skeletal muscles have not been examined. This study aims to demonstrate the subcellular localization of MTA1 in skeletal muscles and reveal its possible roles in skeletal muscle pathogenesis. Striated muscles (skeletal and cardiac) from C57BL/6 mice of 4-5 weeks were collected to examine the expression of MTA1 by Western blotting and immunohistochemistry. Immunofluorescence and immunoelectron microscopy were performed for MTA1, α-actinin (a Z-disc marker protein), and SMN (survival of motor neuron) proteins. Gene Expression Omnibus (GEO) data sets were analyzed using the GEO2R online tool to explore the functional implications of MTA1 in skeletal muscles. MTA1 expression was detected by Western blotting and immunohistochemistry in skeletal and cardiac muscles. Subcellular localization of MTA1 was found in the Z-disc of sarcomeres, where α-actinin and SMN were expressed. Data mining of GEO profiles suggested that MTA1 dysregulation is associated with multiple skeletal muscle defects, such as Duchenne muscular dystrophy, Emery-Dreifuss muscular dystrophy, nemaline myopathy, and dermatomyositis. The GEO analysis also showed that MTA1 expression gradually decreased with age in mouse skeletal muscle precursor cells. The subcellular localization of MTA1 in sarcomeres of skeletal muscles implies its biological roles in sarcomere structures and its possible contribution to skeletal muscle pathology.

Triptolide inhibits proliferation and invasion of colorectal cancer cells by blocking Nrf2 expression.

Triptolide (TPL), the main active ingredient of Tripterygium wilfordii, has anti-inflammatory, immunomodulatory, and antitumor actions. It can also inhibit cell proliferation and metastasis while promoting apoptosis of several tumors, such as colorectal cancer (CRC). However, the mechanism of TPL against CRC is not clear. This study was designed to investigate the effects and molecular mechanisms of TPL on the proliferation and invasion ability of CRC cells. A human CRC cell line (HT29 cell line) cultured in vitro was treated with different concentrations of TPL (0, 25, 50, and 100 nmol/L). The proliferation of cells was detected by MTT, the invasion ability of cells by Transwell, and the apoptosis level by flow cytometry. The protein expression levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), matrix metalloproteinase (MMP)-2, and MMP-9 were detected by western blotting. After transfection with sh-Nrf2, HT29 cells were divided into NC group, NC + TPL group and sh-Nrf2 + TPL group, and the above assays were repeated for each group. TPL significantly inhibited the proliferation and invasion ability of HT29 cells and promoted apoptosis (p < .05). Notably, its inhibitory or promotional effects were concentration-dependent, which were enhanced with increasing drug concentration (p < .05). After silencing Nrf2 expression, the proliferation, and invasion ability of HT29 cells were further significantly inhibited while cells apoptosis was further promoted (p < .05). Besides, the decreased Nrf2 expression reduced the protein expression levels of MMP-2 and MMP-9 (p < .05). TPL can effectively inhibit the proliferation and invasion while promoting apoptosis of HT29 cells. And its mechanism of action may be related to the inhibition of Nrf2 signaling expression.

Increased dominance of terrestrial component in dissolved organic matter in Chinese lakes.

The source composition of chromophoric dissolved organic matter (CDOM) in lakes is closely related to regional environmental changes, human activities, and the carbon cycle. The spectral slope ratio (SR) is an important parameter of CDOM optical components, and combined with remote sensing technology, the source composition of CDOM can be tracked comprehensively and efficiently in large regions. Here, we proposed a CDOM source tracking remote sensing model (CDOM-SR) based on the hue angle (α) to assess the spatial pattern and long-term trend of the CDOM source composition in Chinese lakes (surface area ≥ 1 km2) from 1986 to 2021. Validation results show that the CDOM-SR model has a good SR estimation performance with a median absolute percentage difference, root mean square deviation, median ratio, and median deviation of 17.91 %, 0.23, 1.02, and 0.03, respectively. We found that the average SR of Chinese lakes presents an obvious spatial pattern of high in the west and low in the east due to the difference in human activity intensity and the natural geographical environment. Additionally, we found that the average SR of Chinese lakes from 1986 to 2021 decreased at a rate of - 0.06/10 years, of which 64.37 % of lakes decreased significantly, 15.42 % of lakes had no significant change, and only 20.20 % of lakes increased. The widespread decrease in the average SR indicates that the increasing human activity discharge of terrestrial organic matter has had an important impact on the source composition of the CDOM in Chinese lakes. Our results provide a new resource for remote sensing monitoring of CDOM sources and important insights into lake carbon cycling under the influence of ongoing human activities.

