PM2.5-induced DNA oxidative stress in A549 cells and regulating mechanisms by GST DNA methylation and Keap1/Nrf2 pathway.

Fine particulate matter (PM2.5) increases the risks of lung cancer. Epigenetics provides a new toxicology mechanism for the adverse health effects of PM2.5. However, the regulating mechanisms of PM2.5 exposure on candidate gene DNA methylation changes in the development of lung cancer remain unclear. Abnormal expression of the glutathione S transferase (GST) gene is associated with cancer. However, the relationship between PM2.5 and DNA methylation-mediated GST gene expression is not well understood. In this study, we performed GST DNA methylation analysis and GST-related gene expression in human A549 cells exposed to PM2.5 (0, 50, 100 µg/mL, from Taiyuan, China) for 24 h (n = 4). We found that PM2.5 may cause DNA oxidative damage to cells and the elevation of GSTP1 promotes cell resistance to reactive oxygen species (ROS). The Kelch-1ike ECH-associated protein l (Keap1)/nuclear factor NF-E2-related factor 2 (Nrf2) pathway activates the GSTP1. The decrease in the DNA methylation level of the GSTP1 gene enhances GSTP1 expression. GST DNA methylation is associated with reduced levels of 5-methylcytosine (5mC), DNA methyltransferase 1 (DNMT1), and histone deacetylases 3 (HDAC3). The GSTM1 was not sensitive to PM2.5 stimulation. Our findings suggest that PM2.5 activates GSTP1 to defend PM2.5-induced ROS and 8-hydroxy-deoxyguanosine (8-OHdG) formation through the Keap1/Nrf2 signaling pathway and GSTP1 DNA methylation.

Cu-Catalyzed Methylenation of Alcohols with N-Methyl Amide as a Sustainable Methylene Reagent.

Herein, we report a new approach to methylenation of alcohols using N-methyl amide as a sustainable methylene reagent; the N-methyl delivers the methylene group. This new reagent is easily prepared and stable to both air and moisture. Furthermore, the final byproduct of this methylene reagent can be recycled in excellent yields and then reused in methylenation reactions upon treating with CH3I.

Electrochemical Activation of Nitromethane to Construct Isoxazoline Aldoximes.

Activation of nitromethane to endow new reactivity is an interesting and meaningful but also challenging topic. Herein, we report an electrochemical activation of nitromethane to serve as both the heterocyclic skeleton and oxime sources for the construction of isoxazoline aldoximes. The isoxazoline aldoximes that are prepared by four steps with the reported strategy are synthesized in a single step from low-cost and readily available nitromethane and olefins with moderate to excellent yields under our electrochemical conditions. The reaction also takes advantage of high atom-economy and E-selectivity. Moreover, the mechanism is studied by control experiments, a kinetic isotope effect (KIE) study, cyclic voltammogram (CV) experiments, and density functional theory (DFT) calculations. The mechanistic results reveal that nitromethane may be activated under electrochemical conditions to deliver a 1,2,5-oxadiazole 2-oxide intermediate, which undergoes [3+2] cycloaddition with olefins to yield isoxazoline aldoximes.

The effect of information-driven resource allocation on the propagation of epidemic with incubation period.

In the pandemic of COVID-19, there are exposed individuals who are infected but lack distinct clinical symptoms. In addition, the diffusion of related information drives aware individuals to spontaneously seek resources for protection. The special spreading characteristic and coevolution of different processes may induce unexpected spreading phenomena. Thus we construct a three-layered network framework to explore how information-driven resource allocation affects SEIS (susceptible-exposed-infected-susceptible) epidemic spreading. The analyses utilizing microscopic Markov chain approach reveal that the epidemic threshold depends on the topology structure of epidemic network and the processes of information diffusion and resource allocation. Conducting extensive Monte Carlo simulations, we find some crucial phenomena in the coevolution of information diffusion, resource allocation and epidemic spreading. Firstly, when E-state (exposed state, without symptoms) individuals are infectious, long incubation period results in more E-state individuals than I-state (infected state, with obvious symptoms) individuals. Besides, when E-state individuals have strong or weak infectious capacity, increasing incubation period has an opposite effect on epidemic propagation. Secondly, the short incubation period induces the first-order phase transition. But enhancing the efficacy of resources would convert the phase transition to a second-order type. Finally, comparing the coevolution in networks with different topologies, we find setting the epidemic layer as scale-free network can inhibit the spreading of the epidemic.

The Role of Gibberellins in Regulation of Nitrogen Uptake and Physiological Traits in Maize Responding to Nitrogen Availability.

