Analyzing chemical composition of Sargentodoxae caulis water extract and their hypouricemia effect in hyperuricemic mice.

Hyperuricemia (HUA) is a metabolic disease characterized by the increase of serum uric acid (UA) level. Sargentodoxae Caulis (SC) is a commonly used herbal medicine for the treatment of gouty arthritis, traumatic swelling, and rheumatic arthritis in clinic. In this study, a total of fifteen compounds were identified in SC water extract using UHPLC-Q-TOF-MS/MS, including three phenolic acids, seven phenolic glycosides, four organic acids, and one lignan. Then, to study the hypouricemia effect of SC, a HUA mouse model was induced using a combination of PO, HX, and 20% yeast feed. After 14 days of treatment with the SC water extract, the levels of serum UA, creatinine (CRE), blood urea nitrogen (BUN) were reduced significantly, and the organ indexes were restored, the xanthine oxidase (XOD) activity were inhibited as well. Meanwhile, SC water extract could ameliorate the pathological status of kidneys and intestine of HUA mice. Additionally, quantitative real-time PCR (qRT-PCR) and western blotting results showed that SC water extract could increase the expression of ATP binding cassette subfamily G member 2 (ABCG2), organic cation transporter 1 (OCT1), organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3), whereas decrease the expression of glucose transporter 9 (GLUT9). This study provided a data support for the clinical application of SC in the treatment of HUA.

Structure and properties of acidic polysaccharides isolated from Massa Medicata Fermentata: Neuroprotective and antioxidant activity.

Massa Medicata Fermentata (MMF) is a fermented food with therapeutic effects. Previous studies suggested that after stir-frying, the uronic acid content in MMF crude polysaccharides increases, and the pH value decreases, which is caused by the change in acidic polysaccharides. However, the detailed physicochemical properties and structure-activity correlation of the acidic polysaccharides in MMF have not been fully explored. In this study, two acidic polysaccharides (SMMFAP and CMMFAP) were isolated from the MMF and its stir-fried product, respectively. Their structural characteristics and bioactivities were comparatively studied, and the structure-activity correlation was examined. Our findings revealed that the SMMFAP had a higher average Mw and higher Gal and Man content than the CMMFAP. Both the SMMFAP and CMMFAP were mainly composed of Xyl, Man, and Gal residues, whereas the CMMFAP had fewer linkage types. Additionally, the CMMFAP exhibited stronger neuroprotective activity than the SMMFAP owing to its higher content of 1,6-linked-Galp, while the SMMFAP exhibited better antioxidant activity, which might be related to its higher average Mw. Our findings suggest that acidic polysaccharides may be the active substances that cause differences in effectiveness between the sheng and chao MMF. Furthermore, the research qualified the SMMFAP and CMMFAP with different potential applications.

Therapeutic effects of high-dose vitamin C supplementation in patients with COVID-19: a meta-analysis.

CONTEXT: Coronavirus disease 2019 (COVID-19) could induce the "cytokine storm" due to overactivation of immune system and accompanied by acute respiratory distress syndrome as a serious complication. Vitamin C has been effective in improving lung function of patients by reducing inflammation. OBJECTIVE: The aim was to explore the therapeutic effects of high-dose vitamin C supplementation for patients with COVID-19 using meta-analysis. DATA SOURCES: Published studies were searched from PubMed, Cochrane Library, Web of Science, EMBASE, and China National Knowledge Infrastructure databases up to August 2022 using the terms "vitamin C" and "COVID-19". Data analyses were performed independently by 2 researchers using the PRISMA guidelines. DATA EXTRACTION: Heterogeneity between the included studies was assessed using I2 statistics. When I2 ≥50%, the random-effects model was used; otherwise, a fixed-effects model was applied. Stata 14.0 software was used to pool data by standardized mean differences (SMDs) with 95% CIs or odds ratios (ORs) with 95% CIs. DATA ANALYSIS: The 14 studies had a total of 751 patients and 1583 control participants in 7 randomized controlled trials and 7 retrospective studies. The vitamin C supplement significantly increased ferritin (SMD = 0.272; 95% CI: 0.059 to 0.485; P = 0.012) and lymphocyte count levels (SMD = 0.376; 95% CI: 0.153 to 0.599; P = 0.001) in patients with COVID-19. Patients administered vitamin C in the length of intensive care unit staying (SMD = 0.226; 95% CI: 0.073 to 0.379; P = 0.004). Intake of vitamin C prominently alleviate disease aggravation (OR = 0.344, 95%CI: 0.135 to 0.873, P = 0.025). CONCLUSIONS: High-dose vitamin C supplementation can alleviate inflammatory response and hinder the aggravation of COVID-19.

