One-Week Kava Dietary Supplementation Increases Both Urinary N- and O-Glucuronides of NNAL, a Lung Carcinogen Major Metabolite, among Smokers.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (commonly known as NNK) is one of the most prevalent and potent pulmonary carcinogens in tobacco products that increases the human lung cancer risk. Kava has the potential to reduce NNK and tobacco smoke-induced lung cancer risk by enhancing urinary excretion of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL, the major metabolite of NNK) and thus reducing NNK-induced DNA damage. In this study, we quantified N-glucuronidated NNAL (NNAL-N-gluc), O-glucuronidated NNAL (NNAL-O-gluc), and free NNAL in the urine samples collected before and after 1-week kava dietary supplementation. The results showed that kava increased both NNAL-N-glucuronidation and O-glucuronidation. Since NNAL-N-glucuronidation is dominantly catalyzed by UGT2B10, its representative single-nucleotide polymorphisms (SNPs) were analyzed among the clinical trial participants. Individuals with any of the four analyzed SNPs appear to have a reduced basal capacity in NNAL-N-glucuronidation. Among these individuals, kava also resulted in a smaller extent of increases in NNAL-N-glucuronidation, suggesting that participants with those UGT2B10 SNPs may not benefit as much from kava with respect to enhancing NNAL-N-glucuronidation. In summary, our results provide further evidence that kava enhances NNAL urinary detoxification via an increase in both N-glucuronidation and O-glucuronidation. UGT2B10 genetic status has not only the potential to predict the basal capacity of the participants in NNAL-N-glucuronidation but also potentially the extent of kava benefits.

AB-free kava enhances resilience against the adverse health effects of tobacco smoke in mice.

Tobacco smoke remains a serious global issue, resulting in serious health complications, contributing to the onsets of numerous preventive diseases, and imposing significant financial burdens. Despite regulatory policies and cessation measures aimed at curbing its usage, novel interventions are urgently needed for effective damage reduction. Our preclinical and pilot clinical studies showed that AB-free kava has the potential to reduce tobacco smoke-induced lung cancer risk, mitigate tobacco dependence, and reduce tobacco use. To understand the scope of its benefits in damage reduction and potential limitations, this study evaluated the effects of AB-free kava on a panel of health indicators in mice exposed to 2 - 4 weeks of daily tobacco smoke exposure. Our comprehensive assessments included global transcriptional profiling of the lung and liver tissues, analysis of lung inflammation, evaluation of lung function, exploration of tobacco nicotine withdrawal, and characterization of the causal PKA signaling pathway. As expected, Tobacco smoke exposure perturbed a wide range of biological processes and compromised multiple functions in mice. Remarkably, AB-free kava demonstrated the ability to globally mitigate tobacco smoke-induced deficits at the molecular and functional levels with promising safety profiles, offering a unique promise to mitigate tobacco smoke-related health damages. Further pre-clinical evaluation and clinical translation are warranted to fully harness the potential of AB-free kava in combating tobacco smoke-related harms.

Peroxynitrite imaging in ferroptosis-mediated drug-induced liver injury with a near-infrared fluorescence probe.

BACKGROUND: Over-consumption of drugs can result in drug-induced liver damage (DILI), which can worsen liver failure. Numerous studies have shown the significant role ferroptosis plays in the pathophysiology of DILI, which is typified by a marked imbalance between the generation and breakdown of lipid reactive oxygen species (ROS). The content of peroxynitrite (ONOO-) rapidly increased during this process and was thought to be a significant marker of early liver injury. Therefore, the construction of fluorescence probe for the detection and imaging of ONOO- holds immense importance in the early diagnosis and treatment of ferroptosis-mediated DILI. RESULTS: We designed a probe DILI-ONOO based on the ICT mechanism for the purpose of measuring and visualizing ONOO- in ferroptosis-mediated DILI processes and associated studies. This probe exhibited significant fluorescence changes with good sensitivity, selectivity, and can image exogenous and endogenous ONOO- in cells with low cytotoxicity. Using this probe, we were able to show changes in ONOO- content in ferroptosis-mediated DILI cells and mice models induced by the intervention of acetaminophen (APAP) and isoniazid (INH). By measuring the concentration of ferroptosis-related indicators in mice liver tissue, we were able to validate the role of ferroptosis in DILI. It is worth mentioning that compared to existing alanine transaminase (ALT) and aspartate aminotransferase (AST) detection methods, this probe can achieve early identification of DILI prior to serious liver injury. SIGNIFICANCE: This work has significant reference value in researching the relationship between ferroptosis and DILI and visualizing research. The results indicate a strong correlation between the progression of DILI and ferroptosis. Additionally, the use of DILI-ONOO shows promise in investigating the DILI process and assessing the effectiveness of medications in treating DILI.

