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The largemouth bass is a freshwater aquacultured fish species of great economic importance in China. With the rapid development of aquaculture industry and the increase in the aquaculture density of the fish, various infectious pathogens, including parasites, bacteria, and viruses, have been widely spread, which have caused huge losses to the aquaculture industry. Among them, largemouth bass iridovirus (LMBV) is one of the most harmful pathogens. In the present study, a virus strain named LMBV-GDSD was isolated from cultured largemouth bass and was successfully proliferated in FHM and EPC cells, with numerous viral particles observed in the infected cells under transmission electron microscopy analysis. The annotated complete genome of LMBV-GDSD was 99,285 bp and contained 102 ORFs. Based on genomic sequence alignment and phylogenetic analysis, the identified LMBV-GDSD belonged to the genus Ranavirus of Iridoviridae and was pathogenic to largemouth bass under regression infection experiments. In addition, the infection of LMBV-GDSD in largemouth bass could significantly up-regulate the expression of antiviral immune-related genes such as IRF3, IRF7, and Mx. It is thus providing valuable genetic data for a deeper understanding of the pathogenic mechanism of iridovirus in largemouth bass. [ABSTRACT FROM AUTHOR]

At 12:52 pm on September 5, 2022, an Ms 6.8 earthquake occurred in Luding County, Sichuan Province, China. Based on high-resolution aerial photographs and satellite imageries obtained after the earthquake, as well as field investigation, a total of 8685 earthquake-triggered landslides (EQTLs) were interpreted. The landslides covered an area of 30.7 km2, with a source area of 9.4 km2. These EQTLs were mainly distributed in areas with a seismic intensity of VIII and IX. Most of the landslides were small and medium in size, and their types included landslide, rockfall, and rock slump. Characteristic landslide distributions were found, EQTLs were distributed along the Xianshuihe fault, landslide area decreased gradually with an increased distance to the fault; EQTLs were distributed along the Daduhe River and roads; besides, landslide distribution was associated with ground deformation caused by the earthquake. EQTLs' characteristics indicated that, a large number of EQTLs were located near the foot of the slope; the full area of EQTLs and their source area followed a power function. This study concluded that Luding EQTLs were greater in number and area but relatively smaller in terms of affected area. Investigations on geo-hazards post-earthquake and risk assessment were proposed in the earthquake-stricken area to support the rehabilitation and reconstruction. [ABSTRACT FROM AUTHOR]

Chukrasia tabularis is an economically important tree and widely cultured in the southeast of China. Its barks, leaves, and fruits are consumed as a traditional medicine and perceived as a valuable source for bioactive limonin compounds. The extracts from root barks of C. tabularis showed significant anti‐inflammatory effect. The aim of this research was to explore the material basis of C. tabularis anti‐inflammatory activity, and to purify and identify anti‐inflammatory active ingredients. By a bioassay‐guided isolation of dichloromethane fraction obtained two novel phragmalin limonins, Chukrasitin D and E (1 and 2), together with 12 known limonins (3–14). The chemical structure of these compounds is determined on the basis of extensive spectral analysis and chemical reactivity. In addition, the activities of these isolated limonins on the production of nitric oxide (NO), tumor necrosis factor alpha (TNF‐α), and nuclear factor kappa B (NF‐κB) in RAW264.7 cells induced by lipopolysaccharide (LPS) were evaluated. Limonins 1 and 2 indicated significant anti‐inflammatory activity with IC50 values of 6.24 and 6.13 μM. Compound 1 notably inhibited the production of NF‐κB, TNF‐α and interleukin 6 (IL‐6) in macrophages. The present results suggest that the root barks of C. tabularis exhibited anti‐inflammatory effect and the limonins may be responsible for this activity. [ABSTRACT FROM AUTHOR]