Hollow mesoporous organosilica nanoparticles reduced graphene oxide based nanosystem for multimodal image-guided photothermal/photodynamic/chemo combinational therapy triggered by near-infrared.

Developing a nanosystem that can perform multimodal imaging-guided combination therapy is highly desirable but challenging. In this study, we introduced multifunctional nanoparticles (NPs) consisting of graphene oxide-grafted hollow mesoporous organosilica loaded with the drug doxorubicin (DOX) and photosensitizers tetraphenylporphyrin (TPP). These NPs were encapsulated by thermosensitive liposomes that release their contents once the temperature exceeds a certain threshold. Metal oxide NPs grown on the graphene oxide (GO) surface served multiple roles, including enhancing photothermal efficiency, acting as contrast agents to improve magnetic resonance imaging, increasing the sensitivity and specificity of photoacoustic imaging, and catalysing hydrogen peroxide for the generation of reactive oxygen species (ROS). When locally injected, the HMONs-rNGO@Fe3 O4 /MnOx@FA/DOX/TPP NPs effectively enriched in subcutaneous Hela cell tumour of mice. The photothermal/photodynamic/chemo combination therapy triggered by near-infrared (NIR) successfully suppressed the tumour without noticeable side effects. This study presented a unique approach to develop multimodal imaging-guided combination therapy for cancer.

Nicandra physalodes Extract Exerts Antiaging Effects in Multiple Models and Extends the Lifespan of Caenorhabditis elegans via DAF-16 and HSF-1.

The development of safe and effective therapeutic interventions is an important issue for delaying aging and reducing the risk of aging-related diseases. Chinese herbal medicines for the treatment of aging and other complex diseases are desired due to their multiple components and targets. Through screening for effects on lifespan of 836 Chinese herbal medicine extracts, Nicandra physalodes extract (HL0285) was found to exhibit lifespan extension activity in Caenorhabditis elegans (C. elegans). In further experiments, HL0285 improved healthspan, enhanced stress resistance, and delayed the progression of neurodegenerative diseases in C. elegans. Additionally, it ameliorated senescence in human lung fibroblasts (MRC-5 cells) and reversed liver function damage and reduced senescence marker levels in doxorubicin- (Dox-) induced aging mice. In addition, the longevity effect of HL0285 in C. elegans was dependent on the DAF-16 and HSF-1 signaling pathways, as demonstrated by the results of the mutant lifespan, gene level, and GFP level assays. In summary, we discovered that HL0285 had an antiaging effect in C. elegans, MRC-5 cells, and Dox-induced aging mice and deserves to be explored in the future studies on antiaging agents.

Evaluation method of ex vivo porcine liver reduced scattering coefficient during microwave ablation based on temperature.

The principle of microwave ablation (MWA) is to cause irreversible damage (protein coagulation, necrosis, etc.) to tumor cells at a certain temperature by heating, thereby destroying the tumor. We have long used functional near-infrared spectroscopy (fNIRs) to monitor clinical thermal ablation efficacy. After a lot of experimental verification, it can be found that there is a clear correlation between the reduced scattering coefficient and the degree of tissue damage. During the MWA process, the reduced scattering coefficient has a stable change. Therefore, both temperature (T) and reduced scattering coefficient ( µ s ' ) are related to the thermal damage of the tissue. This paper mainly studies the changing law of T and µ s ' during MWA and establishes a relationship model. The two-parameter simultaneous acquisition system was designed and used to obtain the T and µ s ' of the ex vivo porcine liver during MWA. The correlation model between T and µ s ' is established, enabling the quantitative estimation of µ s ' of porcine liver based on T. The maximum and the minimum relative errors of µ s ' are 79.01 and 0.39%, respectively. Through the electromagnetic simulation of the temperature field during MWA, 2D and 3D fields of reduced scattering coefficient can also be obtained using this correlation model. This study contributes to realize the preoperative simulation of the optical parameter field of microwave ablation and provide 2D/3D therapeutic effect for clinic.

