Raspberry Ketone Attenuates Hepatic Fibrogenesis and Inflammation via Regulating the Crosstalk of FXR and PGC-1α Signaling.

Hepatic fibrosis is a compensatory response to chronic liver injury and inflammation, and dietary intervention is recommended as one of the fundamental prevention strategies. Raspberry ketone (RK) is an aromatic compound first isolated from raspberry and widely used to prepare food flavors. The current study investigated the hepatoprotection and potential mechanism of RK against hepatic fibrosis. In vitro, hepatic stellate cell (HSC) activation was stimulated with TGF-ß and cultured with RK, farnesoid X receptor (FXR), or peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) agonist or inhibitor, respectively. In vivo, C57BL/6 mice were injected intraperitoneally with thioacetamide (TAA) at 100/200 mg/kg from the first to the fifth week. Mice were intragastrically administrated with RK or Cur once a day from the second to the fifth week. In activated HSCs, RK inhibited extracellular matrix (ECM) accumulation, inflammation, and epithelial-mesenchymal transition (EMT) process. RK both activated FXR/PGC-1α and regulated their crosstalk, which were verified by their inhibitors and agonists. Deficiency of FXR or PGC-1α also attenuated the effect of RK on the reverse of activated HSCs. RK also decreased serum ALT/AST levels, liver histopathological change, ECM accumulation, inflammation, and EMT in mice caused by TAA. Double activation of FXR/PGC-1α might be the key targets for RK against hepatic fibrosis. Above all, these discoveries supported the potential of RK as a novel candidate for the dietary intervention of hepatic fibrosis.

Equations for estimating binary mixture toxicity: 3-methyl-2-butanone with a series of electrophiles.

Mixture toxicity was determined for 32 binary combinations. One chemical was the non-reactive, non-polar narcotic 3-methyl-2-butanone (always chemical A) and the other was a potentially reactive electrophile (chemical B). Bioluminescence inhibition in Allovibrio fischeri was measured at 15-, 30-, and 45-minutes of exposure for A, B, and the mixture (MX). Concentration-response curves (CRCs) were developed for each chemical and used to develop predicted CRCs for the concentration addition (CA) and independent action (IA) mixture toxicity models. Also, MX CRCs were generated and compared with model predictions using the 45-minute data. Classification of observed mixture toxicity used three specific criteria: 1) predicted IA EC50 vs. CA EC50 values at 45-minutes, 2) consistency of 45-minute MX CRC fit to IA, CA, or otherwise at three effect levels (EC25, EC50 and EC75), and 3) the known/suspected mechanism of toxicity for chemical B. Mixture toxicity was then classified into one of seven groupings. As a result of the predicted IA EC50 being more toxic than the predicted CA EC50, IA represented the greater toxic hazard. For this reason, non-sham MXs having toxicity consistent with CA were classified as being "coincident" with CA rather than mechanistically-consistent with CA. Multiple linear regression analyses were performed to develop equations that can be used to estimate the toxicity of other 3M2B-containing binary mixtures. These equations were developed from the data for both IA and CA, at each exposure duration and effect level. Each equation had a coefficient of determination (r2) above 0.950 and a variance inflation factor <1.2. This approach can potentially reduce the need for mixture testing and is amenable to other model systems and to assays that evaluate toxicity at low effect levels.

Raspberry Ketone Prevents LPS-Induced Depression-Like Behaviors in Mice by Inhibiting TLR-4/NF-κB Signaling Pathway via the Gut-Brain Axis.

