Liver injury in paraquat poisoning: A retrospective cohort study.

BACKGROUND AND AIMS: Liver injury is one of the common complications of paraquat (PQ) poisoning, but whether the degree of liver injury is related to patient prognosis is still controversial. This study aimed to investigate whether liver injury was a risk factor for death in PQ-poisoned patients. METHODS: We conducted a retrospective cohort study of PQ-poisoned patients from the past 10 years (2011-2020) from a large tertiary academic medical centre in China. PQ-poisoned patients were divided into a normal liver function group (n = 580) and a liver injury group (n = 60). Propensity score matching (PSM) analysis was then performed. RESULTS: A total of 640 patients with PQ poisoning were included in this study. To reduce the impact of bias, dose of PQ, urinary PQ concentration and time from poisoning to hospital admission were matched between the two groups. A 3:1 PSM analysis was performed, ultimately including 240 patients. Compared with the normal liver function group, patients in the liver injury group were older, had a higher R value ([ALT/ULN]/[ALP/ULN]) (p < .001) and had a higher mortality rate. Cox regression analysis showed that there was no significant association between alanine aminotransferase, alkaline phosphatase, total bilirubin levels and hazard of death, but age, PQ dose, creatine kinase isoenzyme, creatine kinase, white blood cell count, neutrophil percentage and lymphocyte percentage were associated with mortality in patients with PQ poisoning. CONCLUSIONS: The occurrence of liver injury within 48 h after PQ poisoning was a risk factor for mortality, and such liver injury was likely of a hepatocellular nature. Age, PQ dose, creatine kinase isoenzyme and white blood cell count were positively correlated with mortality, while creatine kinase, percentage of neutrophils and lymphocytes were inversely correlated.

2-Methoxyestradiol ameliorates paraquat-induced pulmonary fibrosis by inhibiting the TGF-ß1/Smad2/3 signaling pathway.

Paraquat (PQ) is a highly effective and highly toxic herbicide that is highly toxic to both humans and animals. Pulmonary fibrosis is the primary cause of fatality in patients with PQ poisoning, there is no effective drug treatment yet. 2-Methoxyestradiol (2ME) is a natural metabolite of estradiol with anti-tumor, anti-angiogenesis, and anti-proliferative effects. Whether 2ME has the potential to inhibit pulmonary fibrosis induced by PQ is unclear. This study aims to investigate the potential effects and mechanism of 2ME on PQ-induced pulmonary fibrosis. C57BL/6 mice and A549 cells were exposed to PQ to establish pulmonary fibrosis model. In vivo, Hematoxylin and eosin (H&E) staining was utilized to assess the pathological characteristics. Masson's trichrome staining was employed to evaluate the collagen deposition. Western blot and immunohistochemistry were conducted to determine the expressions of fibrosis markers. In vitro, the expressions of epithelial-mesenchymal transition (EMT) markers were detected using western blot and immunofluorescence to evaluated the potential inhibition of PQ-induced EMT by 2ME. And proteins associated with the TGF-ß1/Smad2/3 signaling pathway were measured by western blot in vivo and in vitro. The result found that 2ME can ameliorated PQ-induced pulmonary fibrosis and inhibit the activation of TGF-ß1/Smad2/3 signaling pathway. These findings suggest that 2ME may serve as a potential therapeutic agent for treating PQ-induced pulmonary fibrosis.

Circumdatin-Aspyrone Conjugates from the Coral-Associated Aspergillus ochraceus LCJ11-102.

Ochrazepines A-D (1-4), four new conjugates dimerized from 2-hydroxycircumdatin C (5) and aspyrone (6) by a nucleophilic addition to epoxide, were isolated from the fermentation broth of the coral-associated Aspergillus ochraceus strain LCJ11-102. Their structures including absolute configurations were determined based on spectroscopic analysis and chemical methods. Compounds 1-4 were also obtained by the semisynthesis from a nucleophilic addition of 2-hydroxycircumdatin C (5) to aspyrone (6). New compound 1 exhibited cytotoxic activity against 10 human cancer cell lines while new compounds 2 and 4 selectively inhibited U251 (human glioblastoma cell line) and compound 3 was active against A673 (human rhabdomyoma cell line), U87 (human glioblastoma cell line), and Hep3B (human liver cancer cell line) with IC50 (half maximal inhibitory concentration) values of 2.5-11.3 µM among 26 tested human cancer cell lines.

Azaphilones from the Marine Sponge-Derived Fungus Penicillium sclerotiorum OUCMDZ-3839.