Genetic manipulation of bermudagrass photosynthetic biosynthesis using Agrobacterium-mediated transformation.

Bermudagrass is one of the most extensively used warm-season grasses. It is widely used in landscaping, stadium construction and soil remediation due to its excellent regeneration, trampling and stress tolerances. However, studies on its regulatory mechanism and variety improvement by genetic engineering are still at a standstill, owing to its genetic variability and intrinsic limits linked with some resistance to Agrobacterium infection. In this study, we established a higher efficient Agrobacterium-mediated transformation via screening for vital embryogenic callus and improving infection efficiency. The superior callus was light yellow, hard granular and compact, determined with a differentiation rate of more than 95%. The optimized infestation courses by gentle shaking, vacuuming and sonicating were used. The infested calluses were co-cultured for 3 days, followed by desiccation treatments for 1 day to get higher infection efficiency. Then the CdHEMA1 gene, essential for chlorophyll biosynthesis, was cloned and transferred into bermudagrass to validate the aforementioned optimization procedures integrally. Molecular-level analyses indicated that the CdHEMA1 gene had successfully integrated and was greatly increased in transgenic seedlings. Results of the photosynthetic capacity assessment showed that CdHEMA1 overexpression may considerably enhance the contents of photosynthetic pigments, OJIP curve and reaction center density (RC/CSo) to absorb (ABS/CSo, ABS/CSM) and capture (TRo/CSo) more light energy, hence improve the performance indices PIABS and PICS compared to the wild type. The successful completion of this project would provide a solid platform for further gene function study and molecular breeding of bermudagrass.

Antiaging Effects of Vicatia thibetica de Boiss Root Extract on Caenorhabditis elegans and Doxorubicin-Induced Premature Aging in Adult Mice.

The roots of Vicatia thibetica de Boiss are a kind of Chinese herb with homology of medicine and food. This is the first report showing the property of the extract of Vicatia thibetica de Boiss roots (HLB01) to extend the lifespan as well as promote the healthy parameters in Caenorhabditis elegans (C. elegans). For doxorubicin- (Doxo-) induced premature aging in adult mice, HLB01 counteracted the senescence-associated biomarkers, including P21 and γH2AX. Interestingly, HLB01 promoted the expression of collagen in C. elegans and mammalian cell systemically, which might be one of the essential factors to exert the antiaging effects. In addition, HLB01 was also found as a scavenger of free radicals, thereby performing the antioxidant ability. Lifespan extension by HLB01 was also dependent on DAF-16 and HSF-1 via oxidative stress resistance and heat stress resistance. Taken together, overall data suggested that HLB01 could extend the lifespan and healthspan of C. elegans and resist Doxo-induced senescence in mice via promoting the expression of collagen, antioxidant potential, and stress resistance.

Effects of andrographolide on renal tubulointersticial injury and fibrosis. Evidence of its mechanism of action.

BACKGROUND: Diabetic nephropathy (DN) is associated with renal interstitial injury and fibrosis. Our previous study showed that andrographolide protected against the progression of DN and high glucose (HG)-induced mesangial dysfunction. However, the protective effects of andrographolide on renal tubular epithelial cells have not been fully elucidated. PURPOSE: To determine the protective effects of andrographolide on renal tubular damage and explore the underlying mechanism. STUDY DESIGN: Human tubular epithelial cells (HK-2 cells) were treated with andrographolide (5 and 10 µM) under HG conditions. Diabetic mice were treated with andrographolide (i.p. 2 and 4 mg/kg, twice per week). METHODS: Western blotting, reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence and flow cytometry were used to analyze the effects of andrographolide on renal tubular injury and fibrotic mechanisms in HK-2 cells. The protective effects of andrographolide against renal tubulointerstitial injury and fibrosis were investigated in diabetic mice fed a high-fat diet (HFD). Renal interstitial tissue was collected at sacrifice for immunohistochemistry, immunofluorescence analysis, RT-PCR and Western blotting to analyze the effects of andrographolide on renal tubular injury and fibrosis. RESULTS: In vitro assay results indicated that andrographolide (5 and 10 µM) effectively inhibited HG-induced apoptosis, epithelial-mesenchymal transition (EMT) and collagen deposition in HK-2 cells. Mechanistically, HG stimulated mitochondrial reactive oxygen species (mtROS)-mediated NOD-like receptor family and pyrin domain-containing protein 3 (NLRP3) inflammasome activation and EMT in tubular epithelial cells, and andrographolide (5 and 10 µM) inhibited these effects by ameliorating mitochondrial dysfunction. In vivo, treatment with andrographolide (2 and 4 mg/kg) inhibited renal tubular cell apoptosis, EMT and tubulointerstitial fibrosis, mitochondrial dysfunction and NLRP3 inflammasome activation in diabetic mice. CONCLUSION: Andrographolide (5 and 10 µM) prevents HG-induced renal tubular cell damage, and andrographolide (2 and 4 mg/kg) protects against the progression of diabetic tubular injury and fibrosis in mice by suppressing mitochondrial dysfunction and NLRP3 inflammasome activation.

