Advances in 4-Nitrophenol Detection and Reduction Methods and Mechanisms: An Updated Review.

This review emphasizes the progress in identifying and eliminating para-nitrophenol (4-NP), a toxic organic compound. It covers various strategical methods and materials, including organic and inorganic nanomaterials, for detecting and reducing 4-NP. Detection techniques such as electrochemical methods. Optical fiber-based surface plasmon resonance and photoluminescence, as well as the mechanisms of Förster Resonance Energy Transfer (FRET) and Inner Filter Effect (IFE) in fluorescence detection, are presented. Removal techniques for this contaminant include homogeneous catalysis, electrocatalysis, photocatalysis, and thermocatalysis, and their reaction mechanisms are also discussed. Further, the theoretical perspectives of 4-NP detection and reduction, parameters influencing the activities, and future perspectives are also reviewed in detail.

αKG-mediated carnitine synthesis promotes homologous recombination via histone acetylation.

Homologous recombination (HR) deficiency enhances sensitivity to DNA damaging agents commonly used to treat cancer. In HR-proficient cancers, metabolic mechanisms driving response or resistance to DNA damaging agents remain unclear. Here we identified that depletion of alpha-ketoglutarate (αKG) sensitizes HR-proficient cells to DNA damaging agents by metabolic regulation of histone acetylation. αKG is required for the activity of αKG-dependent dioxygenases (αKGDDs), and prior work has shown that changes in αKGDD affect demethylases. Using a targeted CRISPR knockout library consisting of 64 αKGDDs, we discovered that Trimethyllysine Hydroxylase Epsilon (TMLHE), the first and rate-limiting enzyme in de novo carnitine synthesis, is necessary for proliferation of HR-proficient cells in the presence of DNA damaging agents. Unexpectedly, αKG-mediated TMLHE-dependent carnitine synthesis was required for histone acetylation, while histone methylation was affected but dispensable. The increase in histone acetylation via αKG-dependent carnitine synthesis promoted HR-mediated DNA repair through site- and substrate-specific histone acetylation. These data demonstrate for the first time that HR-proficiency is mediated through αKG directly influencing histone acetylation via carnitine synthesis and provide a metabolic avenue to induce HR-deficiency and sensitivity to DNA damaging agents.

ATR promotes mTORC1 activation via de novo cholesterol synthesis in p16-low cancer cells.

DNA damage and cellular metabolism are intricately linked with bidirectional feedback. Two of the main effectors of the DNA damage response and control of cellular metabolism are ATR and mTORC1, respectively. Prior work has placed ATR upstream of mTORC1 during replication stress, yet the direct mechanism for how mTORC1 is activated in this context remain unclear. We previously published that p16-low cells have mTORC1 hyperactivation, which in part promotes their proliferation. Using this model, we found that ATR, but not ATM, is upstream of mTORC1 activation via de novo cholesterol synthesis and is associated with increased lanosterol synthase (LSS). Indeed, p16-low cells showed increased cholesterol abundance. Additionally, knockdown of either ATR or LSS decreased mTORC1 activity. Decreased mTORC1 activity due to ATR knockdown was rescued by cholesterol supplementation. Finally, using both LSS inhibitors and multiple FDA-approved de novo cholesterol synthesis inhibitors, we found that the de novo cholesterol biosynthesis pathway is a metabolic vulnerability of p16-low cells. Together, our data provide new evidence coupling the DNA damage response and cholesterol metabolism and demonstrate the feasibility of using FDA-approved cholesterol-lowering drugs in tumors with loss of p16.

De novo purine metabolism is a metabolic vulnerability of cancers with low p16 expression.

