Extension of nature's NIR-I chromophore into the NIR-II region.

The development of chromophores that absorb in the near-infrared (NIR) region beyond 1000 nm underpins numerous applications in medical and energy sciences, yet also presents substantial challenges to molecular design and chemical synthesis. Here, the core bacteriochlorin chromophore of nature's NIR absorbers, bacteriochlorophylls, has been adapted and tailored by annulation in an effort to achieve absorption in the NIR-II region. The resulting bacteriochlorin, Phen2,1-BC, contains two annulated naphthalene groups spanning meso,ß-positions of the bacteriochlorin and the 1,2-positions of the naphthalene. Phen2,1-BC was prepared via a new synthetic route. Phen2,1-BC is an isomer of previously examined Phen-BC, which differs only in attachment via the 1,8-positions of the naphthalene. Despite identical π-systems, the two bacteriochlorins have distinct spectroscopic and photophysical features. Phen-BC has long-wavelength absorption maximum (912 nm), oscillator strength (1.0), and S1 excited-state lifetime (150 ps) much different than Phen2,1-BC (1292 nm, 0.23, and 0.4 ps, respectively). These two molecules and an analogue with intermediate characteristics bearing annulated phenyl rings have unexpected properties relative to those of non-annulated counterparts. Understanding the distinctions requires extending concepts beyond the four-orbital-model description of tetrapyrrole spectroscopic features. In particular, a reduction in symmetry resulting from annulation results in electronic mixing of x- and y-polarized transitions/states, as well as vibronic coupling that together reduce oscillator strength of the long-wavelength absorption manifold and shorten the S1 excited-state lifetime. Collectively, the results suggest a heuristic for the molecular design of tetrapyrrole chromophores for deep penetration into the relatively unutilized NIR-II region.

CC Chemokine Family Members' Modulation as a Novel Approach for Treating Central Nervous System and Peripheral Nervous System Injury-A Review of Clinical and Experimental Findings.

Despite significant progress in modern medicine and pharmacology, damage to the nervous system with various etiologies still poses a challenge to doctors and scientists. Injuries lead to neuroimmunological changes in the central nervous system (CNS), which may result in both secondary damage and the development of tactile and thermal hypersensitivity. In our review, based on the analysis of many experimental and clinical studies, we indicate that the mechanisms occurring both at the level of the brain after direct damage and at the level of the spinal cord after peripheral nerve damage have a common immunological basis. This suggests that there are opportunities for similar pharmacological therapeutic interventions in the damage of various etiologies. Experimental data indicate that after CNS/PNS damage, the levels of 16 among the 28 CC-family chemokines, i.e., CCL1, CCL2, CCL3, CCL4, CCL5, CCL6, CCL7, CCL8, CCL9, CCL11, CCL12, CCL17, CCL19, CCL20, CCL21, and CCL22, increase in the brain and/or spinal cord and have strong proinflammatory and/or pronociceptive effects. According to the available literature data, further investigation is still needed for understanding the role of the remaining chemokines, especially six of them which were found in humans but not in mice/rats, i.e., CCL13, CCL14, CCL15, CCL16, CCL18, and CCL23. Over the past several years, the results of studies in which available pharmacological tools were used indicated that blocking individual receptors, e.g., CCR1 (J113863 and BX513), CCR2 (RS504393, CCX872, INCB3344, and AZ889), CCR3 (SB328437), CCR4 (C021 and AZD-2098), and CCR5 (maraviroc, AZD-5672, and TAK-220), has beneficial effects after damage to both the CNS and PNS. Recently, experimental data have proved that blockades exerted by double antagonists CCR1/3 (UCB 35625) and CCR2/5 (cenicriviroc) have very good anti-inflammatory and antinociceptive effects. In addition, both single (J113863, RS504393, SB328437, C021, and maraviroc) and dual (cenicriviroc) chemokine receptor antagonists enhanced the analgesic effect of opioid drugs. This review will display the evidence that a multidirectional strategy based on the modulation of neuronal-glial-immune interactions can significantly improve the health of patients after CNS and PNS damage by changing the activity of chemokines belonging to the CC family. Moreover, in the case of pain, the combined administration of such antagonists with opioid drugs could reduce therapeutic doses and minimize the risk of complications.