SCOPE: Depression, a prevalent mental disorder, has significantly impacted the lives of 350 million people, yet it holds promise for amelioration through food-derived phenolics. Raspberries, renowned globally for their delectable flavor, harbor a phenolic compound known as raspberry ketone (RK). However, the impact of RK on depressive symptoms remains ambiguous. This study aims to investigate the impact of RK on lipopolysaccharide (LPS)-induced depressed mice and elucidates its potential mechanisms, focusing on the gut-brain axis. METHODS AND RESULTS: Through behavioral tests, RK exerts a notable preventive effect on LPS-induced depression-like behaviors in mice. RK proves capable of attenuating gut inflammation, repairing gut barrier impairment, modulating the composition of the gut microbiome (Muribaculaceae, Streptococcus, Lachnospiraceae, and Akkermansia), and promoting the production of short-chain fatty acids. Furthermore, RK alleviates neuroinflammation by suppressing the TLR-4/NF-κB pathway and bolsters synaptic function by elevating levels of neurotrophic factors and synapse-associated proteins. CONCLUSION: The current study provides compelling evidence that RK effectively inhibits the TLR-4/NF-κB pathway via the gut-brain axis, leading to the improvement of LPS-induced depression-like behaviors in mice. This study addresses the research gap in understanding the antidepressant effects of RK and illuminates the potential of utilizing RK as a functional food for preventing depression.

Exploring transient global transcriptional changes induced by ascorbic acid revealed via atKAS-seq profiling.

Transcription initiates the formation of single-stranded DNA (ssDNA) regions within the genome, delineating transcription bubbles, a highly dynamic genomic process. Kethoxal-assisted single-stranded DNA sequencing (KAS-seq) utilizing N3-kethoxal has emerged as a potent tool for mapping specific guanine positions in ssDNA on a genome-wide scale. However, the original KAS-seq method required the costly Accel-NGS Methyl-seq DNA library kit. This study introduces an optimized iteration of the KAS-seq technique, referred to as adapter-tagged KAS-seq (atKAS-seq), incorporating an adapter tagging strategy. This modification involves integrating sequencing adapters via complementary strand synthesis using random N9 tagging. Additionally, by harnessing the potential of ascorbic acid (ASC), recognized for inducing global epigenetic changes, we employed the atKAS-seq methodology to elucidate critical pathways influenced by short-term, high-dose ASC treatment. Our findings underscore that atKAS-seq enables rapid and precise analyses of transcription dynamics and enhancer activities concurrently. This method offers a streamlined, cost-efficient, and low-input approach, affirming its utility in probing intricate genomic regulatory mechanisms.

Agrimol B alleviates cisplatin-induced acute kidney injury by activating the Sirt1/Nrf2 signaling pathway in mice.

Cisplatin (CDDP) is a widely used chemotherapeutic agent that has remarkable antineoplastic effects. However, CDDP can cause severe acute kidney injury (AKI), which limits its clinical application. Agrimol B is the main active ingredient found in Agrimonia pilosa Ledeb and has a variety of pharmacological activities. The effect of agrimol B on CDDP-induced renal toxicity has not been determined. To investigate whether agrimol B has a protective effect against CDDP-induced AKI, we first identify Sirtuin 1 (Sirt1) as a critical target protein of agrimol B in regulating AKI through network pharmacology analysis. Subsequently, the AKI mouse model is induced by administering a single dose of CDDP via intraperitoneal injection. By detecting the serum urea nitrogen and creatinine levels, as well as the histopathological changes, we confirm that agrimol B effectively reduces CDDP-induced AKI. In addition, treatment with agrimol B counteracts the increase in renal malondialdehyde level and the decrease in superoxide dismutase (SOD), catalase and glutathione levels induced by CDDP. Moreover, western blot results reveal that agrimol B upregulates the expressions of Sirt1, SOD2, nuclear factor erythroid2-related factor 2, and downstream molecules, including heme oxygenase 1 and NAD(P)H quinone dehydrogenase 1. However, administration of the Sirt1 inhibitor EX527 abolishes the effects of agrimol B. Finally, we establish a tumor-bearing mouse model and find that agrimol B has a synergistic antitumor effect with CDDP. Overall, agrimol B attenuates CDDP-induced AKI by activating the Sirt1/Nrf2 signaling pathway to counteract oxidative stress, suggesting that this compound is a potential therapeutic agent for the treatment of CDDP-induced AKI.

Methyl vinyl ketone and its analogs covalently modify PI3K and alter physiological functions by inhibiting PI3K signaling.