p16 is a tumor suppressor encoded by the CDKN2A gene whose expression is lost in ~50% of all human cancers. In its canonical role, p16 inhibits the G1-S phase cell cycle progression through suppression of cyclin dependent kinases. Interestingly, p16 also has roles in metabolic reprogramming, and we previously published that loss of p16 promotes nucleotide synthesis via the pentose phosphate pathway. Whether other nucleotide metabolic genes and pathways are affected by p16/CDKN2A loss and if these can be specifically targeted in p16/CDKN2A-low tumors has not been previously explored. Using CRISPR KO libraries in multiple isogenic human and mouse melanoma cell lines, we determined that many nucleotide metabolism genes are negatively enriched in p16/CDKN2A knockdown cells compared to controls. Indeed, many of the genes that are required for survival in the context of low p16/CDKN2A expression based on our CRISPR screens are upregulated in p16 knockdown melanoma cells and those with endogenously low CDKN2A expression. We determined that cells with low p16/Cdkn2a expression are sensitive to multiple inhibitors of de novo purine synthesis, including anti-folates. Tumors with p16 knockdown were more sensitive to the anti-folate methotrexate in vivo than control tumors. Together, our data provide evidence to reevaluate the utility of these drugs in patients with p16/CDKN2A-low tumors as loss of p16/CDKN2A may provide a therapeutic window for these agents.

PDDA induced step-pyramidal growth of nickel-platinum (Ni-Pt) nanoparticles for enhanced 4-nitrophenol reduction.

Herein, we report the synthesis of novel platinum-based nanoparticles with step-pyramidal growth induced by poly(diallyldimethylammonium chloride) (PDDA). The complex stepped pyramidal shape became the central point for outstanding catalytic reduction of 4-nitrophenol, overcoming the activity of bare Pt nanoparticles. These results are valuable for the catalytic degradation of reactive molecules.

ATM inhibition drives metabolic adaptation via induction of macropinocytosis.

Macropinocytosis is a nonspecific endocytic process that may enhance cancer cell survival under nutrient-poor conditions. Ataxia-Telangiectasia mutated (ATM) is a tumor suppressor that has been previously shown to play a role in cellular metabolic reprogramming. We report that the suppression of ATM increases macropinocytosis to promote cancer cell survival in nutrient-poor conditions. Combined inhibition of ATM and macropinocytosis suppressed proliferation and induced cell death both in vitro and in vivo. Supplementation of ATM-inhibited cells with amino acids, branched-chain amino acids (BCAAs) in particular, abrogated macropinocytosis. Analysis of ATM-inhibited cells in vitro demonstrated increased BCAA uptake, and metabolomics of ascites and interstitial fluid from tumors indicated decreased BCAAs in the microenvironment of ATM-inhibited tumors. These data reveal a novel basis of ATM-mediated tumor suppression whereby loss of ATM stimulates protumorigenic uptake of nutrients in part via macropinocytosis to promote cancer cell survival and reveal a potential metabolic vulnerability of ATM-inhibited cells.

Combination of Paraconiothyrium brasiliense fabricated titanium dioxide nanoparticle and antibiotics enhanced antibacterial and antibiofilm properties: A toxicity evaluation.

Antimicrobial resistance (AMR) causes global consequences through increased mortality and economic loss. Antimicrobial drugs including nanomaterials are an emerging environmental impact. Hence, this work aimed to synthesize and characterize the titanium dioxide nanoparticles (TiO2 NPs) using the aqueous extract of endophytic fungus Paraconiothyrium brasiliense (Pb) for enhancing the antibacterial efficiency of existing standard antibiotics at minimum concentration. The FTIR and XRD results confirmed the capping of functional molecules and the crystalline nature of Pb-TiO2 NPs. The spherical-shaped TiO2 NPs with the size of 57.39 ± 13.65 nm were found in TEM analysis. The average hydrodynamic size (68.43 ± 1.49 d. nm) and the zeta potential (-19.6 ± 1.49 mV) was confirmed the stability of Pb-TiO2 NPs. Antibacterial studies revealed that bare Pb-TiO2 NPs (20 µg/mL) did not exhibit significant antibacterial activity while combination of TCH + Pb-TiO2 NPs considerably increased the inhibition of E. coli biofilm evidenced by CLSM and SEM analysis. Further, Pb-TiO2 NPs (100 µg/mL) were found to be moderately toxic to cell line (NIH3T3), red blood cells (RBC), and egg embryos. Hence, this study concluded that <50 µg/mL of TiO2 NPs can be mixed with antibiotics for enhanced antibacterial application thereby minimizing the AMR and the environmental toxicity.

Heavy metal ion detection using green precursor derived carbon dots.