Modified gibberellin (GA) signaling leads to semi-dwarfism with low nitrogen (N) use efficiency (NUE) in crops. An understanding of GA-mediated N uptake is essential for the development of crops with improved NUE. The function of GA in modulating N uptake capacity and nitrate (NO3-) transporters (NRTs) was analyzed in the GA synthesis-deficient mutant zmga3ox grown under low (LN) and sufficient (SN) N conditions. LN significantly suppressed the production of GA1, GA3, and GA4, and the zmga3ox plants showed more sensitivity in shoots as well as LN stress. Moreover, the higher anthocyanin accumulation and the decrease of chlorophyll content were also recorded. The net NO3- fluxes and 15N content were decreased in zmga3ox plants under both LN and SN conditions. Exogenous GA3 could restore the NO3- uptake in zmga3ox plants, but uniconazole repressed NO3- uptake. Moreover, the transcript levels of ZmNRT2.1/2.2 were downregulated in zmga3ox plants, while the GA3 application enhanced the expression level. Furthermore, the RNA-seq analyses identified several transcription factors that are involved in the GA-mediated transcriptional operation of NRTs related genes. These findings revealed that GAs influenced N uptake involved in the transcriptional regulation of NRTs and physiological responses in maize responding to nitrogen supply.

A Human Activity Recognition Algorithm Based on Stacking Denoising Autoencoder and LightGBM.

Recently, the demand for human activity recognition has become more and more urgent. It is widely used in indoor positioning, medical monitoring, safe driving, etc. Existing activity recognition approaches require either the location information of the sensors or the specific domain knowledge, which are expensive, intrusive, and inconvenient for pervasive implementation. In this paper, a human activity recognition algorithm based on SDAE (Stacking Denoising Autoencoder) and LightGBM (LGB) is proposed. The SDAE is adopted to sanitize the noise in raw sensor data and extract the most effective characteristic expression with unsupervised learning. The LGB reveals the inherent feature dependencies among categories for accurate human activity recognition. Extensive experiments are conducted on four datasets of distinct sensor combinations collected by different devices in three typical application scenarios, which are human moving modes, current static, and dynamic behaviors of users. The experimental results demonstrate that our proposed algorithm achieves an average accuracy of 95.99%, outperforming other comparative algorithms using XGBoost, CNN (Convolutional Neural Network), CNN + Statistical features, or single SDAE.

Constructing an Indoor Floor Plan Using Crowdsourcing Based on Magnetic Fingerprinting.

A large number of indoor positioning systems have recently been developed to cater for various location-based services. Indoor maps are a prerequisite of such indoor positioning systems; however, indoor maps are currently non-existent for most indoor environments. Construction of an indoor map by external experts excludes quick deployment and prevents widespread utilization of indoor localization systems. Here, we propose an algorithm for the automatic construction of an indoor floor plan, together with a magnetic fingerprint map of unmapped buildings using crowdsourced smartphone data. For floor plan construction, our system combines the use of dead reckoning technology, an observation model with geomagnetic signals, and trajectory fusion based on an affinity propagation algorithm. To obtain the indoor paths, the magnetic trajectory data obtained through crowdsourcing were first clustered using dynamic time warping similarity criteria. The trajectories were inferred from odometry tracing, and those belonging to the same cluster in the magnetic trajectory domain were then fused. Fusing these data effectively eliminates the inherent tracking errors originating from noisy sensors; as a result, we obtained highly accurate indoor paths. One advantage of our system is that no additional hardware such as a laser rangefinder or wheel encoder is required. Experimental results demonstrate that our proposed algorithm successfully constructs indoor floor plans with 0.48 m accuracy, which could benefit location-based services which lack indoor maps.

The role of pro-/anti-inflammation imbalance in Aß42 accumulation of rat brain co-exposed to fine particle matter and sulfur dioxide.

Taiyuan is a center of coal-based electricity production and many chemicals industries, where mixtures of sulfur dioxide (SO2) and particulate matter may be more prominent. The focus of the present study was to determine if there is a link between adverse effects in the brain and the combined-exposure to SO2 and fine particulate matter (PM2.5). Rats were exposed alternately to PM2.5 with different dosages (1.5, 6.0 and 24.0 mg/kg body weight) and SO2 at the level of 5.6 mg/m3. The results showed that the combined exposure to PM2.5 and SO2 enhanced the mRNA expression and protein level of TNF-α and IL-6 in rat cortex and hippocampus relative to the control, SO2 and PM2.5 alone. Instead, TGF-ß1 mRNA and protein level were down-regulated in the brain. Additionally, PM2.5 at medium and/or high dose caused marked increase in Aß42 level and PM2.5 + SO2 induced further increase of Aß42 level in the cortex and hippocampus. It suggests that SO2 and PM2.5 can synergistically exert inflammation responses and induce Aß42 accumulation in the brain. Also, it is notable that the Aß42 accumulation of rat cortex and hippocampus were closely associated with pro-/anti-inflammatory cytokines ratio. These results clearly demonstrated that the combined exposure to PM2.5 and SO2 can induce the imbalance of pro-/anti-inflammatory cytokine, resulting in Aß42 accumulation of rat brain cortex and hippocampus.

