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The catalytic mechanism of the oxygen reduction reaction and the effect of spatial confinement and ligands on MOF-derived materials are studied using DFT calculations.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising candidate for spinal cord injury (SCI) repair owing to their advantages of low immunogenicity and easy accessibility over other MSC sources. However, modest clinical efficacy hampered the progression of these cells to clinical translation. This discrepancy may be due to many variables, such as cell source, timing of implantation, route of administration, and relevant efficacious cell dose, which are critical factors that affect the efficacy of treatment of patients with SCI. Previously, we have evaluated the safety and efficacy of 4 × 106 hUC-MSCs/kg in the treatment of subacute SCI by intrathecal implantation in rat models. To search for a more accurate dose range for clinical translation, we compared the effects of three different doses of hUC-MSCs – low (0.25 × 106 cells/kg), medium (1 × 106 cells/kg) and high (4 × 106 cells/kg) – on subacute SCI repair through an elaborate combination of behavioral analyses, anatomical analyses, magnetic resonance imaging-diffusion tensor imaging (MRI-DTI), biotinylated dextran amine (BDA) tracing, electrophysiology, and quantification of mRNA levels of ion channels and neurotransmitter receptors. Our study demonstrated that the medium dose, but not the low dose, is as efficient as the high dose in producing the desired therapeutic outcomes. Furthermore, partial restoration of the γ-aminobutyric acid type A (GABAA) receptor expression by the effective doses indicates that GABAA receptors are possible candidates for therapeutic targeting of dormant relay pathways in injured spinal cord. Overall, this study revealed that intrathecal implantation of 1 × 106 hUC-MSCs/kg is an alternative approach for treating subacute SCI.

Coronavirus disease 2019 (COVID-19) is caused by infection of the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with typical respiratory symptoms. SARS-CoV-2 invades not only the respiratory system, but also other organs expressing the cell surface receptor angiotensin converting enzyme 2. In particular, the digestive system is a susceptible target of SARS-CoV-2. Gastrointestinal symptoms of COVID-19 include anorexia, nausea, vomiting, diarrhea, abdominal pain, and liver damage. Patients with digestive damage have a greater chance of progressing to severe or critical illness, a poorer prognosis, and a higher risk of death. This paper aims to summarize the digestive system symptoms of COVID-19 and discuss fecal-oral contagion of SARS-CoV-2. It also describes the characteristics of inflammatory bowel disease patients with SARS-CoV-2 infection and discusses precautions for preventing SARS-CoV-2 infection during gastrointestinal endoscopy procedures. Improved attention to digestive system abnormalities and gastrointestinal symptoms of COVID-19 patients may aid health care providers in the process of clinical diagnosis, treatment, and epidemic prevention and control.

Research on noncoding ribonucleic acids (ncRNAs) is mostly and broadly focused on microRNAs (miRNAs), cyclic RNAs (circRNAs), and long ncRNAs (lncRNAs), which have been confirmed to play important roles in tumor cell proliferation, invasion, and migration. Specifically, recent studies have shown that ncRNAs contribute to tumorigenesis and tumor development by mediating changes in enzymes related to lipid metabolism. The purpose of this review is to discuss the characterized ncRNAs involved in the lipid metabolism of tumors to highlight ncRNA-mediated lipid metabolism-related enzyme expression in malignant tumors and its importance to tumor development. In this review, we describe the types of ncRNA and the mechanism of tumor lipid metabolism and analyze the important role of ncRNA in tumor lipid metabolism and its future prospects from the perspectives of ncRNA biological function and lipid metabolic enzyme classification. However, several critical issues still need to be resolved. Because ncRNAs can affect tumor processes by regulating lipid metabolism enzymes, in the future, we can study the unique role of ncRNAs from four aspects: disease prevention, detection, diagnosis, and treatment. Therefore, in the future, the development of ncRNA-targeted therapy will become a hot direction and shoulder a major task in the medical field.

Three new xanthone compounds, 1,3,5-trihydroxy-2-(2-hydroxy-3-methylbut-3-enyl)-4-(3-methylbut-2-enyl)xanthone (1), toxyloxanthone E (2), dehydrocycloguanandin B (3) along with 15 known xanthones (4-18) were isolated from the aerial parts of Calophyllum polyanthum Wall. ex Choisy. Their structures were fully characterised using spectroscopic data, as well as comparison with the previous literature data. All isolated compounds had inhibitory effects against CYP1A1, CYP1A2 and CYP1B1 enzymes at working concentration of 10 μM, 1 μM and 10 μM, respectively. Among them, compounds 10, 11, and 12 exhibited better CYP1A2 enzyme inhibitory effects than that of the positive control α-naphthoflavone, with 51.05 %, 56.82 % and 44.93 % inhibition, respectively.

A green and efficient procedure for the preparation of valuable 2,3-dihydrofurans and benzoxazines has been achieved through halocyclization of olefinic 1,3-dicarbonyls or olefinic amides. This protocol could be conducted under catalyst-, base-, and oxidant-free conditions in aqueous media open to the air at room temperature with good to excellent yields. Notably, the practicality of this method is further highlighted by gram-scale reactions in good yields.