Reactive carbonyl species (RCS), which are abundant in the environment and are produced in vivo under stress, covalently bind to nucleophilic residues such as Cys in proteins. Disruption of protein function by RCS exposure is predicted to play a role in the development of various diseases such as cancer and metabolic disorders, but most studies on RCS have been limited to simple cytotoxicity validation, leaving their target proteins and resulting physiological changes unknown. In this study, we focused on methyl vinyl ketone (MVK), which is one of the main RCS found in cigarette smoke and exhaust gas. We found that MVK suppressed PI3K-Akt signaling, which regulates processes involved in cellular homeostasis, including cell proliferation, autophagy, and glucose metabolism. Interestingly, MVK inhibits the interaction between the epidermal growth factor receptor and PI3K. Cys656 in the SH2 domain of the PI3K p85 subunit, which is the covalently binding site of MVK, is important for this interaction. Suppression of PI3K-Akt signaling by MVK reversed epidermal growth factor-induced negative regulation of autophagy and attenuated glucose uptake. Furthermore, we analyzed the effects of the 23 RCS compounds with structures similar to MVK and showed that their analogs also suppressed PI3K-Akt signaling in a manner that correlated with their similarities to MVK. Our study demonstrates the mechanism of MVK and its analogs in suppressing PI3K-Akt signaling and modulating physiological functions, providing a model for future studies analyzing environmental reactive species.

The Recent Rise of Eutylone Intoxications in Onondaga County and Surrounding Counties.

ABSTRACT: Eutylone is an emerging synthetic stimulant that is quickly gaining popularity due to its affordability and wide availability. A recent surge has been observed in Upstate New York. This study presents a retrospective review of deaths in which eutylone was identified in postmortem samples from January 2018 to December 2021 in the electronic database of the Onondaga County medical examiner's office in Syracuse, NY. Of the 176 subjects who met the study criteria, 128 (73%) were male and 48 (27%) were female, with a mean age of 37.6 years. Most of the subjects were listed as White (89%), followed by African American (9%). Most of the cases had multiple medical comorbidities (89%), with anxiety and hypertension being the most common illnesses. Chromatography/mass spectrometry was used to perform a qualitative analysis of femoral blood and urine samples to detect multiple drugs, including eutylone. Substance abuse disorder was present in 135 (77%) cases, with opiates and cocaine being the most common additional drugs detected. The most common cause and manner of death were drug toxicity and accident, in 137 (78%) and 143 (81%) cases, respectively. Overall, the study suggests that eutylone is a growing concern in Upstate New York, and its use is increasing in prevalence. Policymakers and health care providers should take steps to address this emerging issue and prevent further harm to individuals and communities affected by drug overdose.

LC-MS/MS method for quantification of raspberry ketone in rat plasma: application to preclinical pharmacokinetic studies.

Background: Raspberry ketone (RK), derived from red raspberry fruit (Rubus idaeus, family Rosaceae), is a reported potent antiobesity agent. This study aims to investigate method development, validation, and in vitro and in vivo pharmacokinetics in rats. Materials & methods: LC-MS/MS was used to conduct method development, validation, stability, and oral PK samples of RK in plasma analyses. Results: RK was highly soluble in Tris buffer and stable in gastrointestinal fluids as well as plasma. Rat liver microsomal stability of RK in phase I and II studies was 84.96 ± 2.39 and 69.98 ± 8.69%, respectively, after 60 min. Intestinal permeability was 4.39 ± 1.37 × 10-5 cm/s. Maximal concentration was 1591.02 ± 64.76 ng/ml, which was achieved after 1 h (time to maximal concentration), and absolute oral bioavailability was 86.28%. Conclusion: Pharmacokinetic data serve as a keystone for preclinical and clinical adjuvant therapy.

Using LC­MS/MS, a method was developed and validated for RK, and investigated the preclinical pharmacokinetics and bioavailability in Sprague Dawley rats.

Inhibition of mycobacteria proliferation in macrophages by low cisplatin concentration through phosphorylated p53-related apoptosis pathway.