Design, Synthesis and Biological Evaluation of Novel Phenyl-Substituted Naphthoic Acid Ethyl Ester Derivatives as Strigolactone Receptor Inhibitor.

Strigolactones (SLs) are plant hormones that regulate several key agronomic traits, including shoot branching, leaf senescence, and stress tolerance. The artificial regulation of SL biosynthesis and signaling has been considered as a potent strategy in regulating plant architecture and combatting the infection of parasitic weeds to help improve crop yield. DL1b is a previously reported SL receptor inhibitor molecule that significantly promotes shoot branching. Here, we synthesized 18 novel compounds based on the structure of DL1b. We performed rice tillering activity assay and selected a novel small molecule, C6, as a candidate SL receptor inhibitor. In vitro bioassays demonstrated that C6 possesses various regulatory functions as an SL inhibitor, including inhibiting germination of the root parasitic seeds Phelipanche aegyptiaca, delaying leaf senescence and promoting hypocotyl elongation of Arabidopsis. ITC analysis and molecular docking experiments further confirmed that C6 can interact with SL receptor proteins, thereby interfering with the binding of SL to its receptor. Therefore, C6 is considered a novel SL receptor inhibitor with potential applications in plant architecture control and prevention of root parasitic weed infestation.

Determination of genotoxic impurities of aromatic aldehydes in pharmaceutical preparations by high performance liquid chromatography after derivatization with N-Cyclohexyl-4-hydrazino-1,8-naphthalenediimide.

The detection of aromatic aldehydes, considered potential genotoxic impurities, holds significant importance during drug development and production. Current analytical methods necessitate complex pre-treatment processes and exhibit insufficient specificity and sensitivity. This study presents the utilization of naphthalenediimide as a pre-column derivatisation reagent to detect aromatic aldehyde impurities in pharmaceuticals via high-performance liquid chromatography (HPLC). We screened a series of derivatisation reagents through density functional theory (DFT) and investigated the phenomenon of photoinduced electron transfer (PET) for both the derivatisation reagents and the resulting products. Optimal experimental conditions for derivatisation were achieved at 40 °C for 60 min. This approach has been successfully applied to detect residual aromatic aldehyde genotoxic impurities in various pharmaceutical preparations, including 4-Nitrobenzaldehyde, 2-Nitrobenzaldehyde, 1,4-Benzodioxane-6-aldehyde, and 5-Hydroxymethylfurfural. The pre-column derivatisation method significantly enhanced detection sensitivity and reduced the limit of detection (LOD), which ranged from 0.002 to 0.008 µg/ml for the analytes, with relative standard deviations < 3 %. The correlation coefficient (R2) >0.998 demonstrated high quality. In chloramphenicol eye drops, the concentration of 4-Nitrobenzaldehyde was measured to be 8.6 µg/mL below the specified concentration, with recoveries ranging from 90.0 % to 119.2 %. In comparison to existing methods, our work simplifies the pretreatment process, enhances the sensitivity and specificity of the analysis, and offers comprehensive insights into impurity detection in pharmaceutical preparations.

Dual channel chemosensor for successive detection of environmentally toxic Pd2+ and CN- ions and its application to cancer cell imaging.