The discovery of carbon dots (CDs) for environmental remediation has gained awareness because of the diverse economically viable and environmental friendly green precursors generated from biowastes and biomass compared to the toxic inorganic quantum dots and CDs prepared from chemical precursors. This review presents the recent progress in green CDs, including their synthesis methods and sensing applications for the detection of heavy metal ions such as Iron (III), Mercury (II), Copper (II), Chromium (VI), Lead (II), Arsenic (III), Cobalt (II), Aluminum (III), Silver (I), and Gold (III) which are prominent environmental pollutants. The comparison based on selectivity, sensitivity, quantum yield, detection limit, linear concentration range, and sensing mechanisms are also reported. This review also covers the performance of doped green CDs using heteroatoms, toward the detection of heavy metal ions. Apart from the future perspectives, this review provides a general guide to use such environmental friendly CDs to detect harmful pollutants.

DOT1L modulates the senescence-associated secretory phenotype through epigenetic regulation of IL1A.

Oncogene-induced senescence (OIS) is a stable cell cycle arrest that occurs in normal cells upon oncogene activation. Cells undergoing OIS express a wide variety of secreted factors that affect the senescent microenvironment termed the senescence-associated secretory phenotype (SASP), which is beneficial or detrimental in a context-dependent manner. OIS cells are also characterized by marked epigenetic changes. We globally assessed histone modifications of OIS cells and discovered an increase in the active histone marks H3K79me2/3. The H3K79 methyltransferase disruptor of telomeric silencing 1-like (DOT1L) was necessary and sufficient for increased H3K79me2/3 occupancy at the IL1A gene locus, but not other SASP genes, and was downstream of STING. Modulating DOT1L expression did not affect the cell cycle arrest. Together, our studies establish DOT1L as an epigenetic regulator of the SASP, whose expression is uncoupled from the senescence-associated cell cycle arrest, providing a potential strategy to inhibit the negative side effects of senescence while maintaining the beneficial inhibition of proliferation.

Synthesis of cetyl trimethyl ammonium bromide (CTAB) capped copper oxide nanocubes for the remediation of organic pollutants using photocatalysis and catalysis.

The aim of this report is to synthesize copper oxide nanocubes (CuO NCs) at room temperature, using sodium borohydride as a reducing agent, and Cetyl Trimethyl Ammonium Bromide (CTAB) as a stabilizing agent. The crystallinity and morphology of the synthesized CuO NCs are investigated via X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscope (TEM). The optical properties were analyzed by means of UV-visible absorbance and Raman spectroscopy. The existence of specific functional groups and structural stability were established via FTIR spectroscopy and thermogravimetric analysis (TGA). Furthermore, the catalytic efficiency of the as-prepared CuO NCs was tested using catalytic and photocatalytic studies of para-nitrophenol (p-NP) reduction and methylene blue (MB) degradation, respectively. The catalytic results demonstrated the nanocubes' excellent catalytic and photocatalytic responses with respect to the abatement of p-NP and MB within 50 s and 240 min, with kinetic rate constants of 3.9 × 10-2 s-1 and 6.47 × 10-3 min-1, respectively.

Investigating the accuracy of imputing autosomal variants in Nellore cattle using the ARS-UCD1.2 assembly of the bovine genome.

BACKGROUND: Imputation accuracy among other things depends on the size of the reference panel, the marker's minor allele frequency (MAF), and the correct placement of single nucleotide polymorphism (SNP) on the reference genome assembly. Using high-density genotypes of 3938 Nellore cattle from Brazil, we investigated the accuracy of imputation from 50 K to 777 K SNP density using Minimac3, when map positions were determined according to the bovine genome assemblies UMD3.1 and ARS-UCD1.2. We assessed the effect of reference and target panel sizes on the pre-phasing based imputation quality using ten-fold cross-validation. Further, we compared the reliability of the model-based imputation quality score (Rsq) from Minimac3 to the empirical imputation accuracy. RESULTS: The overall accuracy of imputation measured as the squared correlation between true and imputed allele dosages (R2dose) was almost identical using either the UMD3.1 or ARS-UCD1.2 genome assembly. When the size of the reference panel increased from 250 to 2000, R2dose increased from 0.845 to 0.917, and the number of polymorphic markers in the imputed data set increased from 586,701 to 618,660. Advantages in both accuracy and marker density were also observed when larger target panels were imputed, likely resulting from more accurate haplotype inference. Imputation accuracy increased from 0.903 to 0.913, and the marker density in the imputed data increased from 593,239 to 595,570 when haplotypes were inferred in 500 and 2900 target animals. The model-based imputation quality scores from Minimac3 (Rsq) were systematically higher than empirically estimated accuracies. However, both metrics were positively correlated and the correlation increased with the size of the reference panel and MAF of imputed variants. CONCLUSIONS: Accurate imputation of BovineHD BeadChip markers is possible in Nellore cattle using the new bovine reference genome assembly ARS-UCD1.2. The use of large reference and target panels improves the accuracy of the imputed genotypes and provides genotypes for more markers segregating at low frequency for downstream genomic analyses. The model-based imputation quality score from Minimac3 (Rsq) can be used to detect poorly imputed variants but its reliability depends on the size of the reference panel and MAF of the imputed variants.