Spatial-temporal evolution of production-living-ecological space and layout optimization strategy in eco-sensitive areas: a case study of typical area on the Qinghai-Tibetan Plateau, China.

To achieve sustainable development goals and to solve environmental problems, land resources in eco-sensitive areas should be used and optimized. Qinghai, which is an important eco-sensitive area in China, represents a typical ecological vulnerable region on the Qinghai-Tibetan Plateau. Using land use/cover data for 2000, 2010 and 2020, this study applied a series of quantitative methods to analyze the spatial pattern and structure of the production-living-ecological space (PLES) in Qinghai. The results indicated that the spatial pattern of the PLES in Qinghai was stable over time, but the spatial distribution was very different. The structure of the PLES in Qinghai was stable, and the proportion of each space from high to low was ecological (81.01%), production (18.13%) and living (0.86%). We found that the proportion of ecological space in both the Qilian Mountains and the Three River Headwaters Region was lower than the rest of the study area, except for the Yellow River-Huangshui River Valley. Our study objectively and credibly presented the characteristics of the PLES in an important eco-sensitive area in China. This study further formulated targeted policy suggestions to provide a basis for regional sustainable development, ecological environment protection, and land and space optimization in Qinghai.

Efficacy of conversion surgery on stage IV gastric cancer and its prognosis analysis.

BACKGROUND: The aim of this study was to explore the clinical efficacy and safety of conversion surgery in the treatment of stage IV gastric cancer, and to analyze the influencing factors for the prognosis of patients. METHODS: The clinical data of 84 patients with stage IV gastric cancer treated in our hospital from September 2014 to March 2016 were collected. All patients were treated with S-1 + oxaliplatin or S-1 + docetaxel chemotherapy, among which 42 patients had surgical indications after chemotherapy and received gastrectomy (R0 resection or R1 resection) (conversion surgery group); the remaining 42 patients had no surgical indications after chemotherapy (simple chemotherapy group). The patients in both groups were followed-up to record the survival status; moreover, the possible influencing factors for the prognosis were analyzed. RESULTS: In the conversion surgery group, the median chemotherapy cycle was 4.3, and the objective response rate (ORR) was 73.8% (31/42). During chemotherapy in the two groups, there were 22 cases (52.3%) and 24 cases (57.1%) of hematological toxicity, and 28 cases (66.7%) and 32 cases (76.2%) of non-hematological toxicity, mainly in grade I-II, which could be relieved after symptomatic treatment, and chemotherapy was successfully completed. After chemotherapy, 42 out of 84 patients met the surgical indications. All patients were followed-up for 6-36 months. The 3-year overall survival was 35.7% (15/42) and 9.5% (4/42), respectively, in the two groups, and the difference was statistically significant according to the log-rank test (P<0.05). The results of multivariate analysis showed that whether the surgical margin was R0 was an independent influencing factor for the prognosis of patients (HR=8.012, 95% CI: 2.522-14.384, P=0.027). CONCLUSIONS: Radical surgery after conversion therapy can raise the survival rate of patients, with tolerable adverse reactions. Whether the surgical margin is R0 in conversion therapy it is an independent influencing factor for the prognosis of patients with stage IV gastric cancer.

A hybrid remote sensing approach for estimating chemical oxygen demand concentration in optically complex waters: A case study in inland lake waters in eastern China.

