Nonlinear Relationship Between Low Density Lipoprotein and the Probability of Diabetic Macular Edema.

Purpose: Previous studies simply linearized the relationship between low density lipoprotein (LDL) and diabetic macular edema's (DME) probability, ignoring the possibility of a nonlinear relationship between them. We aimed to investigate the nonlinear relationship between LDL and DME probability in patients with type 2 diabetes mellitus (T2DM). Patients and methods: The study recruited 431 T2DM patients who attended Guangdong Provincial People's Hospital from December 2017 to November 2018. A multivariate logistic regression model was conducted to evaluate the association between LDL and DME probability. The nonlinear relationship was identified by generalized additive model. Subgroup analyses were performed to assess the consistency of the association in different subgroups. Results: LDL was positively associated with DME probability (OR=1.60, 95% CI: 1.10~2.34, P=0.0145) after adjusting for covariates. A nonlinear relationship between LDL and DME probability was discovered, with an inflection point for LDL around 4.85 mmol/L (95% CI: 4.18~4.93, P=0.037). The effect sizes and the confidence intervals on the left and right sides of inflection point were 2.17 (1.31 to 3.58) and 0.26 (0.04 to 1.77), respectively. Subgroup analyses revealed other variables had no effect on the association between them. Conclusion: Our finding suggested LDL was positively correlated with DME probability in T2DM patients. And the relationship between LDL and DME probability was nonlinear. Our findings need to be confirmed by further causal researches.

(+)- and (-)-Tedanine, a pair of new enantiomeric indolone alkaloids from the marine sponge Tedania sp.

(+)- and (-)-Tedanine [(+)-1 and (-)-1], a pair of new enantiomeric indolone alkaloids, along with nine compounds (2-10) were isolated from the marine sponge Tedania sp. The structures of (+)-1 and (-)-1 including absolute configurations were determined by spectroscopic analysis and quantum chemical calculation. Compounds (+)-1 and (-)-1 were the first examples of indolone alkaloids isolated from this genus. In addition, the cytotoxic and antibacterial activities of these compounds were also evaluated.

Two New Pairs of Enantiomeric Butenolides from the Marine Sponge Suberties sp.

Two new pairs of enantiomeric butenolides, (+)- and (-)-suberiteslide A, (+)- and (-)-subertieslide B had been obtained from the marine sponge Suberties sp. The structures with absolute configurations of these compounds were unequivocally determined by spectroscopic analyses and ECD (Electronic Circular Dichroism) method. It was the first separation of butenolides from the marine sponges of genus Suberites. Additionally, the anti-inflammatory, antibacterial and cytotoxic activities of these compounds were evaluated. The result indicated that only (-)-subertieslide B showed weak anti-inflammatory activity with the IC50 value of 40.8 µM.

Controllable Regulation of Ag2 S Quantum-Dot-Mediated Protein Nanoassemblies for Imaging-Guided Synergistic PDT/PTT/Chemotherapy against Hypoxic Tumor.

The combination of phototherapy and chemotherapy holds great potential for cancer treatment, while hypoxia in tumor as well as unexpected drug release largely restricts anticancer therapy. Inspired by the natural intelligence, herein, for the first time, a "bottom-up" protein self-assembly strategy mediated by near-infrared (NIR) quantum dots (QDs) with multicharged electrostatic interactions is presented to develop a tumor microenvironment (TME)-responsive theranostic nanoplatform for imaging-guided synergistic photodynamic therapy (PDT)/photothermal therapy (PTT)/chemotherapy. Catalase (CAT) possesses diverse surface charge distribution under different pH conditions. After modification by chlorin e6 (Ce6), the formulated CAT-Ce6 with patchy negative charges can be assembled with NIR Ag2 S QDs by regulating their electrostatic interactions, allowing for effective incorporation of specific anticancer drug oxaliplatin (Oxa). Such Ag2 S@CAT-Ce6@Oxa nanosystems are able to visualize nanoparticle (NP) accumulation to guide subsequent phototherapy, together with significant alleviation of tumor hypoxia to further enhance PDT. Moreover, the acidic TME triggers controllable disassembly through weakening the CAT surface charge to disrupt electrostatic interactions, allowing for sustained drug release. Both in vitro and in vivo results demonstrate remarkable inhibition of colorectal tumor growth with a synergistic effect. Overall, this multicharged electrostatic protein self-assembly strategy provides a versatile platform for realizing TME-specific theranostics with high efficiency and safety, promising for clinical translation.

Lentinuses A-B, two alkaloids from the marine-derived fungus Lentinus sajor-caju with potent anti-pulmonary fibrosis activity.