Portable and Battery-Powered PCR Device for DNA Amplification and Fluorescence Detection.

Polymerase chain reaction (PCR) is a technique for nucleic acid amplification, which has been widely used in molecular biology. Owing to the limitations such as large size, high power consumption, and complicated operation, PCR is only used in hospitals or research institutions. To meet the requirements of portable applications, we developed a fast, battery-powered, portable device for PCR amplification and end-point detection. The device consisted of a PCR thermal control system, PCR reaction chip, and fluorescence detection system. The PCR thermal control system was formed by a thermal control chip and external drive circuits. Thin-film heaters and resistance temperature detectors (RTDs) were fabricated on the thermal control chip and were regulated with external drive circuits. The average heating rate was 32 °C/s and the average cooling rate was 7.5 °C/s. The disposable reaction chips were fabricated using a silicon substrate, silicone rubber, and quartz plate. The fluorescence detection system consisted a complementary metal-oxide-semiconductor (CMOS) camera, an LED, and mirror units. The device was driven by a 24 V Li-ion battery. We amplified HPV16E6 genomic DNA using our device and achieved satisfactory results.

Identification of herbal categories active in pain disorder subtypes by machine learning help reveal novel molecular mechanisms of algesia.

Chronic pain is highly prevalent and poorly controlled, of which the accurate underlying mechanisms need be further elucidated. Herbal drugs have been widely used for controlling various pain disorders. The systematic integration of pain herbal data resources might be promising to help investigate the molecular mechanisms of pain phenotypes. Here, we integrated large-scale bibliographic literatures and well-established data sources to obtain high-quality pain relevant herbal data (i.e. 426 pain related herbs with their targets). We used machine learning method to identify three distinct herb categories with their specific indications of symptoms, targets and enriched pathways, which were characterized by the efficacy of treatment to the chronic cough related neuropathic pain, the reproduction and autoimmune related pain, and the cancer pain, respectively. We further detected the novel pathophysiological mechanisms of the pain subtypes by network medicine approach to evaluate the interactions between herb targets and the pain disease modules. This work increased the understanding of the underlying molecular mechanisms of pain subtypes that herbal drugs are participating and with the ultimate aim of developing novel personalized drugs for pain disorders.

Symptom network topological features predict the effectiveness of herbal treatment for pediatric cough.

Pediatric cough is a heterogeneous condition in terms of symptoms and the underlying disease mechanisms. Symptom phenotypes hold complicated interactions between each other to form an intricate network structure. This study aims to investigate whether the network structure of pediatric cough symptoms is associated with the prognosis and outcome of patients. A total of 384 cases were derived from the electronic medical records of a highly experienced traditional Chinese medicine (TCM) physician. The data were divided into two groups according to the therapeutic effect, namely, an invalid group (group A with 40 cases of poor efficacy) and a valid group (group B with 344 cases of good efficacy). Several well-established analysis methods, namely, statistical test, correlation analysis, and complex network analysis, were used to analyze the data. This study reports that symptom networks of patients with pediatric cough are related to the effectiveness of treatment: a dense network of symptoms is associated with great difficulty in treatment. Interventions with the most different symptoms in the symptom network may have improved therapeutic effects.

The Diversity of the Endobiotic Bacterial Communities in the Four Jellyfish Species.