Four new azaphilones, sclerotiorins A-D (1-4), as well as the dimeric sclerotiorin E (5) of which we first determined its absolute configuration, and 12 known analogues (5-16) were isolated from the fermentation broth of Penicillium sclerotiorum OUCMDZ-3839 associated with a marine sponge Paratetilla sp.. The new structures, including absolute configurations, were elucidated by spectroscopic analyses, optical rotation, ECD spectra, X-ray single-crystal diffraction, and chemical transformations. Compounds 11 and 14 displayed significant inhibitory activity against α-glycosidase, with IC50 values of 17.3 and 166.1 µM, respectively. In addition, compounds 5, 7, 10, 12-14, and 16 showed moderate bioactivity against H1N1 virus.

Enhancing water quality and ecosystems of reclaimed water-replenished river: A case study of Dongsha River, Beijing, China.

The use of reclaimed water for urban river replenishment has raised concerns regarding its impact on water quality and aquatic ecosystems. This study aims to reveal the improvements seen in an urban river undergoing a practical water eco-remediation after being replenished with reclaimed water. A one-year monitoring of water quality, phytoplankton, and zooplankton was carried out in Dongsha River undergoing eco-remediation in Beijing, China. The results showed that compared to the unrestored river, the concentrations of COD, NH4+-N, TP, and TN decreased by 28.22 ± 7.88 %, 40.24 ± 11.77 %, 44.17 ± 17.29 %, and 28.66 ± 10.39 % in the restoration project area, respectively. The concentration of Chlorophyll-a in the restoration area was maintained below 40 µg/L. During summer, when algal growth is vigorous, the density of Cyanophyta in the unrestored river decreased from 46.84 × 104cells/L to 16.32 × 104cells/L in the restored area, while that of Chlorophyta decreased from 41.61 × 104cells/L to 11.87 × 104cells/L, a reduction of 65.16 % and 71.47 %, respectively. The dominant phytoplankton species were replaced with Bacillariophyta, such as Synedra sp. and Nitzschia sp., indicating that the restoration of aquatic plants reduces the risk of Cyanophyta blooms. Zooplankton species also changed in the restoration area, especially during summer. The density of pollution-tolerant Rotifer and Protozoa decreased by 31.06 % and 27.22 %, while the density of clean water indicating Cladocera increased by 101.19 %. We further calculated the diversity and evenness index of phytoplankton and zooplankton within and outside the restoration area. The results showed that the Shannon-Weaver index for phytoplankton and zooplankton in the restoration area was 2.1 and 1.91, which was higher than those in the river (1.84 and 1.82). This further confirmed that aquatic plant restoration has positive effects. This study can provide a practical reference and theoretical basis for the implementation of water ecological restoration projects in other reclaimed water rivers in China.

Genome-wide identification of CXE and PuCXE15 functions in the catabolism of volatile ester in 'Nanguo' pear fruit.

Volatile esters are the main aromatic components that affect consumer sensory preferences. Aroma is a crucial characteristic of the 'Nanguo' pear (Pyrus ussriensis Maxim). Carboxylesterases (CXEs) are positively correlated with the catabolism of volatile esters in peaches; however, the mechanism of action of CXE family members in 'Nanguo' pear is poorly understood. In this study, 40 PuCXEs were identified in the 'Nanguo' pear and assigned into seven groups. In addition, we found that most PuCXEs were relatively conserved and contained cytoplasmic proteins. This hypothesis was supported by phylogenetic analysis, investigation of conserved domains and gene structures, and prediction of subcellular localization. Based on the content of volatile esters and expression levels of PuCXEs analysis, four PuCXEs, including PuCXE7, PuCXE15, PuCXE20, and PuCXE25, had a significant negative correlation with volatile ester accumulation. Particularly, the correlation of PuCXE15 far exceeded that of the other PuCXEs. The results of the transient expression assay showed that PuCXE15 promoted the degradation of ester in vivo. Subcellular localization experiment revealed that PuCXE15 is located in the plasma membrane and nucleus. These results show that PuCXE15 functions in the catabolism of volatile ester in 'Nanguo' pear fruit, and provides a foundation for enhancing aroma quality by artificial control in pear.

Lactobacillus rhamnosus GG Regulates Host IFN-I Through the RIG-I Signalling Pathway to Inhibit Herpes Simplex Virus Type 2 Infection.