Newborn Screening for Mucopolysaccharidoses: Results of a Pilot Study with 100 000 Dried Blood Spots.

OBJECTIVE: To test, in a newborn screening (NBS) laboratory, the performance of liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assay 5 enzymatic activities in dried blood spots (DBS) for NBS of 5 lysosomal storage diseases (mucopolysaccharidosis [MPS]-II, MPS-IIIB, MPS-IVA, MPS-VI, and MPS-VII). STUDY DESIGN: Three mm punches from de-identified DBS were obtained from the Washington NBS laboratory and submitted to the 5-plex LC-MS/MS assay. Screen cut-offs were established by analyzing the enzymatic activity in patients confirmed to have the MPS disorder. DNA sequencing of the relevant gene was performed on a second DBS punch for all samples with enzyme activity below 10% of the mean daily activity. RESULTS: (1) For MPS-II, 18 below cut-off samples, 1 pathogenic genotype, and 2 "high risk" genotypes; (2) For MPS-IIIB, no below cut-off samples; (3) For MPS-IVA, 8 below cut-off samples, 4 non-pathogenic genotypes, 4 genotypes unobtainable; (4) For MPS-VI, 4 below cut-off samples and no high-risk genotypes; (5) For MPS-VII, 1 below cut-off sample confirmed by genotype and clinical report to be affected. CONCLUSIONS: These results establish that the number of initial screen positive samples is low and manageable. Thus, population newborn screening for these conditions is feasible in a state newborn screening laboratory.

Nitrogen-Doped Graphene Oxide Dots-Based "Turn-OFF" H2O2, Au(III), and "Turn-OFF-ON" Hg(II) Sensors as Logic Gates and Molecular Keypad Locks.

Fluorescent nitrogen-doped graphene oxide dots (NGODs) have been demonstrated as an on-off nanosensor for the detection of Hg2+, Au3+, and H2O2. As compared to l-cystine, where the luminescence signal recovery results from the detachment of Hg2+ from the NGODs, signal recovery through l-ascorbic acid (turn-off-on model) has been attributed to the reduction of Hg2+ to Hg0. The sustainable recovery of the photoluminescence signal is demonstrated using common citrus fruits containing vitamin C (l-AA), suggesting a promising practical usage of this sensing system. Additionally, the sensitivity of NGOD- and AA-originated signal recovery from the Hg(II)-NGODs mixture has been successfully tested in Hg2+ ion-spiked tap water from three different places. Mimic devices were executed and verified on the basis of characteristic spectral changes, and the possible utility of this system in electronic security and memory element devices has also been demonstrated. Considering an easy synthesis process and excellent performance of NGODs, this investigation opens up new opportunities for preparing high-quality fluorescent NGODs to meet the requirements of many applications.

Taiwan National Newborn Screening Program by Tandem Mass Spectrometry for Mucopolysaccharidoses Types I, II, and VI.