BACKGROUND: Drug resistance is a prominent problem in the treatment of tuberculosis, so it is urgent to develop new anti- tuberculosis drugs. Here, we investigated the effects and mechanisms of cisplatin (DDP) on intracellular Mycobacterium smegmatis to tap the therapeutic potential of DDP in mycobacterial infection. RESULTS: Macrophages infected with Mycobacterium smegmatis were treated with DDP alone or combined with isoniazid or rifampicin. The results showed that the bacterial count in macrophages decreased significantly after DDP (≤ 6 µg/mL) treatment. When isoniazid or rifampicin was combined with DDP, the number of intracellular mycobacteria was also significantly lower than that of isoniazid or rifampicin alone. Apoptosis of infected cells increased after 24 h of DDP treatment, as shown by flow cytometry and transmission electron microscopy detection. Transcriptome sequencing showed that there were 1161 upregulated and 645 downregulated differentially expressed genes (DEGs) between the control group and DDP treatment group. A Trp53-centered protein interaction network was found based on the top 100 significant DEGs through STRING and Cytoscape software. The expression of phosphorylated p53, Bax, JAK, p38 MAPK and PI3K increased after DDP treatment, as shown by Western blot analysis. Inhibitors of JAK, PI3K or p38 MAPK inhibited the increase in cell apoptosis and the reduction in the intracellular bacterial count induced by DDP. The p53 promoter Kevetrin hydrochloride scavenges intracellular mycobacteria. If combined with DDP, Kevetrin hydrochloride could increase the effect of DDP on the elimination of intracellular mycobacteria. In conclusion, DDP at low concentrations could activate the JAK, p38 MAPK and PI3K pathways in infected macrophages, promote the phosphorylation of p53 protein, and increase the ratio of Bax to Bcl-2, leading to cell apoptosis, thus eliminating intracellular bacteria and reducing the spread of mycobacteria. CONCLUSION: DDP may be a new host-directed therapy for tuberculosis treatment, as well as the p53 promoter Kevetrin hydrochloride.

Enzymatic synthesis of mono- and disubstituted phospholipids by direct condensation of oleic acid and glycerophosphocholine with immobilized lipases and phospholipase.

Lysophospholipids which contain polyunsaturated fatty acids play a key role in food and cosmetic industries because of their bioactivity. Therefore, the formation of mono- and disubstituted phospholipids is quite interesting as they could be used for the formation of different natural liposomes. Using immobilized derivatives of lipases and phospholipases, the esterification of oleic acid with glycerophosphocholine (GPC) has been studied. Thus, derivatives were quite active in completely anhydrous media and in solvent-free reaction systems where the reaction takes place. CALB biocatalyst was able to successfully form oleoyl-LPC at 60 °C in the presence of 30 % butanone, where the synthesis rate was 100 times higher than in the absence of solvents at 40 °C. On the other hand, the best synthesis rate for dioleoyl-PC was achieved with immobilized Lecitase in a solvent-free process at 60 °C, an 83 % synthesis yield was achieved with an initial synthesis rate of 4.32 mg/mL × h × g.

[Butane-2-one oxime as a potential carcinogen for humans - evidence and effects on businesses resulting from reclassification]. / Oksym butan-2-onu jako potencjalny czynnik rakotwórczy dla ludzi ­ dowody i skutki dla przedsiebiorstw wynikajace ze zmiany klasyfikacji.