Chemical oxygen demand concentration (CCOD) is widely used to indicate the degree of organic pollution of lakes, reservoirs and rivers. Mastering the spatiotemporal distribution of CCOD is imperative for understanding the variation mechanism and controlling of organic pollution in water. In this study, a hybrid approach suitable for Sentinel 3A/Ocean and Land Colour Instrument (OLCI) data was developed to estimate CCOD in inland optically complex waters embedding the interaction between CCOD and the absorption coefficients of optically active constituents (OACs). Based on in-situ sampling in different waters, the independent validations of the proposed model performed satisfactorily in Lake Taihu (MAPE = 23.52 %, RMSE = 0.95 mg/L, and R2 = 0.81), Lake Qiandaohu (MAPE = 21.63 %, RMSE = 0.50 mg/L and R2 = 0.69), and Yangtze River (MAPE = 29.34 %, RMSE = 0.83 mg/L, and R2 = 0.64). In addition, the approach not only showed significant superiority compared with previous algorithms, but also was suitable for other common satellite sensors equipped same or similar bands. The hybrid approach was applied to OLCI images to retrieve CCOD of Lake Taihu from 2016 to 2020 and reveals substantial interannual and seasonal variations. The above results indicate that the proposed approach is effective and stable for studying spatiotemporal dynamic of CCOD in optically complex waters, and that satellite-derived products can provide reliable information for lake water quality management.

Cu Nanowires and Nanoporous Ag Matrix Fabricated through Directional Solidification and Selective Dissolution of Ag-Cu Eutectic Alloys.

Cu nanowires and a nanoporous Ag matrix were fabricated through directional solidification and selective dissolution of Ag-Cu eutectic alloys. Ag-39.9at.%Cu eutectic alloys were directionally solidified at growth rates of 14, 25, and 34 µm/s at a temperature gradient of 10 K/cm. The Cu phase in the Ag matrix gradually changed from lamellar to fibrous with an increase in the growth rate. The Ag matrix phase was selectively dissolved, and Cu nanowires of 300-600 nm in diameter and tens of microns in length were prepared in 0.1 M borate buffer with a pH of 9.18 at a constant potential of 0.7 V (vs. SCE). The nanoporous Ag matrix was fabricated through selective dissolution of Cu fiber phase in 0.1 M acetate buffer with a pH of 6.0 at a constant potential of 0.5 V (vs. SCE). The diameter of Ag pores decreased with increasing growth rate. The diameter and depth of Ag pores increased when corrosion time was extended. The depth of the pores was 30 µm after 12 h.

B16 Membrane-Coated Vesicles for Combined Photodynamic Therapy and Immunotherapy Shift Immune Microenvironment of Melanoma.

Introduction: Coating of nanomedicine with cell membranes has attracted increasing attention as it can boost biocompatibility and improve the efficiency of treatment. Herein, we prepared innovative tumor cell-membrane-coated vesicles based on photodynamic therapy (PDT) drug indocyanine green (ICG) and explore the effect on melanoma in vitro and in vivo. Methods: ICG was coated with B16 cell membranes (I@BM NVs) by sonication and extrusion, and the morphological characteristics of I@BM NVs were evaluated by transmission electron microscopy (TEM) and NP-tracking analysis. Homologous cellular uptake was evaluated by flow cytometry (FCM) after staining by DiD dye. Cellular cytotoxicity was evaluated by cell counting kit-8 assay and the anti-tumor effect in vitro was assessed by FCM and western blotting. The anti-tumor effect in vivo was evaluated in a B16 xenograft model in mice. The tumor micro-environment was investigated by FCM and real-time PCR. Results: The vesicles are stable and uniform in nature, and show strong homologous targeting in vivo and in vitro. The vesicles can generate reactive oxygen species to induce apoptosis of B16 cells under near-infrared irradiation. Furthermore, the I@BM NVs induce a significant anti-tumor response in vivo, and perform better with respect to both tumor growth inhibition and lifespan extension. Analysis of immunocytes in the tumor microenvironment showed significant reductions in numbers of myeloid-derived suppressor cells and tumor-associated M2 macrophages in mice in the I@BM NVs group. This was accompanied by significant increases in numbers of M1 macrophages and proliferative CD4+/CD8+ T cells. Expression levels of IFN-γ and IL-2 increased in the I@BM NVs group, while expression of TGF-ß and IL-10 decreased. Conclusion: The results show that the I@BM NVs are feasible drugs for the treatment of melanoma by inducing cell apoptosis under NIR and shifting the immunosuppressive tumor microenvironment in vivo.

