An effective and facile fluorescence sensing approach for the determination of 2,4,6-trinitrophenol (TNP) using the chemically oxidized and liquid exfoliated graphitic carbon nitride (g-C3N4) ...nanosheets was developed. The strong inner filter effect and molecular interactions (electrostatic, π–π, and hydrogen bonding interactions) between TNP and the g-C3N4 nanosheets led to the fluorescence quenching of the g-C3N4 nanosheets with efficient selectivity and sensitivity. Under optimal conditions, the limit of detection for TNP was found to be 8.2 nM. The proposed approach has potential application for visual detection of TNP in natural water samples for public safety and security.
Using graphitic carbon nitride (g-C3N4) nanosheets, an effective and facile fluorescence sensing approach for the label-free and selective determination of chromium (VI) (Cr(VI)) was developed. The ...fluorescence of the solution of g-C3N4 nanosheets was quenched effectively by Cr(VI) via the inner filter effect. Under optimal conditions, a wide detection linear range for Cr(VI) was found to be from 0.6 μM to 300 μM with a limit of detection (LOD) of 0.15 μM. In addition, the fluorescence of the solution of g-C3N4 nanosheets-Cr(VI) could be sensitively turned on in the presence of a reductant such as ascorbic acid (AA) via an "on-off-on" fluorescence response through the oxidation-reduction between Cr(VI) and AA. And a wide detection linear range for AA was found to be from 0.5 μM to 200 μM with an LOD of 0.13 μM. Furthermore, the proposed method has the potential application for detection of Cr(VI) in lake waters and AA in biological fluids.
Inspired by marine mussel, an ultralight, three dimensional (3D), and nitrogen doped graphene aerogel (NGA) is developed by virtue of dopamine (DA). DA undergoes self-polymerization that can ...functionalize the graphene surface and also embeds nitrogen atoms onto the graphene sheets upon pyrolysis. The morphology and textural properties were investigated by scanning and transmission electron microscopy, X-ray photoelectron spectroscopy and Raman spectrum. By adjusting the amount of graphene oxide and DA in the precursor mixture, NGA with a density as low as 1.9mgcm−3 can be prepared. The resultant NGA is macroscopic-assembled, mechanically stable, and fire-resistant. It has very high adsorption capacity and efficient space utilization towards oil uptake, thereby prompting practical applications as a suction skimmer in marine oil spillage or chemical leakage recovery. The high conductivity and 3D interconnected porous structure of the NGA permit good performance as electrode material for electrochemical sensors.
Osimertinib (Osm) is the preferred treatment for non-small cell lung cancer (NSCLC) patients with the epidermal growth factor receptor (EGFR) T790M mutation. Nevertheless, the resistance of NSCLC ...cells to Osm will eventually develop, which remains the biggest obstacle to treating such diseases. Raddeanin A (RA) exhibits a potent anti-tumor effect on various types of cancer cells. In this study, we aimed to investigate whether RA suppresses NSCLC growth and increases the therapeutic effect of Osm.
The effects of RA on inhibiting NSCLC cell viability and proliferation were tested using cell counting kit 8 (CCK-8) and EdU assay. The roles of RA in improving the anti-tumor effect of Osm were tested with CCK-8 and colony formation assays. The roles of RA in regulating reactive oxygen species (ROS)/NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3)-mediated pyroptosis were assessed using quantitative real- time PCR (qRT-PCR) and western blotting analysis.
RA treatment decreased A549 and H1975 cell viability in a dose- and time-dependent way. RA inhibited NSCLC cell proliferation and tumor growth
. Mechanistically, RA induced ROS overgeneration and resulted in subsequent NLRP3-mediated pyroptosis. In particular, combination treatment with Osm and RA reduced cell viability and clonogenic growth capacity more efficiently than Osm mono treatment in A549 and H1975 cells. Combination treatment also promoted NLRP3-mediated pyroptosis more efficiently than Osm mono treatment.
RA inhibited the NSCLC growth and increased the anti-tumor role of Osm in NSCLC by facilitating ROS/NLRP3-mediated pyroptosis. These results suggested that combination therapy with RA and Osm might be an effective strategy to treat Osm-resistant NSCLC.