• A calc-alkaline bimodal volcanic complex in the Yinshan Block was formed at ∼ 2570 Ma. • The high-Mg basalt/andesite were derived from a metasomatised depleted mantle. • The adakitic rhyolites were derived from a thickened juvenile mafic lower crust. • This bimodal complex was formed in a modern-style arc setting. Plate tectonics plays an important role in Earth's evolution, but it is a difficult and controversial issue to trace the operation of plate tectonics in the Archean. Calc-alkaline magmas are a diagnostic feature of modern subduction-related magmatism and thus identification of Archean subduction-related calc-alkaline magmas is crucial for understanding when Archean plate tectonics operated. Here we present zircon U-Pb, whole-rock geochemical and Sr-Nd isotopic data for a metamorphosed Neoarchean calc-alkaline bimodal volcanic complex from the Yinshan Block, the North China Craton. Zircon U-Pb dating results indicate that these meta -volcanic rocks were erupted in the late Neoarchean (∼2570 Ma). Its mafic unit is characterized by high contents of K 2 O (0.68–4.20 wt%), MgO (Mg# = 62.0-73.4), Cr (332-904 ppm), Ni (105-269 ppm), and is enriched in light rare earth elements (REEs), but depleted in heavy REEs and Nb, Ta and Ti. These geochemical features are similar to those of high-Mg basalts in the Phanerozoic arc setting. They have positive ε Nd (t) values (+1.3 to + 2.4), indicating that they were derived from the depleted mantle wedge. The felsic unit has variable K 2 O content (1.42–4.95 wt%) and K 2 O/Na 2 O ratios of 0.23–1.36 with positive ε Nd (t) values (+0.7 to + 3.1). They show characteristics of modern adakites with high Sr/Y and La N /Yb N ratios, suggesting that they were generated by partial melting of the thickened juvenile mafic lower crust. We conclude that the studied Neeoarchean bimodal meta -volcanic complex was formed during subduction-zone retreating and root delamination in a Neoarchean arc. Our results further indicate that plate tectonics had already operated in the Neoarchean in the Yinshan Block. [ABSTRACT FROM AUTHOR]

Background: This study aimed to develop and validate a novel nomogram to predict the cancer-specific survival (CSS) of patients with ascending colon adenocarcinoma after surgery. Methods: Patients with ascending colon adenocarcinoma were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2015 and randomly divided into a training set (5930) and a validation set (2540). The cut-off values for age, tumour size and lymph node ratio (LNR) were calculated via X-tile software. In the training set, independent prognostic factors were identified using univariate and multivariate Cox analyses, and a nomogram incorporating these factors was subsequently built. Data from the validation set were used to assess the reliability and accuracy of the nomogram and then compared with the 8th edition of the American Joint Committee on Cancer (AJCC) tumour-node-metastasis (TNM) staging system. Furthermore, external validation was performed from a single institution in China. Results: A total of 8470 patients were enrolled from the SEER database, 5930 patients were allocated to the training set, 2540 were allocated to the internal validation set and a separate set of 473 patients was allocated to the external validation set. The optimal cut-off values of age, tumour size and lymph node ratio were 73 and 85, 33 and 75 and 4.9 and 32.8, respectively. Univariate and multivariate Cox multivariate regression revealed that age, AJCC 8th edition T, N and M stage, carcinoembryonic antigen (CEA), tumour differentiation, chemotherapy, perineural invasion and LNR were independent risk factors for patient CSS. The nomogram showed good predictive ability, as indicated by discriminative ability and calibration, with C statistics of 0.835 (95% CI, 0.823–0.847) and 0.848 (95% CI, 0.830–0.866) in the training and validation sets and 0.732 (95% CI, 0.664–0.799) in the external validation set. The nomogram showed favourable discrimination and calibration abilities and performed better than the AJCC TNM staging system. Conclusions: A novel validated nomogram could effectively predict patients with ascending colon adenocarcinoma after surgery, and this predictive power may guide clinicians in accurate prognostic judgement. [ABSTRACT FROM AUTHOR]