OBJECTIVE: To evaluate the initial cutoff values, rates of screen positives, and genotypes for the large-scale newborn screening program for multiple mucopolysaccharidoses (MPS) in Taiwan. STUDY DESIGN: More than 100 000 dried blood spots were collected consecutively as part of the national Taiwan newborn screening programs. Enzyme activities were measured by tandem mass spectrometry from dried blood spot punches. Genotypes were obtained when a second newborn screening specimen again had a decreased enzyme activity. Additional clinical evaluation was then initiated based on enzyme activity and/or genotype. RESULTS: Molecular genetic analysis for cases with low enzyme activity revealed 5 newborns with pathogenic alpha-L-iduronidase mutations, 3 newborns with pathogenic iduronate-2-sulfatase mutations, and 1 newborn was a carrier of an arylsulfatase B mutation. Several variants of unknown pathogenic significance were also identified, most likely causing pseudodeficiency. CONCLUSIONS: The highly robust tandem mass spectrometry-based enzyme assays for MPS-I, MPS-II, and MPS-VI allow for high-throughput newborn screening for these lysosomal storage disorders. Optimized cutoff values combined with second tier testing could largely eliminate false-positive results. Accordingly, newborn screening for these lysosomal storage disorders is possible.

Simultaneous biodegradation of phenol and cyanide present in coke-oven effluent using immobilized Pseudomonas putida and Pseudomonas stutzeri

ABSTRACT Discharge of coke-oven wastewater to the environment may cause severe contamination to it and also threaten the flora and fauna, including human beings. Hence before dumping it is necessary to treat this dangerous effluent in order to minimize the damage to the environment. Conventional technologies have inherent drawbacks however, biological treatment is an advantageous alternative method. In the present study, bacteria were isolated from the soil collected from the sites contaminated by coke-oven effluent rich in phenol and cyanide. Nucleotides sequence alignment and phylogenetic analysis showed the identity of the selected phenol and cyanide degrading isolates NAUN-16 and NAUN-1B as Pseudomonas putida and Pseudomonas stutzeri, respectively. These two isolates tolerated phenol up to 1800 mg L-1 and cyanide up to 340 mg L-1 concentrations. The isolates were immobilized on activated charcoal, saw dust and fly ash. The effluent was passed through the column packed with immobilized cells with a flow rate of 5 mL min-1. The isolates showed degradation of phenol up to 80.5% and cyanide up to 80.6% and also had the ability to reduce biological oxygen demand, chemical oxygen demand and lower the pH of effluent from alkaline to near neutral. The study suggests the utilization of such potential bacterial strains in treating industrial effluent containing phenol and cyanide, before being thrown in any ecosystem.

Simultaneous biodegradation of phenol and cyanide present in coke-oven effluent using immobilized Pseudomonas putida and Pseudomonas stutzeri

Discharge of coke-oven wastewater to the environment may cause severe contamination to it and also threaten the flora and fauna, including human beings. Hence before dumping it is necessary to treat this dangerous effluent in order to minimize the damage to the environment. Conventional technologies have inherent drawbacks however, biological treatment is an advantageous alternative method. In the present study, bacteria were isolated from the soil collected from the sites contaminated by coke-oven effluent rich in phenol and cyanide. Nucleotides sequence alignment and phylogenetic analysis showed the identity of the selected phenol and cyanide degrading isolates NAUN-16 and NAUN-1B as Pseudomonas putida and Pseudomonas stutzeri, respectively. These two isolates tolerated phenol up to 1800 mg L-1 and cyanide up to 340 mg L-1 concentrations. The isolates were immobilized on activated charcoal, saw dust and fly ash. The effluent was passed through the column packed with immobilized cells with a flow rate of 5 mL min-1. The isolates showed degradation of phenol up to 80.5% and cyanide up to 80.6% and also had the ability to reduce biological oxygen demand, chemical oxygen demand and lower the pH of effluent from alkaline to near neutral. The study suggests the utilization of such potential bacterial strains in treating industrial effluent containing phenol and cyanide, before being thrown in any ecosystem.(AU)

Simultaneous biodegradation of phenol and cyanide present in coke-oven effluent using immobilized Pseudomonas putida and Pseudomonas stutzeri.