Background. After radical hysterectomy for cervical cancer, the most common complication is lower urinary tract symptoms. Post-operatively, bladder capacity can alter bladder function for a prolonged period. This study aimed to identify factors affecting bladder storage function. Methods. A multicenter, retrospective cohort study was conducted. Information of patients with stages IA2 to IIB cervical cancer with urodynamic study results were retrospectively collected from nine hospitals between June 2013 and June 2018 according to the inclusion criteria. Demographic, surgical, and oncological data were collected. The univariate and multivariate logistic regression was used to identify clinical factors associated with bladder storage function. Results. Two hundred and three patients with cervical cancer had urodynamic testing post-operatively. Ninety-five (46.8%) patients were diagnosed with stress urinary incontinence (SUI). The incidence of low bladder compliance (LBC) was 23.2%. Twenty-seven (13.3%) patients showed detrusor overactivity (DO). Fifty-seven patients (28.1%) presented with a decreased maximum cystometric capacity (DMCC). The probability of composite bladder storage dysfunction was 68.0%. Multivariate analysis confirmed that laparoscopy represents a protective factor for SUI with an odds ratio of 0.498 (P = 0.034). Patients who underwent a nerve-sparing procedure were less odds to experience SUI (P = 0.014). A significant positive correlation between LBC and DO was observed (P

We disclose a mild and practical catalyst-free transformation for the expeditious construction of biuret-guanidine derivatives using aromatic isocyanates. This synthetic transformation is featured with mild reaction conditions and high efficiency.

Chronic pain damages the balance between excitation and inhibition in the sensory cortex. It has been confirmed that the activity of cortical glutamatergic pyramidal cells increases after chronic pain. However, whether the activity of inhibitory interneurons synchronized changed remains obscure, especially in in vivo conditions. In the present study, we checked the firing rate of pyramidal cells and interneurons in the anterior cingulate cortex, a main cortical area for the regulation of nociceptive information in mice with spared nerve injury by using in vivo multi-channel recording system. We found that the firing rate of pyramidal cells but not interneurons increased in the ACC, which was further confirmed by the increased FOS expression in pyramidal cells but not interneurons, in mice with neuropathic pain. Selectively high frequency stimulation of the ACC nociceptive afferent fibers only potentiated the activity of pyramidal cells either. Our results thus suggest that the increased activity of pyramidal cells contributes to the damaged E/I balance in the ACC and is important for the pain hypersensitivity in mice with neuropathic pain.

Background. Chinese medicinal properties (CMP) are an important part of the basic theory of traditional Chinese medicines (TCMs). Quantitative research on the properties of TCMs is of great significance to deepen the understanding and application of the theory of drug properties and promoting the modernization of TCMs. However, these studies are limited to strong subjectivity or distinguish different drug properties based on certain indicators since CMP studies are diverse. Objective. To realize quantitative comparison of same medicinal properties of different Chinese medicines. Method. To solve the above problem, we proposed and explored quantification of Chinese medicinal properties (QMP) and the quantification value of medicinal properties “ R ”. The correlation between primary metabolites and “cold-hot” medicinal properties was explored on the premise of material basis of Chinese herbal medicines and Fisher’s analysis. Based on indicators related to “cold-hot” medicinal properties, we utilized quantitative values “ R ” to characterize the strength or weakness of “cold-hot” medicinal properties. Results. According to QMP, the same medicinal properties were quantified and compared by quantification value of medicinal properties that expressed by alphabet “ R ”. The general theoretical formula of “ R ” deduced is R = l × cos θ / L = ∑ i = 1 n j i p i / ∑ i = 1 n p i 2 , in which n ≥ 1 . In the light of formula of “ R ” and indicators related to “cold-hot” medicinal properties, we got “ R ” value of “cold-cool” and “warm-hot” medicinal properties. “ R ” values of “cold-cool” medicinal properties of Phellodendri chinensis cortex, Coptidis rhizoma, and Menthae haplocalycis herba were 0.63, 1.00, and 0.49, respectively. The result showed that Coptidis rhizoma is the most “cold-cool”, followed by Phellodendri chinensis cortex, with Menthae haplocalycis herba is the weakest in the three Chinese medicines, consistent with cognition of TCM theory. Conclusion. QMP has certain guiding significance for the quantification of “cold and hot” drug properties. “ R ” is feasible to realize the quantitative comparison of the same drug properties of different traditional Chinese medicine, which is helpful to promote process of modern Chinese medicine construction.

During an exploration of plant pathogens in vegetables occuring in Zhejiang province, China, a novel fungal species, was found. Three strains ZJUP0033-4, ZJUP0038-3 and ZJUP0132 were isolated from black round lesions in the stems and leaves of Amaranthus sp. Phylogenetic analyses based on sequences from four genes including rDNA internal transcribed spacer (ITS), translation elongation factor 1-α (EF1-α), histone (HIS) and β-tubulin (TUB) indicated that D. sinensis clustered in a distinct clade closely related to D. neoarctii, D. angelicae, D. subordinaria, D. arctii, D. cuppatea, D. lusitanicae, D. novem, D. infecunda, D. ganjae and D. manihotia. Morphologically, D. sinensis is distinguished by brown, scattered, globose pycnidia and ellipsoid alpha conidia with bi- to multiguttulate.

Chronic pain damages the balance between excitation and inhibition in the sensory cortex. It has been confirmed that the activity of cortical glutamatergic pyramidal cells increases after chronic pain. However, whether the activity of inhibitory interneurons synchronized changed remains obscure, especially in in vivo conditions. In the present study, we checked the firing rate of pyramidal cells and interneurons in the anterior cingulate cortex, a main cortical area for the regulation of nociceptive information in mice with spared nerve injury by using in vivo multi-channel recording system. We found that the firing rate of pyramidal cells but not interneurons increased in the ACC, which is further confirmed by the increased FOS expression in pyramidal cells but not interneurons, in mice with neuropathic pain. Selectively high frequency stimulation of the ACC nociceptive afferent fibers only potentiated the activity of pyramidal cells either. Our results thus suggest that the increased activity of pyramidal cells contributes to the damaged E/I balance in the ACC and is important for the pain hypersensitivity in mice with neuropathic pain.