Numerous recent studies have demonstrated that the commensal microbiota plays an important role in host immunity against infections. During the infection process, viruses can exhibit substantial and close interactions with the commensal microbiota. However, the associated mechanism remains largely unknown. Therefore, in this study, we explored the specific mechanisms by which the commensal microbiota modulates host immunity against viral infections. We found that the expression levels of type I interferon (IFN-I) and antiviral priming were significantly downregulated following the depletion of the commensal microbiota due to treatment with broad-spectrum antibiotics (ABX). In addition, we confirmed a unique molecular mechanism underlying the induction of IFN-I mediated by the commensal microbiota. In vivo and in vitro experiments confirmed that Lactobacillus rhamnosus GG (LGG) can suppress herpes simplex virus type 2 (HSV-2) infection by inducing IFN-I expression via the retinoic acid-inducible gene-I (RIG-I) signalling pathway. Therefore, the commensal microbiota-induced production of IFN-I provides a potential therapeutic approach to combat viral infections. Altogether, understanding the complexity and the molecular aspects linking the commensal microbiota to health will help provide the basis for novel therapies already being developed.

Chirality from D-guanosine to L-guanosine shapes a stable gel for three-dimensional cell culture.

It is proved that L-guanosine (L-G) as an enantiomer of D-guanosine (D-G) forms more stable gels than D-G, suggesting that alteration of chirality may be a new strategy for improving the lifetime stability of supramolecular hydrogels. Experiments for three-dimensional cell culture reveal that the L-G gel is a candidate for the extracellular matrix.

Recurrent oral erythema multiforme: a case series report and review of the literature.

Recurrent oral erythema multiforme (ROEM) is now accepted as a less-recognized subtype of erythema multiforme (EM). The diagnosis is based on the exclusion of other similar diseases; typical clinical features, such as mutiple recurrent irregular painful erosions of oral mucosa without skin lesions, and, frequently, evidence of past herpes simplex virus infection. Here, we report 3 cases diagnosed as ROEM according to the 3 characteristics mentioned before. In addition, the article reviews the epidemiology, etiology, clinical manifestations, basis for diagnosis, and treatment of ROEM and highlights the need for prophylaxis.

Cytotoxic and Optically Active Pyrisulfoxins From the Endophytic Streptomyces albolongus EA12432.

R-Pyrisulfoxin C (1), S-pyrisulfoxin D [(+)-2], R-pyrisulfoxin D [(-)-2], pyrisulfoxin E (13), S-pyrisulfoxin F [(+)-14], and R-pyrisulfoxin F [(-)-14], six new caerulomycin derivatives with a 2,2'-bipyridine skeleton, were obtained from the cultures of the endophytic Streptomyces albolongus EA12432 with Aconitum carmichaeli (Ranunculaceae). Additionally, the racemic pyrisulfoxins A [(±)-3] and B [(±)-4] were further purified as optically pure compounds and identified the configurations for the first time. The racemic pyrisulfoxin D [(±)-2] displayed significant cytotoxicity against a series of cancer cell lines with IC50 values ranging from 0.92 to 9.71 µM. Compounds 7, 8, and (±)-3 showed cytotoxicity against the HCT-116, HT-29, BXPC-3, P6C, and MCF-7 cell lines. Notably, compounds 7 and 8 have a strong inhibition both on the proliferation of human colon cancer cells HCT-116 and HT-29 with IC50 values ranging from 0.048 to 0.2 µM (doxorubicin, 0.21 and 0.16 µM), and compound 1 showed a selective inhibition on the proliferation of the gastric carcinoma cell lines, N87, with an IC50 value of 8.09 µM. Optically pure compounds R(-)-14 and S(+)-14 showed weak cytotoxicity against HCT-116 and MCF-7 cell lines with the IC50 values of 14.7 µM and 10.4 µM, respectively. Interestingly, compounds 1 and (±)-2 didn't show cytotoxic activity against two human normal cell lines, HEK-293F and L02, with IC50 values >100 µM.

Dual-functional guanosine-based hydrogel integrating localized delivery and anticancer activities for cancer therapy.

Supramolecular hydrogel delivery systems have attracted widely attention owing to incorporating various therapeutic agents in carriers to decrease unpredictable toxicities, improve curative efficacy, and protect drug bioactivity. Nonetheless, the dual-functional supramolecular hydrogel integrating localized delivery and antineoplastic activities in one system have rarely observed. In this study, we successfully developed a novel supramolecular hydrogel, isoguanosine-borate-guanosine (isoGBG), with reversibly and dynamic borate ester bonds formed via boric acids and diols derived from nature products guanosine and isoguanosine in one pot by following a simple procedure. Both in vivo and in vitro results demonstrated that the isoGBG hydrogel not only displays excellent stability, self-healing properties and biocompatibility, but also has highly anti-tumor activities through inducing tumor cell apoptosis and excellent inhibition effect of tumor recurrence. These findings suggested that isoGBG hydrogel can serve as a dual-function hydrogel system integrating drug carrier and anti-cancer compound in one system, which provided a promising strategy for the design of functional supramolecular hydrogel in the local management of cancer in the future.