OPIA: an open archive of plant images and related phenotypic traits.

High-throughput plant phenotype acquisition technologies have been extensively utilized in plant phenomics studies, leading to vast quantities of images and image-based phenotypic traits (i-traits) that are critically essential for accelerating germplasm screening, plant diseases identification and biotic & abiotic stress classification. Here, we present the Open Plant Image Archive (OPIA, https://ngdc.cncb.ac.cn/opia/), an open archive of plant images and i-traits derived from high-throughput phenotyping platforms. Currently, OPIA houses 56 datasets across 11 plants, comprising a total of 566 225 images with 2 417 186 labeled instances. Notably, it incorporates 56 i-traits of 93 rice and 105 wheat cultivars based on 18 644 individual RGB images, and these i-traits are further annotated based on the Plant Phenotype and Trait Ontology (PPTO) and cross-linked with GWAS Atlas. Additionally, each dataset in OPIA is assigned an evaluation score that takes account of image data volume, image resolution, and the number of labeled instances. More importantly, OPIA is equipped with useful tools for online image pre-processing and intelligent prediction. Collectively, OPIA provides open access to valuable datasets, pre-trained models, and phenotypic traits across diverse plants and thus bears great potential to play a crucial role in facilitating artificial intelligence-assisted breeding research.

Distribution of ultrasound cyclo plasty probe models in Chinese patients with glaucoma.

PURPOSE: To investigate the distribution of ultrasound cyclo plasty (UCP) probe models in Chinese patients with glaucoma. METHODS: Patients needing glaucoma surgery were recruited at Zhongshan Ophthalmic Center from January 2019 to December 2019. Patient demographics were recorded and analyzed. Visual acuity, intraocular pressure (IOP), retinal nerve fiber layer (RNFL), mean defect of visual field (MD), ocular axial length (AL) and horizontal corneal diameter (white to white, WTW) of eyes with glaucoma were measured. In addition, the UCP probe models were calculated using a nomogram tool and two ocular anatomical parameters: WTW and AL. RESULTS: A total of 1281 patients (2000 eyes) were included in the study, including 559 males (43.64%) and 722 females (56.36%). The age of the patients ranged from 18 to 91 years, with a mean age of 61.43 ± 12.21 years. IOP ranged from 22.0 to 60.0 mmHg, with a mean of 26.17 ± 3.52 mmHg. The mean AL and WTW were 22.96 ± 1.43 (ranging from 19.07 to 35.00) and 11.55 ± 0.50 (ranging from 9.6 to 13.7), respectively. According to the results calculated by the nomogram tool, Chinese patients' eyes mainly adapted to Model 12, with a percentage of 69.05%. Model 13 and Model 11 were suitable for 26.65% and 3.35% of the patients, respectively. A total of 0.95% of Chinese patients did not have a suitable probe model. CONCLUSION: For Chinese patients who needed glaucoma surgery, UCP probe models were mainly attributed to Model 12, followed by Model 13, and Model 11 was the least used.

Ionic strength-mediated protein and flavor studies on thermally processed hairtail pieces.

This study aimed to investigate the impact of different ionic strengths on the texture, protein, and flavor of thermally processed hairtail pieces. Incorporating salt ions into the heat treatment process had a positive impact on the quality of the cooked hairtail pieces. The pieces treated with 2 M NaCl showed superior texture and sensory scores. The ionic strength had a significant positive correlation with the chewiness and cohesion of cooked hairtail (p < 0.01). Furthermore, the myofibrillar protein content and total sulfhydryl content increased significantly. Circular dichroism spectra analysis revealed a transition in the protein structure from a ß-sheet structure to an α-helical structure as the ionic strength decreased. The ionic strength had a significant impact on the interaction between protein and flavor compounds. Specifically, it impacted the expression of certain volatile components (p < 0.05). Our study suggests that selecting the appropriate cooking method is crucial for both healthiness and sensory quality of processed hairtail products, and ionic strength mediation is superior in both aspects.