In this study, we firstly used alginate to enhance an electrokinetic technology to remediate soil contaminated with divalent heavy metals (Pb2+, Cu2+, Zn2+). The mechanisms of alginate-associated migration of metal ions in electric field were confirmed. Alginate resulted in a high electrical current during electrokinetic process, and soil conductivity also increased after remediation. Obvious changes in both electroosmotic flow and soil pH were observed. Moreover, these factors were affected by increasing alginate dosage. The highest Cu (95.82%) and Zn (97.33%) removal efficiencies were obtained by introducing 1 wt% alginate. Alginate can desorb Cu2+ and Zn2+ ions from soil by forming unstable gels, which could be dissociated through electrolysis. However, Pb2+ ions did not easily migrate out of the contaminated soil. The density functional theory (DFT) calculations show Pb2+ ions could form a more stable coordination sphere in metal complexes than Cu2+ and Zn2+ ions. The metal removal efficiency was decreased by increasing alginate dosage at a high level. More alginate could provide more carboxyl ligands for divalent metal ions to stabilize gels, which were difficult to dissociate by electrolysis. In summary, the results indicate it is potential for introducing alginate into an electrokinetic system to remediate Cu- and Zn- contaminated soil.

Epidermal growth factor receptor (EGFR) activation is involved in blood spinal cord barrier (BSCB) disruption and secondary injury after spinal cord injury (SCI). However, the underlying mechanisms of EGFR activation mediating BSCB disruption and secondary injury after SCI remain unclear. An in vitro model of oxygen and glucose deprivation/reoxygenation (OGD/R) induced BSCB damage and in vivo rat SCI model were employed to define the role of EGFR/p38/NF-κB signal pathway activation and its induced inflammatory injury in main cellular components of BSCB. Genetic regulation (lentivirus delivered shRNA and overexpression system) or chemical intervention (agonist or inhibitor) were applied to activate or inactivate EGFR and p38 in astrocytes and microvascular endothelial cells (MEC) under which conditions, the expression of pro-inflammatory factors (TNF-α, iNOS, COX-2, and IL-1β), tight junction (TJ) protein (ZO-1 and occludin), nuclear translocation of NF-κB and permeability of BSCB were analyzed. The pEGFR was increased in astrocytes and MEC which induced the activation of EGFR and p38 and NF-κB nuclear translocation. The activation of EGFR and p38 increased the TNF-α, iNOS, COX-2, and IL-1β responsible for the inflammatory injury and reduced the ZO-1 and occludin which caused BSCB disruption. While EGFR or p38 inactivation inhibited NF-κB nuclear translocation, and markedly attenuated the production of pro-inflammatory factors and the loss of TJ protein. This study suggests that the EGFR activation in main cellular components of BSCB after SCI mediates BSCB disruption and secondary inflammatory injury via the EGFR/p38/NF-κB pathway.

Without employing any catalyst and base, an economical, practical, and efficient protocol has been first developed for the one-pot synthesis of various functionalized polycyclic γ-lactams from easi...

A regioselective cyclization of 1,6-enynes is reported by a tert-butyl hydroperoxide (TBHP)-mediated, one-pot, cascade reaction with commercially available carbonyl compounds under metal- and additive-free conditions. The reaction scope includes both 1,6-enynes and carbonyl compounds. A possible cascade reaction mechanism, consisting of acyl radical addition, intramolecular cyclization, and hydrogen abstraction, is proposed.

Objective To observe the effect of different processing methods on the quality of Codonopsis Radix and provide data reference for the reasonable processing in the producing areas. Methods An analytical strategy that combined quantitative and HPLC fingerprint analysis with chemometrics was developed for the quality evaluation of Codonopsis Radix. Lobetyolin, polysaccharide, sucrose, glucose, and fructose were detected simultaneously in Codonopsis Radix samples treated with different processing methods including dryer-drying, sun-drying, shade-drying, sulfur fumigation, and kneading, etc. Results The results showed that different processing methods had an obvious impact on the quality of Codonopsis Radix. Sun-drying or shade-drying was recommended, and sulfur fumigation should be avoided. And dryer-drying at 40 °C−50 °C was suggested to meet the requirement for large scale processing. In addition, based on the content of polysaccharide, glucose, and fructose, it was advised to knead for three times. As for lobetyolin and sucrose, kneading should be avoided. Conclusions Our findings demonstrated that processing method had a big impact on the quality of Codonopsis Radix. Based on the results, the appropriate processing methods directed at different requirements were recommended. The study could lay a foundation for the reasonable processing of Codonopsis Radix in producing areas.

Recent work has focused on the removal of Pb2+, Hg2+, and Cd2+ by using an organ of Aspergillus niger – spores, which were spherical particles with small diameter (2 µm) characterized by ne...