Construction of Fused Pyrrolidines and ß-Lactones by Carbene-Catalyzed C-N, C-C, and C-O Bond Formations.

A carbene-catalyzed intermolecular C-N bond formation, which initiates a highly selective cascade reaction for the synthesis of pyrrolidine fused ß-lactones, is disclosed. The nitrogen-containing bicyclic ß-lactone products are obtained with good yields and excellent stereoselectivities. Synthetic transformations of the reaction products into useful functional molecules, such as amino catalysts, can be efficiently realized under mild reaction conditions. Mechanistically, this study provides insights into modulating the reactivities of heteroatoms, such as nitrogen atoms, in challenging carbene-catalyzed asymmetric carbon-heteroatom bond-forming reactions.

Polyhalides as Efficient and Mild Oxidants for Oxidative Carbene Organocatalysis by Radical Processes.

Simple and inexpensive polyhalides (CCl4 and C2 Cl6 ) have been found to be effective and versatile oxidants in removing electrons from Breslow intermediates under N-heterocyclic carbene (NHC) catalysis. This oxidative reaction involves multiple single-electron-transfer (SET) processes and several radical intermediates. The α, ß, and γ-carbon atoms of aldehydes and enals could be readily functionalized. Given the low cost of the oxidants and the broad applicability of the reactions, this study is expected to greatly enhance the feasibility of oxidative NHC catalysis for large-scale applications. Also this new SET radical process with polyhalides as single-electron oxidants will open a new avenue in the development of NHC-catalyzed radical reactions.

Enantioselective Nucleophilic ß-Carbon-Atom Amination of Enals: Carbene-Catalyzed Formal [3+2] Reactions.

An enantioselective ß-carbon amination for enals is disclosed. The nitrogen atom from a protected hydrazine with suitable electronic properties readily behaves as a nucleophile. Addition of the nitrogen nucleophile to a catalytically generated N-heterocyclic-carbene-bound α,ß-unsaturated acyl azolium intermediate constructs a new carbon-nitrogen bond asymmetrically. The pyrazolidinone products from our catalytic reactions are common scaffolds in bioactive molecules, and can be easily transformed into useful compounds such as ß(3) -amino-acid derivatives.

N-heterocyclic carbene-catalyzed radical reactions for highly enantioselective ß-hydroxylation of enals.

An N-heterocyclic carbene-catalyzed ß-hydroxylation of enals is developed. The reaction goes through a pathway involving multiple radical intermediates, as supported by experimental observations. This oxidative single-electron-transfer reaction allows for highly enantioselective access to ß-hydroxyl esters that are widely found in natural products and bioactive molecules.

Effect of ambient PM(2.5) on lung mitochondrial damage and fusion/fission gene expression in rats.

Exposure to ambient fine particulate matter (PM2.5) increases the risk of respiratory disease. Although previous mitochondrial research has provided new information about PM toxicity in the lung, the exact mechanism of PM2.5-mediated structural and functional damage of lung mitochondria remains unclear. In this study, changes in lung mitochondrial morphology, expression of mitochondrial fission/fusion markers, lipid peroxidation, and transport ATPase activity in SD rats exposed to ambient PM2.5 at different dosages were investigated. Also, the release of reactive oxygen species (ROS) via the respiratory burst in rat alveolar macrophages (AMs) exposed to PM2.5 was examined by luminol-dependent chemiluminescence (CL). The results showed that (1) PM2.5 deposited in the lung and induced pathological damage, particularly causing abnormal alterations of mitochondrial structure, including mitochondrial swelling and cristae disorder or even fragmentation in the presence of higher doses of PM2.5; (2) PM2.5 significantly affected the expression of specific mitochondrial fission/fusion markers (OPA1, Mfn1, Mfn2, Fis1, and Drp1) in rat lung; (3) PM2.5 inhibited Mn superoxide dismutase (MnSOD), Na(+)K(+)-ATPase, and Ca(2+)-ATPase activities and elevated malondialdehyde (MDA) content in rat lung mitochondria; and (4) PM2.5 induced rat AMs to produce ROS, which was inhibited by about 84.1% by diphenyleneiodonium chloride (DPI), an important ROS generation inhibitor. It is suggested that the pathological injury observed in rat lung exposed to PM2.5 is associated with mitochondrial fusion-fission dysfunction, ROS generation, mitochondrial lipid peroxidation, and cellular homeostasis imbalance. Damage to lung mitochondria may be one of the important mechanisms by which PM2.5 induces lung injury, contributing to respiratory diseases.