Clematis florida is widely used in She Ethnopharmacy in China owing to its significant anti-inflammatory activities. This study aimed to investigate the anti-inflammatory effect of the active fraction of C. florida (CFAF) in an arthritis animal model and its possible mechanism. Pre-inflammatory cytokine levels were examined by ELISA. CFAF can significantly improve the symptoms of arthritis such as paw swelling, arthritic index, and histological condition in AA rat. CFAF can also reduce levels of IL-1β, TNF-α and IL-6. Further studies showed that triterpene saponins from CFAF induced anti-inflammatory activity inhibited inflammatory mediators by blocking JAK/STAT signalling pathways in the LPS-treated macrophages. [ABSTRACT FROM AUTHOR]

The clinical pathway (CP) as a novel medical management schema is beneficial for reducing the length of stay, decreasing heath care costs, standardizing clinical activities, and improving medical quality. However, the practicability of CPs is limited by the complexity and expense of adding the standard functions of electronic CPs to existing electronic medical record (EMR) systems. The purpose of this study was to design and develop an independent clinical pathway (ICP) system that is sharable with different EMR systems. An innovative knowledge base pattern was designed with separate namespaces for global knowledge, local knowledge, and real-time instances. Semantic web technologies were introduced to support knowledge sharing and intelligent reasoning. The proposed system, which was developed in a Java integrated development environment, achieved standard functions of electronic CPs without modifying existing EMR systems and integration environments in hospitals. The interaction solution between the pathway system and the EMR system simplifies the integration procedures with other hospital information systems. Five categories of transmission information were summarized to ensure the interaction process. Detailed procedures for the application of CPs to patients and managing exceptional alerts are presented by explicit data flow analysis. Compared to embedded pathway systems, independent pathway systems feature greater feasibility and practicability and are more advantageous for achieving the normalized management of standard CPs. [ABSTRACT FROM AUTHOR]

To explore the practical role of enhanced vegetation index (EVI) time series data in improving the accuracy of forest type recognition could promote the deep application of optical remote sensing data in forest resources investigation and monitoring. With Cuigang Forest Farm of Xinlin Forestry Bureau in Daxing'anling as the object, we constructed six classification schemes, using random forest algorithm with spectral feature, texture feature and EVI time series feature. The data sources were 20-view Landsat 8 OLI time series data from 2014 to 2018, 56 fixed plots data from 2017-2019, and the 2016 Class II survey data. Our aims were to realize the classification of forest types in Cuigang Forest Farm and to evaluate the accuracy of different classification schemes. The results showed the EVI values of Larix gmelinii forest, Betula platyphylla forest, coniferous-broadleaved mixed forest, coniferous mixed forest and broadleaved mixed forest were significantly different in non-growing seasons (36-111 days and 287-367 days), with the EVI value of mixed conifer forest being significantly higher, and that of mixed broadleaf forest being always lower than the other four forest types. In the early growing season (111-143 days), the EVI value of B. platyphylla forest were higher than L. gmelinii forest, which could effectively distinguish the two forests. Among the six classification schemes, spectral feature, texture feature, and EVI time series feature had the highest classification accuracy, with a Kappa of 0.82 and a classification accuracy of 86.1%. The comparison results showed that the overall accuracy of adding vegetation index time series feature was improved by 14.3% compared with that of spectral feature. The random forest algorithm with combined spectral, texture and EVI time series features could effectively classify forest stand types in Cuigang Forest Farm, with good recognition accuracy and confidence.