Flos Carthami, the dried flower of Carthamus tinctorius L. (Compositae), is among the most popular traditional Chinese medicines due to its diverse biological activities such as anticoagulation, vasodilation, antihypertension, antioxidation, neuroprotection, melanin production inhibition, immunosuppression and antitumor activity. At present, Carthamus tinctorius L. is cultivated in various regions under diverse environmental conditions which has led to quality instability of Flos Carthami in the market and may in turn influence its therapeutic efficacy. So it is necessary to characterize the chemical profiles of different geographical origins of Flos Carthami and find differential metabolites contributing to this difference. In this study, a UPLC-QTOF/MS method was developed to characterize chemical differences of Flos Carthami collected in the Xinjiang Uygur Autonomous Region and Henan, Gansu and Yunnan provinces, China. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were used to differentiate Flos Carthami samples cultivated in the above-mentioned regions. 32 differential metabolites accountable for such variations were identified through variable importance in the projection (VIP). Grey correlation analysis (GCA) was conducted between 32 differential metabolites and climate factors. Climate factors such as XASD, XRH, XHTJ and XATJ had higher significant correlation with most differential metabolites. Conversely, lower significant correlations were observed between climate factors such as XLTA and XATA and the 32 differential metabolites. So, in order to improve the stability of the chemical quality and guarantee the clinical use of Flos Carthami, its phytogeographical variation cannot be neglected and the differential metabolites could be used to guide the quality control of Flos Carthami.

Background: the study of drug-target interactions (DTIs) affinity plays an important role in safety assessment and pharmacology. Currently, quantitative structure-activity relationship (QSAR) and molecular docking (MD) are most common methods in research of DTIs affinity. However, they often built for a specific target or several targets and most QSAR and MD were based either only on structure of drug molecules or on structure of targets with low accuracy and small scope of application. How to construct quantitative prediction models with high accuracy with wide applicability remains a challenge. To this end, this paper screened molecular descriptors based on molecular vibrations and took molecule-target as a whole system to construct prediction model with high accuracy-wide applicability based on Kd and EC50, and to provide reference for quantifying affinity of DTIs.Methods: Through parametric characterization based on molecular vibrations and protein sequences, taking molecule-target as whole system and feature selection of drug molecule-target, we constructed feature datasets of DTIs quantified by Kd and EC50, respectively. Then, prediction models were constructed using above datasets and SVM, RF and ANN. In addition, optimal models were selected for application evaluation and comprehensive comparison.Results: Under ten-fold cross-validation, evaluation parameters based on RF for EC50 dataset are as follows: R2 (RF) of training and test sets are 0.9611, 0.9641; MSE (RF) of training and test sets are 0.0891, 0.0817. Evaluation parameters based on RF for Kd dataset are as follows: R2 (RF) of training and test sets are 0.9425, 0.9485; MSE (RF) of training and test sets are 0.1208, 0.1191. After comprehensive comparison, the results showed that RF model in this paper is optimal model. In application evaluation of RF model, the errors of most prediction results were in range of 1.5-2.0.Conclusion: Through screening molecular descriptors based on molecular vibrations and taking molecule-target as whole system, we obtained optimal model based on RF with more accurate-widely applicable, which indicated that selection of molecular descriptors associated with molecular vibrations and the use of molecular-target as whole system are reliable methods for improving performance of model. It can provide reference for quantifying affinity of DTIs.

Background:Epidermal growth factor receptor (EGFR) activation may play an important role in blood spinal cord barrier (BSCB) disruption and secondary injury after SCI as it is significantly upregulated in the astrocytes (AS) and microvascular endothelial cells (MEC), which are the main component of cells in BSCB. EGFR inhibition alleviates the disruption of BSCB and improves the functional recovery in rats following spinal cord injury (SCI). However, the biological mechanisms underlying EGFR activation mediating secondary damage after SCI remain unclear. Methods:An in vitro model of Oxygen and glucose deprivation/reoxygenation (OGD/R) induced BSCB damage and in vivo rat SCI model was employed to define the role of EGFR activation and its induced inflammatory injury during this pathological process in AS and MEC. AS and MEC were exposed to EGFR or p38 MAPK up-regulation in the presence and absence of EGFR inhibitor, p38 MAPK inhibitor, NF-κB inhibitor, and/or appropriate shRNA. RT-PCR, ELISA and western blotting were used for mRNA and protein expression analyses of TNF-α, iNOS, COX-2 and IL-1β. Immunohistochemical staining and confocal microscopy were used to demonstrate cellular EGFR activation and to investigate the expression of tight junction (TJ) protein (ZO-1 and occludin). Measurement of transendothelial electrical resistance (TEER) and transendothelial FITC-dextran permeability were used to measure permeability of BSCB in vitro, while Evans blue dye extravasation test and evaluation spinal cord edema were used to detect permeability of BSCB in vivo.Results:The expression of pEGFR was significantly increased in BSCB component cells (AS and MEC) after SCI and BSCB damage model. EGFR activation induced inflammation injury by upregulating the expression of TNF-α, iNOS, COX-2, and IL-1β and BSCB disruption with loss of TJ protein by downregulating the expression of ZO-1 and occludin in BSCB damage model and SCI rats. Moreover, EGFR or p38 activation leads to NF-κB nuclear translocation in primary AS and MEC after OGD/R. The EGFR inhibitor as well as shRNA against EGFR markedly attenuated pro-inflammatory factor excessive producing and loss of TJ protein, and activation of the EGFR/p38/NF-κB pathway. While, EGFR overexpression significantly increased the expression of TNF-α, iNOS, COX-2, and IL-1β and decrease the expression of ZO-1 and occludin, inducing activation of the EGFR/p38/NF-κB pathway in both AS and MEC. Conclusion:This study strongly suggests that EGFR activation in BSCB component cells after SCI and BSCB damage model mediates both upregulation of pro-inflammation expression and downregulation of TJ protein downregulation via the EGFR/p38/NF-κB pathway. These findings contribute to a better understanding of the biological mechanisms underlying BSCB disruption and secondary injury following SCI mediating by EGFR activation.

