Aims
To investigate the phenanthrene‐degrading abilities of the halophilic Martelella species AD‐3 under different conditions and to propose a possible metabolic pathway.
Methods and Results
Using ...HPLC and GC‐MS analyses, the phenanthrene‐degrading properties of the halophilic strain AD‐3 and its metabolites were analysed. This isolate efficiently degraded phenanthrene under multiple conditions characterized by different concentrations of phenanthrene (100–400 mg l−1), a broad range of salinities (0·1–15%) and varying pHs (6·0–10·0). Phenanthrene (200 mg l−1) was completely depleted under 3% salinity and a pH of 9·0 within 6 days. The potential toxicity of phenanthrene and its generated metabolites towards the bacterium Vibrio fischeri was significantly reduced 10 days after the bioassay. On the basis of the identified metabolites, enzyme activities and the utilization of probable intermediates, phenanthrene degradation by strain AD‐3 was proposed in two distinct routes. In route I, metabolism of phenanthrene was initiated by the dioxygenation at C‐3,4 via 1‐hydroxy‐2‐naphthoic acid, 1‐naphthol, salicylic acid and gentisic acid. In route II, phenanthrene was metabolized to 9‐phenanthrol and 9,10‐phenanthrenequinone. Further study indicated that strain AD‐3 exhibited a wide spectrum of substrate utilization including other polycyclic aromatic hydrocarbons (PAHs).
Conclusions
The results suggest that strain AD‐3 possesses a high phenanthrene biodegradability and that the degradation occurs via two routes that remarkably reduce toxicity.
Significance and Impact of the Study
To the best of our knowledge, this work presents the first report of phenanthrene degradation by a halophilic PAH‐degrading strain via two routes. In the future, the use of halophilic strain AD‐3 provides a potential application for efficient PAH‐contaminated hypersaline field remediation.
Background This study was to investigate the effects of the novel cannabinoid receptor – G protein‐coupled receptor 55 (GPR55) – and its ligands O‐1602 and cannabidiol (CBD) on gastrointestinal (GI) ...motility in rodents.
Methods Lipopolysaccharide (LPS) was used in vivo to produce the model of septic ileus. The intestinal motility was measured by recording myoelectrical activity of jejunum in rats, and by measuring GI transit with a charcoal marker in mice, in presence of O‐1602 or CBD. Inflammatory response was assessed serologically and histologically. The expression and distribution of GPR55 in the different parts of rat intestine were investigated by real‐time PCR and immunohistochemistry. In vitro, the effects of the drugs on the GI movement were investigated by measuring the contraction of the intestinal muscle strips in organ bath, and the intracellular responses of the muscle cells with microelectrode technique.
Key Results G protein‐coupled receptor 55 was expressed in different parts of rat intestine. Lipopolysaccharide significantly inhibited the intestinal motility, increased inflammatory cytokines and GPR55 expression. Pretreatment with CBD normalized LPS‐induced hypomotility and improved the inflammatory responses serologically and histologically. Both O‐1602 and CBD counteracted LPS‐induced disturbances of the gut contraction, but had no effect on the membrane potential of the muscle cells, while cannabinoid type 1 receptor antagonist AM251 and cannabinoid type 2 receptor antagonist AM630 increased the potential.
Conclusions & Inferences G protein‐coupled receptor 55 existed throughout the whole intestine of rats. O‐1602 or CBD selectively normalized the motility disturbances. Possible mechanisms involved systemic anti‐inflammation and the regulation of myoelectrical activity of the intestine.
Generating ion-photon entanglement is a crucial step for scalable trapped-ion quantum networks. To avoid the crosstalk on memory qubits carrying quantum information, it is common to use a different ...ion species for ion-photon entanglement generation such that the scattered photons are far off-resonant for the memory qubits. However, such a dual-species scheme can be subject to inefficient sympathetic cooling due to the mass mismatch of the ions. Here we demonstrate a trapped-ion quantum network node in the dual-type qubit scheme where two types of qubits are encoded in the S and F hyperfine structure levels of
Yb
ions. We generate ion photon entanglement for the S-qubit in a typical timescale of hundreds of milliseconds, and verify its small crosstalk on a nearby F-qubit with coherence time above seconds. Our work demonstrates an enabling function of the dual-type qubit scheme for scalable quantum networks.
High tumor mutational burden (TMB-H) is correlated with enhanced objective response rate (ORR) and progression-free survival (PFS) for certain cancers receiving immunotherapy. This study aimed to ...investigate the safety and efficacy of toripalimab, a humanized programmed death-1 (PD-1) antibody, in advanced gastric cancer (AGC), and the predictive survival benefit of TMB and PD-L1.
We reported on the AGC cohort of phase Ib/II trial evaluating the safety and activity of toripalimab in patients with AGC, oesophageal squamous cell carcinoma, nasopharyngeal carcinoma and head and neck squamous cell carcinoma. In cohort 1, 58 chemo-refractory AGC patients received toripalimab (3 mg/kg d1, Q2W) as a monotherapy. In cohort 2, 18 chemotherapy-naive AGC patients received toripalimab (360 mg d1, Q3W) with oxaliplatin 130 mg/m2 qd, d1, capecitabine 1000 mg/m2 b.i.d., d1–d14, Q3W as first-line treatment. Primary end point was ORR. Biomarkers such as PD-L1 and TMB were evaluated for correlation with clinical efficacy.