Evidence of a change in the carcinogenicity category of butan-2-one oxime (MEKO) and the results of this change for manufacturing and using companies was presented and assessed. The online databases of scientific journals were reviewed, taking into account the reports on the harmonization of MEKO classification and labeling at EU level available on the ECHA website. Commission Regulation (EU) 2020/1182 introduced harmonized classification and labeling of MEKO for carcinogenicity to category 1B. The induction of tumors, the nature and importance of tumors for humans, and the sensitivity of the 2 species tested, both sexes - all of these factors support the classification of MEKO into the carcinogenicity category 1B. On the other hand, MEKO is negative in genotoxicity studies, including in mammalian cells and in vivo in animals. This is the argument that the classification of MEKO as carcinogen category 2 remains appropriate. The change in the MEKO carcinogenicity category results in legal consequences for companies, such as compliance with the conditions of REACH restriction, which includes restrictions on placing MEKO on the market for sale to the general public, keeping a register of works that require contact with MEKO or its mixtures containing MEKO in a concentration ≥0.1%. According to the opinion of MEKO suppliers, there is currently no practical MEKO substitute that has been so well researched, despite attempts to find it in recent years. The risk of additional liver cancer in the case of 40-year occupational exposure to MEKO is 4:100 000 at a concentration of approx. 0.7 mg/m3, and it is an acceptable risk in accordance with the arrangements adopted in Poland. Compliance with the permissible concentrations of MEKO in the air of the working environment at this level should protect employees against the carcinogenic effect of MEKO. Med Pr. 2022;73(6):457-70.

Insulin/IGF signaling regulates presynaptic glutamate release in aversive olfactory learning.

Insulin/insulin-like growth factor (IGF) receptor signaling (IIS) supports context-dependent learning in vertebrates and invertebrates. Here, we identify cell-specific mechanisms of IIS that integrate sensory information with food context to drive synaptic plasticity and learning. In the nematode Caenorhabditis elegans, pairing food deprivation with an odor such as butanone suppresses attraction to that odor. We find that aversive olfactory learning requires the insulin receptor substrate (IRS) protein IST-1 and atypical signaling through the insulin/IGF-1 receptor DAF-2. Cell-specific knockout and rescue demonstrate that DAF-2 acts in the AWCON sensory neuron, which detects butanone, and that learning preferentially depends upon the axonally localized DAF-2c isoform. Acute food deprivation increases DAF-2 levels in AWCON post-transcriptionally through an insulin- and insulin receptor substrate-1 (ist-1)-dependent process. Aversive learning alters the synaptic output of AWCON by suppressing odor-regulated glutamate release in wild-type animals, but not in ist-1 mutants, suggesting that axonal insulin signaling regulates synaptic transmission to support aversive memory.

Risk factors of delayed hemorrhage after LigaSure hemorrhoidectomy.

BACKGROUND: As one of the most popular methods for treating hemorrhoidal diseases, hemorrhoidectomy with LigaSure devices has been proven to have less postoperative pain and has gained in popularity among surgeons. However, our previous study found higher incidence of delayed post-hemorrhoidectomy bleeding (DPHB) in patients who underwent LigaSure hemorrhoidectomy compared to those who underwent the traditional Ferguson's method. This follow-up study aimed to reveal the relationship between DPHB and the surgeon's experience. METHODS: This retrospective study included 437 consecutive patients with symptomatic grade II to IV hemorrhoids who received hemorrhoidectomy by LigaSure devices from March 2009 to December 2017. Twenty-two patients who experienced DPHB were analyzed to identify risk factors. Cumulative incidence of DPHB were calculated and visualized to assess the improvement of DPHB rate by time. RESULTS: All operations were performed by a single surgeon. The most common postoperative complication was constipation, followed by urinary retention. DPHB developed in 22 patients (5%). Multivariate analysis showed that the male sex was an independent risk factor for DPHB in patients who underwent hemorrhoidectomy with LigaSure devices. The cumulative incidence was initially higher (about 10%) in the earlier cases and stabilized at around 5% with more cases. The change in cumulative incidence indicated a lower complication rate as the surgeon's experience increased. CONCLUSION: Male sex is an independent risk factor for DHBP. The risk of DPHB is higher in patients undergoing hemorrhoidectomy with LigaSure in a surgeon's earlier cases, and decreases to a rate similar to that for the traditional hemorrhoidectomy once the surgeon becomes more familiar with the procedure and postoperative care.

Gingerol fractions bioactivity against butanone cytotoxicity induced in newborns of mice.