BACKGROUND: Detecting and neutralizing Pd2+ ions are a significant challenge due to their cytotoxicity, even at low concentrations. To address this issue, various chemosensors have been designed for advanced detection systems, offering simplicity and the potential to differentiate signals from different analytes. Nonetheless, these chemosensors often suffer from limited emission response and complex synthesis procedures. As a result, the tracking and quantification of residual palladium in biological systems and environments remain challenging tasks, with only a few chemosensing probes available for commercial use. RESULTS: In this paper, a straightforward approach for the selective detection of Pd2+ ions is proposed, which involves the design, synthesis, and utilization of a propargylated naphthalene-derived probe (E)-N'-((2-(prop-2-yn-1-yloxy)naphthalen-1-yl)methylene)benzohydrazide (NHP). The NHP probe exhibits sensitive dual-channel colorimetry and fluorescence Pd2+ detection over other tested metal ions. The detection process is performed through a catalytic depropargylation reaction, followed by an excited state intramolecular proton transfer (ESIPT) process, the detection limit is as low as 11.58 × 10-7 M under mild conditions. Interestingly, the resultant chemodosimeter adduct (E)-N'-((2-hydroxynaphthalen-1-yl)methylene)benzohydrazide (NHH) was employed for the consecutive detection of CN- ions, exhibiting an impressive detection limit of 31.79 × 10-8 M. Validation of both detection processes was achieved through 1H nuclear magnetic resonance and density functional theory calculations. For real-time applications of the NHP and NHH probes, smartphone-assisted detection, and intracellular detection of Pd2+ and CN- ions within HeLa cells were studied. SIGNIFICANCE: This research presents a novel naphthalene derivative for visually detecting environmentally toxic Pd2+ and CN- ions. The synthesized probe selectively binds to Pd2+, forming a chemodosimeter. It successfully detects CN- ions through colorimetry and fluorimetry, offering a low detection limit and quick response. Notably, it's the first naphthalene-based small molecule to serve as a dual probe for toxic analytes - palladium and cyanide. Moreover, it effectively detects Pd2+ and CN- intracellularly in cancer cells.

Supermolecular Confined Silicon Phosphorescence Nanoprobes for Time-Resolved Hypoxic Imaging Analysis.

Room temperature phosphorescence (RTP) nanoprobes play crucial roles in hypoxia imaging due to their high signal-to-background ratio (SBR) in the time domain. However, synthesizing RTP probes in aqueous media with a small size and high quantum yield remains challenging for intracellular hypoxic imaging up to present. Herein, aqueous RTP nanoprobes consisting of naphthalene anhydride derivatives, cucurbit[7]uril (CB[7]), and organosilicon are reported via supermolecular confined methods. Benefiting from the noncovalent confinement of CB[7] and hydrolysis reactions of organosilicon, such small-sized RTP nanoprobes (5-10 nm) exhibit inherent tunable phosphorescence (from 400 to 680 nm) with microsecond second lifetimes (up to ∼158.7 µs) and high quantum yield (up to ∼30%). The as-prepared RTP nanoprobes illustrate excellent intracellular hypoxia responsibility in a broad range from ∼0.1 to 21% oxygen concentrations. Compared to traditional fluorescence mode, the SBR value (∼108.69) of microsecond-range time-resolved in vitro imaging is up to 2.26 times greater in severe hypoxia (<0.1% O2), offering opportunities for precision imaging analysis in a hypoxic environment.

Effects of Cannabidiol, ∆9-Tetrahydrocannabinol, and WIN 55-212-22 on the Viability of Canine and Human Non-Hodgkin Lymphoma Cell Lines.

In our previous study, we demonstrated the impact of overexpression of CB1 and CB2 cannabinoid receptors and the inhibitory effect of endocannabinoids (2-arachidonoylglycerol (2-AG) and Anandamide (AEA)) on canine (Canis lupus familiaris) and human (Homo sapiens) non-Hodgkin lymphoma (NHL) cell lines' viability compared to cells treated with a vehicle. The purpose of this study was to demonstrate the anti-cancer effects of the phytocannabinoids, cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), and the synthetic cannabinoid WIN 55-212-22 (WIN) in canine and human lymphoma cell lines and to compare their inhibitory effect to that of endocannabinoids. We used malignant canine B-cell lymphoma (BCL) (1771 and CLB-L1) and T-cell lymphoma (TCL) (CL-1) cell lines, and human BCL cell line (RAMOS). Our cell viability assay results demonstrated, compared to the controls, a biphasic effect (concentration range from 0.5 µM to 50 µM) with a significant reduction in cancer viability for both phytocannabinoids and the synthetic cannabinoid. However, the decrease in cell viability in the TCL CL-1 line was limited to CBD. The results of the biochemical analysis using the 1771 BCL cell line revealed a significant increase in markers of oxidative stress, inflammation, and apoptosis, and a decrease in markers of mitochondrial function in cells treated with the exogenous cannabinoids compared to the control. Based on the IC50 values, CBD was the most potent phytocannabinoid in reducing lymphoma cell viability in 1771, Ramos, and CL-1. Previously, we demonstrated the endocannabinoid AEA to be more potent than 2-AG. Our study suggests that future studies should use CBD and AEA for further cannabinoid testing as they might reduce tumor burden in malignant NHL of canines and humans.