Generation of New Synthons for Synthesis Through Activation of Nitromethane.

Nitromethane is used as a common solvent, stabilizer, and fuel additive. Nitromethane has also been used as a sustainable building block and convenient reagent in chemical synthesis. In this Minireview, we summarize the recent advances in activation of nitromethane, using nitromethane as the source of cyano group, nitrogen, methylamine, formyl group, C1, nitroso, and oxime.

Sustainable Electrochemical Benzylic C-H Oxidation Using MeOH as an Oxygen Source.

New methods and strategies for the direct oxidation of benzylic C-H bonds are highly desirable, owing to the importance of ketone motifs in significant organic transformations and the synthesis of valuable molecules, including pharmaceuticals, pesticides, and fine chemicals. Herein, we describe an electrochemical benzylic C-H oxidation strategy for the synthesis of ketones using MeOH as an oxygen source. Inexpensive and safe KBr serves as both an electrolyte and a bromide radical precursor in the reaction. This transformation also offers several advantages such as mild conditions, broad functional group tolerance, and operational simplicity. Mechanistic investigations by control experiments, radical scavenging experiments, electron paramagnetic resonance (EPR), kinetic studies, cyclic voltammetry (CV), and in-situ Fourier transform infrared (FTIR) spectroscopy support a pathway involving the formation and transformation of benzyl methyl ether via hydrogen atom transfer (HAT) and single-electron transfer (SET). The practical application of our strategy is highlighted by the successful synthesis of five pharmaceuticals, namely lenperone, melperone, diphenhydramine, cinnarizine, and flunarizine.

Philadelphia chromosome-positive acute myeloid leukemia successfully treated by allogeneic hematopoietic stem cell transplantation: A case report and review of the literature.

RATIONAL: The Philadelphia chromosome (Ph) is seen in most patients with chronic myeloid leukemia and some patients with acute lymphoblastic leukemia. However, Ph-positive acute myeloid leukemia (Ph + AML) is a rare entity with a poor prognosis and a short median survival period. To date, there have been few clinical reports on this disease. And the treatment regimen of this disease has not been uniformly determined. PATIENT CONCERNS: We report a case of a Ph + AML. A 32-year-old male who was admitted to our hospital with weakness for 2 months. DIAGNOSIS: Philadelphia chromosome-positive acute myeloid leukemia. INTERVENTIONS: The patient achieved complete remission by the administration of a tyrosine kinase inhibitor, combined with low-intensity chemotherapy and a B-cell lymphoma 2 inhibitor. Then, allogeneic hematopoietic stem cell transplantation (allo-HSCT) from his sister was successfully performed. OUTCOMES: The patient has been in a continuous remission state for 6 months after transplantation. LESSONS: We reported a rare Ph + AML case, successfully treated with allo-HSCT. This case provided strong support for treating Ph + AML with allo-HSCT.

Myeloid sarcoma in JAK2-positive myelodysplastic neoplasms with fibrosis: a case report and literature review.

Myeloid sarcoma (MS) occurs in patients with acute myeloid leukemia (AML). In rare cases, MS can represent a form of blast transformation in patients with myeloproliferative neoplasms (MPN), myelodysplastic neoplasms (MDS), or MDS/MPN. The most frequent chromosomal alterations in MS are t(8;21) or inv(16), with other alterations being reported. Cases of MS in Janus kinase 2 (JAK2)-positive MDS with fibrosis are exceedingly rare. Here, we describe such a case. To the best of our knowledge, this is the first report of a JAK2 V617F mutation-positive MDS case occurring concurrently with MS involving the posterior aspect of the left seventh rib. No clear association has been previously demonstrated between the intramedullary AML cytogenetics and extramedullary disease occurrence. Interestingly, samples from the intramedullary MDS and extramedullary mass in this patient presented the same JAK2 V617F mutation. Following a treatment regimen of azacitidine and venetoclax, the patient achieved complete remission. The chest CT scan showed that the seventh posterior rib mass disappeared. This case provides valuable information for the potential future treatment of this disease.

