Technological advancements in research on circulating biomarkers from patient derived blood have enabled a less invasive means of diagnosing non-hematologic cancers. Considered a more practical way ...of real-time patient monitoring than traditional tumor biopsy, liquid biopsy markers including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and extracellular vesicles (EVs) and exosomes certainly have the potential to change the dynamics of cancer management and treatment. Liquid biopsy essentially presents a snapshot of the disease from the primary and/or distant tumor locations and can be utilized for repeated sampling of tumor markers to adjust therapy according to the patient's response to treatment, also known as personalized or precision treatment. In this review, we discuss the research progress in this field with respect to each of the liquid biopsy markers ranging from CTCs, EVs to ctDNA. First, we highlight key CTC technologies that have been commercialized and extensively employed for patient sample analysis. Next, we present some recent developments with regards to exosome and ctDNA research. We then conclude with some future perspectives on the areas of research for these biomarkers. Taken together, we believe these non-invasive capabilities and their potential for diagnostic development can influence treatment selections and aid precision cancer therapies.
Research on circulating biomarkers have enabled the development of new diagnostic tools that complement conventional biopsies through less invasive sampling of the tumor cells, also known as liquid biopsy.
In this study, a gold nanobox with 40 nm edge length has been transformed into nanoframe gradually by increasing the square-hole length in each {100} facet of the hexahedron. The local dielectric ...environment-dependent plasmon spectra and refractive index sensitivity of this face-holed single gold nanocage were investigated based on the discrete dipole approximation method. Both the redshift of the resonance peak position and the sensitivity factor increased near exponentially with increasing hole length, which could be attributed to the changing of hot regions of plasmonic field coupling. Moreover, the shift of their resonance peak position to the refractive index of environmental medium increased linearly, and the face-holed nanocage-based sensor shows an excellent sensitivity factor of 955.7 nm/RIU figure of merit (FOM) = 3.58. It was also noticed that the non-monotonic transform of the local field enhancement factor (|
E
/
E
0
|) with a maximum of 80.9 is also extremely affected by the refractive index. The physical mechanism discussed herein may be that the polarized field in local dielectric environment becomes intense as the refractive index increases, resulting in an improvement of field enhancement factor on the corners. We therefore believe that the square-hole length of {100} facets could enhance the plasmonic optical sensitivity of nanocage-based nanoparticles.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This paper proposes an adaptive protection scheme for distribution systems with distributed generations (DGs). To mitigate the influences on the protection devices by DGs, an online calculation ...method of fault current under various system operation conditions is presented. By sampling local available measurements in the buses, a proposed optimized estimation method is used to calculate the Thevenin equivalent circuit parameters of the system dynamically. Moreover, the short-circuit current can be calculated accurately to set the overcurrent relay protection value considering the behavior of DGs during the fault. To ensure the accurate operation of the protection devices, a coordinated protection scheme, including primary and backup protection is presented. Performances of the proposed method and scheme have been verified by simulations on a sample distribution system based on PSCAD/EMTDC. The sensitivity and selectivity of the coordination between primary and backup protection are satisfied under different system operation conditions, fault locations, and types.
The root-knot nematode (RKN) is one of the most damaging agricultural pests.Effective biological control is need for controlling this destructive pathogen in organic farming system. During October ...2010 to 2011, the nematicidal effects of the Syncephalastrum racemosum fungus and the nematicide, avermectin, alone or combined were tested against the RKN (Meloidogyne incognita) on cucumber under pot and field condition in China. Under pot conditions, the application of S. racemosum alone or combined with avermectin significantly increased the plant vigor index by 31.4% and 10.9%, respectively compared to the M. incognita-inoculated control. However, treatment with avermectin alone did not significantly affect the plant vigor index. All treatments reduced the number of root galls and juvenile nematodes compared to the untreated control. Under greenhouse conditions, all treatments reduced the disease severity and enhanced fruit yield compared to the untreated control. Fewer nematodes infecting plant roots were observed after treatment with avermectin alone, S. racemosum alone or their combination compared to the M. incognita-inoculated control. Among all the treatments, application of avermectin or S. racemosum combined with avermectin was more effective than the S. racemosum treatment. Our results showed that application of S. racemosum combined with avermectin not only reduced the nematode number and plant disease severity but also enhanced plant vigor and yield. The results indicated that the combination of S. racemosum with avermectin could be an effective biological component in integrated management of RKN on cucumber.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A rhodium‐catalyzed synthesis of isoquinolino1,2‐bquinazolines via C−H annulation using vinylene carbonate as an oxidizing acetylene surrogate in biomass‐derived γ‐valerolactone (GVL) has been ...developed. The reactions proceeded smoothly to give the corresponding products in moderate to good yields without any external oxidant and base. This protocol can also be applied for the synthesis of 5,6‐dihydro‐8H‐isoquinolino1,2‐bquinazolin‐8‐ones.