In order to promote information interaction, intelligent regulation, and scale management in Chinese medicines industry, in this paper, a Chinese medicines intelligent service platform with characteristics of flexibility, versatility, and individuation was designed under the guidance of theoretical model of intelligent manufacturing of Chinese medicines (TMIM). TCM-ISP is a comprehensive intelligent service platform that can be flexibly applied to all links of Chinese medicines industry chain, which realizes data integration and real-time transmission as well as intelligent-flexible scheduling of equipment in response to different demand. The platform took logical framework of data flow as the core and adopts the modular design in which microcontroller and sensor module are independent to obtain overall design scheme of TCM-ISP that contains the diagram of overall framework, hardware structure, and software technology. Then, on the groundwork of overall design scheme and modern science technology, TCM-ISP was successfully constructed with flexible, intelligent, and networked characteristics in which TTL-USB and TTL-RS485S were utilized to build unified interface between boards with supporting hot-plugging mode. The results of platform tests show that TCM-ISP can not only successfully realize the integration, real-time transmission, and display of data information but also well accomplish remote intelligent-flexible control of equipment and allow flexible configuration and expansion of sensors and devices according to the needs of each link in TCM’s industry chain. It is of great practical significance to the pursuit of intelligent manufacturing of Chinese medicines and the promotion of modernization of Chinese medicines industry.

Ethnopharmacological relevance Species of the genus Codonopsis are perennial herbs mainly distributed throughout East, Southeast and Central Asia. As recorded, they have been used as traditional Chinese medicines since the Qing Dynasty, where they were claimed for strengthening the spleen and tonifying the lung, as well as nourishing blood and engendering liquid. Some species are also used as food materials in southern China and Southeast Asia, such as tea, wine, soup, plaster, and porridge. Aim of the review The review aims to assess the ethnopharmacological uses, explicit the material basis and pharmacological action, promote the safety of medical use, and suggest the future research potentials of Codonopsis. Materials and methods Information on the studies of Codonopsis was collected from scientific journals, books, and reports via library and electronic data search (PubMed, Elsevier, Scopus, Google Scholar, Springer, Science Direct, Wiley, Researchgate, ACS, EMBASE, Web of Science and CNKI). Meanwhile, it was also obtained from published works of material medica, folk records, ethnopharmacological literatures, Ph.D. and Masters Dissertation. Plant taxonomy was confirmed to the database “The Plant List” ( www.theplantlist.org ). Results Codonopsis has been used for medicinal purposes all around the world. Some species are also used as food materials in southern China and Southeast Asia. The chemical constituents of Codonopsis mainly are polyacetylenes, polyenes, flavonoids, lignans, alkaloids, coumarins, terpenoids, steroids, organic acids, saccharides, and so on. Extract of Codonopsis exhibit extensive pharmacological activities, including immune function regulation, hematopoiesis improvement, cardiovascular protection, neuroprotection, gastrointestinal function regulation, endocrine function regulation, cytotoxic and antibacterial effects, anti-aging and anti-oxidation, etc. Almost no obvious toxicity or side effect are observed and recorded for Codonopsis. Conclusions The traditional uses, phytochemistry, pharmacology and toxicology of Codonopsis are reviewed in this paper. Species of the genus have long been used as traditional medicines and food materials, they are reported with a large number of chemical constituents with different structures, extensive pharmacological activities in immune system, blood system, digestive system, etc. and almost no toxicity. More profound studies on less popular species, pharmacodynamic material basis and pharmacological mechanism, and quality assurance are suggested to be carried out to fulfil the research on the long-term clinical use and new drug research of Codonopsis.

Background and Aims: Esophageal squamous cell carcinoma (ESCC), a major histologic subtype of esophageal cancer, is increasing in incidence, but the genetic underpinnings of this disease remain unexplored. The aim of this study is to identify the recurrent genetic changes, elucidate their roles and discover new biomarkers for improving clinical management of ESCC. Methods: Western blotting and immunohistochemistry were performed to detect the expression level of RHCG. Bisulfite genomic sequencing (BGS) and methylation-specific PCR (MSP) were used to study the methylation status in the promoter region of RHCG. The tumor-suppressive effect of RHCG was determined by both in-vitro and in-vivo assays. Affymetrix cDNA microarray was used to identify the underlying molecular mechanism. Results: RHCG was frequently downregulated in ESCCs, which was significantly correlated with poor differentiation (P = 0.001), invasion (P = 0.003), lymph node metastasis (P = 0.038) and poorer prognosis (P < 0.001). Demethylation treatment and bisulfite genomic sequencing analyses revealed that the downregulation of RHCG in both ESCC cell lines and clinical samples was associated with its promoter hypermethylation. Functional assays demonstrated that RHCG could inhibit clonogenicity, cell motility, tumor formation and metastasis in mice. Further study revealed that RHCG could stabilize IκB by decreasing its phosphorylation, and subsequently inhibit NF-κB/p65 activation by blocking the nuclear translocation of p65, where it acted as a transcription regulator for the upregulation of MMP1 expression. Conclusions: Our results support the notion that RHCG is a novel tumor suppressor gene that plays an important role in the development and progression of ESCC.