The associated microbiota plays an essential role in the life process of jellyfish. The endobiotic bacterial communities from four common jellyfish Phyllorhiza punctata, Cyanea capillata, Chrysaora melanaster, and Aurelia coerulea were comparatively analyzed by 16S rDNA sequencing in this study. Several 1049 OTUs were harvested from a total of 130 183 reads. Tenericutes (68.4%) and Firmicutes (82.1%) are the most abundant phyla in P. punctata and C. melanaster, whereas C. capillata and A. coerulea share the same top phylum Proteobacteria (76.9% vs. 78.3%). The classified OTUs and bacterial abundance greatly decrease from the phylum to genus level. The top 20 matched genera only account for 9.03% of the total community in P. punctata, 48.9% in C. capillata, 83.05% in C. melanaster, and 58.1% in A. coerulea, respectively. The heatmap of the top 50 genera shows that the relative abundances in A. coerulea and C. capillata are far richer than that in P. punctata and C. melanaster. Moreover, a total of 41 predictive functional categories at KEGG level 2 were identified. Our study indicates the independent diversity of the bacterial communities in the four common Scyphomedusae, which might involve in the metabolism and environmental information processing of the hosts.The associated microbiota plays an essential role in the life process of jellyfish. The endobiotic bacterial communities from four common jellyfish Phyllorhiza punctata, Cyanea capillata, Chrysaora melanaster, and Aurelia coerulea were comparatively analyzed by 16S rDNA sequencing in this study. Several 1049 OTUs were harvested from a total of 130 183 reads. Tenericutes (68.4%) and Firmicutes (82.1%) are the most abundant phyla in P. punctata and C. melanaster, whereas C. capillata and A. coerulea share the same top phylum Proteobacteria (76.9% vs. 78.3%). The classified OTUs and bacterial abundance greatly decrease from the phylum to genus level. The top 20 matched genera only account for 9.03% of the total community in P. punctata, 48.9% in C. capillata, 83.05% in C. melanaster, and 58.1% in A. coerulea, respectively. The heatmap of the top 50 genera shows that the relative abundances in A. coerulea and C. capillata are far richer than that in P. punctata and C. melanaster. Moreover, a total of 41 predictive functional categories at KEGG level 2 were identified. Our study indicates the independent diversity of the bacterial communities in the four common Scyphomedusae, which might involve in the metabolism and environmental information processing of the hosts.

[Clinical observation on the inflammatory indexes in septic gastrointestinal dysfunction treated with acupuncture at Jiaji (EX-B 2)].

OBJECTIVE: To evaluate the effect on the inflammatory indexes of septic gastrointestinal dysfunction treated with acupuncture at Jiaji (EX-B 2). METHODS: A total of 118 patients of septic gastrointestinal dysfunction were randomized into an observation group and a control group, 59 cases in each one. In the control group, mosapride citrate was prescribed for oral administration, 5 mg each time, 3 times a day, bifidobacterium triple viable capsules, 420 mg each time, twice a day, intravenous drip with omeprazole, 40 mg, twice a day. Additionally, the antibiotics and the symptomatic treatment were selected rationally for maintaining the functions of the important organs, e.g. heart, lung, brain and kidney, and water-electrolyte balance. In the observation group, on the routine management as the control group, acupuncture at Jiaji (EX-B 2, T6-T12) was added, the needles were retained for 30 min in each treatment, once a day, 10 days as one course and 1 course was required. Separately, on the 1st, 3rd, 6th and 10th days of treatment, the white blood cell (WBC) count, the levels of hypersensitive C-reactive protein (hs-CRP) and procalcitonin (PCT) were observed, the enteral nutrition feeding dose and gastrointestinal dysfunction score before and after treatment as well as the clinical effect were assessed in the two groups. RESULTS: The differences were not significant in the indexes mentioned above on 1st and 3rd days of treatment between the two groups (P>0.05). On the 6th and 10th days of treatment, regarding the gastrointestinal dysfunction score and inflammatory indexes count, the results in the observation group were lower than the control group (all P<0.05), and feeding dose in the observation group was higher than the control group (P<0.05). After treatment, the gastrointestinal dysfunction scores and inflammatory indexes count were all reduced and feeding dose was increased as compared with those before treatment in the patients of the two groups (all P<0.05). After treatment, the total effective rate was 91.5% (54/59) in the observation group, higher than 76.3% (45/59) in the control group (P<0.05). CONCLUSION: Acupuncture at Jiaji (EX-B 2) points achieves the satisfactory effect on septic gastrointestinal dysfunction and reduces the inflammatory indexes count.