Efficacy and safety of Naoxintong capsule for acute ischemic stroke: A protocol for systematic review and meta-analysis.

BACKGROUND: Acute ischemic stroke (AIS) is one of the most common causes of mortality and disability worldwide, which has become a global health concern due to the high prevalence, mortality, and disability rate. Naoxintong capsule is an oral Chinese patent preparation used extensively to treat AIS in China. However, the systematic evaluation on the clinical efficacy and safety of Naoxintong capsule is still absent. Therefore, we attempt to perform a systematic review and meta-analysis based on the existing evidence, in order to provide solid support for the clinical practice of Naoxintong capsule in the treatment of AIS. METHODS: We will search both English and Chinese databases, including Scopus, EMBASE, PubMed, Cochrane library, Google Scholar, Web of Science, CNKI, VIP, Wanfang, and Chinese Biomedical Literature Database, for randomized controlled trials which focus on Naoxintong capsule treating AIS. The retrieving time was from inception to August 2021. According to eligibility criteria, 2 researchers will independently screen information and assess the quality of selected articles. The RevMan 5.3 (Copenhagen, The Nordic Cochrane Centre, The Cochrane Collaboration) software will be used for meta-analysis. RESULTS: The clinical efficacy and safety of Naoxintong capsule in the treatment of AIS will be systematically evaluated or descriptive analyzed. CONCLUSION: The study will provide rigorous evidence to identify whether the application of Naoxintong capsule for treating AIS appeared to be adequate reliability regarding on the efficacy and safety. INPLASY REGISTRATION NUMBER: INPLASY202180052.

Source analysis and influencing factors of historical changes in PAHs in the sediment core of Fuxian Lake, China.

In this study, the influencing factors and sources of historical changes in polycyclic aromatic hydrocarbons (PAHs) in the sediment core of Fuxian Lake were analyzed. Before 1970, the Σ16PAH concentration fluctuated widely, with one or more maximum values. During 1971-2004, the Σ16PAH concentration showed a slow growth trend, while during 2005-2017, the concentration increased sharply, reaching a peak value of 821 ng g-1. dw in 2017. The results of a positive matrix factorization (PMF) model demonstrated that before 1970, PAHs were mainly derived from biomass burning in the Fuxian Lake sediment core, with an overall contribution of 40 %. During 1971-2004, the source of PAHs was mainly coal combustion, with an overall contribution of 34 %. During 2005-2017, PAHs primarily originated from traffic, with an overall contribution of 33 %. Population, coal, GDP, motor, and petroleum had a significant influence on low molecular weight (LMW) PAHs in 1980-2004 and 2005-2017. Motor, coal, population, and GDP had a greater impact on high molecular weight (HMW) PAHs. Before 1970 and in 1971-2004, meteorological factors had little effect on PAHs in the sediment core in Fuxian Lake. During 2005-2017, day and rainfall were significantly negatively correlated with HMW PAHs, while temperature and wind were not correlated with PAH concentrations. During 2005-2017, total organic carbon (TOC) and total nitrogen (TN) had greater adsorption effects on HMW PAHs than on LMW PAHs. Before 1970 and in 1971-2004, the adsorption effects of TOC and TN on 3-4-ring PAHs were greater than those of 2-ring and 5-6-ring PAHs. Total phosphorus (TP) had no adsorption effect on PAHs in the entire sedimentary column.

