Concordance of ctDNA and tissue mutations in NSCLC: A meta-analysis.

Systematic evaluation of the consistency between circulating tumor DNA (ctDNA) in plasma and tumor tissue samples in mutations in non-small cell lung cancer (NSCLC) patients. To collect publicly published literature from numerous important international medical databases through computer retrieval. To compare the differences in literature data related to gene mutations between plasma ctDNA and tumor tissue samples, a meta-analysis was performed using Stata 12.0 software while taking into account the inclusion and exclusion criteria. This article includes a total of 15 research data and collected data reports from 15 groups of NSCLC patients. The results are displayed using tissue samples as the gold standard. The Pearson correlation coefficients of sensitivity and specificity were used to calculate rho=0.044, and P=0.893. The Q-test found poor homogeneity and high heterogeneity in sensitivity and specificity among research data from various literature studies (I2>50%, P<0.1). The area under the SROC curve is 0.97 (95% CI: 0.96~0.99). The small sample subgroup has high heterogeneity, and the combined diagnosis effect size is 26[6~111], lower than the large sample subgroup 185320 [0~2.7×1012]. When taking 200 as the cut-off point, the combined effect size of the small sample subgroup is 46 [12~183], still lower than that of the large sample subgroup 429 [52~3574]. From this, it can be concluded that the consistency of small-sample studies is higher than the quality of large-sample studies, and the heterogeneity is relatively low. From the perspective of mutation types, the heterogeneity of literature with EGFR gene mutations alone is higher than that of literature with non-EGFR mutations alone, and the consistency is lower. The consistency of using plasma ctDNA to detect mutations in NSCLC patients with tumor tissue samples is influenced by the type of mutation gene and sample size measured by the patient, and there is a significant bias in related studies.

P53 regulates mitochondrial biogenesis via transcriptionally induction of mitochondrial ribosomal protein L12.

The well-documented tumor suppressor p53 is also a major stress response factor for its diverse regulation on cellular energetics. However, the effect of p53 on mitochondrial biogenesis, which plays a predominant role in response to the elevated energy demands, appears to be pleiotropic in various conditions and has not reached agreement. Mitochondrial ribosomal protein L12 (MRPL12), reported as a bi-functional protein for its roles in both mitochondrial ribosomes and transcriptional complexes, is a core regulatory component in mitochondrial biogenesis. Here we proved that MRPL12 is transcriptionally regulated by p53. Furthermore, the p53/MRPL12 regulation of mitochondria is part of the signaling pathway that maintains the basal mitochondrial content and positively coordinates the mitochondrial biogenesis and oxidative phosphorylation (OXPHOS) in response to metabolic perturbation. Since p53 serves as the'Guardian of the Genome', our findings may revealed a new mechanism underlying the conditions when more ATP is warranted to maintain the genome integrity and cell survival. Therefore the pharmacological intervention or metabolic modulation (e.g., through fasting or exercise) of the p53/MRPL12 pathway promises to be a therapeutic approach that can safeguard health.

Comparing biochar- and bentonite-supported Fe-based catalysts for selective degradation of antibiotics: Mechanisms and pathway.

The selective degradation of recalcitrant antibiotics into byproducts with low toxicity and high biodegradability has been increasingly popular using peroxymonosulfate (PMS) based advanced oxidation processes (AOPs). In this paper, two Fe-based heterogeneous catalysts, bentonite supported Fe-Ni composite (BNF) and biochar-supported Fe composite (Fe/C), were tailored and comprehensively characterized for distinctive physicochemical properties, crystalline structures, and interfacial behaviors. Two widely used antibiotics, sulfapyridine (SPY) and oxytetracycline (OTCs) at their common concentrations in pharmaceutical wastewaters (250 and 10 mg L-1) were tested for degradation in three PMS-based oxidation processes, i.e., PMS, PMS-BNF, and PMS-Fe/C, respectively. Results demonstrated that a large amount of PMS (10 and 1 mM) could effectively remove SPY (0.385 min-1, 100% removal) and OTC (2.737 min-1, 100% removal) via1O2 derived from PMS self-decomposition and non-radical pathway, respectively. Additional Fe-based catalysts (0.5 g L-1 Fe/C and BNF) significantly reduced the PMS consumption (1 and 0.25 mM) and accelerated the reaction rate (1.08 and 5.05 min-1) of SPY and OTC removal. Moreover, the supplementary catalysts shifted the degradation route. The biochar matrix in Fe/C composite contributed to predominant interaction with PMS forming 1O2, which preferably attacked SPY via hydroxylation. In contrast, the redox-active Fe-Ni pairs induced SO4- formation, which could selectively degrade OTC through decarboxylation. Thus, these results are conducive to tailoring advanced yet low-cost heterogeneous catalysts for eco-friendly treatment of antibiotics-rich industrial wastewaters.