Comparative proteomic analysis of Aurelia coerulea for its locomotion system molecular structure-function inference.

BACKGROUND: Rhythmic contraction and autonomous movement play a key role in the predation, production and displacement of jellyfish. METHODS: Four independent body parts of the jellyfish Aurelia coerulea, including Bell, Tentacle, Oral arm and Gastric pouch were extracted and have been carried out a compared proteomics by liquid chromatography-mass spectrometry/mass-spectrometry (LC-MS/MS). ResultsA total of 13,429 peptides and 1916 proteins with molecular weights in the range of 10.6-980.9 kDa were identified, where 1916, 1562, 1474 and 1441 proteins were matched in the Gastric pouch, Tentacle, Oral arm and Bell, respectively. Gene Ontology (GO) analysis showed that translation, cytoplasma and ATP binding occupy the top differential terms of the three subdomains Biological process, Cellular Component and Molecular Function. A total of 326 pathways were successfully mapped that are mainly associated with intracellular synthesis, metabolism as well as intracellular functions. Moreover, a total of 27 contractile machinery associated proteins including 22 myosin, 3 actin and 2 tropomyosin were identified. CONCLUSIONS: Our results provide a composition profile in the four independent body parts of the jellyfish A. coerulea, of which the identified muscular proteins will greatly help in the understanding of the structural and functional relationship, as well as their operating mechanisms in the jellyfish locomotion system. SIGNIFICANCE: Omics studies have gained a new overall insight into the function of gene and protein networks during the development of motor systems in both bilateral and radial symmetrical animals. A compared proteomics using the label-free method of nano-LC-MS/MS has been performed through the four independent body parts of the moon jellyfish A. coerulea, including Bell, Tentacle, Oral arm and Gastric pouch. In addition to conventional bioinformatics analyses such as GO and KEGG, we have scanned the locomotion-related components, aligned their sequences, simulated three dimensional structures as well as did the molecular phylogenetic analyses. Our investigation provides a composition profile in the four independent body parts of the jellyfish A. coerulea, of which the identified muscular proteins will greatly help in the understanding of the structural and functional relationship, as well as their operating mechanisms in the jellyfish locomotion system.

An integrated transcriptomic and proteomic analysis reveals toxin arsenal of a novel Antarctic jellyfish Cyanea sp.

Jellyfish is a common toxic zooplankton in ocean. We successfully captured a kind of jellyfish 200 m underwater in Antarctica, and identified it as a jellyfish Cyanea sp. through morphological examination and MT-CO1 phylogenetic analysis. A total of 40,468 unigenes were harvested through transcriptome sequencing. We also successfully annotated 12,955 (32.01%) unigenes with the NR database, 10,882 (26.89%) unigenes with the SWISSPROT database, 4951 (12.23%) unigenes with the GO database, and 4901 (12.11%) unigenes with the KEGG database. In the proteomic analysis, a total of 11,159 peptides and 2630 proteins were harvested using the constructed transcriptome as the database. A number of 771 (29.31%) and 841 (31.98%) proteins were annotated against the GO and KEGG database, respectively. Moreover, a number of 29 toxic proteins matched from the 145 toxin-related unigenes were successfully screened, including 6 metalloproteinases, 4 phospholipases, 2 serine proteases, 1 serine protease inhibitor, 7 toxin-related venom and 9 other toxins. Our study is the first to identify a polar jellyfish Cyanea sp. with transcriptomics and proteomics, and these data can further serve as a public database for the identification of potential polar jellyfish-derived lead compounds feasibly functioning in the cold environment. SIGNIFICANCE: With increasing discussions on marine biodiversity and global warming, polar species have gradually become a focus for research. To the best of our knowledge, there is only one paper in pubMed about the mitochondrial genome of the Antarctic stalked jellyfish Haliclystus antarcticus Pfeffer. In this study, we captured a type of jellyfish (named BD-4) from the Southern Ocean (60°29'57" S, 52°11'44"W) on the scientific expedition ship "Xue Long" at the end of 2016. Although the samples were stored and transported by the ship at only -20 °C for more than two month, we successfully extracted the total RNA, and performed molecular species identification and combined analyses of de novo transcriptomics and proteomics. In addition to conventional bioinformatics techniques such as GO and KEGG annotation, we screened and listed toxic proteins, aligned the sequences, simulated three-dimensional structures and performed molecular phylogenetic analysis for typical components, including metalloproteinase and serine proteinase. Our study is the first to identify a polar jellyfish Cyanea sp. with de novo transcriptomics and proteomics, and these data can further serve as a public database for the identification of potential polar jellyfish-derived lead compounds.