OBJECTIVE: Accumulating studies have demonstrated the potential activity of ginger in treating and managing several diseases but little is known about its protective effects against teratogenicity of chemical toxins. Thus, in this study, we have evaluated the protective effect of gingerol fraction (GF) against methyl ethyl ketone (MEK) induced teratogenic effects in newborns of mice. MATERIALS AND METHODS: A total of 30 mature females and fifteen male mice (Mus musculus) weighing 25-30 g were included in this study. The pregnant mice were divided into three groups (10 mice each); control group (GI, mice received normal drinking water; NDW), methyl ethyl ketone (MEK) treated group (GII, received MEK at a dose of 350 mg/kg body weight in NDW), and GF treated group (GIII; mice received GF at a dose of 25 mg/kg in NDR). Histological analysis, cellular oxidative, and antioxidant enzymes, fibrosis, and apoptosis of brain, liver, and kidney tissues were estimated by histological and immunoassay techniques. RESULTS: In this study, the treatment of pregnant female mice with gingerol fractions (GF) at a dose of 25 mg/kg significantly protected all tissues organs of mothers and their offspring against the teratogenic effects induced by MEK at a dose of 350 mg/kg. A significant improvement in cellular antioxidant enzymes GSH, SOD, and peroxidase activities along with a reduction in the initiation of cellular oxidative free radicals (TBARS) was reported in GF treated mice compared to mice intoxicated with MEK (350 mg/kg). In addition, a significant reduction in cellular fibrosis and apoptosis was reported in all tissues of mothers and their offspring's following treatment with GF. HPLC analysis of ginger extracts estimated a set of polyphenolic compounds such [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol which are responsible for the antioxidant, anti-fibrotic, and anti-apoptotic protective effects against teratogenic effects of MEK. CONCLUSIONS: Gingerol fractions (GF) at a dose of 25 mg/kg significantly protected all tissues organs of mothers and their offspring against the teratogenic effects induced by MEK at a dose of 350 mg/kg. The beneficial effects of ginger phenolic compounds; [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol against teratogenic effects of MEK proceeded through their antioxidant, anti-fibrotic, and anti-apoptotic properties.

Substituent Effects on the Electronic Spectroscopy of Four-Carbon Criegee Intermediates.

Atmospheric ozonolysis of biogenic and anthropogenic alkenes generates zwitterionic carbonyl oxide intermediates (R1R2C═O+O-), known as Criegee intermediates, with different structural motifs and conformations. This study reports a systematic laboratory study of substituent effects on the electronic spectroscopy of four-carbon Criegee intermediates (CIs) with methyl-ethyl (MECI) and isopropyl (IPCI) groups, which are isomers produced in ozonolysis of asymmetric branched alkenes. The four-carbon CIs are separately generated by an alternative synthetic route, and spectroscopically characterized on the strong π* ← π transition associated with the carbonyl oxide group in a pulsed supersonic expansion with VUV photoionization at 118 nm and UV-induced depletion of the m/z 88 signal. The resultant broad and unstructured UV spectral features for MECI and IPCI are peaked at ca. 320 and 330 nm, respectively, with large absorption cross-sections of ca. 10-17 cm2. Comparisons are made with the four-carbon CIs formed in isoprene ozonolysis, methyl vinyl ketone oxide (MVK-oxide) and methacrolein oxide (MACR-oxide), which have the same backbone connectivity as MECI and IPCI but have extended conjugation across the vinyl and carbonyl groups. A remarkable 50 nm shift of the peak absorption to longer wavelength is observed for MVK-oxide and MACR-oxide compared to MECI and IPCI, respectively. Vertical excitation energies computed theoretically agree well with the experimental findings, confirming that the spectral shifts are caused by the extended π conjugation in the isoprene-derived Criegee intermediates.

Acrolein Increases the Pulmonary Tumorigenic Activity of the Tobacco-Specific Nitrosamine 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).