In this study, cobalt-doped and biochar-cocatalyst bismuth oxychloride (Co(Ⅱ)-BiOCl@biochar) photocatalysts were hydrothermally synthesized for the photodegradation of p-nitrophenol (PNP) and characterized via a series of analytical techniques. Results indicated that the addition of Co2+ and biochar to BiOCl resulted in 99.4% degradation of PNP in 90 min under vacuum ultraviolet (VUV) illumination. It was found that 5% doping of Co2+ and 30% loading of biochar significantly enhanced the photocatalytic performance of the as-prepared catalysts. After five cycles, the obtained hybrid catalysts still exhibited a good stability. Although the structure of BiOCl was not changed by the modification, the growth face changed from (0 0 1) to (1 1 0), which led to the narrow band gap, wide wavelength of the light source, effective separation of e-/h+ pairs, and high photocatalytic activity. The vast improvement was related to the formation of ·OH, h+, e−, ·O2−, and eaq−, which was confirmed by the radical-trapping experiments. Furthermore, a plausible mechanism for the photocatalysis of PNP over CO(Ⅱ)-BiOCl@biochar hybrid catalysts under VUV irradiation was also proposed.

This study was focused on the prevalence and antimicrobial susceptibilities of Salmonella directly isolated at animal clinics in Guangdong, People's Republic of China. The isolation rates from chickens, ducks, and pigs were 11.3% (11 of 97 samples), 15.4% (53 of 344 samples), and 3.0% (13 of 434 samples), respectively. Among the 77 Salmonella enterica isolates, the most predominant serovar was Typhimurium (81.8%, 63 isolates), followed by serovars Meleagridis (2.6%, 2 isolates) and Abaetetuba (1.3%, 1 isolate). Salmonella isolates were resistant to ciprofloxacin (16.9% of isolates) and nalidixic acid (66.2% of isolates), and 68 isolates (88.3%) were multidrug resistant, displaying resistance to three or more classes of antimicrobial agents. Eighteen isolates (23.4%) had at least one plasmid-mediated quinolone resistance gene, which was identified using PCR and DNA sequencing. The most prevalent plasmid-mediated quinolone resistance gene was aac(6')-Ib-cr, found in 14 isolates (18.2%), followed by oqxAB (9.1%) and qnrS (7.8%). Alterations in the gyrA gene were detected in 24 (57.1%) of 42 strains with a ciprofloxacin MIC of ≥0.25 μg/mL; the same level of susceptibility was found for enrofloxacin. Six types of mutations were found in the quinolone resistance determining regions of gyrA, and the predominant one (S83Y) was found singly in 15 (62.5%) of 24 isolates. We also found 22 different pulsed-field gel electrophoresis types among the Salmonella isolates. The Salmonella serovars and MICs of ciprofloxacin were similar within clusters, although individual differences were noted. This finding suggests that resistance plasmids were horizontally transmitted but also clonally spread.

// Ting-Ting Cao 1 , Di Xiang 1 , Bei-Lei Liu 1 , Tu-Xiong Huang 1 , Bin-Bin Tan 1 , Chui-Mian Zeng 1 , Zhong-Yuan Wang 1 , Xiao-Yan Ming 2 , Li-Yi Zhang 2 , Guangyi Jin 1 , Feng Li 3, 4 , Jian-Lin Wu 5 , Xin-Yuan Guan 2 , Desheng Lu 1 and Li Fu 1 1 Department of Pharmacology and Cancer Research Centre, School of Medicine, Shenzhen University, Shenzhen, China 2 Department of Clinical Oncology, The University of Hong Kong Faculty of Medicine, Hong Kong, China 3 Wuhan University Shenzhen Research Institute, Shenzhen, China 4 Department of Medical Genetics, School of Basic Medical Sciences, Wuhan University, Wuhan, China 5 State Key Laboratory for Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, China Correspondence to: Li Fu, email: gracelfu@szu.edu.cn Desheng Lu, email: delu@szu.edu.cn Keywords: FZD7, ESCC, metastasis, WNT, EMT Received: May 24, 2017 Accepted: June 29, 2017 Published: July 26, 2017 ABSTRACT Frizzled (FZD) proteins are receptors for secreted WNT proteins and play a critical role in the malignant progression of various cancers. However, the role of human FZD family members in esophageal squamous cell carcinoma (ESCC) was rarely investigated. In this study, we found that the FZD7 gene was the most commonly up-regulated FZD member in ESCC cell lines compared with other FZDs . TMA studies further validated that FZD7 protein was up-regulated in 165 of 252 (65.5%) informative ESCC patients and significantly correlated with poor overall survival (P=0.001). Additionally, multivariate Cox regression analysis showed that FZD7 overexpression was an independent prognostic factor for ESCC patients. Ectopic expression of FZD7 could promote ESCC cell metastasis both in vitro and in vivo . Under WNT3A stimulation, FZD7 was able to induce the nuclear translocation of β-catenin and activate the downstream targets of WNT/β-catenin signaling, as well as promote epithelial-mesenchymal transition (EMT) potential in ESCC cells. Our study demonstrated for the first time that FZD7 contributes to the malignant progression of ESCC and represents a novel prognostic marker and a potential therapeutic target for ESCC patients.

The external environment plays a critical role in shaping the structure of the gut microbiome. One potential health threat lies in the release of antibiotic resistant genes (ARGs) from cross-contaminated microbiomes. We focused this study on a comparison of fecal microbial composition and antibiotic resistant genes between farm workers, local villagers and swine. We used a high-throughput next-generation sequencing of 16S rRNA and real-time PCR for these studies. Our results indicated that workers had less species diversity as compared to the local villagers. Moreover, the bacterial communities of the farm workers, the local villagers and swine feces were clearly divided into three groups. The workers had a greater abundance of Proteobacteria as compared to swine and the local villagers. The Clostridiaceae in the workers and swine were more abundant than the local villagers. In addition, there were ARG differences between the farm workers or local villager’s and swine feces. The farm workers and the local villagers had similar relative abundance except for macrolide ARGs. Taken together, these data suggest that the swine farm environment affects the fecal bacterial composition of swine farm workers. However, ARG spread was influenced by factors independent of the swine farm environment.