A rhodium‐catalyzed synthesis of isoquinolino1,2‐bquinazolines via C−H annulation in biomass‐derived γ‐valerolactone (GVL) has been developed.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
NaClO based chemically enhanced backwash (CEB) is often administered to maintain membrane permeability during the operation of MBR. However, the effect and working mechanism of NaClO concentrations ...in CEB were rarely investigated. The current investigation examined the changes in membrane resistance, permeate production and membrane morphology with or without CEB in an anammox MBR to reveal the scrubbing effect of different NaClO concentrations (0–596 mg/L). Good cleaning effect indicated by membrane fouling rate of 1.98–2.26 kPa/day and membrane permeate production of 80–88 L was observed when NaClO concentration of 149–596 mg/L was used. The best cleaning effect was observed when 298 mg/L of NaClO was used. To explore the mechanism of CEB action, backwashing foulants were also analyzed. Insoluble EPS transformed into soluble forms like S-EPS or SMP after the sludge was exposed to NaClO. The NaClO based CEB removed 112–675 mg of polysaccharide (PS)/m2 in foulants at NaClO concentration of 149–596 mg/L, which was significantly higher than the value obtained by pure water (35 mg PS/m2). The possible mechanisms behind the detachment of soluble PS seemed as oxidation and sterilization by NaClO. The current investigation provides useful guidelines on NaClO concentrations applied during CEB for anammox MBR.
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•Different cleaning effects could be obtained at different NaClO concentrations.•The function of NaClO CEB could be correlated to be mainly on PS in foulants.•PS has a stronger tendency than PN to deposit on membrane.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Abstract Intrahepatic accumulation dominates organ distribution for most nanomedicines. However, obscure intrahepatic fate largely hampers regulation on their in vivo performance. Herein, PEGylated ...liposomal doxorubicin is exploited to clarify the intrahepatic fate of both liposomes and the payload in male mice. Kupffer cells initiate and dominate intrahepatic capture of liposomal doxorubicin, following to deliver released doxorubicin to hepatocytes with zonated distribution along the lobule porto-central axis. Increasing Kupffer cells capture promotes doxorubicin accumulation in hepatocytes, revealing the Kupffer cells capture-payload release-hepatocytes accumulation scheme. In contrast, free doxorubicin is overlooked by Kupffer cells, instead quickly distributing into hepatocytes by directly crossing fenestrated liver sinusoid endothelium. Compared to free doxorubicin, liposomal doxorubicin exhibits sustained metabolism/excretion due to the extra capture-release process. This work unveils the pivotal role of Kupffer cells in intrahepatic traffic of PEGylated liposomal therapeutics, and quantitively describes the intrahepatic transport/distribution/elimination process, providing crucial information for guiding further development of nanomedicines.
Although traditional chemotherapy kills a fraction of tumor cells, it also activates the stroma and can promote the growth and survival of residual cancer cells to foster tumor recurrence and ...metastasis. Accordingly, overcoming the host response induced by chemotherapy could substantially improve therapeutic outcome and patient survival. In this study, resistance to treatment and metastasis has been attributed to expansion of stem-like tumor-initiating cells (TICs). Molecular analysis of the tumor stroma in neoadjuvant chemotherapy-treated human desmoplastic cancers and orthotopic tumor xenografts revealed that traditional maximum-tolerated dose chemotherapy, regardless of the agents used, induces persistent STAT-1 and NF-κB activity in carcinoma-associated fibroblasts. This induction results in the expression and secretion of ELR motif-positive (ELR
) chemokines, which signal through CXCR-2 on carcinoma cells to trigger their phenotypic conversion into TICs and promote their invasive behaviors, leading to paradoxical tumor aggression after therapy. In contrast, the same overall dose administered as a low-dose metronomic chemotherapy regimen largely prevented therapy-induced stromal ELR
chemokine paracrine signaling, thus enhancing treatment response and extending survival of mice carrying desmoplastic cancers. These experiments illustrate the importance of stroma in cancer therapy and how its impact on treatment resistance could be tempered by altering the dosing schedule of systemic chemotherapy.