[Clinical trials of acupuncture of Jiaji (EX-B2) for treatment of gastrointestinal dysfunction in sepsis patients].

OBJECTIVE: To observe the clinical therapeutic effect of acupuncture of Huatuo Jiaji (EX-B2) in the treatment of gastrointestinal dysfunction in sepsis patients, aiming at providing new clinical approach and evidence for improving septic gastrointestinal activity. METHODS: A total of 40 patients with septic gastrointestinal dysfunction who met our inclusive criteria were randomly divided into control group and treatment group (n＝20 cases in each). Patients in the control group received routine treatment of nasogastric mosapride citrate (5 mg/time, three times a day) and tifidobacterium triple viable capsules (420 mg, twice a day), intravenous infusion of omeprazole (40 mg, twice a day), rational dose of antibiotics, maintenance treatment of functions of the heart, lung, brain, kidney and other important organs and water electrolyte balance, as well as symptomatic treatment. Patients of the treatment group were treated by acupuncture of EX-B2 on the basis of routine treatment mentioned above in the control group. The acupuncture needle was inserted into EX-B2, twirled for a while and retained for 30 min, once a day for 10 successive days. The acute physiology and chronic health evaluation (APACHE II) score was given according to Knaus and colleagues' method, the intra-abdominal pressure was detected by using a manometer which was connected to an inserted canal in the urinary bladder, and the intragatric residul volume detected by using an injection syriange pumping via a nasal feeding tube. RESULTS: After the treatment, the APACHE II score, intra-abdominal pressure and intragastric residual volume on day 10 were significantly decreased in both groups in comparison with their own pre-treatment (P<0.05), while the borborygmus levels on day 10 were considerably increased in both groups relevant to their own pre-treatment (P<0.05). The APACHE II scores, intra-abdominal pressure and intragastric residual volume on day 3, 6 and 10 were significantly lower in the treatment group than those in the control group (P<0.05), whereas the borborygmus levels at the 3rd , 6th and 10th day in the treatment group were apparently higher than those of the control group (P<0.05)．. CONCLUSION: Acupuncture stimulation of EX-B2 has a good curative effect in improving gastrointestinal dysfunction in sepsis patients.

Symptom-based network classification identifies distinct clinical subgroups of liver diseases with common molecular pathways.

BACKGROUND AND OBJECTIVE: Liver disease is a multifactorial complex disease with high global prevalence and poor long-term clinical efficacy and liver disease patients with different comorbidities often incorporate multiple phenotypes in the clinic. Thus, there is a pressing need to improve understanding of the complexity of clinical liver population to help gain more accurate disease subtypes for personalized treatment. METHODS: Individualized treatment of the traditional Chinese medicine (TCM) provides a theoretical basis to the study of personalized classification of complex diseases. Utilizing the TCM clinical electronic medical records (EMRs) of 6475 liver inpatient cases, we built a liver disease comorbidity network (LDCN) to show the complicated associations between liver diseases and their comorbidities, and then constructed a patient similarity network with shared symptoms (PSN). Finally, we identified liver patient subgroups using community detection methods and performed enrichment analyses to find both distinct clinical and molecular characteristics (with the phenotype-genotype associations and interactome networks) of these patient subgroups. RESULTS: From the comorbidity network, we found that clinical liver patients have a wide range of disease comorbidities, in which the basic liver diseases (e.g. hepatitis b, decompensated liver cirrhosis), and the common chronic diseases (e.g. hypertension, type 2 diabetes), have high degree of disease comorbidities. In addition, we identified 303 patient modules (representing the liver patient subgroups) from the PSN, in which the top 6 modules with large number of cases include 51.68% of the whole cases and 251 modules contain only 10 or fewer cases, which indicates the manifestation diversity of liver diseases. Finally, we found that the patient subgroups actually have distinct symptom phenotypes, disease comorbidity characteristics and their underlying molecular pathways, which could be used for understanding the novel disease subtypes of liver conditions. For example, three patient subgroups, namely Module 6 (M6, n = 638), M2 (n = 623) and M1 (n = 488) were associated to common chronic liver disease conditions (hepatitis, cirrhosis, hepatocellular carcinoma). Meanwhile, patient subgroups of M30 (n = 36) and M36 (n = 37) were mostly related to acute gastroenteritis and upper respiratory infection, respectively, which reflected the individual comorbidity characteristics of liver subgroups. Furthermore, we identified the distinct genes and pathways of patient subgroups and the basic liver diseases (hepatitis b and cirrhosis), respectively. The high degree of overlapping pathways between them (e.g. M36 with 93.33% shared enriched pathways) indicates the underlying molecular network mechanisms of each patient subgroup. CONCLUSIONS: Our results demonstrate the utility and comprehensiveness of disease classification study based on community detection of patient network using shared TCM symptom phenotypes and it can be used to other more complex diseases.