Tigecycline has been used as one of the therapeutic choices for the treatment of infections caused by multidrug-resistant
Klebsiella pneumoniae
. However, the emergence of tigecycline ...heteroresistance has led to great challenges in treating these infections. The purpose of this study was to investigate whether tigecycline-heteroresistant
K. pneumoniae
(TGCHR-Kp) exists in clinical isolates, and to further characterize the underlying molecular mechanisms involved in the development of tigecycline-resistant subpopulations. Of the 268 tigecycline-susceptible clinical
K. pneumoniae
isolates, 69 isolates were selected as tigecycline-heteroresistant candidates in the preliminary heteroresistant phenotypic selection by a modified disk diffusion method, and only 21 strains were confirmed as TGCHR-Kp by the population analysis profile (PAP). Pulsed-field gel electrophoresis (PFGE) analysis demonstrated that all the parental TGCHR-Kp isolates were clonally unrelated, and colonies confirmed as the heteroresistant subpopulation showed no significant differences from their respective parental TGCHR-Kp isolates. Efflux pump inhibitors reversed the tigecycline susceptibility in heteroresistant subpopulations. Mutations in the
ramR
and
soxR
genes lead to upregulation of the
ramA
and
soxS
transcriptional regulators, which in turn induced overexpression of the AcrAB-TolC efflux pump genes in TGCHR-Kps-resistant subpopulations. Moreover, mutations of
rpsJ
were also found in resistant subpopulations, which suggested that the
rpsJ
mutation may also lead to tigecycline resistance. Time-kill assays showed that the efficacy of tigecycline against TGCHR-Kps was weakened, whereas the number of resistant subpopulations was enriched by the presence of tigecycline. Our findings imply that the presence of TGCHR-Kps in clinical strains causes severe challenges for tigecycline therapy in clinical practice.
The information collected through multi-environment testing of wheat genotypes not only provides basis to identify promising genotypes but also to ascertain their yield potential and the genetic ...gains. For this purpose, in the presented study, the data originated from the Yunnan provincial Regional Yield Trials (RYT) conducted during 2006 and 2018 was used. During this period, 107 genotypes were evaluated at 18 locations under Upland Wheat (UW) management scheme, while 116 genotypes were evaluated at 21 locations under Field Wheat (FW) management scheme. By adopting standard statistical approaches and through repeated elimination procedures, 7 genotypes emerged as promising for UW and 11 for FW cultivation. These genotypes have genetic variance >1 and 44/33% higher average yield than that of UW/FW genotypes. Most of these promising genotypes were tested during 2016 and 2018 cropping seasons. This indicated a good genetic gain of around 0.7 t/ha in recent years from that of base year. These genotypes, however, needs to be further evaluated in diverse environments suitable for spring type wheat cultivation to ascertain the extent of their interaction with wider environmental conditions and possibility of using in local breeding programs of those target environments.
Bacterial infection or Demodex infestation has been reported to contribute to chronic blepharitis. The association between Demodex mites and bacterial flora in this disease remains to be elucidated. ...Fifty-six consecutive patients diagnosed with chronic blepharitis and 46 healthy volunteers were recruited for this study. Using specimens of three epilated eyelashes and lid margin swabs, Demodex were identified microscopically and bacteria were determined by cultures, followed by colony counting and mass spectrometry. We found 191 Demodex mites, 161 D. folliculorum and 30 D. brevis, in 45 patients. Correspondingly, 101 Demodex, 63 D. folliculorum and 38 D. brevis, were found in 21 controls (
< 0.05, both). Bacterial culture-positivity was obtained in samples (eyelashes, lid margins, or both) from 54 patients and in eyelashes from 37 controls. The total colony counts and the incidences and colony counts of
and
from patients' eyelashes were significantly higher than that of the controls. Furthermore, bacterial colony counts in blepharitis patients' eyelashes with D. folliculorum were higher than that of controls with D. folliculorum (
< 0.01). Similarly,
colonies increased significantly in patients' eyelashes with D. folliculorum (
< 0.05). These results suggest that D. folliculorum and
have a role in the occurrence of the chronic blepharitis. Further studies are required to reveal the relationship between these two organisms in blepharitis.
