Bioaugmentation has the potential to enhance the ability of ecological technology to treat sulfonamide-containing wastewater, but the low viability of the exogenous degraders limits their practical ...application. Understanding the mechanism is important to enhance and optimize performance of the bioaugmentation, which requires a multifaceted analysis of the microbial communities. Here, DNA-stable isotope probing (DNA-SIP) and metagenomic analysis were conducted to decipher the bioaugmentation mechanisms in stabilization pond sediment microcosms inoculated with sulfamethoxazole (SMX)-degrading bacteria (Pseudomonas sp. M2 or Paenarthrobacter sp. R1).
The bioaugmentation with both strains M2 and R1, especially strain R1, significantly improved the biodegradation rate of SMX, and its biodegradation capacity was sustainable within a certain cycle (subjected to three repeated SMX additions). The removal strategy using exogenous degrading bacteria also significantly abated the accumulation and transmission risk of antibiotic resistance genes (ARGs). Strain M2 inoculation significantly lowered bacterial diversity and altered the sediment bacterial community, while strain R1 inoculation had a slight effect on the bacterial community and was closely associated with indigenous microorganisms. Paenarthrobacter was identified as the primary SMX-assimilating bacteria in both bioaugmentation systems based on DNA-SIP analysis. Combining genomic information with pure culture evidence, strain R1 enhanced SMX removal by directly participating in SMX degradation, while strain M2 did it by both participating in SMX degradation and stimulating SMX-degrading activity of indigenous microorganisms (Paenarthrobacter) in the community.
Our findings demonstrate that bioaugmentation using SMX-degrading bacteria was a feasible strategy for SMX clean-up in terms of the degradation efficiency of SMX, the risk of ARG transmission, as well as the impact on the bacterial community, and the advantage of bioaugmentation with Paenarthrobacter sp. R1 was also highlighted. Video Abstract.
Aim
To explore whether and to what extent, nurse–patient assessment differences mediate the association between nurse‐to‐patient ratios and readiness for hospital discharge, and examine whether ...nurse–patient characteristics moderate the indirect and/or direct effect of mediation model.
Design
A cross‐sectional study was carried out from March 2021 to December 2022.
Methods
A total of 523 pairs of gastrointestinal cancer patients with PICC and their nurses were recruited. All the participants were invited to complete the general information questionnaire and the Readiness for Hospital Discharge Scale. Outcome measure was patient‐reported readiness for hospital discharge. This study was reported according to the STROBE checklist.
Results
The patients reported a low level of readiness for hospital discharge. Nurse–patient assessment differences were positively associated with nurse‐to‐patient ratios but negatively associated with readiness for hospital discharge. Furthermore, nurse–patient assessment differences fully mediated the effect of nurse‐to‐patient ratios on readiness for hospital discharge, and age and gender of patients only moderated the indirect path of mediation model.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK, VSZLJ
Gypenosides (GYP) exerted anticancer activity against various cancers. However, the mechanism of GYP against lung cancer (LC)
remains unclear. This study aims to reveal the potential mechanism of GYP ...against LC and enhancing cisplatin efficacy using a comprehensive analysis of metabolomics, network analysis. Pharmacodynamic results showed that GYP inhibited tumor growth, reduced tumor volume and tumor weight, and alleviated pathological symptoms in Lewis tumor-bearing mice, and GYP could enhance the anti-LC effects of cisplatin. Using serum metabolomics methods, 53 metabolites were found to be significantly altered in the model group, and the levels of 23 biomarkers were significantly restored after GYP treatment. GYP-related metabolic pathways involved six pathways, including alpha-linolenic acid metabolism, glutathione metabolism, sphingolipid metabolism, glycerophospholipid metabolism, tryptophan metabolism, and primary bile acid biosynthesis. 57 genes associated with differential metabolites of GYP recovery and 7 genes of 11 saponins of GYP against LC were screened by network analysis, the STRING database was used to find the association between 57 genes and 7 genes, and a compound-intersection gene-metabolite related gene-metabolite-pathway network was constructed, and STAT3, MAPK14, EGFR and TYMS might be the crucial targets of GYP against LC. Western blot results showed that GYP restored the levels of STA3, MAPK14, EGFR, and TYMS in the model group, and GYP also restored the levels of STAT3 and MAPK14 in the cisplatin group, indicating that GYP might exert anti-LC effects and enhance the pharmacological effects of cisplatin through MAPK14/STAT3 signaling pathway. Our method revealed the effect and mechanism of GYP on LC and the pharmacological effects of GYP-enhanced chemotherapeutic agent cisplatin, which provided some reference for the development of anti-cancer drugs.