The Mechanism of Inhibition of Mycobacterial (p)ppGpp Synthetases by a Synthetic Analog of Erogorgiaene.

The synthesis of (p)ppGpp alarmones plays a vital role in the regulation of metabolism suppression, growth rate control, virulence, bacterial persistence, and biofilm formation. The (p)ppGpp alarmones are synthesized by proteins of the RelA/SpoT homolog (RSH) superfamily, including long bifunctional RSH proteins and small alarmone synthetases. Here, we investigated enzyme kinetics and dose-dependent enzyme inhibition to elucidate the mechanism of 4-(4,7-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)pentanoic acid (DMNP) action on the (p)ppGpp synthetases RelMsm and RelZ from Mycolicibacterium smegmatis and RelMtb from Mycobacterium tuberculosis. DMNP was found to inhibit the activity of RelMtb. According to the enzyme kinetics analysis, DMNP acts as a noncompetitive inhibitor of RelMsm and RelZ. Based on the results of molecular docking, the DMNP-binding site is located in the proximity of the synthetase domain active site. This study might help in the development of alarmone synthetase inhibitors, which includes relacin and its derivatives, as well as DMNP - a synthetic analog of the marine coral metabolite erogorgiaene. Unlike conventional antibiotics, alarmone synthetase inhibitors target metabolic pathways linked to the bacterial stringent response. Although these pathways are not essential for bacteria, they regulate the development of adaptation mechanisms. Combining conventional antibiotics that target actively growing cells with compounds that impede bacterial adaptation may address challenges associated with antimicrobial resistance and bacterial persistence.

A dual-targeting antifungal is effective against multidrug-resistant human fungal pathogens.

Drug-resistant fungal infections pose a significant threat to human health. Dual-targeting compounds, which have multiple targets on a single pathogen, offer an effective approach to combat drug-resistant pathogens, although ensuring potent activity and high selectivity remains a challenge. Here we propose a dual-targeting strategy for designing antifungal compounds. We incorporate DNA-binding naphthalene groups as the hydrophobic moieties into the host defence peptide-mimicking poly(2-oxazoline)s. This resulted in a compound, (Gly0.8Nap0.2)20, which targets both the fungal membrane and DNA. This compound kills clinical strains of multidrug-resistant fungi including Candida spp., Cryptococcus neoformans, Cryptococcus gattii and Aspergillus fumigatus. (Gly0.8Nap0.2)20 shows superior performance compared with amphotericin B by showing not only potent antifungal activities but also high antifungal selectivity. The compound also does not induce antimicrobial resistance. Moreover, (Gly0.8Nap0.2)20 exhibits promising in vivo therapeutic activities against drug-resistant Candida albicans in mouse models of skin abrasion, corneal infection and systemic infection. This study shows that dual-targeting antifungal compounds may be effective in combating drug-resistant fungal pathogens and mitigating fungal resistance.

Evaluating workplace protection factors (WPFs) of different firefighter PPE interface control measures for select volatile organic compounds (VOCs).