Functional multipotency renders human umbilical cord mesenchymal stem cell (hUC-MSC) a promising candidate for the treatment of spinal cord injury (SCI). However, its safety and efficacy have not been fully understood for clinical translation. In this study, we performed cellular, kinematic, physiological, and anatomical analyses, either in vitro or in vivo, to comprehensively evaluate the safety and efficacy associated with subarachnoid transplantation of hUC-MSCs in rats with subacute incomplete SCI. Concerning safety, hUC-MSCs were shown to have normal morphology, excellent viability, steady proliferation, typical biomarkers, stable karyotype in vitro, and no tumorigenicity both in vitro and in vivo. Following subarachnoid transplantation of hUC-MSCs in the subject rodents, the biodistribution of hUC-MSCs was restricted to the spinal cord, and no toxicity to immune system or organ function was observed. Body weight, organ weight, and the ratio of the latter upon the former between stem cell-transplanted rats and placebo-injected rats revealed no statistical differences. Regarding efficacy, hUC-MSCs could differentiate into osteoblasts, chondrocytes, adipocytes and neural progenitor cells in vitro. While in vivo studies revealed that subarachnoid transplantation of stem cells resulted in significant improvement in locomotion, earlier automatic micturition recovery and reduced lesion size, which correlated with increased regeneration of tracking fiber and reduced parenchymal inflammation. In vivo luminescence imaging showed that a few of the transplanted luciferase-labeled hUC-MSCs tended to migrate towards the lesion epicenter. Shortened latency and enhanced amplitude were also observed in both motor and sensory evoked potentials, indicating improved signal conduction in the damaged site. Immunofluorescent staining confirmed that a few of the administrated hUC-MSCs integrated into the spinal cord parenchyma and differentiated into astrocytes and oligodendrocytes, but not neurons. Moreover, decreased astrogliosis, increased remyelination, and neuron regeneration could be observed. To the best of our knowledge, this preclinical study provides detailed safety and efficacy evidence regarding intrathecal transplantation of hUC-MSCs in treating SCI for the first time and thus, supports its initiation in the following clinical trial.

In recent years, the variety and volume of multimedia services have increased exponentially. Like most of other multimedia services, the conversational video service has stringent quality of service and experience requirements. In order to better support users QoE (Quality of Experience) and allocate network resources more effectively, this paper focuses on the QoS (Quality of Service)-QoE association modeling of conversational video flows. Through statistical analysis of the network video flow data, statistical distribution association between QoE and some network layer QoS parameters of the conversational video service is studied by use of the ITU-T P.1201.1 model, and relevant distribution functions are fitted. From the perspective of user’s experience, the QoS parameter recommendation indices are given for each MOS (Mean Opinion Score) value interval, and a QoE connected QoS model is established. Through the verification and comparison with an existing work, the rationality of the recommended QoS indices is demonstrated, which can help the network operators strike a balance between saving network resources and satisfying user’s quality of experience.

In the process of transforming and upgrading of traditional Chinese medicine( TCM) intelligent manufacturing,the TCM enterprises lack systematic and in-depth research on intelligent manufacturing of TCM,leading to insufficient understanding of relevant concepts,development direction,development content and other aspects,to some extent,causing fuzzy and chaotic phenomena. The theoretical model,as a higher expression level of scientific thinking,has the function of interpretation and prediction,and can provide theoretical basis as well as guide for scientific research. Therefore,this article aims to construct a theoretical model of TCM intelligent manufacturing based on the concept of flexible production and intelligent equipment for some unhealthy phenomena in the development process of TCM intelligent manufacturing. In the TCM intelligent manufacturing system,with theory model as the core,the new-generation information technology was integrated with the TCM manufacturing technology to realize the integration of informationization and industrilization as well as the landing of theoretical model. Then,a 3 D simulation model was established to provide a visual environment for intelligent manufacturing of TCM and simulate the virtual reality throughout the TCM intelligent manufacturing process. The new theoretical model in this paper,to a certain extent,can play a guiding role in the development of TCM intelligent manufacturing,and can also provide reference for the realization of TCM intelligent manufacturing.

A good regioselective, high atom-economical and transition-metal-free method for the synthesis of α-functionalized ether derivatives via the domino radical cyclization of 1,6-enynes is described. A series of α-functionalized ether derivatives could be easily obtained in good yields with wide functional group tolerance by using less toxic and inexpensive Cs2CO3 as the base. The control experiment results show that the reaction involves a radical process. This strategy provides a regioselective way toward the formation of dual C-C bonds in one step.