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high morbidity and mortality. Targeting abnormal cholesterol metabolism is a potential therapeutic direction. Therefore, ...more natural drugs targeting cholesterol in HCC need to be developed. Gypenosides (Gyp), the major constituent of Gynostemma pentaphyllum, has been demonstrated to have pharmacological properties on anti-cancer, anti-obesity, and hepatoprotective. We investigated whether Gyp, isolated and purified by our lab, could inhibit HCC progression by inhibiting cholesterol synthesis. The present research showed that Gyp inhibited proliferation and migration, and induced apoptosis in Huh-7 and Hep3B cells. Metabolomics, transcriptomics, and target prediction all suggested that lipid metabolism and cholesterol biosynthesis were the mechanisms of Gyp. Gyp could limit the production of cholesterol and target HMGCS1, the cholesterol synthesis-related protein. Downregulation of HMGCS1 could suppress the progression and abnormal cholesterol metabolism of HCC. In terms of mechanism, Gyp suppressed mevalonate (MVA) pathway mediated cholesterol synthesis by inhibiting HMGCS1 transcription factor SREBP2. And the high expression of HMGCS1 in HCC human specimens was correlated with poor clinical prognosis. The data suggested that Gyp could be a promising cholesterol-lowering drug for the prevention and treatment of HCC. And targeting SREBP2-HMGCS1 axis in MVA pathway might be an effective HCC therapeutic strategy.
Display omitted
•Gypenosides could suppress HCC by blocking cholesterol biosynthesis.•HMGCS1 downregulation inhibited proliferation and migration in HCC.•Mevalonate pathway was a potential target for HCC therapy.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective
To determine the association of serum cardiac troponin (cTn) with the mortality of pulmonary hypertension (PH) patients via a meta‐analysis.
Date Source
We searched PubMed and EMBASE from ...inception to October 25, 2017.
Study Selection
The reference lists of the retrieved articles were also consulted. The Q test and I2 test were used for to assess heterogeneity. The relationship between cTn elevation and mortality was analysed. Studies were stratified according to type of troponin (cTnT vs cTnI), region (Europe vs America) and follow‐up length (≤3 years vs >3 years).
Results
Eight studies with 739 patients were included in the meta‐analysis. Cardiac troponin elevation ranged from 14.3% to 94.5%. Overall, 48.8% (39/80) of patients with elevated cTn died compared to 18.6% (45/242) of patients with normal cTn levels. These findings showed cTn elevation was significantly related to an increased mortality risk in PH patients hazard ratio (HR) = 3.05, 95% confidence interval (95% CI) = 2.16‐4.32, I2 = 24.9%. cTnI was better at predicting mortality than cTnT (HR = 3.37, 95%CI = 2.05‐5.55 vs HR = 2.80, 95%CI = 1.97‐3.98, respectively). American populations had increased mortality compared to European populations (HR = 4.23, 95%CI = 2.29‐7.80 vs HR = 2.70, 95% CI = 1.95‐3.74, respectively). This finding was independent of the follow‐up length of the studies (≤3 years: HR = 2.36, 95%CI = 1.65‐3.38; >3 years: HR = 4.55, 95%CI = 2.80‐7.39).
Conclusions
Although different studies detected the expression cTnT or cTnI by various methods, the mortality in the cTn‐positive group was higher than that in the cTn‐negative group. Serum cTn elevation emerged as an independent predictor of increased risk of mortality in PH patients.
Full text
Available for:
FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
In this paper, based on reciprocal chiral substrate specificity, taking achiral molecules, ethanolamine (EA) and malachite green (MG) as two model targets, biostable L- DNA aptamers and L-RNA ...aptamers were generated respectively by chiral inversion of existing D-aptamers. In the detection of EA with L-DNA aptamer-based sensors, the feasibility of our strategy was confirmed, while in the detection of MG with L-RNA aptamers, linear calibration curves were obtained in the range from 0.1 to 5µm with the detection limit of 0.065µm under optimized experimental conditions. The results demonstrated that the mirror-image L-aptamers have identical recognition capability as D-aptamers. Meanwhile, L-aptamers have superior biostability to resist nuclease digestion, protein binding interference and off-target effects, enabling their applications in complex practical samples, such as lake water and fish tissue extractions. Our work provides a simple, yet universal and efficient way to develop biostable aptamers.
