A fluorescent terbium-metal-organic framework material for high-sensitivity detection of vomitoxin and oxytetracycline hydrochloride in water.

A unique luminescent lanthanide metal-organic framework (LnMOF)-based fluorescence detection platform was utilized to achieve sensitive detection of vomitoxin (VT) and oxytetracycline hydrochloride (OTC-HCL) without the use of antibodies or biomolecular modifications. The sensor had a fluorescence quenching constant of 9.74 × 106 M-1 and a low detection limit of 0.68 nM for vomitoxin. Notably, this is the first example of a Tb-MOF sensor for fluorescence detection of vomitoxin. We further investigated its response to two mycotoxins, aflatoxin B1 and ochratoxin A, and found that their Stern-Volmer fluorescence quenching constants were lower than those of VT. In addition, the fluorescence sensor realized sensitive detection of OTC-HCL with a detection limit of 0.039 µM. In conclusion, the method has great potential as a sensitive and simple technique to detect VT and OTC-HCL in water.

143D, a novel selective KRASG12C inhibitor exhibits potent antitumor activity in preclinical models.

The KRASG12C mutant has emerged as an important therapeutic target in recent years. Covalent inhibitors have shown promising antitumor activity against KRASG12C-mutant cancers in the clinic. In this study, a structure-based and focused chemical library analysis was performed, which led to the identification of 143D as a novel, highly potent and selective KRASG12C inhibitor. The antitumor efficacy of 143D in vitro and in vivo was comparable with that of AMG510 and of MRTX849, two well-characterized KRASG12C inhibitors. At low nanomolar concentrations, 143D showed biochemical and cellular potency for inhibiting the effects of the KRASG12C mutation. 143D selectively inhibited cell proliferation and induced G1-phase cell cycle arrest and apoptosis by downregulating KRASG12C-dependent signal transduction. Compared with MRTX849, 143D exhibited a longer half-life and higher maximum concentration (Cmax) and area under the curve (AUC) values in mouse models, as determined by tissue distribution assays. Additionally, 143D crossed the blood‒brain barrier. Treatment with 143D led to the sustained inhibition of KRAS signaling and tumor regression in KRASG12C-mutant tumors. Moreover, 143D combined with EGFR/MEK/ERK signaling inhibitors showed enhanced antitumor activity both in vitro and in vivo. Taken together, our findings indicate that 143D may be a promising drug candidate with favorable pharmaceutical properties for the treatment of cancers harboring the KRASG12C mutation.

Compression therapy following posterior lumbar interbody fusion: a prospective, randomized, clinical study.

BACKGROUND: Wound-related complications are an inevitable issue faced by spinal surgeons. Negative pressure drainage remains the most commonly used method to prevent postoperative hematoma and related complications. This prospective, randomized, controlled study was conducted to evaluate the efficacy of compression therapy following posterior lumbar interbody fusion, with emphasis on pain, anemia, and inflammation. METHODS: Sixty consecutive patients who have undergone posterior lumbar interbody fusion in the age range 43-78 years, with an average age of 59 years, were selected and randomly assigned into two groups. Factors, such as drainage volume, visual analog scale (VAS) pain score for back pain, white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (Hb) levels, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels assessed on the 1st, 3rd, and 10th days postoperatively, were compared between the two groups. RESULTS: The average follow-up was 6 months, ranging from 3 to 11 months. Drainage volume, VAS score, and CRP levels on the 10th day after the surgery were found to be significantly lower in the treatment group than in the control group. RBC count and Hb levels on the 3rd and 10th postoperative days were observed to be significantly higher in the treatment group than in the control group (P < 0.05). During discharge, the wounds of the patients of the both groups had healed and neither showed any symptoms of infection, hematoma, or necrosis. CONCLUSION: Compression therapy relieves pain, alleviates anemia, and the inflammatory response following posterior lumbar interbody fusion. TRIAL REGISTRATION: ChiCTR1800015825 on chictr.org.cn, April 23, 2018, the trial registry is Chinese Clinical Trial Registry.

Conjunctive encoding of exploratory intentions and spatial information in the hippocampus.