Objective: Pancreatic ductal adenocarcinoma (PDAC) shows a remarkable predilection for liver metastasis. Pro-oncogenic secretome delivery and trafficking via exosomes are crucial for pre-metastatic microenvironment formation and metastasis. This study aimed to explore the underlying mechanisms of how PDAC-derived exosomes (Pex) modulate the liver microenvironment and promote metastasis., Design: C57BL/6 mice were 'educated' by tail vein Pex injection. The intrasplenic injection liver metastasis and PDAC orthotopic transplantation models were used to evaluate liver metastasis. Stable cell lines CD44v6 (CD44 variant isoform 6) or C1QBP (complement C1q binding protein) knockdown or overexpression was established using lentivirus transfection or gateway systems. A total of 142 patients with PDAC in Huashan Hospital were retrospectively enrolled. Prognosis and liver metastasis were predicted using Kaplan-Meier survival curves and logistic regression models., Results: Pex tail vein injection induced the deposition of liver fibrotic extracellular matrix, which promoted PDAC liver metastasis. Specifically, the exosomal CD44v6/C1QBP complex was delivered to the plasma membrane of hepatic satellite cells (HSCs), leading to phosphorylation of insulin-like growth factor 1 signalling molecules, which resulted in HSC activation and liver fibrosis. Expression of Pex CD44v6 and C1QBP in PDAC patients with liver metastasis was significantly higher than in PDAC patients without liver metastasis, and simultaneous high expression of exosomal CD44v6 and C1QBP correlated with a worse prognosis and a higher risk of postoperative PDAC liver metastasis., Conclusion: The Pex-derived CD44v6/C1QBP complex is essential for the formation of a fibrotic liver microenvironment and PDAC liver metastasis. Highly expressed exosomal CD44v6 and C1QBP are promising biomarkers for predicting prognosis and liver metastasis in patients with PDAC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Three undescribed azaphilones, phomopsones A-C (1-3) and two known azaphilones (4-5) were isolated from the culture of endophytic fungus Phomopsis sp. CGMCC No.5416 from the stems of Achyranthes bidentata. Their structures were determined by spectroscopic analysis (HRESIMS, 1D and 2D NMR), and the absolute configurations were determined by CD spectroscopy. Compounds 2 and 3 showed significant inhibitory activities against HIV-1 with against HIV-1 with IC 50 values of 7.6 and 0.5 μmol/L, respectively. Compounds 2 and 3 also displayed moderate cytotoxicity with CC 50 values of 3.2-303 μmol/L against A549, MDA-MB-231 and PANC-1 cell lines. Moreover, compound 3 can induce the early apoptosis of PANC-1 cancer cells with the apoptosis rate of 28.54%., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: Imrecoxib is one type of cyclooxygenase-2 inhibitor with the capability of reducing the potential cardiovascular risk caused by other NSAIDs. Co-administration with other medications can affect the cytochrome P450 (CYP) 2C9 enzyme function; thus, imrecoxib metabolism can be affected. The purpose of this research was to evaluate the effects of fluconazole, which is known to inhibit CYP2C9, on imrecoxib's pharmacokinetic (PK) parameters., Methods: In this single-center, single-arm, open-label, self-controlled study, 12 healthy Chinese male volunteers (mean [SD] age, 22.6 [2.43] years) received the following 2 treatments separated by a washout period of 8 days under a fasting state: (1) a single oral dose of imrecoxib 100 mg; and (2) fluconazole 200 mg/d over 6 days followed by concurrent dosing of imrecoxib 100 mg and fluconazole 200 mg. Plasma concentrations of imrecoxib (M0) and its metabolites (4'-hydroxymethyl metabolite [M1] and 4'-carboxylic acid metabolite [M2]) for PK analysis were obtained at 0 (baseline) and 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 48, and 72 hours after imrecoxib dosing. Safety and tolerability assessments were performed throughout the study., Findings: All subjects completed the study. There was 1 adverse event; drug-induced liver damage in 1 subject occurred after he received imrecoxib plus fluconazole, and the subject recovered without any sequelae. Coadministration with fluconazole resulted in much higher plasma imrecoxib concentrations, with an increase of 88% in C max and 72% in AUC 0-t compared with only imrecoxib treatment, which showed that fluconazole may increase plasma exposure to imrecoxib. Fluconazole also caused a small, but not clinically relevant, decrease in M1 and M2 mean C max (13% and 14%, respectively), but there was minimal change in M1 and M2 mean AUC 0-t (3% and 2%). However, there were no statistically significant differences in vital signs, clinical laboratory test results, ECGs, or adverse events between treatments., Implications: Concurrent administration of imrecoxib and fluconazole did not seem to change imrecoxib's safety profile. The ratio (imrecoxib + fluconazole/imrecoxib) for AUC 0-t was 1.72 (90% CI, 1.41-2.11) and for Cmax it was 1.88 (90% CI, 1.59-2.21). Hence, it is necessary to adjust the imrecoxib dose when it is concurrently used with other CYP2C9 inhibitors., (Copyright © 2018. Published by Elsevier Inc.)