Generation of Biostable L-aptamers against Achiral Targets by Chiral Inversion of Existing D-aptamers Display omitted
•L-aptamers shows robust biostability to realize detection in complex samples.•The straightforward transformation of the mirror structure is simple in design.•RNA and DNA aptamers are both suitable for this strategy, which shows generality.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Using the current tumor lymph node metastasis (TNM) staging system to make treatment decisions and predict survival in patients with nasopharyngeal carcinoma (NPC) lacks sufficient accuracy. Patients ...at the same stage often have different survival prognoses.
In the current study 802 NPC patients who underwent concurrent radiotherapy and chemotherapy from January 2010 to December 2014 at Sun Yat-sen University Cancer Center in China were retrospectively assessed. The optimal cut-off points for skeletal muscle index (SMI) and monocyte-to-lymphocyte ratio (MLR) were determined
receiver operating characteristic curves. SMI-MLR (S-M) grade and a nomogram were developed and used as clinical indicators in NPC patients. The consistency index (C-index) and a calibration curve were used to measure the accuracy and discriminative capacity of prediction.
The predictive performance of S-M grade was better than that of TNM staging (C-index 0.639, range 0.578-0.701
0.605, range 0.545-0.665;
= 0.037). In multivariate analysis S-M grade, T stage, and N stage were independent prognostic factors. These three factors were then combined, yielding a nomogram with a C-index of 0.71 (range 0.64-0.77), indicating good predictive capacity.
We developed and validated a prognostic parameter, S-M grade, which increased prediction accuracy significantly and can be combined with TNM staging to predict survival in patients with NPC undergoing concurrent chemoradiotherapy.
With the rapid development of synthetic biology, a variety of biopolymers can be obtained by recombinant microorganisms. Polyhydroxyalkanoates (PHA) is one of the most popular one with promising ...material properties, such as biodegradability and biocompatibility against the petrol-based plastics. This study reviews the recent studies focusing on the microbial synthesis of PHA, including chassis engineering, pathways engineering for various substrates utilization and PHA monomer synthesis, and PHA synthase modification. In particular, advances in metabolic engineering of dominant workhorses, for example
Halomonas, Ralstonia eutropha, Escherichia coli
and
Pseudomonas,
with outstanding PHA accumulation capability, were summarized and discussed, providing a full landscape of diverse PHA biosynthesis. Meanwhile, we also introduced the recent efforts focusing on structural analysis and mutagenesis of PHA synthase, which significantly determines the polymerization activity of varied monomer structures and PHA molecular weight. Besides, perspectives and solutions were thus proposed for achieving scale-up PHA of low cost with customized material property in the coming future.
Background Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus ...(T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. Methods Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. Results After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval CI: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group. Conclusions In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM. Trial registration ClinicalTrail.gov NCT05782192. Keywords: Dipeptidyl peptidase-4 inhibitors, Fotagliptin, Type 2 diabetes mellitus, HbA1c
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ploidy manipulation is effective in seedless loquat breeding, in which flesh color is a key agronomic and economic trait. Few techniques are currently available for detecting the genotypes of ...polyploids in plants, but this ability is essential for most genetic research and molecular breeding. We developed a system for genotyping by quantitative PCR (qPCR) that allowed flesh color genotyping in multiple tetraploid and triploid loquat varieties (lines). The analysis of 13 different ratios of DNA mixtures between two homozygous diploids (AA and aa) showed that the proportion of allele A has a high correlation (R.sup.2 = 0.9992) with parameter b b = a.sub.1/(a.sub.1 + a.sub.2), which is derived from the two normalized allele signals (a.sub.1 and a.sub.2) provided by qPCR. Cluster analysis and variance analysis from simulating triploid and tetraploid hybrids provided completely correct allelic configurations. Four genotypes (AAA, AAa, Aaa, aaa) were found in triploid loquats, and four (AAAA, AAAa, AAaa, Aaaa; absence of aaaa homozygotes) were found in tetraploid loquats. DNA markers analysis showed that the segregation of flesh color in all F.sub.1 hybrids conformed to Mendel's law. When tetraploid B431 was the female parent, more white-fleshed triploids occurred among the progeny. qPCR can detect the flesh color genotypes of loquat polyploids and provides an alternative method for analyzing polyploid genotype and breeding, dose effects and allele-specific expression.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
