It has been confirmed that the triglyceride to high-density lipoprotein cholesterol ratio (THR) is associated with insulin resistance and metabolic syndrome. However, to the best of our knowledge, ...only a few studies with small sample sizes have investigated the relationship between THR and coronary artery disease (CAD). Therefore, we aimed to assess the correlation between the THR and long-term mortality in patients with CAD after undergoing percutaneous coronary intervention (PCI) in our study that enrolled a large number of patients.
A total of 3269 post-PCI patients with CAD were enrolled in the CORFCHD-ZZ study from January 2013 to December 2017. The mean follow-up time was 37.59 ± 22.24 months. Patients were divided into two groups according to their THR value: the lower group (THR < 2.84, n = 1232) and the higher group (THR ≥ 2.84, n = 2037). The primary endpoint was long-term mortality, including all-cause mortality (ACM) and cardiac mortality (CM). The secondary endpoints were major adverse cardiac events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs).
In our study, ACM occurred in 124 patients: 30 (2.4%) in the lower group and 94 (4.6%) in the higher group (P = 0.002). MACEs occurred in 362 patients: 111 (9.0%) in the lower group and 251 (12.3%) in the higher group (P = 0.003). The number of MACCEs was 482: 152 (12.3%) in the lower group and 320 (15.7%) in the higher group (P = 0.008). Heart failure occurred in 514 patients: 89 (7.2%) in the lower group and 425 (20.9%) in the higher group (P < 0.001). Kaplan-Meier analyses showed that elevated THR was significantly related to long-term ACM (log-rank, P = 0.044) and the occurrence of heart failure (log-rank, P < 0.001). Multivariate Cox regression analyses showed that the THR was an independent predictor of long-term ACM (adjusted HR = 2.042 1.264-3.300, P = 0.004) and heart failure (adjusted HR = 1.700 1.347-2.147, P < 0.001).
An increased THR is an independent predictor of long-term ACM and heart failure in post-PCI patients with CAD.
Mushrooms are consumed worldwide as they constitute a part of traditional cuisine culture in many countries. However, chromium (Cr) accumulation in mushrooms may constitute a potential pathway for ...its chronical exposure to humans. In this work, the Cr contents, distribution and bioaccessibility in 140 cultivated mushrooms from 14 species in 10 top-producing provinces in China were examined. Total Cr contents were 0.09–4.71 mg·kg−1 dw (mean 0.74 mg kg−1), with 59% exceeding the 0.5 mg kg−1standard. Additionally, less Cr was accumulated in the caps than stipes, with Cr ratio in caps/stipes being 0.28–2.6, averaging 0.91. Based on the Solubility Bioaccessibility Research Consortium (SBRC) assay, the mean Cr bioaccessibility in the mushrooms was 24.8% and 50.1% in the gastric phase (GP) and intestinal phase (IP). However, samples from Guizhou show the lowest Cr bioaccessibility at 12.5% in GP and 24.8% in IP. Further, a negative correlation between total Cr contents and Cr bioaccessibility suggests that Cr bioaccessibility is critical for accurate assessment of Cr exposure. In addition, drying mushrooms increased their bioaccessibility in the gastric phase. This study shows a high Cr exceeding rate of cultivated mushrooms, which may indicate a potential exposure risk, with Cr contents and bioaccessibility showing species and regional variation.
Display omitted
•140 mushrooms were from 14 species in 10 top-producing provinces in China.•Total Cr contents were 0.09–4.71 mg·kg−1, with 59% exceeding 0.5 mg kg−1 standard.•More Cr was concentrated in the stipes than caps (1.11 vs. 0.92 mg·kg−1).•Cr bioaccessibility negatively correlated with Cr contents via SBRC assay.•Greater Cr bioaccessibility in the gastric phase in dried mushrooms than in fresh samples.
Theranostic prodrug was highly desirable for precise diagnosis and anti-cancer therapy to decrease side effects. However, it is difficult to conjugate chemo-drug and molecular probe for combined ...therapy due to the complex pharmacokinetics of different molecules. Here, a novel anticancer theranostic prodrug (BTMP-SS-PTX) had been designed and synthesized by conjugating paclitaxel (PTX) with 2-(benzodthiazol-2-yl)-4-methoxyphenol (BTMP) through a disulphide (-S-S-) linkage, which was redox-sensitive to the high concentration of glutathione in tumors. Upon activation with glutathione in weakly acid media, the BTMP-SS-PTX can be dissociated to release free PTX and visible BTMP, which realized the visual tracking of free drug. The cytotoxicity study demonstrated that soluble prodrug BTMP-SS-PTX displayed more outstanding anticancer activity in HepG2, MCF-7 and HeLa cells, lower toxicity to non-cancer cells (293 T) than free drugs. Furthermore, BTMP-SS-PTX was still able to induce apoptosis of HeLa cells and significantly inhibited tumor growth in HeLa-xenograft mouse model. On the basis of these findings, BTMP-SS-PTX could play a potential role in cancer diagnosis and therapy.