In cohort 1, the ORR was 12.1% and the disease control rate (DCR) was 39.7%. Median PFS was 1.9 months and median OS was 4.8 months. The TMB-H group showed significant superior OS than the TMB-L group 14.6 versus 4.0 months, HR = 0.48 (96% CI 0.24–0.96), P = 0.038, while PD-L1 overexpression did not correlate with significant survival benefit. A 77.6% of patients experienced at least one treatment-related adverse event (TRAE), and 22.4% of patients experienced a grade 3 or higher TRAE. In cohort 2, the ORR was 66.7% and the DCR was 88.9%. A 94.4% of patients experienced at least one TRAE and 38.9% of patients experienced grade 3 or higher TRAEs.
Toripalimab has demonstrated a manageable safety profile and promising antitumor activity in AGC patients, especially in combination with XELOX. High TMB may be a predictive marker for OS of AGC patients receiving toripalimab as a single agent.
ClinicalTrials.gov NCT02915432.
Aims
This study investigated the role of L‐3‐n‐Butylphthalide (NBP) in cardiac protection.
Methods
The left anterior descending coronary arteries (LAD) of the rats were occluded for 30 min following ...by 2‐h reperfusion to make the ischaemia/reperfusion models. Neonatal cardiomyocytes were cultured and subjected to hypoxia. L‐3‐n‐Butylphthalide was administered intraperitoneally 2 h before the surgery and right after the reperfusion in the in vivo experiments or added to the culture medium in vitro. Haemodynamic parameters were recorded to evaluate the cardiac functions, triphenyltetrazolium chloride (TTC) and Evens blue staining were used to determine the area of risk and infarct area, apoptotic cell numbers were counted with terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining. Western blotting was used to determine the apoptotic protein levels and immune staining to determine the translocation of Glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) protein.
Results
Our research showed for the first time that L‐3‐n‐Butylphthalide had great effects in improving cardiac hemodynamic function and decreasing cardiac infarct areas and apoptotic cell numbers in the peri‐infarct areas. The apoptotic signals investigation showed that L‐3‐n‐Butylphthalide affected the mitochondrial pathway including Bcl‐2 protein expression, inhibition of caspase 3 activation and cytochrome C releasing. Besides, Glyceraldehyde‐3‐phosphate dehydrogenase protein translocation was inhibited by L‐3‐n‐Butylphthalide treatment, and this effect was mediated by endogenous reactive oxygen species (ROS).
Conclusion
L‐3‐n‐Butylphthalide protects cardiomyocytes from ischaemia/reperfusion‐induced apoptosis by antioxidant effect and affecting mitochondrial apoptotic pathway.
Cardiac progenitor cells derived from adult heart have emerged as one of the most promising stem cell types for cardiac protection and repair. Exosomes are known to mediate cell-cell communication by ...transporting cell-derived proteins and nucleic acids, including various microRNAs (miRNAs). Here we investigated the cardiac progenitor cell (CPC)-derived exosomal miRNAs on protecting myocardium under oxidative stress. Sca1(+)CPCs-derived exosomes were purified from conditional medium, and identified by nanoparticle trafficking analysis (NTA), transmission electron microscopy and western blotting using CD63, CD9 and Alix as markers. Exosomes production was measured by NTA, the result showed that oxidative stress-induced CPCs secrete more exosomes compared with normal condition. Although six apoptosis-related miRNAs could be detected in two different treatment-derived exosomes, only miR-21 was significantly upregulated in oxidative stress-induced exosomes compared with normal exosomes. The same oxidative stress could cause low miR-21 and high cleaved caspase-3 expression in H9C2 cardiac cells. But the cleaved caspase-3 was significantly decreased when miR-21 was overexpressed by transfecting miR-21 mimic. Furthermore, miR-21 mimic or inhibitor transfection and luciferase activity assay confirmed that programmed cell death 4 (PDCD4) was a target gene of miR-21, and miR-21/PDCD4 axis has an important role in anti-apoptotic effect of H9C2 cell. Western blotting and Annexin V/PI results demonstrated that exosomes pre-treated H9C2 exhibited increased miR-21 whereas decreased PDCD4, and had more resistant potential to the apoptosis induced by the oxidative stress, compared with non-treated cells. These findings revealed that CPC-derived exosomal miR-21 had an inhibiting role in the apoptosis pathway through downregulating PDCD4. Restored miR-21/PDCD4 pathway using CPC-derived exosomes could protect myocardial cells against oxidative stress-related apoptosis. Therefore, exosomes could be used as a new therapeutic vehicle for ischemic cardiac disease.
Micro-structural evolution and grain refinement in ANSI 304 stainless steel subjected to multiple laser shock processing (LSP) impacts were investigated by means of cross-sectional optical microscopy ...and transmission electron microscopy observations. The plastic strain-induced grain refinement mechanism of the face-centered cubic (fcc) materials with very low stacking fault energy was identified. The micro-structure was obviously refined due to the ultra-high plastic strain induced by multiple LSP impacts. The minimum grain size in the top surface was about 50–200
nm. Multidirectional mechanical twin matrix (MT)–MT intersections led to grain subdivision at the top surface during multiple LSP impacts. Furthermore, a novel structure with submicron triangular blocks was found at the top surface subjected to three LSP impacts. The grain refinement process along the depth direction after multiple LSP impacts can be described as follows: (i) formation of planar dislocation arrays (PDAs) and stacking faults along multiple directions due to the pile up of dislocation lines; (ii) formation of submicron triangular blocks (or irregularly shaped blocks) by the intersection of MT–MT (or MT–PDA or PDA–PDA) along multiple directions; (iii) transformation of MTs into subgrain boundaries; (iv) evolution by continuous dynamic recrystallization of subgrain boundaries to refined grain boundaries. The experimental results and analyses indicate that a high strain with an ultra-high strain rate play a crucial role in the grain refinement process of fcc materials subjected to multiple LSP impacts.
PDF