Structural firefighters are exposed to a complex set of contaminants and combustion byproducts, including volatile organic compounds (VOCs). Additionally, recent studies have found structural firefighters' skin may be exposed to multiple chemical compounds via permeation or penetration of chemical byproducts through or around personal protective equipment (PPE). This mannequin-based study evaluated the effectiveness of four different PPE conditions with varying contamination control measures (incorporating PPE interface design features and particulate blocking materials) to protect against ingress of several VOCs in a smoke exposure chamber. We also investigated the effectiveness of long-sleeve base layer clothing to provide additional protection against skin contamination. Outside gear air concentrations were measured from within the smoke exposure chamber at the breathing zone, abdomen, and thigh heights. Personal air concentrations were collected from mannequins under PPE at the same general heights and under the base layer at abdomen and thigh heights. Sampled contaminants included benzene, toluene, styrene, and naphthalene. Results suggest that VOCs can readily penetrate the ensembles. Workplace protection factors (WPFs) were near one for benzene and toluene and increased with increasing molecular weight of the contaminants. WPFs were generally lower under hoods and jackets compared to under pants. For all PPE conditions, the pants appeared to provide the greatest overall protection against ingress of VOCs, but this may be due in part to the lower air concentrations toward the floor (and cuffs of pants) relative to the thigh-height outside gear concentrations used in calculating the WPFs. Providing added interface control measures and adding particulate-blocking materials appeared to provide a protective benefit against less-volatile chemicals, like naphthalene and styrene.

Insights into the hydrolysis/alcoholysis/ammonolysis mechanisms of ethylene naphthalate dimer using density functional theory (DFT) method.

Hydrolysis, alcoholysis and ammonolysis are viable routes for the efficient degradation and recycling of polyethylene naphthalate (PEN) plastic waste. Various possible hydrolysis/alcoholysis/ammonolysis reaction pathways for the degradation mechanism of the ethylene naphthalate dimer were investigated using the density functional theory (DFT) B3P86/6-31++G(d,p). To determine the thermodynamic and kinetic parameters, geometric structure optimization and frequency calculation were performed on a range of intermediates, transition states, and products associated with the reaction. The calculation results show that the highest energy barrier of the main element reaction step in hydrolysis is about 169.0 kJ/mol, the lowest is about 151.0 kJ/mol for ammonolysis, and the second is about 155.0 kJ/mol for alcoholysis. The main hydrolysis products of the ethylene naphthalate dimer are 2,6-naphthalenedicarboxylic acid and ethylene glycol; the main products of alcoholysis are dimethyl naphthalene-2,6-dicarboxylate and ethylene glycol, and the main products of ammonolysis are naphthalene-2,6-dicarboxamide and ethylene glycol. Furthermore, in the process of ethylene naphthalate dimer hydrolysis/alcoholysis/ammonolysis, the decomposition reaction in the NH3 atmosphere is better than that in methanol, and the reaction in CH3OH is better than that in the H2O molecular environment, and the increase in reaction temperature can increase its spontaneity. Our study presents the molecular mechanism of PEN hydrolysis/alcoholysis/ammonolysis and provides a reference for studying the degradation of other plastic wastes.

Isolation of undescribed cladosporols and spirobisnaphthalenes from a plant pathogen Cladosporium cladosporioides F-10-2-A.

Two undescribed cladosporol derivatives, cladosporols J-K (1-2), and three previously unreported spirobisnaphthalenes, urnucratins D-F (3-5), as well as eleven known cladosporols (6-16), were characterized from Cladosporium cladosporioides (Cladosporiaceae), a common plant pathogen isolated from the skin of Chinese toad. Cladosporols J-K (1-2) with a single double bond have been rarely reported, while urnucratins D-F (3-5) featured an unusual benzoquinone bisnaphthospiroether skeleton, contributing to an expanding category of undiscovered natural products. Their structures and absolute configurations were determined using extensive spectroscopic methods, including NMR, HRESIMS analyses, X-ray single crystal diffraction, as well as through experimental ECD analyses. Biological assays revealed that compounds 1 and 2 exhibited inhibitory activity against A549 cells, with IC50 values of 30.11 ± 3.29 and 34.32 ± 2.66 µM, respectively.

Discriminative stimulus properties of Cannabis sativa terpenes in rats.