Novel Near-Infrared Fluorescence Probe for Bioimaging and Evaluating Superoxide Anion Fluctuations in Ferroptosis-Mediated Epilepsy.

Ferroptosis is an iron-regulated, caspase-mediated pathway of cell death that is associated with the excessive aggregation of lipid-reactive oxygen species and is extensively involved in the evolution of many diseases, including epilepsy. The superoxide anion (O2•-), as the primary precursor of ROS, is closely related to ferroptosis-mediated epilepsy. Therefore, it is crucial to establish a highly effective and convenient method for the real-time dynamic monitoring of O2•- during the ferroptosis process in epilepsy for the diagnosis and therapy of ferroptosis-mediated epilepsy. Nevertheless, no probes for detecting O2•- in ferroptosis-mediated epilepsy have been reported. Herein, we systematically conceptualized and developed a novel near-infrared (NIR) fluorescence probe, NIR-FP, for accurately tracking the fluctuation of O2•- in ferroptosis-mediated epilepsy. The probe showed exceptional sensitivity and outstanding selectivity toward O2•-. In addition, the probe has been utilized effectively to bioimage and evaluate endogenous O2•- variations in three types of ferroptosis-mediated epilepsy models (the kainic acid-induced chronic epilepsy model, the pentylenetetrazole-induced acute epilepsy model, and the pilocarpine-induced status epilepticus model). The above applications illustrated that NIR-FP could serve as a reliable and suitable tool for guiding the accurate diagnosis and therapy of ferroptosis-mediated epilepsy.

Screening of H2S donors with a red emission mitochondria-targetable fluorescent probe: Toward discovering a new therapeutic strategy for Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder caused by various factors such as neuroinflammation, oxidative stress, mitochondrial dysfunction, and neuronal apoptosis. Recent studies have shown that H2S supplementation reverses neuronal loss and mitigates motor deficits in PD patients through anti-inflammatory, antioxidant, improved mitochondrial function and proautophagic. Therefore, the discovery and use of H2S donors may be an exciting and intriguing strategy for the treatment of PD. Herein, we report a red emission mitochondria-targetable fluorescent probe, Rho-H2S, which can specifically and sensitively detect H2S with a limit of detection of 62.5 nM. Bioimaging experiments have shown that the probe has excellent mitochondrial targeting and good imaging capabilities for the detection of exogenous and endogenous H2S in cells. More importantly, based on the Rho-H2S probe, we first confirmed the sulforaphane (SFN) among 15 glucosinolate and isothiocyanate compounds from cruciferous vegetables with an outstanding ability to release H2S and we further proved that SFN could alleviate the symptoms of PD in vivo. All results demonstrate that Rho-H2S could be an effective tool for screening H2S donors and can contribute to the development of new therapeutic strategies for PD.

A Strategy for the Acquisition and Analysis of Image-Based Phenome in Rice during the Whole Growth Period.

As one of the most widely grown crops in the world, rice is not only a staple food but also a source of calorie intake for more than half of the world's population, occupying an important position in China's agricultural production. Thus, determining the inner potential connections between the genetic mechanisms and phenotypes of rice using dynamic analyses with high-throughput, nondestructive, and accurate methods based on high-throughput crop phenotyping facilities associated with rice genetics and breeding research is of vital importance. In this work, we developed a strategy for acquiring and analyzing 58 image-based traits (i-traits) during the whole growth period of rice. Up to 84.8% of the phenotypic variance of the rice yield could be explained by these i-traits. A total of 285 putative quantitative trait loci (QTLs) were detected for the i-traits, and principal components analysis was applied on the basis of the i-traits in the temporal and organ dimensions, in combination with a genome-wide association study that also isolated QTLs. Moreover, the differences among the different population structures and breeding regions of rice with regard to its phenotypic traits demonstrated good environmental adaptability, and the crop growth and development model also showed high inosculation in terms of the breeding-region latitude. In summary, the strategy developed here for the acquisition and analysis of image-based rice phenomes can provide a new approach and a different thinking direction for the extraction and analysis of crop phenotypes across the whole growth period and can thus be useful for future genetic improvements in rice.