By adding natural amino acids into the medium as sole nitrogen source, twenty-four compounds, including two new alkaloids lentinuses A-B (1-2) with a rare oxazinone core in marine natural products, one new natural product 3-acetamido-4-phenylfurazan (3), 9ß-ergosterol (22) were firstly discovered from a marine fungus, and twenty known compounds (4-21, 23-24) were isolated from the marine-derived fungus Lentinus sajor-caju. The chemical structures of all these compounds were elucidated by HRMS, NMR spectroscopy and X-ray diffraction. Compounds 1-24 were evaluated for their inhibitory activity against TGF-ß1-induced collagen accumulation in human fetal lung fibroblasts (HFL1). Compounds 2, 3, 12, 22, and 23 showed potent activity against TGF-ß1-induced collagen accumulation and low toxicity to HFL1 cells. The binding mode of lentinus B (2) with TGF-ß1 receptor was then performed by using Schrödinger software, and the result showed that lentinus B possesses a strong binding force such as hydrogen bonding and hydrophobic interactions to the protein, which may provide a theoretical basis to design more potent anti-fibrotic drugs in the future.

Identification of a Novel IncHI1B Plasmid in MDR Klebsiella pneumoniae 200 from Swine in China.

Multidrug-resistant (MDR) Klebsiella pneumoniae poses a seriously threat to public health. The aim of this study was to better understand the genetic structure of its plasmids and chromosomes. The whole-genome sequence of K. pneumoniae 200 isolated from the liver of a swine with diarrhea in China was determined using PacBio RS II and Illumina MiSeq sequencing. The complete sequences of the chromosomal DNA and the plasmids were analyzed for the presence of resistance genes. The phylogenetic trees revealed that K. pneumoniae 200 displayed the closest relationship to a human-associated K. pneumoniae strain from Thailand. K. pneumoniae 200 contained two plasmids, pYhe2001 and pYhe2002, belonging to the incompatibility groups IncH-HI1B and IncF-FIA. The plasmid pYhe2001 was a novel plasmid containing four types of heavy metal resistance genes and a novel Tn6897 transposon flanked by two copies of IS26 at both ends. Mixed plasmids could be transferred from K. pneumoniae 200 to Escherichia coli DH5α through transformation together. This study reported the first time a novel plasmid pYhe2001 from swine origin K. pneumoniae 200, suggesting that the plasmids may act as reservoirs for various antimicrobial resistance genes and transport multiple resistance genes in K. pneumoniae of both animal and human origin.

High-throughput sequencing of 16S rRNA gene analysis reveals novel taxonomic diversity among vaginal microbiota in healthy and affected sows with endometritis.

In sows afflicted with endometritis, vaginal microbiota can provide valuable information regarding bacterial community diversity. Our aim was to compare the vaginal microbiotas between endometritis and healthy sows and characterize the vaginal microbiota of endometritis sows using high-throughput sequencing of the 16S rRNA gene. Vaginal swabs were collected from healthy (Healthy_A, n = 10; Healthy_B, n = 10) and diseased (Endometritis_A, n = 10; Endometritis_B, n = 10) sows from two swine farms located in Guangdong and Yunnan province, in Southern China. The results of V3-V4 region of the 16S rRNA gene showed that Corynebacterium_1, Clostridium_sensu_stricto_1, Porphyromonas, Anaerococcus, Streptococcus, and Bacteroides comprised the core microbiota in all healthy sows. Two type of endometritis microbiota patterns were presented in two farms: the first comprised mostly of Burkholderia in farm A and the second comprised of Parvimonas in farm B. In farm A, the percentages of Burkholderia, Serratia, and Enterobacter were higher in the endometritis group, while only Parvimonas was significantly increased in the endometritis group in farm B (p < 0.05). Interestingly, the genus Burkholderia and Serratia were found only in the endometritis sows from farm A. Burkholderia was the most dominant genus found in endometritis sows and was confirmed by full-length 16S rRNA analysis using PacBio sequencing.

Characterization, Antioxidant and Antitumor Activities of Oligosaccharides Isolated from Evodia lepta (Spreng) Merr. by Different Extraction Methods.

Evodia lepta (E. lepta) is a traditional Chinese herbal medicine with various biological activities. One of the active components of this widely used medicinal plant is believed to be an oligosaccharide. The extraction yields, structural characteristics, antioxidant, and antitumor activities of four oligosaccharide extracts obtained by hot water extraction (HEO), ultrasound-assisted extraction (UEO), enzyme-assisted (EEO), and microwave-assisted extraction (MEO) were investigated. Matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS), X-ray diffraction (XRD), and Scanning electron microscopy (SEM) results indicated that the extraction methods had a difference on the molecular mass distribution, structure, and morphology of the EOs. In addition, HEO and MEO showed strong antioxidant activities, which might be related to their uronic acid and protein contents. More interestingly, MEO was more active toward MDA-MB-231 cells compared to other cells, and cell growth inhibition was proposed to occur through apoptosis. Overall, microwave-assisted extraction is a promising technique for the extraction of high quality EO.

A novel alkaloid glycoside isolated from Atalantia buxifolia.

From the dried root and rhizomes of Atalantia buxifolia afford 11 compounds, one new compound 1 and ten known compounds 2-11 were isolated and identified. The novel compound 1 was alkaloid glycoside. Its mother nuclear was the acridone, which was relatively rare. The structure of compound 1 was established identified by spectrum and elucidated as ß-D-Glu-4,5-dimethoxy-1,6-dihydroxy-10-methyl-acridone. The compound 1 enriched the compound library and laid the material foundation for the subsequent study of pharmacological activities.