Cannabis is a pharmacologically complex plant consisting of hundreds of potentially active compounds. One class of compounds present in cannabis that has received little attention are terpenes. Traditionally thought to impart aroma and flavor to cannabis, it has become increasingly recognized that terpenes might exert therapeutic effects themselves. Several recent reports have also indicated terpenes might behave as cannabinoid type 1 (CB1) receptor agonists. This study aimed to investigate whether several terpenes present in cannabis produce discriminative stimulus effects similar to or enhance the effects of Δ 9 -tetrahydrocannabinol (THC). Subsequent experiments explored other potential cannabimimetic effects of these terpenes. Rats were trained to discriminate THC from vehicle while responding under a fixed-ratio 10 schedule of food presentation. Substitution testing was performed with the CB receptor agonist JWH-018 and the terpenes linalool, limonene, γ-terpinene and α-humulene alone. Terpenes were also studied in combination with THC. Finally, THC and terpenes were tested in the tetrad assay to screen for CB1-receptor agonist-like effects. THC and JWH-018 dose-dependently produced responding on the THC-paired lever. When administered alone, none of the terpenes produced responding predominantly on the THC-paired lever. When administered in combination with THC, none of the terpenes enhanced the potency of THC, and in the case of α-humulene, decreased the potency of THC to produce responding on the THC-paired lever. While THC produced effects in all four tetrad components, none of the terpenes produced effects in all four components. Therefore, the terpenes examined in this report do not have effects consistent with CB1 receptor agonist properties in the brain.

A derivative of trihydroxynaphthalenone and a pyrone metabolite from the endophytic fungus Talaromyces purpurpgenus.

A newly discovered trihydroxynaphthalenone derivative, epoxynaphthalenone (1) involving the condensation of ortho-hydroxyl groups into an epoxy structure, and a novel pyrone metabolite characterized as pyroneaceacid (2), were extracted from Talaromyces purpurpgenus, an endophytic fungus residing in Rhododendron molle. The structures of these compounds were elucidated through a comprehensive analysis of their NMR and HRESIMS data. The determination of absolute configurations was accomplished using electronic circular dichroism (ECD) calculations and CD spectra. Notably, these recently identified metabolites exhibited a moderate inhibitory activity against xanthine oxidase (XOD).

Inhibition of calcium-sensing receptor by its antagonist promotes gastrointestinal motility in a Parkinson's disease mouse model.

BACKGROUND: The Calcium-sensing receptor (CaSR) participates in the regulation of gastrointestinal (GI) motility under normal conditions and might be involved in the regulation of GI dysmotility in patients with Parkinson's disease (PD). METHODS: CaSR antagonist-NPS-2143 was applied in in vivo and ex vivo experiments to study the effect and underlying mechanisms of CaSR inhibition on GI dysmotility in the MPTP-induced PD mouse model. FINDINGS: Oral intake of NPS-2143 promoted GI motility in PD mice as shown by the increased gastric emptying rate and shortened whole gut transit time together with improved weight and water content in the feces of PD mice, and the lack of influence on normal mice. Meanwhile, the number of cholinergic neurons, the proportion of serotonergic neurons, as well as the levels of acetylcholine and serotonin increased, but the numbers of nitrergic and tyrosine hydroxylase immunoreactive neurons, and the levels of nitric oxide synthase and dopamine decreased in the myenteric plexus in the gastric antrum and colon of PD mice in response to NPS-2143 treatment. Furthermore, the numbers of c-fos positive neurons in the nucleus tractus solitarius (NTS) and cholinergic neurons in the dorsal motor nucleus of the vagus (DMV) increased in NPS-2143 treated PD mice, suggesting the involvement of both the enteric (ENS) and central (CNS) nervous systems. However, ex vivo results showed that NPS-2143 directly inhibited the contractility of antral and colonic strips in PD mice via a non-ENS mediated mechanism. Further studies revealed that NPS-2143 directly inhibited the voltage gated Ca2+ channels, which might, at least in part, explain its direct inhibitory effects on the GI muscle strips. INTERPRETATION: CaSR inhibition by its antagonist ameliorated GI dysmotility in PD mice via coordinated neuronal regulation by both ENS and CNS in vivo, although the direct effects of CaSR inhibition on GI muscle strips were suppressive.