MiR-506 Promotes Antitumor Immune Response in Pancreatic Cancer by Reprogramming Tumor-Associated Macrophages toward an M1 Phenotype.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer with a poor prognosis, and effective treatments for PDAC are lacking. In this study, we hypothesized that miR-506 promotes antitumor immune response in PDAC by reprogramming tumor-associated macrophages toward an M1 phenotype to reverse its immunosuppressive tumor microenvironment (TME). First, the relationship between TME and the expression of miR-506 was assessed using clinical samples. Our results provided evidence that lower expression of miR-506 was associated with poor prognosis and immunosuppressive TME in PDAC patients. In addition, miR-506 inhibit the PDAC progression and reversed its immunosuppressive microenvironment in a macrophage-dependent manner. Next, we established a PDAC mouse model by orthotopic injection to further explore the role of miR-506 in vivo. Mechanistic investigations demonstrated that miR-506 could reprogram the polarization of M2-like macrophages toward an M1-like phenotype through targeting STAT3. Meanwhile, miR-506 could also sensitize PDAC to anti-PD-1 immunotherapy, because the tumor microenvironment remodeling effects of miR-506 could reprogram macrophage polarization and subsequently promote cytotoxic T lymphocyte (CTL) infiltration. These findings suggest a relationship between miR-506 and TME, especially M2-like macrophages, thus providing novel insights into mechanisms of tumor progression and potential immunotherapeutic targets for further clinical treatment.

Gel properties and network structure of the hydrogel constructed by iota-carrageenan and Ala-Lys dipeptide.

Gel properties of hydrogel-forming by Ala-Lys dipeptide (AK) and iota-carrageenan (ι-C) were investigated by rheological behavior, fourier transform infrared analysis, cryo-scanning electron microscopy, low field-NMR relaxometry and magnetic resonance imaging. Iota-carrageenan was changed from a liquid to a gel with the addition of AK, and the existence of AK significantly increased the storage modulus (G') of ι-C from 590.4 to 1077.8 Pa. In the ι-C/AK gel, the blue-shift of OH stretching and water deformation were observed, meanwhile, the presence of amide I band at 1682 cm-1 was observed. The network of ι-C/AK gel showed a dense honeycomb structure with flocculating continuous phase and rough entanglement morphology. After adding AK, the water free in the pores of ι-C entered the ι-C/AK gel matrix, and the binding capacity of bound water was enhanced. These scenarios proved that the AK as the cationic dipeptide could control the conversion of negatively charged ι-C from an original random structure to a helical structure due to electrostatic interactions and hydrogen bonds. This study provides a new opportunity for the peptides into carbohydrate-based gel matrices, which could provide insights for the further application of ι-C/AK gels in the fields of food industry, tissue engineering and drug delivery.

In silico-screened cationic dipeptides from scallop with synergistic gelation effect on ι-carrageenan.

In this paper, some cationic dipeptides from scallop (Patinopecten yessoensis) male gonads (SMGs), which can synergistically gel with ι-carrageenan (ι-C), were screened by the in silico approach. Fourteen protein sequences of SMGs were obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and nano liquid chromatography-mass spectrometry/mass spectrometry (nanoLC-MS/MS) analysis and were then hydrolyzed via in silico simulation. A total of 414 sequences were obtained with 56 duplicates, half of which were positively charged at pH 7. Among the cation sequences, 171 had good water solubility, including two amino acids (Lys and Arg). The molecular weight analysis of the cationic water-soluble sequences showed that 0.2-0.3 kDa accounted for the highest proportion. Based on the obvious synergistic effect of Lys and ι-C, 11 Lys-containing dipeptides, including Ser-Lys (SK), Thr-Lys (TK), Trp-Lys (WK), Ala-Lys (AK), Leu-Lys (LK), Gly-Lys (GK), Val-Lys (VK), Cys-Lys (CK), Asn-Lys (NK), Phe-Lys (FK), and Met-Lys (MK), were finally screened out to study gelation with ι-C. It was found that the dipeptides/ι-C formed firm gels except WK/ι-C. The values of the storage modulus (G') of 11 dipeptides/ι-C were investigated by a rheometer. The G' of 8 dipeptides/ι-C was higher than 1000 Pa. These results indicated that the in silico-screened dipeptides from SMGs can form composite gels with ι-C, which can be used for the design and development of functional hydrogels.