Objective Schizophrenia is a common mental disorder, and mitochondrial function represents a potential therapeutic target for psychiatric diseases. The role of mitochondrial metabolism-related genes ...(MRGs) in the diagnosis of schizophrenia remains unknown. This study aimed to identify candidate genes that may influence the diagnosis and treatment of schizophrenia based on MRGs.Methods Three schizophrenia datasets were obtained from the Gene Expression Omnibus database. MRGs were collected from relevant literature. The differentially expressed genes between normal samples and schizophrenia samples were screened using the limma package. Venn analysis was performed to identify differentially expressed MRGs (DEMRGs) in schizophrenia. Based on the STRING database, hub genes in DEMRGs were identified using the MCODE algorithm in Cytoscape. A diagnostic model containing hub genes was constructed using LASSO regression and logistic regression analysis. The relationship between hub genes and drug sensitivity was explored using the DSigDB database. An interaction network between miRNA-transcription factor (TF)-hub genes was created using the Network-Analyst website.Results A total of 1,234 MRGs, 172 DEMRGs, and 6 hub genes with good diagnostic performance were identified. Ten potential candidate drugs (rifampicin, fulvestrant, pentadecafluorooctanoic acid, etc.) were selected. Thirty-four miRNAs targeting genes in the diagnostic model (ANGPTL4, CPT2, GLUD1, MED1, and MED20), as well as 137 TFs, were identified.Conclusion Six potential candidate genes showed promising diagnostic significance. rifampicin, fulvestrant, and pentadecafluorooctanoic acid were potential drugs for future research in the treatment of schizophrenia. These findings provided valuable evidence for the understanding of schizophrenia pathogenesis, diagnosis, and drug treatment.
Abstract Human hepatocellular carcinoma (HCC) is one of the major causes of death worldwide. Targeted uptake of therapeutic agent in the cell-, tissue- or disease-specific manner represents a ...potential technology for the treatment of HCC. A new docetaxel-loaded hepatoma-targeted solid lipid nanoparticle (tSLN) was designed and prepared with galactosylated dioleoylphosphatidyl ethanolamine. The cellular cytotoxicity, cellular uptake, subcellular localization, in vivo toxicity, therapeutic effect, biodistribution and histology of tSLNs were investigated. The tSLNs showed the particle size about 120 n m with encapsulation efficiency >90%, a low burst effect within the first day and a sustained release for the next 29 days in vitro. Cytotoxicity of tSLNs against hepatocellular carcinoma cell line BEL7402 was superior to Taxotere® and non-targeted SLNs (nSLNs). The tSLNs also showed better tolerant and antitumor efficacy in murine model bearing hepatoma compared with Taxotere® or nSLNs. The studies on cellular uptake and biodistribution indicated that the better antitumor efficacy of tSLNs was attributed to both the increased accumulation of drug in tumor and more cellular uptake by hepatoma cells. The histology demonstrated that tSLNs had no detrimental effect on both healthy liver and liver with fibrosis. These results implied that this targeted nanocarrier of docetaxel could enhance its antitumor effect in vivo with low systemic toxicity for the treatment of locally advanced and metastatic HCC.
The current study explored whether intra-articular (IA) injection of autologous adipose mesenchymal stem cells (ASCs) combined with hyaluronic acid (HA) achieved better therapeutic efficacy than ...autologous stromal vascular fraction (SVF) combined with HA to prevent osteoarthritis (OA) progression and determined how long autologous ASCs combined with HA must remain in the joint to observe efficacy. OA models were established by performing anterior cruciate ligament transection (ACLT) and medial meniscectomy (MM). Autologous SVF (1×107 mononuclear cells), autologous low-dose ASCs (1×107), and autologous high-dose ASCs (5×107) combined with HA, and HA alone, or saline alone were injected into the OA model animals at 12 and 15 weeks after surgery, respectively. Compared with SVF+HA treatment, low-dose ASC+HA treatment yielded better magnetic resonance imaging (MRI) scores and macroscopic results, while the cartilage thickness of the tibial plateau did not differ between low, high ASC+HA and SVF+HA treatments detected by micro-computed tomography (µCT). Immunohistochemistry revealed that high-dose ASC+HA treatment rescued hypertrophic chondrocytes expressing collagen X in the deep area of articular cartilage. Western blotting analysis indicated the high- and low-dose ASC+HA groups expressed more collagen X than did the SVF+HA group. Enzyme-linked immunosorbent assay showed treatment with both ASC+HA and SVF+HA resulted in differing anti-inflammatory and trophic effects. Moreover, superparamagnetic iron oxide particle (SPIO)-labeled autologous ASC signals were detected by MRI at 2 and 18 weeks post-injection and were found in the lateral meniscus at 2 weeks and in the marrow cavity of the femoral condyle at 18 weeks post-injection. Thus, IA injection of autologous ASC+HA may demonstrate better efficacy than autologous SVF+HA in blocking OA progression and promoting cartilage regeneration, and autologous ASCs (5×107 cells) combined with HA potentially survive for at least 18 weeks after IA injection.
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