Proposed route for the traceable activation of prodrug BTMP-SS-PTX. Display omitted
•The prodrug BTMP-SS-PTX and its control substance BTMP-CC-PTX were synthesized.•More outstanding anticancer activity in Hep G2, MCF-7 and HeLa cells, lower toxicity to 293T cells than free drugs.•BTMP-SS-PTX played a potential role in cancer diagnosis and therapy in vivo.
Background
Previous evidences have been proved that age, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and ejection fraction are tightly associated with the long-term outcomes in patients ...suffered from coronary artery disease (CAD). Therefore, the present study aimed to assess the prognosis value of age, NT-proBNP, and ejection fraction (ABEF) score in CAD patients who underwent percutaneous coronary intervention (PCI).
Methods
Observational cohort methodology was used in this study which enrolled totally 3561 patients. And the patients were followed up regularly for 37.59 ± 22.24 months. Patients were classed into three groups based on the tertiles of ABEF sore: first tertile (<5.06, n = 831), second tertile (5.06-6.25, n = 839), and third tertile (≥ 6.25, n = 834). The ABEF score was calculated as follows: age (years)/ejection fraction (%) + NT-proBNP (NT-proBNP<177pg/mL was 1, 177≤NT-proBNP≥524pg/mL was 2 and NT-proBNP > 524pg/mL is 3). The association between ABEF score and adverse prognosis, including all-cause death (ACD), cardiac death (CD), major adverse cardiovascular events (MACEs) and major adverse cardiac and cerebrovascular events (MACCEs), in patients who underwent PCI was analyzed.
Results
According to the risk category of ABEF score, the incidences of ACD (P < .001), CD (P < .001) and MACCEs (P = .021) among the three groups showed significant differences. Multivariate Cox regression analysis suggested that the respective risks of ACD and CD were increased 3.013 folds (hazard risk HR = 4.013 95% confidence interval CI: 1.922-8.378, P < .001) and 4.922 folds (HR = 5.922 95% CI: 2.253-15.566, P < .001) in the third tertile compared with those in the first tertile. Kaplan-Meier survival analyses showed that the cumulative risks of ACD,CD and MACCEs in patients with the high ABEF score tended to increase.
Conclusion
The present study indicated ABEF score was a novel biomarker suitable for predicting adverse prognosis in patients after PCI, which may be used for early recognition and risk stratification.
A new class of potent liver injury protective compounds, phychetins A−D (1−4) featuring an unique 6/6/5/6/5 pentacyclic framework, were isolated and structurally characterized from a Chinese ...medicinal plant Phyllanthus franchetianus. Compounds 2−4 are three pairs of enantiomers that were initially obtained in a racemic manner, and were further separated by chiral HPLC preparation. Compounds 1−4 were proposed to be originated biosynthetically from a coexisting lignan via an intramolecular Friedel–Crafts reaction as the key step. A bioinspired total synthesis strategy was thus designated, and allowed the effective syntheses of compounds 2−4 in high yields. Some of compounds exhibited significant anti-inflammatory activities in vitro via suppressing the production of pro-inflammatory cytokine IL-1β. Notably, compound 4, the most active enantiomeric pair in vitro, displayed prominent potent protecting activity against liver injury at a low dose of 3 mg/kg in mice, which could serve as a promising lead for the development of acute liver injury therapeutic agent.
A new class of liver injury protective lignans was discovered from a medicinal plant and chemically synthesized. The most potent 4 exhibits anti-inflammatory and liver protective effects by interfering HIF-1α‒IL-1β axis. Display omitted
The essence of primary ovarian insufficiency (POI) is the premature exhaustion of primordial follicles in the follicle pool, which is caused by the excessive premature activation of primordial ...follicles after birth. Bisphenol A (BPA) exposure promotes the transition of primordial follicles to primary follicles, thus the number of primordial follicles in the primordial follicle pool decreases significantly. However, the molecular mechanisms underlying abnormal follicle activation are poorly understood. Phosphatase and tensin homologue (PTEN) signal system is a negative regulator of follicle activation, which is called the brake of follicle activation. Besides, BPA induces Michigan Cancer Foundation-7 breast cancer cells proliferation by dysregulating PTEN/serine/threonine kinase/p53 axis. Whether BPA initiates the excessive premature activation of primordial follicles in the mouse ovaries via PTEN signaling pathway is unclear. In this study, we treated 6-week-old female CD-1 mice with different concentrations of BPA to study the effect of BPA on follicular activation and development in vivo, as well as the role of PTEN signaling in this process. We observed that BPA in concentrations from 1 μg/kg to 10 mg/kg groups downregulated PTEN expression and initiated excessive premature activation of primordial follicles in the mouse ovaries, and this effect was partly reversible by PTEN overexpression. Our results improve the understanding of both the effect of BPA in occurrence of POI and molecular mechanisms underlying initiation of primordial follicle pool activation, thus providing insight for POI treatment and theoretical basis for reducing the risk of POI.