Biochar-supported nanoscale zero-valent iron as an efficient catalyst for organic degradation in groundwater.

High-efficiency and cost-effective catalysts are critical to completely mineralization of organic contaminants for in-situ groundwater remediation via advanced oxidation processes (AOPs). The engineered biochar is a promising method for waste biomass utilization and sustainable remediation. This study engineers maize stalk (S)- and maize cob (C)-derived biochars (i.e., SB300, SB600, CB300, and CB600, respectively) with oxygen-containing functional groups as a carbon-based support for nanoscale zero-valent iron (nZVI). Morphological and physiochemical characterization showed that nZVI could be impregnated within the framework of the synthesized Fe-CB600 composite, which exhibited the largest surface area, pore volume, iron loading capacity, and Fe0 proportion. Superior degradation efficiency (100% removal in 20 min) of trichloroethylene (TCE, 0.1 mM) and fast pseudo-first-order kinetics (kobs =22.0 h-1) were achieved via peroxymonosulfate (PMS, 5 mM) activation by the Fe-CB600 (1 g L-1) under groundwater condition (bicarbonate buffer solution at pH = 8.2). Superoxide radical and singlet oxygen mediated by Fe0 and oxygen-containing group (i.e., CO) were demonstrated as the major reactive oxygen species (ROSs) responsible for TCE dechlorination. The effectiveness and mechanism of the Fe/C composites for rectifying organic-contaminated groundwater were depicted in this study.

A comparison of the effects of natural organic matter on sulfidated and nonsulfidated nanoscale zerovalent iron colloidal stability, toxicity, and reactivity to trichloroethylene.

Sulfidated nanoscale zerovalent iron (S-NZVI) is a new remediation material with higher reactivity and greater selectivity for chlorinated organic contaminants such as trichloroethene (TCE) than NZVI. The properties of S-NZVI and the effects of groundwater constituents like natural organic matter (NOM) on its reactivity are less well-characterized than for NZVI. In this study, S-NZVI (Fe/S mole ratio = 15) was synthesized by sonicating NZVI in a Na2S solution, yielding particles with greater surface charge, less aggregation, and higher reactivity with TCE compared to NZVI. The cytotoxicity of S-NZVI was not mitigated effectively due to the smaller size. The addition of Suwannee River humic acid (SRHA) increased the negative surface charge magnitude and dispersion stability and reduced the toxicity of both NZVI and S-NZVI significantly, but also enhanced the corrosion of particles and the formation of non-conductive film. The degradation rate constant (ksa) of both NZVI and S-NZVI was thus reduced with the increasing concentration of SRHA, which decreased by 78% and 60% to be 0.0004 and 0.0053 L m-2 h-1, respectively, with 200 mg C/L SRHA. Additionally, the performance of S-NZVI in field was evaluated to be depressed in simulated groundwater and the negative effect was exacerbated with increased concentration of SRHA. Hydro-chemical conditions like dissolved oxygen (DO), pH, and temperature also influenced the reactivity of S-NZVI. Hence, S-NZVI was a preferred candidate for in-situ remediation of TCE than NZVI. Nevertheless, the integrity of the FeS shell on S-NZVI influenced by NOM need to be considered during the long-term use of S-NZVI in groundwater remediation.

Bone-derived biochar and magnetic biochar for effective removal of fluoride in groundwater: Effects of synthesis method and coexisting chromium.