Aim: To evaluate the effects of an Al(3+)- and Mg(2+)-containing antacid, ferrous sulfate, and calcium carbonate on the absorption of nemonoxacin in healthy humans., Methods: Two single-dose, open-label, randomized, crossover studies were conducted in 24 healthy male Chinese volunteers (12 per study). In Study 1, the subjects orally received nemonoxacin (500 mg) alone, or an antacid (containing 318 mg of Al(3+) and 496 mg of Mg(2+)) plus nemonoxacin administered 2 h before, concomitantly or 4 h after the antacid. In Study 2, the subjects orally received nemonoxacin (500 mg) alone, or nemonoxacin concomitantly with ferrous sulfate (containing 60 mg of Fe(2+)) or calcium carbonate (containing 600 mg of Ca(2+))., Results: Concomitant administration of nemonoxacin with the antacid significantly decreased the area under the concentration-time curve from time 0 to infinity (AUC0-∞) for nemonoxacin by 80.5%, the maximum concentration (Cmax) by 77.8%, and urine recovery (Ae) by 76.3%. Administration of nemonoxacin 4 h after the antacid decreased the AUC0-∞ for nemonoxacin by 58.0%, Cmax by 52.7%, and Ae by 57.7%. Administration of nemonoxacin 2 h before the antacid did not affect the absorption of nemonoxacin. Administration of nemonoxacin concomitantly with ferrous sulfate markedly decreased AUC0-∞ by 63.7%, Cmax by 57.0%, and Ae by 59.7%, while concomitant administration of nemonoxacin with calcium carbonate mildly decreased AUC0-∞ by 17.8%, Cmax by 14.3%, and Ae by 18.4%., Conclusion: Metal ions, Al(3+), Mg(2+), and Fe(2+) markedly decreased the absorption of nemonoxacin in healthy Chinese males, whereas Ca(2+) had much weaker effects. To avoid the effects of Al(3+) and Mg(2+)-containing drugs, nemonoxacin should be administered ≥2 h before them.

With the increasing public access to urban water bodies for aesthetical and recreational purposes, it is of critical importance for densely populated urban areas to conduct microbial risk assessment and accordingly implement effective risk management. Based on the methodology of quantitative microbial risk assessment, a case study was conducted on three typical urban water bodies for aesthetical and recreational uses in a southern city in China. Exposure assessment was carried out through water quality monitoring, field survey and literature review, and accordingly human health risk was assessed with different dose-response equations based on fecal coliforms (FC), Escherichia coli (EC) and Enterococci (ENT). Microbial risk estimated by different dose-response equations was found consistent with and comparable to each other. Stream B located in a residential area was not suitable for primary- or secondary-contact recreational uses, and its microbial risk to the public mainly came from water abstraction for household miscellaneous uses. Stream C and Lake E, located in a public open space and a scenic area respectively, could meet the current recreational requirements, and their microbial risk to the public was generally attributed to various recreational activities. It was necessary to address the public health risk associated with the unauthorized or inappropriate water uses (e.g. abstraction for household miscellaneous uses) of urban aesthetical and recreational water bodies.