Research on an Identification Method for Gas Disaster Risk Based on the Selective Ensemble Classification Model.

To improve the accuracy of gas disaster risk identification, a selective ensemble classification model is proposed based on clustering selection and a new degree of combination fitness (CS-NDCF). First, nine base classifiers for gas disasters are constructed on the training data set, including the backpropagation (BP) neural network classifier, naive Bayes (NB) classifier, K-nearest neighbor (KNN) classifier, logistic regression (LR) classifier, decision tree (DT) classifier, support vector machine (SVM) classifier, SVM classifier with cross-validation (SVMCV), random forest (RF) classifier, and gradient boosting DT (GBDT) classifier. Second, the K-means clustering algorithm is used to cluster the base classifiers according to their classification performance. Then, the best performing classifier in each cluster is selected to compose the first selection set. Third, the degree of combination fitness is used to filter the first selection set again to obtain the optimal base classifier result set. Finally, an ensemble classification model is constructed with the optimal base classifier result set. The experimental results on actual mine monitoring data show that compared with the BP, NB, KNN, LR, DT, SVM, SVMCV, RF, and GBDT classifiers, the accuracy of CS-NDCF increases by 7.34, 34.83, 8.28, 12.94, 5.51, 11.72, 6.47, 1.31, and 1.20%, respectively, and CS-NDCF achieves the best forecasting results. Thus, CS-NDCF is an effective method for identifying gas disasters and has a good application value.

Source identification of particulate organic carbon using stable isotopes and n-alkanes: modeling and application.

Particulate organic carbon (POC) sources, which regulate dissolved organic carbon, sediment organic carbon, and inorganic carbon via deposition, degradation, and mineralization, play an important role in lake ecosystems. Linear or Bayesian algorithms on isotope and n-alkanes have been widely used to identify the source proportion of organic carbon. However, the applicability of these methods is ambiguous because of the unilateral advantages of each model and trace factors. To test the applicability of the various methods for identifying POC sources, we analyzed dual isotopes and n-alkanes in surface water samples of Lake Taihu, and Multi-source mixing model and Bayesian mixing model were used to distinguish between endogenous and exogenous contributions. Carbon isotope presented a clear advantage in West Taihu (-21.85 ± 0.78‰) and Southwest Taih (-22.61 ± 1.35‰); nitrogen isotope also showed high values in Meiliang Bay (9.76 ± 0.92‰). The majority of the lake was dominated by short-chain n-alkanes, except for East Taihu Lake (dominated by medium-chain n-alkanes) and areas with riverine input (dominated by long-chain n-alkanes). Different principles between the Bayesian mixing model (based on the Markov Chain Monte Carlo algorithm) and the Multi-source mixing model (based on linear estimation) caused discrepancies in the estimations of source contributions. But the fraction of chemical compounds during the migration process, and the overlap of potential sources play important role in the inconsistency of results. The estimations from the different models were consistent in indicating the dominance of endogenous organic carbon in Lake Taihu (mean of 60.18 ± 20.26%), particularly in the north and western regions (West Taihu, Meiliang Bay, and Southwest Taihu). This was likely due to algal aggregation influenced by human activities and climatic factors.

The specific effect of (R)-(+)-pulegone on growth and biofilm formation in multi-drug resistant Escherichia coli and molecular mechanisms underlying the expression of pgaABCD genes.