Using generalized additive models to investigate factors influencing cyanobacterial abundance through phycocyanin fluorescence in East Lake, China.

East Lake is a shallow lake (in Wuhan, China) where cyanobacteria blooms occurred frequently from 1970 to 1985. During the study period, all Carlson trophic state index values were > 50, indicating that East Lake is in a eutrophic state. In this study, phycocyanin concentrations were measured through phycocyanin fluorometry for rapid assessment of cyanobacterial abundance. The smoothing splines of the optimal generalized additive model (GAM) indicated that Secchi depth (SD), total phosphorus (TP) and dissolved oxygen (DO) concentrations, electrical conductivity (EC), chemical oxygen demand (COD), and ratios of total nitrogen (TN) to TP (TN:TP) were the main environmental factors in a moderate nonlinear relationship with cyanobacterial phycocyanin concentrations in East Lake. The shape of the GAM smoother can be used to quantify the relationship between a response variable and an explanatory variable in the scatterplot. Phycocyanin concentrations were sharply and negatively related to both SD and EC when the SD was 20-80 cm and EC was > 270 mg/L. Phycocyanin concentrations increased with concentrations of TP, DO, and COD. Phycocyanin concentrations increased sharply with TP concentrations when TP concentrations were > 0.10 mg/L and approached to a constant when DO concentrations were > 8.20 mg/L. Approximately, 85% of the phycocyanin concentrations were negatively correlated with TN:TP of < 26. In summary, organic compounds and TP were inferred to the key factors limiting the potential growth of cyanobacteria in East Lake. These change points/thresholds of smoothing splines of aforementioned variables may serve as a framework for managing the cyanobacterial growth.

Stress-Induced Mucus Secretion and Its Composition by a Combination of Proteomics and Metabolomics of the Jellyfish Aurelia coerulea.

BACKGROUND: Jellyfish respond quickly to external stress that stimulates mucus secretion as a defense. Neither the composition of secreted mucus nor the process of secretion are well understood. METHODS: Aurelia coerulea jellyfish were stimulated by removing them from environmental seawater. Secreted mucus and tissue samples were then collected within 60 min, and analyzed by a combination of proteomics and metabolomics using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS), respectively. RESULTS: Two phases of sample collection displayed a quick decrease in volume, followed by a gradual increase. A total of 2421 and 1208 proteins were identified in tissue homogenate and secreted mucus, respectively. Gene Ontology (GO) analysis showed that the mucus-enriched proteins are mainly located in extracellular or membrane-associated regions, while the tissue-enriched proteins are distributed throughout intracellular compartments. Tryptamine, among 16 different metabolites, increased with the largest-fold change value of 7.8 in mucus, which is consistent with its involvement in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway 'tryptophan metabolism'. We identified 11 metalloproteinases, four serpins, three superoxide dismutases and three complements, and their presence was speculated to be related to self-protective defense. CONCLUSIONS: Our results provide a composition profile of proteins and metabolites in stress-induced mucus and tissue homogenate of A. coerulea. This provides insight for the ongoing endeavors to discover novel bioactive compounds. The large increase of tryptamine in mucus may indicate a strong stress response when jellyfish were taken out of seawater and the active self-protective components such as enzymes, serpins and complements potentially play a key role in innate immunity of jellyfish.