Metahemoglobinemia y hemólisis intravascular aguda después de una intoxicación por naftaleno en un paciente pediátrico / Methemoglobinemia and acute intravascular hemolysis after naphthalene poisoning in a pediatric patient

La intoxicación por naftaleno es poco frecuente en los niños. Es causada por la ingesta, la inhalación o el contacto con la piel de sustancias que contienen naftaleno. Los pacientes suelen tener orina de color marrón oscuro, diarrea acuosa y vómito bilioso. Los signos incluyen fiebre, taquicardia, hipotensión y valores bajos en la oximetría de pulso, incluso con oxigenoterapia. Los análisis de sangre detectan anemia hemolítica, metahemoglobinemia, insuficiencia renal e hiperbilirrubinemia. Además del tratamiento sintomático, se hacen transfusiones de eritrocitos y se les administran ácido ascórbico, azul de metileno y N-acetilcisteína. En este artículo, presentamos el caso de un paciente masculino de 23 meses de edad con metahemoglobinemia y hemólisis intravascular aguda que recibió atención en la unidad de cuidados intensivos durante cinco días por intoxicación por naftaleno. Si bien la intoxicación por naftaleno es muy poco frecuente, tiene consecuencias mortales y se debe ejercer precaución con su uso y venta.

Poisoning by naphthalene is uncommon in children. It is a type of poisoning brought on by ingesting, inhaling, or coming into touch with naphthalene-containing substances on the skin. Patients typically present with an initial onset of dark brown urine, watery diarrhea, and bile vomit. The signs include fever, tachycardia, hypotension, and low pulse oximetry readings even with oxygen support. Hemolytic anemia, methemoglobinemia, renal failure, and hyperbilirubinemia are all detected in blood tests. Erythrocyte transfusion, ascorbic acid, methylene blue, and N-acetylcysteine (NAC) therapies are provided to inpatients in addition to symptomatic treatment. We present a 23-month-old male patient who developed methemoglobinemia and acute intravascular hemolysis, who was followed up in the intensive care unit for five days due to naphthalene intoxication. Although naphthalene poisoning is very rare, it should be known that it has fatal consequences, and more care should be taken in its use and sale.

NPS-2143 inhibit glioma progression by suppressing autophagy through mediating AKT-mTOR pathway.

Gliomas are the most common tumours in the central nervous system. In the present study, we aimed to find a promising anti-glioma compound and investigate the underlying molecular mechanism. Glioma cells were subjected to the 50 candidate compounds at a final concentration of 10 µM for 72 h, and CCK-8 was used to evaluate their cytotoxicity. NPS-2143, an antagonist of calcium-sensing receptor (CASR), was selected for further study due to its potent cytotoxicity to glioma cells. Our results showed that NPS-2143 could inhibit the proliferation of glioma cells and induce G1 phase cell cycle arrest. Meanwhile, NPS-2143 could induce glioma cell apoptosis by increasing the caspase-3/6/9 activity. NPS-2143 impaired the immigration and invasion ability of glioma cells by regulating the epithelial-mesenchymal transition process. Mechanically, NPS-2143 could inhibit autophagy by mediating the AKT-mTOR pathway. Bioinformatic analysis showed that the prognosis of glioma patients with low expression of CASR mRNA was better than those with high expression of CASR mRNA. Gene set enrichment analysis showed that CASR was associated with cell adhesion molecules and lysosomes in glioma. The nude mice xenograft model showed NPS-2143 could suppress glioma growth in vivo. In conclusion, NPS-2143 can suppress the glioma progression by inhibiting autophagy.

Thermo-chemical behaviour of Dunaliella salina biomass and valorising their biochar for naphthalene removal from aqueous rural environment.

Thermo-chemical behavior of a microalgal biomass; Dunaliella salina was investigated through thermo-gravimetric analyses. Fully-grown D. salina biomass were subjected for biochar conversion using pyrolytic treatment at three distinct heating rates such as 2.5, 5, and 15 °C min-1. The kinetic appraisals were explained by using model-free kinetics viz., Kissinger-Akahira-Sanose, Flynn-Waal-Ozawa and Starink iso-conversional correlations with concomitant evaluation of activation energies (Ea). The Ea value is 194.2 kJ mol-1 at 90% conversion in FWO model, which is higher as compared to other two models. Moisture, volatile substances, and other biochemical components of the biomass were volatilized between 400 and 1000 K in two separate thermo-chemical breakdown regimes. Microscopic and surface characterization analyses were carried out to elucidate the elemental and morphological characteristics of the biomass and biochar. Further, the proficiency of the prepared biochar was tested for removing naphthalene from the watery media. The novelty of the present study lies in extending the applicability of biochar prepared from D. salina for the removal of a model polyaromatic hydrocarbon, naphthalene.