Vacuum-ultraviolet (VUV) photo-initiated oxidation of phenolic homologues in simulative natural water were investigated, including phenol, o-dihydroxybenzene (ODB), m-dihydroxybenzene (MDB), p-dihydroxybenzene (PDB), paranitrophenol (PNP) and o-chlorophenol (OCP). Results showed the phenolic homologues removal rate reached at least 90% in pure water, which was dependent on temperature, pH, concentration of HA, and functional group of HA. Experimental results indicated that 0.2 mg/L HA might be a critical point. Additionally, the rate constant of the six phenolic homologues reduced by 76.85%, 77.81%, 71.91%, 79.15%, and 55.69%, respectively in the MDB solution, and 79.73%, 82.80%, 95.36%, 80.38%, and 92.64%, respectively in the benzoic acid (BA) solution, compared to the rate constant in pure water. Moreover, quantum chemistry calculation indicated that the variances between phenolic compounds in removal rate were attributed to the substituent on the benzene ring. And, to some extent, the carboxy group of HA was supposed to arose the suppression for phenolic homologues removal rate. Mechanism involved phenolic homologues degradation using vacuum-ultraviolet (VUV) was summarized, where it underwent the formation of quinone structures, ring opening, short-chain organic acid, even eventually the transformation into NO3− and Cl− of PNP and OCP.

The silk sericin hydrolysate (SSH) from the waste of silk processing as a substitute of fetal bovine serum (FBS) was used for the culture of Chinese hamster ovary (CHO) cells and Henrietta Lacks (Hela) strain of human cervical cancer cells. The survival ratio of these cells cultured in SSH media were similar to or higher than those in FBS media. Especially after the serum was replaced by low concentration of SSH at 15.0 μg/ml for 5 d, the proliferation of both cells was also similar to or higher than that of FBS group; the percentages of CHO and Hela cells in S-phase were 28.9 and 28.0%, respectively. The former is nearly two times that of FBS group, the latter is also higher than the control group. Reverse transcription-polymerase chain reaction (RT-PCR) revealed that among the differentially expressed genes, the relative expression of CXCL12 gene of CHO cells in SSH group increased, was three times that of serum group, and the relative expression of LCN2 gene of Hela cells increased 2.8 times, indicating that these related genes were activated to promote cell growth and proliferation. These results fully illustrated the hydrolysated sericin has a potential use as serum substitutes in cell culture.

Phenolic pollutants (PPs) are regarded as hazardous pollutants, posing severe threats to humans. In this study, a vacuum ultraviolet (VUV) lamp was used to decay PPs with different functional groups, including phenol, paradioxybenzene (PDB), and p-nitrophenol (PNP). Results showed the removal rate for phenol, PDB, and PNP reached 99.78 %, 97.78 %, and 80.73 % within 60 min. Density functional theory (DFT) involving in quantum chemical descriptors (QCD), frontier molecular orbitals (FMO), thermochemical properties, and the Gibbs free energy was applied to reveal the reactivity and mechanism between ·OH and PPs with various functional groups. Results confirmed that PDB and phenol with the electron-donating group exhibited favorable reactivity, while PNP with an electron-withdrawing group presented a lower one. Furthermore, the oxidation mechanism between PPs and ·OH in the VUV system was also deeply investigated, mainly following four steps: photo-excitation, ·OH substitution, molecular rearrangement, and finally ring-opening. Among them, the required energy for the ring-opening was about 145 and 787-fold higher than that of ·OH substitution and molecular rearrangement. Results suggested that the formation of micro-fatty acids were the primary rate-controlling step.

The purpose of this work is to evaluate the spatial and seasonal variability of water quality from the Mopanshan Reservoir, which is a typical reservoir in the northern cold regions of China. The results indicate that preventive or remediation actions are necessary to improve its water quality. Water samples were collected between 2012 and 2013 at five sampling stations at the Mopanshan Reservoir, and analyzed for CODMn and total nitrogen (TN). SPSS software was used to carry out analysis of variance and correlation analysis. Spatially, CODMn and TN exhibited a rather small distinction in the horizontal direction, but there was a significant difference regarding TN in the vertical orientation. The concentration of TN also increased with the increase in sampling depth. Seasonally, the concentration of CODMn and TN showed a pronounced seasonal pattern and was divided into four periods. CODMn reached a maximum in September and was at a minimum in June. And TN reached a maximum in June and was at a minimum in November or December. The use of correlation analysis shows that the regular variations of TN were primarily affected by temperature. The main form of nitrogen in the Mopanshan Reservoir is NO3-N, and the change of TN is consistent with that of NO3-N. By Pearson correlation coefficient, the seasonal variability of CODMn correlated to changes in the reservoir's water level. The results showed that the concentration of TN exceeded the guideline values in most months and CODMn was slightly over the standard limit. Thus, it is urgent that preventive actions and remediation processes are developed to improve the water quality in this reservoir.

Elucidation of altered metabolic pathways by using metabolomics may open new avenues for basic research on disease mechanisms and facilitate the development of novel therapeutic strategies. Here, we report the development of ultrahigh performance liquid chromatography-tandem mass spectrometry-based metabolomics platform with capability of measuring both cationic and anionic intermediates in cellular metabolism. The platform was established based on the hydrophobic ion-pairing interaction chromatography coupled with tandem mass spectrometry in multiple reaction monitoring (MRM) mode. The MRM transitions were created and optimized via energy-resolved collision-induced dissociation experiments, serving as an essential reference point for the quantification and identification. For chromatographic separation, application of hydrophobic ion-pairing interaction led to dramatic enhancement on retention of water-soluble metabolites and provision of good peak shapes. Two volatile ion-pairing reagents, namely heptafluorobutyric acid and tributylamine, were used with dedicated C18 columns as complementary separation systems coupled with the MRM analysis, allowing measurement of the metabolites of interest at nanomolar levels. The developed platform was successfully applied to investigate the altered metabolism in hepatic cells with over-expression of an oncogene, thus can provide important information on the rewired metabolism.