E. coli is associated with high rates of infection and resistance to drugs not only in China but also the rest of the world. In addition, the number of E. coli biofilm infections continue to increase with time. Notably, biofilms are attractive targets for the prevention of infections caused by multidrug-resistant bacteria. Moreover, the pgaABCD-encoded Poly-ß-1,6-N-acetyl-d-glucosamine (PNAG) plays an important role in biofilm formation. Therefore, this study aimed to explore the specific effect of the (R)-(+)-pulegone (PU) on growth and biofilm formation in multi-drug resistant E. coli. The molecular mechanisms involved were also examined. The results showed that PU had significant antibacterial and antibiofilm formation activity against E. coli K1, with MIC and MBC values of 23.68 and 47.35 mg/mL, respectively. On the other hand, the maximum inhibition rate for biofilm formation in the bacterium was 52.36 % at 94.70 mg/mL of PU. qRT-PCR data showed that PU significantly down-regulated expression of the pgaABCD genes (P < 0.05). PU was also broadly effective against biofilm formation in MG1655 and MG1655/ΔpgaABCD, exhibiting the maximum inhibition rates were 98.23 % and 93.35 %, respectively. In addition, PU destroyed pre-formed mature biofilm in both MG1655 and MG1655/ΔpgaABCD about 95.03 % and 92.4 %, respectively. The study therefore verified that pgaA was a potential and key target for PU in E. coli although it was not the only one. Overall, the findings indicated that PU is a potential and novel inhibitor of drug resistance, This therefore gives insights on new ways of preventing and treating biofilm-associated infections in the food industry as well as in clinical practice.

Determination of PEGylation homogeneity of polyethylene glycol-modified canine uricase.

Polyethylene glycol-modified canine uricase (PEG-UHC) was prepared by modifying the ε-amino group of lysine residues on the canine uricase (UHC) protein to near-saturation with 5 kDa monomethoxyl-polyethylene glycol succinimide (mPEG-SPA-5k). In order to accurately determine the PEGylation uniformity of PEG-UHC, CZE, 3-8% gradient gel SDS-PAGE, and imaging CIEF (iCIEF) analyses were compared. CZE could not effectively separate PEG-UHC proteins with different degrees of modification, 3-8% gradient gel SDS-PAGE could separate PEG-UHC into seven gel bands; however, most of the gel bands were smeared or blurred, and the separation of PEG-UHC samples by iCIEF was significantly better than that by 3-8% gradient gel SDS-PAGE. Under denatured conditions, iCIEF separated 12 pI peaks, and could also accurately quantify the relative monomer PEG-UHC content. More than 85% of the total monomeric PEG-UHC was conjugated with 7-12 PEG molecules; of this 85%, approximately 40% was conjugated with 9-10 PEG molecules. These results demonstrated that iCIEF exhibits good potential for determining the PEGylation homogeneity of PEGylated protein drugs.

Metabolism and Pharmacological Mechanisms of Active Ingredients in Erigeron breviscapus.

BACKGROUND: Erigeron breviscapus (Vant.) Hand-Mazz. is a plant species in the Compositae family. More than ten types of compounds-such as flavonoids, caffeinate esters, and volatile oils-have been identified in Erigeron breviscapus; however, it remains unknown as to which compounds are associated with clinical efficacy. In recent years, flavonoids and phenolic acids have been considered as the main effective components of Erigeron breviscapus. The metabolism and mechanisms of these compounds in vivo have been extensively studied to improve our understanding of the drug. METHODS: In the present review, we summarize the relationships among these compounds, their metabolites, and their pharmacodynamics. Many methods have been implemented to improve the separation and bioavailability of these compounds from Erigeron breviscapus. RESULTS: In China, Erigeron breviscapus has been used for many years. In recent years, through the study of its metabolism and the mechanisms of its effective components, the effects of Erigeron breviscapus in the treatment of various diseases have been extensively studied. Findings have indicated that Erigeron breviscapus improves cardiovascular and cerebrovascular function and that one of its ingredients, scutellarin, has potential value in the treatment of Alzheimer's disease, cancer, diabetic vascular complications, and other conditions. In addition, phenolic acid compounds and their metabolites also play an important role in anti-oxidation, anti-inflammation, and improving blood lipids. CONCLUSION: Erigeron breviscapus plays an important role in the prevention and treatment of cardiovascular/ cerebrovascular diseases, neuroprotection, and cancer through many different mechanisms of action. Further investigation of its efficacious components and metabolites may provide more possibilities for the clinical application of traditional Chinese medicine and the development of novel drugs.