The presence of fluoride in groundwater in excess of 1.5 mg L-1 is a major environmental health concern, and biochar is a promising low-cost adsorbent for the treatment of such water. In the present study, pristine and magnetic biochars were synthesized by peanut hull and bovine bone for the adsorption of fluoride. The biochars were systematically characterized by SEM-EDS, BET, XRD, VSM, FT-IR, and XPS. The experiment results showed that the magnetic biochar prepared by soaking biomass in FeCl3 solution and then pyrolyzing ("prepyrolysis") had a higher adsorption capacity than that prepared by mixing pristine biochar with Fe2+ /Fe3+ solution and then treating with NaOH ("postpyrolysis"). The bone-derived biochar and magnetic biochar exhibited high adsorption capacity of fluoride (>5 mg g-1 ) due to the presence of hydroxyapatite (HAP) and γ-Fe2 O3 . The 0.1 M NaOH solution could be optimal desorption agent, and the adsorption-desorption experiments indicated the bone biochars maintained the reasonable adsorption capacity after several cycles. Moreover, the coexisting Cr(VI) and fluoride could be removed simultaneously by bone-derived biochars. It is suggested that bovine bone-derived pristine and magnetic biochars can be used as preferential adsorbents for fluoride removal from contaminated groundwater. PRACTITIONER POINTS: Bone-derived pristine and magnetic biochars exhibit high adsorption capacity for fluoride in weakly alkaline solution. The presence of hydroxyapatite and γ-Fe2 O3 in bone-derived biochars plays an important role for fluoride adsorption. Magnetic biochars prepared by soaking biomass in FeCl3 solution and then pyrolyzing ("prepyrolysis") perform better. The coexisting Cr(VI) and fluoride can be simultaneously removed in groundwater by bone biochars.

Adsorption kinetics of magnetic biochar derived from peanut hull on removal of Cr (VI) from aqueous solution: Effects of production conditions and particle size.

Magnetic biochar was made from peanut hull biomass using iron chloride in a simplified aqueous phase approach and pyrolysis at alternative peak temperatures (450-650 °C). Magnetic biochar showed an extreme capacity for adsorption of hexavalent chromium Cr (VI) from aqueous solution, which was 1-2 orders of magnitude higher compared to standard (non-magnetic) biochar from the same feedstock. Adsorption increased with pyrolysis temperature peaking at 77,542 mg kg(-1) in the sample pyrolysed at 650 °C. In contrast to magnetic biochar, the low adsorption capacity of standard biochar decreased with increasing pyrolysis temperature. The fine particle size of magnetic biochar and low aqueous pH were also important for adsorption. Surfaces of products from batch adsorption experiments were characterized by scanning electron microscopy, energy-dispersive X-ray analysis, X-ray diffraction, X-ray photoelectron spectroscopy and vibrating sample magnetometer. This revealed that γ-Fe2O3 was crucial to the properties (adsorbance and magnetism) of magnetic biochar. The removal mechanism was the Cr (VI) electrostatic attracted on protonated -OH on γ-Fe2O3 surface and it could be desorbed by alkaline solution. Findings suggest that pyrolysis has potential to create effective, magnetically recoverable adsorbents relevant to environmental application.

Controlled synthesis of mixed-valent Fe-containing metal organic frameworks for the degradation of phenol under mild conditions.

A series of MIL-53(Fe)-type materials, Fe(BDC)(DMF,F), were prepared by using different ratios of n(FeCl3)/n(FeCl2), which have varied amounts of Fe(2+) in their frameworks. From FeCl3 to FeCl2, the structures of the synthesized samples transform from MIL-53(Fe) to Fe(BDC)(DMF,F). Along with this structure transformation, the crystal morphology goes through a striking change from a small irregular shape to a big triangular prism. This phenomenon indicates that the addition of FeCl2 is beneficial for the formation of a Fe(BDC)(DMF,F) structure. The catalytic activity of these iron-containing MOFs was tested in phenol degradation with hydrogen peroxide as an oxidant at near neutral pH and 35 °C. The degradation efficiency of these samples increases gradually from MIL-53(Fe) to Fe(BDC)(DMF,F). (57)Fe Mössbauer spectra reveal that Fe(2+) and Fe(3+) coexist in the Fe(BDC)(DMF,F) framework, and the highest amount of Fe(2+) in the sample prepared with mixed FeCl3 and FeCl2 is 26.0%. The result illustrates that the amount of Fe(2+) in the samples can be controlled using varied n(FeCl3)/n(FeCl2) in the feed. The diverse amount of Fe(2+) in this series of FeMOF materials exactly explains the distinction of reaction efficiency. The iron leaching tests, structures of the fresh and used catalysts, and the data of the recycling runs show that the Fe-containing MOFs are stable in this liquid-phase reaction.