Aim: To evaluate the pharmacokinetics of tacrolimus in Chinese stable liver transplant recipients converted from immediate release (IR) tacrolimus-based immunosuppression to modified release (MR) tacrolimus-based immunosuppression., Methods: Open-label, multi-center study with a one-way conversion design was conducted. Eighty-three stable liver recipients (6-24 months post-transplant) with normal renal and stable hepatic function were converted from IR tacrolimus twice-daily treatment to MR tacrolimus once-daily treatment on a 1:1 (mg: mg) total daily dose basis. Twenty-four hour pharmacokinetic studies were carried out on d 0 (pre-conversion), d 1, and d 84 (post-conversion)., Results: The area under the blood concentration-time curve of MR tacrolimus from 0 to 24 h (AUC(0-24)) on d 1 was comparable to that of IR tacrolimus on d 0, with a 90% confidence interval (CI) for MR/IR tacrolimus of 92%-97%. The AUC(0-24) value for MR tacrolimus on d 84 with the daily dose increased by 14% was approximately 17% lower than that for IR tacrolimus. The 90% CI was 77%-90%, outside the bioequivalence range of 80%-125%. There was a good correlation between AUC(0-24) and concentration at 24 h (C(24)) for IR tacrolimus (d 0, r=0.930) and MR tacrolimus (d 1, r=0.936; d 84, r=0.903)., Conclusion: The exposure to tacrolimus when administered MR tacrolimus once daily is not equivalent to that for IR tacrolimus twice daily after an 84-day conversion in Chinese stable liver transplant recipients. The dose should be adjusted on the basis of trough levels. The therapeutic drug monitoring for patients treated with IR tacrolimus is considered to be applicable to MR tacrolimus.

Aim: To investigate the impact of CYP2C9 * 3 on the pharmacokinetics of glibenclamide and lornoxicam., Methods: CYP2C9 * 3 was measured in 83 non-related Chinese subjects by PCR-RFLP. The pharmacokinetics of lornoxicam and glibenclamide were investigated in 18 subjects (7 with CYP2C9 * 1/* 3 genotype and 11 with * 1/* 1 genotype). Glibenclamide and lornoxicam in plasma were determined by the sensitive liquid chromatography-tandem mass spectrometry, separately., Results: After a single oral dose of 2.5 mg glibenclamide, C(max) was (70.0 +/- 11.5) microg x L(-1) in CYP2C9 * 1/ * 3 subjects and (51.9 +/- 12.3) microg x L(-1) in * 1/ *1 subjects. AUC(0-infinity) were (435 +/- 47) vs (287 +/- 95) microg x h x L(-1) (in * 1/ * 3 vs * 1/ *1 subjects), and CL/F were (96 +/- 9.3) vs (160 +/- 51) mL x min(-1), respectively. Statistic analysis results indicated that glibenclamide AUC(0-infinity) was significantly higher (1.5-fold) and subsequently CL/F was significantly lower (40%) in CYP2C9 * 1/ * 3 subjects than those in * 1/ * 1 subjects (P < 0.01). After a single oral dose of 8 mg lornoxicam, C(max) was (1.54 +/- 0.24) mg x L(-1) in CYP2C9 * 1/ * 3 subjects and (1.19 +/- 0.37) mg x L(-1) in * 1/ * 1 subjects. AUC(o-infinity were (14.9 +/- 2.2) vs (6.92 +/- 1.48) mg x h x L(-1) (in * 1/ *3 vs * 1/ * 1 subjects), and CL/F were (9.1 +/- 1.2) vs (20.1 +/- 4.6) mL x min(-1), respectively. Statistic analysis results indicated that lornoxicam AUC(0-infinity) was significantly higher (2. 2-fold) and subsequently CL/F was significantly lower (55% ) in CYP2C9 * 1/ * 3 subjects than those in * 1/ * 1 subjects (P < 0.001)., Conclusion: CYP2C9 * 3 greatly affects both the pharmacokinetic profiles of glibenclamide and lornoxicam. The elimination of these drugs significantly decreased in subjects with CYP2C9 * 1/ * 3 genotype, especially lornoxicam.