Quantitative analysis and hepatoprotective mechanism of Cistanche deserticola Y. C. Ma against alcohol-induced liver injury in mice.

Cistanche deserticola Y. C. Ma (CD), known as "desert ginseng", has been found to have hepatoprotective effect. This research aimed to investigate the quality control and its alleviating effect on alcoholic liver injury in mice. In this study, for the first time, a sensitive and efficient ultra-high-performance liquid chromatography with quadrupole ion-trap mass spectrometry (UPLC-Q-TRAP/MS) method was developed to rapidly characterize nine representative phenylethanoid glycosides (PhGs) in the CD extract within 14 min, offering a reference for the quality control standard of this plant. In addition, we found that the CD extract significantly inhibited the weight loss, decreased the liver index, and attenuated excessive lipid deposition, inflammatory and oxidative stress in the mice liver. With the help of the high-throughput lipidomics technique, we discovered that CD markedly reversed 17 lipid metabolites and their involved linoleic acid, arachidonic acid and glycerophospholipid metabolic pathways. As these metabolites are mainly associated with lipid metabolism and liver damage, we further used molecular biological tests to found that CD could regulate the upstream genes and proteins of the lipid metabolism pathway, including adenosine 5'-monophosphate-activated protein kinase (AMPK), sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and peroxidase proliferators activate receptors α (PPARα). In conclusion, this study elucidates the modulatory effects of CD on lipid metabolism disorders in alcoholic fatty liver from holistic system and provides a reference for further research and development of CD as a therapeutic agent.

Exploring the effect of Lactiplantibacillus plantarum Lac 9-3 with high adhesion on refrigerated shrimp: Adhesion modeling and biopreservation evaluation.

Lactic acid bacteria (LAB) have recently become ideal candidates for developing food biopreservatives. Adhesion is critical for LAB to perform biocontrol functions in food processing and preservation. In this study, we innovatively proposed an effective adhesion evaluation model related to the surface properties of LAB to excavate a LAB strain with high adhesion on the surface of shrimp. Then, the biocontrol potential regarding the quality of refrigerated shrimp was explored, especially for protein quality. The screening of highly adherent LAB was performed using 54 LAB strains tolerant to the low temperature (4 °C) and present antimicrobial activity. Based on surface hydrophobicity, autoaggregation, and biofilm formation, a new method for predicting LAB adhesion was established by stepwise multiple linear regression. The most relevant relationship between adhesion and biofilm formation was derived from the model. Lactiplantibacillus plantarum Lac 9-3 stood out for the strongest adhesion on the shrimp surface and the highest antimicrobial activity. The preservation results showed that Lac 9-3 significantly (p < 0.05) retarded the accumulation of total volatile basic nitrogen (TVB-N) and the growth of spoilage bacteria. The damage to the texture properties of shrimp was inhibited. Meanwhile, the degradation of myofibrillar protein was alleviated, including a significant delay (p < 0.05) in sulfhydryl (SH) group reduction, surface hydrophobicity increases, and protein conformation changes. This research optimized the evaluation of the bacteria adhesion potential, providing a new idea for developing biocontrol strategies to extend the commercial life of aquatic products.

Effects of environmental pH on protein properties and flavor factors of hairtail (Trichiurus haumela) in thermal processing.

The flavor and texture of hairtail (Trichiurus haumela) products easily change depending on the processing conditions including the programed temperature, environmental pH, and so on. In the present study, we aimed to explore the differences in the overall texture and flavor of hairtail under heat treatment with varied environmental pH. The results indicated that the secondary structure of the myofibrillar protein in thermal processed hairtail meat presented a transformation from α-helix to ß-sheet structure with the decrease of solution pH. Moreover, heat treatment in an acidic solution environment effectively improved the sensory and flavor properties of hairtail. In addition, pH-mediated changes on protein characteristics of cooked hairtail meat showed significant correlation with the texture properties, while weakly correlated with the flavor.

Mitochondria-Targetable Ratiometric Time-Gated Luminescence Probe Activated by Selenocysteine for the Visual Monitoring of Liver Injuries.