Tryptophan (Trp) is one of the essential amino acids, which plays important roles in biological systems and the normal growth of human beings, and it is of great significance to be able to detect Trp ...in a rapid, efficient, and sensitive way. Herein, a 3D network metal-organic framework (Sm
2
(BTEC)
1.5
(H
2
O)
8
·6H
2
O) with excellent thermal and water stability was synthesized by a hydrothermal method. Interestingly, it could discriminate Trp from other natural amino acids in aqueous solution through a significant fluorescence enhancement effect, and showed high detection sensitivity (LOD = 330 nM) and outstanding anti-interference ability. The sensor system was successfully applied to the detection of Trp in practical samples, so it was expected to be a sensitive and efficient Trp sensor. In addition, the sensing mechanism was explained in detail by a series of characterization methods combined with density functional theory (DFT). There were many coordination water molecules in the crystal structure of the complex. Based on the small steric hindrance and molecular structure of water molecules, it provided the possibility for coordination interaction between Trp and Sm
3+
. On the other hand, the triplet energy level (T1) of Trp matched with the
4
G
5/2
vibrational energy level of Sm
3+
, so Trp could be used as the second "antenna molecule" besides 1,2,4,5-benzenetetracarboxylic acid (H
4
BTEC). Therefore, it effectively broadened the way for Sm-MOF to absorb excitation light.
Tryptophan (Trp) is one of the essential amino acids, which plays important roles in biological systems and the normal growth of human beings, and it is of great significance to be able to detect Trp in a rapid, efficient, and sensitive way.
Abstract
Background
Ocular adverse events are common dose-limiting toxicities in cancer patients treated with HSP90 inhibitors, such as AUY922; however, the pathology and molecular mechanisms that ...mediate AUY922-induced retinal toxicity remain undescribed.
Methods
The impact of AUY922 on mouse retinas and cell lines was comprehensively investigated using isobaric tags for relative and absolute quantitation (iTRAQ)‑based proteomic profiling and pathway enrichment analysis, immunohistochemistry and immunofluorescence staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, MTT assay, colony formation assay, and western blot analysis. The effect of AUY922 on the Transient Receptor Potential cation channel subfamily M member 1 (TRPM1)-HSP90 chaperone complex was characterized by coimmunoprecipitation. TRPM1-regulated gene expression was analyzed by RNAseq analysis and gene set enrichment analysis (GSEA). The role of TRPM1 was assessed using both loss-of-function and gain-of-function approaches.
Results
Here, we show that the treatment with AUY922 induced retinal damage and cell apoptosis, dysregulated the photoreceptor and retinal pigment epithelium (RPE) layers, and reduced TRPM1 expression. Proteomic profiling and functional annotation of differentially expressed proteins reveals that those related to stress responses, protein folding processes, regulation of apoptosis, cell cycle and growth, reactive oxygen species (ROS) response, cell junction assembly and adhesion regulation, and proton transmembrane transport were significantly enriched in AUY922-treated cells. We found that AUY922 triggered caspase-3-dependent cell apoptosis, increased ROS production and inhibited cell growth. We determined that TRPM1 is a bona fide HSP90 client and characterized that AUY922 may reduce TRPM1 expression by disrupting the CDC37-HSP90 chaperone complex. Additionally, GSEA revealed that TRPM1-regulated genes were associated with retinal morphogenesis in camera-type eyes and the JAK-STAT cascade. Finally, gain-of-function and loss-of-function analyses validated the finding that TRPM1 mediated the cell apoptosis, ROS production and growth inhibition induced by AUY922.
Conclusions
Our study demonstrates the pathology of AUY922-induced retinal toxicity in vivo. TRPM1 is an HSP90 client, regulates photoreceptor morphology and function, and mediates AUY922-induced cytotoxicity.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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