Viscosities and Densities of Binary and Ternary Mixtures of Aliphatic and Polyaromatic Hydrocarbons: Pyrene +1-Methylnaphthalene + Dodecane at T = (293.15 to 343.15) K. Experiment and Modeling.

This work presents new experimental viscosity and density data for aromatic and polyaromatic compounds in binary and ternary pyrene, 1-methylnaphthalene, and dodecane mixtures. The lack of experimental viscosity data for these mixtures requires the development of a new database, which is vital for understanding the behavior of mixtures in more complex systems, such as asphaltenes and fuels. The mixtures proposed in this work have been measured over a temperature range of (293.15 to 343.15) K at atmospheric pressure. Several mixture compositions have been studied at these conditions: 1.0, 2.5, 5.0, 7.5, 10.0, 12.5, and 15.0% pyrene mass fraction. The concentration of pyrene correlates with an increase in the viscosity and density values. At the lowest temperature in binary mixtures, the corresponding values reach 4.4217 mPa·s for viscosity and 1.0447 × 103 kg·m-3 for density, respectively. In ternary mixtures, the introduction of dodecane leads to the lowest maximum values of 3.5555 mPa·s for viscosity and 1.0112 × 103 kg·m-3 for density at the same temperature. The experimental data have been employed for the specific modification of viscosity models. These modifications could facilitate the prediction of the viscosity of mixtures that are more complex than those presented in this work. Various viscosity models have been employed, such as Linear, Ratcliff and Khan, modified UNIFAC-Visco, and Krieger-Dougherty. The settings in the models used reliably reproduce the experiment reliably. However, the Ratcliff model agrees excellently with the experiment, having a low standard deviation (2.0%) compared to other models. Furthermore, a model based on the equation of state of Guo is proposed to predict the viscosity values by modifying the specific parameters and adjusting them to the mixtures proposed in this work. The results from this study are compared to previous work, where pyrene, toluene, and heptane mixtures were analyzed. In this case, we find that the decrease of aggregation grade in the present systems is predicted by the model fixed in this work.

Repurposed drug agomelatine is therapeutic against collagen-induced arthritis via iNOS targeting.

BACKGROUND: The most promising biologics tumor necrosis factor α (TNFα) inhibitors are effective in treating rheumatoid arthritis (RA) in only 50-70 % of the cases; thus, new drugs targeting TNFα-mediated inflammation are required. METHODS: Firstly, the drugs that could inhibit FLS proliferation and TNFα induced inflammatory cytokine production were screened. Secondly, treatment effects of the identified drugs were screened in collagen-induced arthritis (CIA) mouse model. Thirdly, the inhibitory effect of the identified drug, agomelatine (AOM), on TNFα induced inflammatory cytokine production and NF-κB activity were confirmed. Fourthly, bioinformatics was applied to predict the binding target of AOM and the binding was confirmed, and the already known inhibitor of target was used to test the treatment effect for CIA mouse model. Finally, the effect of AOM on signaling pathway was tested and on TNFα induced inflammatory cytokine production was observed after inhibiting the target. RESULTS: AOM effectively inhibited TNFα-induced NF-κB activation, NF-κB p65 translocation, and inflammatory cytokines production in vitro and was therapeutic against CIA. The mechanistic study indicated inducible nitric oxide synthase (iNOS) as the binding target of AOM. 1400 W, a known inhibitor of iNOS, could effectively treat CIA by decreasing iNOS activity and the levels of inflammatory cytokines. The inhibitory effect of AOM on TNFα-induced inflammation was further elucidated by 1400 W, or NF-κB p65 inhibitor JSH-23, indicating that AOM is therapeutic against CIA via iNOS/ERK/p65 signaling pathway after binding with iNOS. CONCLUSIONS: AOM is therapeutic against CIA via inhibition of the iNOS/ERK/p65 signaling pathway after binding with iNOS.