Liver injury can result from various risk factors including diabetes, virus, alcohol, drugs, and other toxins, which is mainly responsible for global mortality and morbidity. Selenocysteine (Sec), as the main undertaker of selenium function in the life system, features prominently in a series of hepatic injuries and has close association with the pathological progression of liver injuries. Here, we report a mitochondria-targetable lanthanide complex-based probe, Mito-NPTTA-Tb3+/Eu3+, that can be used for accurately determining Sec in live cells and laboratory animals via the ratiometric time-gated luminescence (TGL) technique. This probe is composed of 2,2':6',2″-terpyridine-Tb3+/Eu3+ mixed complexes as the luminophore, 2,4-dinitrophenyl (DNP) as the responsive moiety and a lipophilic triphenylphosphonium cation (PPh3+) as the mitochondria-targeting moiety. Upon reaction with Sec, accompanied by the cleavage of DNP from the probe molecule, the I540/I690 ratio of the probe increased by 55 times, which enabled Sec to be detected with the ratiometric TGL method. After being incubated with living cells, the probe molecules were selectively accumulated in mitochondria to allow the mitochondrial Sec to be successfully imaged under the ratiometric TGL mode. Importantly, using this probe coupled with the ratiometric TGL imaging technique, the fluctuations of liver Sec in various liver injuries of model mice induced by diabetes, drug, toxin, and alcohol were precisely monitored, revealing that Sec plays an important antioxidant role during the oxidative stress process in liver injury, and the Sec levels have a close interrelationship with the degree of liver injury. All the results suggest that the new probe Mito-NPTTA-Tb3+/Eu3+ could be a potential tool for the accurate diagnosis of liver injury.

Component Characterization, In Vitro Activities and Molecular Mechanism of Cydonia oblonga Mill. against Diabetic.

Cydonia Oblonga Mill. is widely distributed in Turkey, Uzbekistan and China and commonly used by the food industry to produce jam, jelly and candies. The aim of this study was to investigate the in vitro antidiabetic activity and anti-diabetic mechanism of Cydonia Oblonga Mill. fruit (COMF). The chemical compositions were further characterized in COMF by UPLC-Q-Orbitrap/MS and 65 components including 22 flavonoids, 16 organic acids, 11 polyphenols, 5 amino acids, 3 pentacyclic triterpenoids and 8 other compounds were identified. The antioxidant activity by DPPH scavenging method and α-glucosidase inhibitory activity were tested. Furthermore, we detected the effects of COMF extract on the proliferation activity of HUVECs, cell viability of HUVECs under H2O2-induced oxidative stress, and NO production. Then, molecular docking activity and α-glucosidase inhibitory activity of seven key flavonoid components selected by bioinformatics analysis and literature in the COMF were studied. Among them, quercetin showed potent inhibitory activity, kaempferol, isorhamnetin, luteolin and apigenin demonstrated moderate inhibitory activity, while rutin and epicatechin exhibited poor inhibitory activity. Subsequently, the effects of quercetin, kaempferol, isorhamnetin, leteolin and apigenin on the gene expression levels of AKT1, IL-6 and VEGFA were verified by real-time fluorescence quantification (RT-qPCR). Molecular biology result showed that different active ingredients can significantly recover the levels of AKT1, IL-6 and VEGFA in HUVECs injured by high glucose.

Precise Monitoring and Assessing Treatment Response of Sepsis-Induced Acute Lung Hypoxia with a Nitroreductase-Activated Golgi-Targetable Fluorescent Probe.

Sepsis-induced acute lung injury (ALI) is mostly attributed to an outbreak of reactive oxygen species (ROS), which makes leukocytes infiltrate into the lung and results in lung hypoxia. Nitroreductase (NTR) is significantly upregulated under hypoxia, which is commonly regarded as a potential biomarker for assessing sepsis-induced acute lung hypoxia. Increasing evidence shows that NTR in the Golgi apparatus could be induced in sepsis-induced ALI. Meanwhile, the prolyl hydroxylase (PHD) inhibitor (dimethyloxalylglycine, DMOG) attenuated sepsis-induced ALI through further increasing the level of Golgi NTR by improving hypoxia inducible factor-1α (HIF-1α) activity, but as yet, no Golgi-targetable probe has been developed for monitoring and assessing treatment response of sepsis-induced ALI. Herein, we report a Golgi-targetable probe, Gol-NTR, for monitoring and assessing treatment response of sepsis-induced ALI through mapping the generation of NTR. The probe displayed high sensitivity with a low detection limit of 54.8 ng/mL and good selectivity to NTR. In addition, due to the excellent characteristics of Golgi-targetable, Gol-NTR was successfully applied in mapping the change of Golgi NTR in cells and zebrafish caused by various stimuli. Most importantly, the production of Golgi NTR in the sepsis-induced ALI and the PHD inhibitor (DMOG) against sepsis-induced ALI were visualized and precisely assessed for the first time with the assistance of Gol-NTR. The results demonstrated the practicability of Gol-NTR for the precise monitoring and assessing of the personalized treatment response of sepsis-induced ALI.