Review of α-nucleosides: from discovery, synthesis to properties and potential applications.

Nucleic acids play an important role in the genetic process of organisms; nucleosides, the building block of nucleic acids, typically exist in nature in a ß configuration. As an anomer of ß-nucleoside, α-nucleoside is extremely rare in nature. Because of their unique and interesting properties such as high stability, specific parallel double-stranded structure and some other biochemical properties, α-nucleosides have attracted wide attention. Various methods including but not limited to the mercuri procedure, fusion reaction and Vorbrüggen glycosylation have been used to synthesize α-nucleosides and their derivatives. However, to the best of our knowledge, there is no review that has summarized these works. Therefore, we systematically review the discovery, synthesis, properties, and potential applications of α-nucleosides in this article and look to provide a reference for subsequent studies in the coming years.

New α-Pyridones with Quorum-Sensing Inhibitory Activity from Diversity-Enhanced Extracts of a Streptomyces sp. Derived from Marine Algae.

Four new α-pyrones (1-4) and eight known analogues (5-12) were identified from the secondary metabolites of Streptomyces sp. OUCMDZ-3436 derived from the marine green algae Enteromorpha prolifera. Seven new α-pyridones (14-20) were constructed by diversity-oriented synthesis, which has been an effective approach to expanding the chemical space of natural-product-like compounds. Compounds 16, 17, 19, and 20 were found to have inhibitory effect on the gene expression controlled by quorum sensing in Pseudomonas aeruginosa QSIS-lasI.

Silver ions blocking crystallization of guanosine-based hydrogel for potential antimicrobial applications.

In this work, the detailed crystallization process of 2'-deoxy-2'-fluoroguanosine (FGd) hydrogel has been studied using single crystal X-ray diffraction, variable-temperature nuclear magnetic resonance (VT-NMR), and scanning electron microscopy (SEM). Both solid and solution results indicated that the K+-mediated G-quartet structures were unstable and easily resulted in the breakdown of the hydrogel to form linear ribbon structures by forming mimic reverse Watson-Crick base pairs between the two faces with an intermolecular hydrogen-bond (N10H-O11). Accordingly, Ag+ was introduced to block the crystallization of FGd to form long lifetime stable supramolecular hydrogel (>6 months) and possible silver-ions-mediated base pair motifs were suggested via NMR, UV, and mass spectroscopy (MS) in combination with powder X-ray diffraction (PXRD) and circular dichroism spectroscopy (CD). Furthermore, FGdAg hydrogel exhibited low toxicity for normal oral keratinocyte cells (NOK-SI) and good antibacterial activities for Fusobacterium nucleatum in vitro.

Natural Products Research in China From 2015 to 2016.

This review covers the literature published by chemists from China during the 2015-2016 on natural products (NPs), with 1,985 citations referring to 6,944 new compounds isolated from marine or terrestrial microorganisms, plants, and animals. The emphasis is on 730 new compounds with a novel skeleton or/and significant bioactivity, together with their source organism and country of origin.

Developing a Self-Healing Supramolecular Nucleoside Hydrogel Based on Guanosine and Isoguanosine.

Recently, supramolecular hydrogels have attracted increasing interest owing to their tunable stability and inherent biocompatibility. However, only few studies have been reported in the literature on self-healing supramolecular nucleoside hydrogels, compared to self-healing polymer hydrogels. In this work, we successfully developed a self-healing supramolecular nucleoside hydrogel obtained by simply mixing equimolar amounts of guanosine (G) and isoguanosine (isoG) in the presence of K+ . The gelation properties have been studied systematically by comparing different alkali metal ions as well as mixtures with different ratios of G and isoG. To this end, rheological and phase diagram experiments demonstrated that the co-gel not only possessed good self-healing properties and short recovery time (only 20 seconds) but also could be formed at very low concentrations of K+ . Furthermore, nuclear magnetic resonance (NMR), powder X-ray diffraction (PXRD), and circular dichroism (CD) spectroscopy suggested that possible G2 isoG2 -quartet structures occurred in this self-healing supramolecular nucleoside hydrogel. This co-gel, to some extent, addressed the problem of isoguanosine gels for the applications in vivo, which showed the potential to be a new type of drug delivery system for biomedical applications in the future.