Engineering the Erythromycin-Producing Strain Saccharopolyspora erythraea HOE107 for the Heterologous Production of Polyketide Antibiotics.

Bacteria of the genus Saccharopolyspora produce important polyketide antibiotics, including erythromycin A (Sac. erythraea) and spinosad (Sac. spinosa). We herein report the development of an industrial erythromycin-producing strain, Sac. erythraea HOE107, into a host for the heterologous expression of polyketide biosynthetic gene clusters (BGCs) from other Saccharopolyspora species and related actinomycetes. To facilitate the integration of natural product BGCs and auxiliary genes beneficial for the production of natural products, the erythromycin polyketide synthase (ery) genes were replaced with two bacterial attB genomic integration sites associated with bacteriophages ϕC31 and ϕBT1. We also established a highly efficient conjugation protocol for the introduction of large bacterial artificial chromosome (BAC) clones into Sac. erythraea strains. Based on this optimized protocol, an arrayed BAC library was effectively transferred into Sac. erythraea. The large spinosad gene cluster from Sac. spinosa and the actinorhodin gene cluster from Streptomyces coelicolor were successfully expressed in the ery deletion mutant. Deletion of the endogenous giant polyketide synthase genes pkeA1-pkeA4, the product of which is not known, and the flaviolin gene cluster (rpp) from the bacterium increased the heterologous production of spinosad and actinorhodin. Furthermore, integration of pJTU6728 carrying additional beneficial genes dramatically improved the yield of actinorhodin in the engineered Sac. erythraea strains. Our study demonstrated that the engineered Sac. erythraea strains SLQ185, LJ161, and LJ162 are good hosts for the expression of heterologous antibiotics and should aid in expression-based genome-mining approaches for the discovery of new and cryptic antibiotics from Streptomyces and rare actinomycetes.

Morphologies, Young's Modulus and Resistivity of High Aspect Ratio Tungsten Nanowires.

High aspect ratio tungsten nanowires have been prepared by selective dissolution of Nickel-aluminum-tungsten (NiAl-W) alloys which were directionally solidified at growth rates varying from 2 to 25 µm/s with a temperature gradient of 300 K·cm-1. Young's modulus and electrical resistivity of tungsten nanowires were measured by metallic mask template method. The results show that the tungsten nanowires with uniform diameter and high aspect ratio are well aligned. The length of tungsten nanowires increases with prolongation of etching time, and their length reaches 300 µm at 14 h. Young's modulus of tungsten nanowires is estimated by Hertz and Sneddon models. The Sneddon model is proper for estimating the Young's modulus, and the value of calculating Young's modulus are 260-460 GPa which approach the value of bulk tungsten. The resistivity of tungsten nanowires is measured and fitted with Fuchs-Sondheimer (FS) + Mayadas-Shatzkes (MS) model. The fitting results show that the specific resistivity of W nanowires is a litter bigger than the bulk W, and its value decreases with decreasing diameter.

On the complexity measures of mutation hotspots in human TP53 protein.

The role of sequence complexity in 23 051 somatic missense mutations including 73 well-known mutation hotspots across 22 major cancers was studied in human TP53 proteins. A role for sequence complexity in TP53 protein mutations is suggested since (i) the mutation rate significantly increases in low amino acid pair bias complexity; (ii) probability distribution complexity increases following single point substitution mutations and strikingly increases after mutation at the mutation hotspots including six detectable hotspot mutations (R175, G245, R248, R249, R273, and R282); and (iii) the degree of increase in distribution complexity is significantly correlated with the frequency of missense mutations (r = -0.5758, P < 0.0001) across 20 major types of solid tumors. These results are consistent with the hypothesis that amino acid pair bias and distribution probability may be used as novel measures for protein sequence complexity, and the degree of complexity is related to its susceptibility to mutation, as such, it may be used as a predictor for modeling protein mutations in human cancers.