The role of AI-2/LuxS system in biopreservation of fresh refrigerated shrimp: Enhancement in competitiveness of Lactiplantibacillus plantarum for nutrients.

Quorum sensing of lactic acid bacteria, mediated by the Autoinducer-2 (AI-2)/LuxS system, positively regulates antibacterial activity, which is an effective strategy for aquatic product preservation. This study revealed that AI-2/LuxS system regulates the nutritional competitiveness of LAB by facilitating membrane transport systems in preservation of vacuum-packaged refrigerated shrimp (VPRS), using Lactiplantibacillus plantarum SS-128 wild-type and the luxS mutant strain. In VPRS preservation, organisms that cause spoilage and total volatile basic nitrogen were significantly lower in the VPRS inoculated with L. plantarum SS-128 than those inoculated with the luxS mutant strain (L. plantarum ΔluxS/SS-128) (p < 0.05). Simulations in vitro using diluted shrimp juice showed the growth inhibitory effects of wild-type strain SS-128 on the main VPRS spoilage microorganism Shewanella baltica. This could potentially be attributed to more efficient nutrient utilization, presumably mediated by AI-2/LuxS system, as revealed by interaction analysis. In support of this, in vitro nutritional competition test showed that L. plantarum SS-128 was more competitive for nutrients when cocultured with S. baltica under conditions of limited nutrient availability. Subsequently, an integrated analysis of transcriptomic and metabolomic revealed that AI-2/LuxS enables a continuous expansion of L. plantarum SS-128 by balancing energy expenditure followed by enhancing membrane transport systems, which is the main driven forces for it to occupy a favourable niche quickly. Our results showed that the AI-2/LuxS system may regulate the nutritional competitiveness of lactic acid bacteria and may be a regulatory strategy for biological preservation of aquatic products.

Accurate quantification, naked eyes detection and bioimaging of nitrite using a colorimetric and near-infrared fluorescent probe in food samples and Escherichia coli.

Nitrite (NO2-) is an inorganic contaminant that exists widely in the environment including water and food products, excessive amounts of NO2- would threaten humans and aquatic life. Developing a rapid and convenient sensing method for NO2- remains a great challenge. Herein, a colorimetric and near-infrared fluorescent probe (TBM) was synthesized and applied for sensitively and selectively detecting NO2- in water, food samples and Escherichia coli (E. coli). With the addition of NO2-, the probe TBM solution has a distinct visual color changed from red to colorless and fluorescence intensity at 620 nm quickly decreased. The probe TBM could detect NO2- quantitatively with a detection limit of 85 nM based on a 3σ/slope. Under optimum conditions, TBM has been successfully used to detect NO2- in real-world environmental and dietary samples, with positive results. Besides, paper strips loaded with TBM have been used to visually determine NO2- levels. Most importantly, TBM has also been proven to be able to discriminate from different concentrations of NO2- in E. coli by fluorescence imaging. In summary, the probe TBM was successfully developed for the accurate quantification, naked eyes detection and bioimaging of NO2- in water, food samples and E. coli, which provides a useful tool to better guarantee the quality and safety of daily life and food industry.

[Atmospheric VOCs Pollution Characteristics and Health Risk Assessment of Large-scale Integrated Industrial Area and Surrounding Areas in Southwest China].