Tobacco smoke is a complex mixture of more than 7000 chemicals, of which many are toxic and/or carcinogenic. Many hazard assessments of tobacco have focused on individual chemical exposures without consideration of how the chemicals may interact with one another. Two chemicals, the human carcinogen 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) and a possible human carcinogen, acrolein, were hypothesized to interact with one another, possibly owing to the additive effects of DNA adduct formation or influence on the repair of mutagenic DNA adducts. To test our hypothesis that coexposure to NNK and acrolein is more carcinogenic than either chemical alone, A/J mice were exposed to NNK (i.p., 0, 2.5, or 7.5 µmol in saline) in the presence or absence of inhaled acrolein (15 ppmV). While the single 3 h exposure to acrolein alone did not induce lung adenomas, it significantly enhanced NNK's lung carcinogenicity. In addition, mice receiving both NNK and acrolein had more adenomas with dysplasia or progression than those receiving only NNK, suggesting that acrolein may also increase the severity of NNK-induced lung adenomas. To test the hypothesis that the interaction was due to effects on DNA adduct formation and repair, NNK- and acrolein pulmonary DNA adduct levels were assessed. There was no consistent effect of the coexposure on NNK-derived DNA adducts, and acrolein DNA adducts were not elevated above endogenous levels. This study supports the hypothesis that tobacco smoke chemicals combine to contribute to the carcinogenic potency of tobacco smoke, and the mechanism of interaction cannot be explained by alterations of DNA adduct levels.

Methyl vinyl ketone disrupts neuronal survival and axonal morphogenesis.

Methyl vinyl ketone (MVK) is an environmental hazardous substrate which is mainly present in cigarette smoke, industrial waste, and exhaust gas. Despite many chances to be exposed to MVK, the cellular toxicity of MVK is largely unknown. Neurons are the main component of the brain, which is one the most vital organs to human beings. Nevertheless, the influence of MVK to neurons has not been investigated. Here, we determined whether MVK treatment negatively affects neuronal survival and axonal morphogenesis using primary hippocampal neuronal cultures. We treated hippocampal neurons with 0.1 µM to 3.0 µM MVK and observed a concentration-dependent increase of neuronal death rate. We also demonstrated that the treatment with a low concentration of MVK 0.1 µM or 0.3 µM inhibited axonal branching specifically without affecting axon outgrowth. Our results suggest that MVK is highly toxic to neurons.

Design, Synthesis and Structure-Activity Relationship of Novel Pinacolone Sulfonamide Derivatives against Botrytis cinerea as Potent Antifungal Agents.

To develop new fungicides with high efficiency, 46 novel sulfonamide derivatives were designed and synthesized by introducing pinacolone fragment into chesulfamide which was used as lead compound. All compounds were characterized by 1H NMR, 13C NMR, and MS spectra, and the structure of compound P-27 was also confirmed by X-ray single crystal diffraction. It was found that a variety of compounds present excellent inhibitory effect against Botrytis cinerea. The inhibition rates of P-29 on tomato and strawberry were 90.24% (200 mg/L) and 100% (400 mg/L) in vivo respectively, which were better than the lead compound chesulfamide (59.23% on tomato seedlings and 29.63% on strawberries).

Selectivity of volatile organic compounds on the surface of zinc oxide nanosheets for gas sensors.

The detection of volatile organic compounds by gas sensors is of great interest for environmental quality monitoring and the early-stage and noninvasive diagnosis of diseases. Experiments found hexane, toluene, aniline, butanone, acetone, and propanol gases in the exhaled breath of patients suffering from COVID-19, lung cancer, and diabetes. However, no studies are available to systematically elucidate the selectivity of these gases on nanosheets of zinc oxide for chemiresistive and direct thermoelectric gas sensors. Therefore, this work performed the elucidation by studying the electronic, electrical, and thermal properties of the bilayered ZnO nanosheets with polar (0001) and non-polar (112̄0) surfaces under the adsorption of the gases. The interaction between the gases and the nanosheets belongs to two groups: electrostatic attraction and charge exchange. The second one occurs due to the peak resonance of the same type of orbitals between the substrates and the gases along the surface normal and the first one for the other cases. The characteristics of the Seebeck coefficient exhibited distinct selectivity of butanone and acetone.