The clinical features, survival outcomes and patterns of treatment failure of advanced non-small cell lung cancer (NSCLC) patients harboring distinct subtypes of EGFR mutations and receiving ...first-line EGFR tyrosine kinases inhibitor (TKIs) are not fully understood.
Consecutive metastatic EGFR-mutant NSCLC patients receiving first-line EGFR-TKIs from October 2010 to March 2020 were enrolled and classified into two main groups based on the EGFR mutation subtypes: common mutation (L858R or exon 19 deletion), uncommon mutation (other EGFR mutations).
Of the 1081 patients included, 74 (6.8%) harbored uncommon mutations. The baseline characteristics were generally balanced between the two groups, except that bone metastasis developed less frequently in patients with uncommon mutations (p = 0.02). No significant difference of survival outcomes was found between the two groups, except that among patients with baseline brain metastasis, the intracranial time to progression was significantly shorter in patients with uncommon mutations. Nine of the 17 patients with de novo T790M mutation received Osimertinib, whose overall survival tended to be longer than the remaining 8 patients without Osimertinib treatment (p = 0.08). The patterns of treatment failure were generally consistent between the two groups, except which patients with uncommon mutations had a higher risk developing progressive disease in the brain.
First-line EGFR-TKIs seemed to be less effective in controlling and preventing brain metastasis in patients with uncommon EGFR mutations and Osimertinib was associated with promising efficacy in patients with de novo T790M mutation, which warranted further validation.
Acetate is a major intermediate in the anaerobic digestion of organic waste to produce CH
. In methanogenic systems, acetate degradation is carried out by either acetoclastic methanogenesis or ...syntrophic degradation by acetate oxidizers and hydrogenotrophic methanogens. Due to challenges in the isolation of syntrophic acetate-oxidizing bacteria (SAOB), the diversity and metabolism of SAOB and the mechanisms of their interactions with methanogenic partners are not fully characterized. In this study, the
activity and metabolic characteristics of potential SAOB and their interactions with methanogens were elucidated through metagenomics and metatranscriptomics. In addition to the reported SAOB classified in the genera
,
, and
, we identified a number of potential SAOB that are affiliated with
, Thermoanaerobacteraceae, Anaerolineae, and Gemmatimonadetes. The potential SAOB possessing the glycine-mediated acetate oxidation pathway dominates SAOB communities. Moreover, formate appeared to be the main product of the acetate degradation by the most active potential SAOB. We identified the methanogen partner of these potential SAOB in the acetate-fed chemostat as
. The dominated potential SAOB in each chemostat had similar metabolic characteristics, even though they were in different fatty-acid-fed chemostats. These novel syntrophic lineages are prevalent and may play critical roles in thermophilic methanogenic reactors. This study expands our understanding of the phylogenetic diversity and
biological functions of uncultured syntrophic acetate degraders and presents novel insights into how they interact with methanogens.IMPORTANCECombining reactor operation with omics provides insights into novel uncultured syntrophic acetate degraders and how they perform in thermophilic anaerobic digesters. This improves our understanding of syntrophic acetate degradation and contributes to the background knowledge necessary to better control and optimize anaerobic digestion processes.
Ammonium-free deliming technology is becoming popular in the leather industry because conventional deliming with ammonium salts results in high ammonia-nitrogen (NH3–N) concentration of tannery ...wastewater. However, existing ammonium-free deliming agents have inadequate buffering capacity and slow penetration rate in limed pelt. In this study, glycine with pKa of –NH3+ = 9.6 was used to delime limed cattle hides. Glycine penetrated the entire limed pelt in only 10 min because a buffer of pH 8.0–9.5 was rapidly formed by the reaction between glycine and the alkali in pelt, thereby leading to a negatively charged pelt surface (isoelectric point 6.3). The appearance and physical properties of the crust leather produced by glycine deliming process were very similar to that produced by ammonium sulfate deliming procedure. The concentration of NH3–N in glycine deliming effluent was dramatically reduced by 99%. Moreover, glycine deliming benefitted the biological treatment of mixed tannery wastewater because of the introduction of additional carbon source to the tannery wastewater. This addition brought the ratio of total organic carbon (TOC) to total nitrogen (TN) in the wastewater much closer to the proper ratio of 10:1 for aerobic biological treatment. After aerobic biological treatment for 24 h, the concentrations of NH3–N, TOC, and TN in the treated tannery wastewater using glycine deliming were reduced by 99%, 20%, and 53%, respectively, compared with those using ammonium sulfate deliming.
Display omitted
•A clean deliming technology was developed by using glycine.•Glycine penetrated limed pelt as quickly as ammonium sulfate.•Glycine and alkali in limed pelt formed a buffer, maintaining the float pH around 9.•Glycine eliminated ammonia-nitrogen pollution in the deliming effluent.•Deliming with glycine benefitted the biological treatment of tannery wastewater.
PDF