Effects of intensive psychological intervention on treatment compliance, psychological status, and quality of life of patients with epilepsy.

BACKGROUND: Epilepsy is a nervous system disease characterized by recurrent attacks, a long disease course, and an unfavorable prognosis. It is associated with an enduring therapeutic process, and finding a cure has been difficult. Patients with epilepsy are predisposed to adverse moods, such as resistance, anxiety, nervousness, and anxiety, which compromise treatment compliance and overall efficacy. AIM: To explored the influence of intensive psychological intervention on treatment compliance, psychological status, and quality of life (QOL) of patients with epilepsy. METHODS: The clinical data of 105 patients with epilepsy admitted between December 2019 and July 2023 were retrospectively analyzed, including those of 50 patients who underwent routine intervention (control group) and 55 who underwent intensive psychological intervention (research group). Treatment compliance, psychological status based on the Self-Rating Anxiety Scale (SAS) and Depression Scale Self-Rating Depression Scale (SDS) scores, hope level assessed using the Herth Hope Scale (HHS), psychological resilience evaluated using the Psychological Resilience Scale, and QOL determined using the QOL in Epilepsy-31 Inventory (QOLIE-31) were comparatively analyzed. RESULTS: Treatment compliance in the research group was 85.5%, which is significantly better than the 68.0% of the control group. No notable intergroup differences in preinterventional SAS and SDS scores were identified (P > 0.05); however, after the intervention, the SAS and SDS scores decreased significantly in the two groups, especially in the research group (P < 0.05). The two groups also exhibited no significant differences in preinterventional HHS, Connor-Davidson Resilience Scale (CD-RISC), and QOLIE-31 scores (P > 0.05). After 6 months of intervention, the research group showed evidently higher HHS, CD-RISC, tenacity, optimism, strength, and QOLIE-31 scores (P < 0.05). CONCLUSION: Intensive psychological intervention enhances treatment compliance, psychological status, and QOL of patients with epilepsy.

Formaldehyde induced the cardiac damage by regulating the NO/cGMP signaling pathway and L-Ca2+ channels.

Background: Formaldehyde (FA) is a common environmental pollutant that has been found to cause negative cardiovascular effects, however, the toxicological mechanism is not well understood. In this study, we investigated the molecular effects of the Nitric Oxide (NO)/cyclic Guanosine Monophosphate (cGMP) signaling pathway and L-type calcium (L-Ca2+) channels in rat hearts. Methods: We designed the short-term FA exposure on the rat heart in different concentrations (0, 0.5, 3, 18 mg/m3). After 7 days of exposure, the rats were sacrificed and the rat tissues were removed for various experiments. Results: Our experimental data showed that FA resulted in the upregulation NO and cGMP, especially at 18 mg/m3. Further, when exposed to high concentrations of FA, Cav1.2 and Cav1.3 expression decreased. We conclude that the NO/cGMP signaling pathway and downstream related channels can be regulated by increasing the production of NO in the low concentration group of FA. High concentration FA directly regulates L-Ca22+ channels. Conclusion: This study suggests that FA damages the function of the cardiovascular system by regulating the NO/cGMP signaling pathway and L-Ca2+ channels.

Detection of oxytetracycline in milk using a novel carbon dots-based fluorescence probe via facile pyrolysis synthesis.

Amphiphilic blue-fluorescence carbon dots (B-CDs) were synthesized via pyrolysis method with citric acid and oleamine as precursors. B-CDs are monodispersed in ethanol, toluene, and ultrapure water with the average particle sizes of 3.33 nm, 2.05 nm, and 4.12 nm, respectively. The maximum emission wavelength of the B-CDs excitation at 370 nm is located at 459 nm. The B-CDs have good optical properties with excellent photostability. The fluorescence quantum yield (QY) of the as-prepared CDs is as high as 30.17%. The fluorescence of B-CDs is quenched because of static quenching by oxytetracycline. A high selective and sensitive fluorescence probe for detecting oxytetracycline was constructed with a linear range of 1.52-27.60 µg/mL and the detection limit of 0.33 µg/mL. The B-CDs-based fluorescence probe can be applied to analyze oxytetracycline in milk; the recoveries and relative standard are satisfactory. Furthermore, the B-CDs were exploited for imaging of SH-SY5Y cells. The results demonstrate that as-synthesized CDs can serve as a cellular imaging reagent owing to remarkable bioimaging performance. This work provides a new strategy for the detection of oxytetracycline in food.