Discharge of coke-oven wastewater to the environment may cause severe contamination to it and also threaten the flora and fauna, including human beings. Hence before dumping it is necessary to treat this dangerous effluent in order to minimize the damage to the environment. Conventional technologies have inherent drawbacks however, biological treatment is an advantageous alternative method. In the present study, bacteria were isolated from the soil collected from the sites contaminated by coke-oven effluent rich in phenol and cyanide. Nucleotides sequence alignment and phylogenetic analysis showed the identity of the selected phenol and cyanide degrading isolates NAUN-16 and NAUN-1B as Pseudomonas putida and Pseudomonas stutzeri, respectively. These two isolates tolerated phenol up to 1800mgL-1 and cyanide up to 340mgL-1 concentrations. The isolates were immobilized on activated charcoal, saw dust and fly ash. The effluent was passed through the column packed with immobilized cells with a flow rate of 5mLmin-1. The isolates showed degradation of phenol up to 80.5% and cyanide up to 80.6% and also had the ability to reduce biological oxygen demand, chemical oxygen demand and lower the pH of effluent from alkaline to near neutral. The study suggests the utilization of such potential bacterial strains in treating industrial effluent containing phenol and cyanide, before being thrown in any ecosystem.

Sensitivity pattern of Salmonella serotypes in Northern India

BACKGROUND: Enteric fever continues to be a major public health problem, especially in the developing countries of the tropics. We determined the incidence of Salmonella bloodstream infections and their antimicrobial resistance patterns from May to August in the years 1997-2001 in Haryana, a large state of India. The minimum inhibitory concentration (MIC) was also determined for 60 isolates of S. typhi to various commonly used antimicrobial agents. MATERIAL AND METHODS: Blood cultures of 6,956 patients (PUO/septicemia) were processed by standard procedures and the Salmonella spp. isolates were identified with specific antisera and with standard biochemical tests. Antimicrobial susceptibilities were determined by Stokes disc diffusion method. The MIC of 60 randomly isolated strains of S. typhi was determined by agar dilution method using Mueller Hinton Agar medium. RESULTS: Isolation rates of Salmonella spp. increased in 2000 and 2001. Multidrug resistance (MDR) in S. typhi had increased while in S. paratyphi it had decreased markedly. Ninety per cent chloramphenicol sensitivity was seen in S. typhi by MIC method. There was a decrease in the susceptibility to ciprofloxacin of S. typhi with MIC showing an upward trend. All S. typhi tested were sensitive to third generation cephalosporins and aminoglycosides with MIC well below the breakpoint. DISCUSSION: Our study indicates that MDR in S. typhi is on the rise in our area. There is also re-emergence of chloramphenicol sensitivity. Rising MIC values of ciprofloxacin may lead to prolonged treatment, delayed recovery or pose treatment failure. Thus, sensitivity pattern of causative organism must be sought before instituting appropriate therapy to prevent further emergence of drug resistance.

Sensitivity pattern of Salmonella serotypes in Northern India.

BACKGROUND: Enteric fever continues to be a major public health problem, especially in the developing countries of the tropics. We determined the incidence of Salmonella bloodstream infections and their antimicrobial resistance patterns from May to August in the years 1997-2001 in Haryana, a large state of India. The minimum inhibitory concentration (MIC) was also determined for 60 isolates of S. typhi to various commonly used antimicrobial agents. MATERIAL AND METHODS: Blood cultures of 6,956 patients (PUO/septicemia) were processed by standard procedures and the Salmonella spp. isolates were identified with specific antisera and with standard biochemical tests. Antimicrobial susceptibilities were determined by Stokes disc diffusion method. The MIC of 60 randomly isolated strains of S. typhi was determined by agar dilution method using Mueller Hinton Agar medium. RESULTS: Isolation rates of Salmonella spp. increased in 2000 and 2001. Multidrug resistance (MDR) in S. typhi had increased while in S. paratyphi it had decreased markedly. Ninety per cent chloramphenicol sensitivity was seen in S. typhi by MIC method. There was a decrease in the susceptibility to ciprofloxacin of S. typhi with MIC showing an upward trend. All S. typhi tested were sensitive to third generation cephalosporins and aminoglycosides with MIC well below the breakpoint. DISCUSSION: Our study indicates that MDR in S. typhi is on the rise in our area. There is also re-emergence of chloramphenicol sensitivity. Rising MIC values of ciprofloxacin may lead to prolonged treatment, delayed recovery or pose treatment failure. Thus, sensitivity pattern of causative organism must be sought before instituting appropriate therapy to prevent further emergence of drug resistance.