To investigate the characteristics of atmospheric volatile organic compound (VOCs) pollution and promote VOCs pollution prevention and control in industrial areas, in December 2020, VOCs samples collected using Summa Canisters at three observation sites were used to study the characteristics of VOCs pollution and source apportionment and to conduct a health risk assessment in large integrated industrial areas and surrounding urban areas in southwest China. The results showed that the mean φ(TVOCs) at site A and site B in an industrial area and at a third urban site were 105.25×10-9, 222.92×10-9, and 82.87×10-9, respectively. Monochloromethane, dichloromethane, acetone, ethanol, and ethane were the species with higher volume fractions at the three sites. Aromatic hydrocarbons and OVOCs had a large contribution to the ozone formation potential (OFP), with a cumulative contribution of more than 50%, and the main reactive species were methyl methacrylate, toluene, p-xylene, and o-xylene; the secondary organic aerosol formation potential (SOAP) of aromatic hydrocarbons contributed more than 80%, with the main active species being toluene, p-xylene, and o-xylene. The results of PMF source analysis showed six main sources of VOCs, in the descending order of the petrochemical industry (21.83%), industrial waste incineration (18.6%), pharmaceutical manufacturing (16.99%), fossil fuel combustion (16.03%), motor vehicle exhaust (14.23%), and chemical manufacturing (12.32%). The mean values of the hazard index (HI) of site A and site B in the industrial area and in the urban site were 0.55, 0.68, and 0.41, respectively, and the mean lifetime cancer risk (LCR) values were 6.71×10-6, 6.72×10-6, and 6.58×10-6, respectively. Both HI and LCR in industrial areas were larger than those in urban areas. The quantitative assessment of risk sources showed that motor vehicle exhaust and fossil fuel combustion contributed relatively high carcinogenic risks.

Therapeutic Targeting PLK1 by ON-01910.Na Is Effective in Local Treatment of Retinoblastoma.

Cell cycle deregulation is involved in the pathogenesis of many cancers and is often associated with protein kinase aberrations, including the polo-like kinase 1 (PLK1). We used retinoblastoma, an intraocular malignancy that lacks targeted therapy, as a disease model and set out to reveal targetability of PLK1 with a small molecular inhibitor ON-01910.Na. First, transcriptomic analysis on patient retinoblastoma tissues suggested that cell cycle progression was deregulated and confirmed that PLK1 pathway was upregulated. Next, antitumor activity of ON-01910.Na was investigated in both cellular and animal levels. Cytotoxicity induced by ON-01910.Na was tumor specific and dose dependent in retinoblastoma cells, while nontumor cells were minimally affected. In three-dimensional culture, ON-01910.Na demonstrated efficient drug penetrability with multilayer cell death. Posttreatment transcriptomic findings revealed that cell cycle arrest and MAPK cascade activation were induced following PLK1 inhibition and eventually resulted in apoptotic cell death. In Balb/c nude mice, a safe threshold of 0.8 nmol intravitreal dosage of ON-01910.Na was established for intraocular safety, which was demonstrated by structural integrity and functional preservation. Furthermore, intraocular and subcutaneous xenograft were significantly reduced with ON-01910.Na treatments. For the first time, we demonstrated targetability of PLK1 in retinoblastoma by efficiently causing cell cycle arrest and apoptosis. Our study is supportive that local treatment of ON-01910.Na may be a novel, effective modality benefiting patients with PLK1-aberrant tumors.

RNA Sequencing and Bioinformatic Analysis on Retinoblastoma Revealing that Cell Cycle Deregulation Is a Key Process in Retinoblastoma Tumorigenesis.

PURPOSE: Retinoblastoma (RB) is a primary pediatric ocular malignancy that can be fatal with inadequate treatment. While multimodal treatments are applied for eye salvage, vision loss and metastasis can occur in some patients. The present study aimed to explore key pathways and factors in RB pathogenesis, which could be potential targets for novel RB treatments. METHODS: RNA sequencing was performed on three RB tissues and referenced with three normal retinas. Differentially expressed genes (DEGs) were identified from sequencing data and further analyzed with clustering analysis, function and pathway enrichment, protein-protein interaction (PPI), and data-mining analysis in order to screen for tumorigenic relevancy. RESULTS: A total of 331 DEGs were identified by clustering analysis of RB tissues, and the expression patterns were significantly distinguishable from normal retinas. Function and pathway enrichment and PPI analysis together showed that cell cycle was the most prominently upregulated pathway found in RB tissues. Following comprehensive bioinformatic analyses, six key genes relevant to cell cycle regulation were identified, namely BUB1, RRM2, TPX2, UBE2C, NUSAP1, and DTL. CONCLUSIONS: Cell cycle pathway and six relevant genes may be potential key factors in RB tumorigenesis and laying the foundation for prospective investigation on development of novel targeted therapies.