The hippocampus creates a cognitive map of the external environment by encoding spatial and self-motion-related information. However, it is unclear whether hippocampal neurons could also incorporate internal cognitive states reflecting an animal's exploratory intention, which is not driven by rewards or unexpected sensory stimuli. In this study, a subgroup of CA1 neurons was found to encode both spatial information and animals' investigatory intentions in male mice. These neurons became active before the initiation of exploration behaviors at specific locations and were nearly silent when the same fields were traversed without exploration. Interestingly, this neuronal activity could not be explained by object features, rewards, or mismatches in environmental cues. Inhibition of the lateral entorhinal cortex decreased the activity of these cells during exploration. Our findings demonstrate that hippocampal neurons may bridge external and internal signals, indicating a potential connection between spatial representation and intentional states in the construction of internal navigation systems.

New eudesmanolides from Artemisia verlotorum and their potential targets of hepatocellular carcinoma by network pharmacology.

Fractionation of the ethanol extract of Artemisia verlotorum led to the identification of eight undescribed eudesmane-type sesquiterpenoids, artemverlolides A-H (1-8). Their structures were determined by spectral analyses (HRESIMS, 1D and 2D NMR, IR, and ECD). Network pharmacology predicted that compounds 1-8 might be target on AURKA, CCNA2, CYP2C19, and EPHX2 with possibly antihepatoma effect from Swiss TargetPrediction and Gene Expression Omnibus database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the targets significantly enriched in FoxO signaling pathway. The molecular docking suggested that compound 8 had high binding affinity with AURKA. Furthermore, the interaction between compound 8 and AURKA was determined by Surface Plasmon Resonance (SPR) assay. The result suggested that compound 8 bound to AURKA with KD value of 68.0µM and was consistent with the predicted data, demonstrating that AURKA might be one of acting targets of 8.

RNF114 facilitates the proliferation, stemness, and metastasis of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC), the fourth of the world's major common malignancy, poses a serious threat to the physical and mental health of the population. Nevertheless, the prognosis of CRC patients remains unsatisfactory. Consequently, it is still imperative to continuously discover the CRC mechanisms. METHODS: The expression profiles of mRNAs were recognized by whole transcriptome sequencing to identity differentially expressed mRNA (DE-mRNA). TCGA COAD cohort, PPOGgene and Kaplan-Meier Plotter databases were utilized to validate RNF114 relevance to CRC prognosis. The effect of RNF114 on the malignant biological behavior of CRC was explored in CRC cells and subcutaneous tumor models and lung metastasis model after exogenous regulation of RNF114. RESULTS: A total of 1358 DE-mRNAs were identified, including 617 up-regulated and 741 down-regulated DE-mRNAs, and they were mainly involved in the term of receptor ligand activity, Wnt signaling pathway and pathway in cancer. Notably, RNF114 was hyper-expressed in tissues and cell of CRC, and significantly correlated with tumor invasion depth and TNM stage of CRC patients. RNF114 expression were significantly associated with overall survival, and had superior diagnostic value in CRC. In vitro, knockdown of RNF114 statistically diminished the proliferation, stemness, invasion and wound healing of CRC cells and facilitated their apoptosis, and the opposite result was observed for overexpression of RNF114. In vivo, knockdown of RNF114 effectively diminished the mass and volume of tumors, and lung metastasis in animal model. CONCLUSIONS: In summary, we identified DE-mRNAs in CRC, and elucidated that RNF114 facilitates CRC process. The discovery will contribute to theoretical foundation for RNF114 as a potential therapeutic target and biomarker, and offer new perspectives for CRC research.

Prevalence, distribution, accumulation, and risk of environmental corticosteroids and estrogens in biofilms from the Pearl River Delta.

Biofilms play a significant role in the biogeochemical processing of organic matter and the environmental fate of emerging pollutants. In this study, we investigated the occurrence and distribution of 32 endocrine-disrupting chemicals (EDCs), including 24 environmental corticosteroids (ECs) and 8 environmental estrogens (EEs), in natural biofilms from the Pearl River system. Their association between biofilms and water and environmental risk were assessed. The ECs and EEs ubiquitously occurred in the biofilms, ranging from <0.61-6.57 ng/g and <0.8-2535 ng/g, respectively. Temporally, there was no obvious variance in either ECs or EEs in the biofilms during the winter and summer, and their concentrations exhibited a spatial trend of upward to midstream, descending downstream, and then seaward attenuation at the estuary. For ECs and EEs, the similar levels of field-derived bioconcentration factors (BCFs) (logarithm values: 2.42-2.86 and 2.72-2.98, respectively) and biofilm organic carbon-normalized partitioning coefficients (Kboc) (3.39-3.69 and 3.35-3.95) suggest the comparable potential of accumulation and sorption by biofilms between these two classes of EDCs. In addition, higher values of BCF and Kboc for the EEs were found in winter and were correspondingly comparable to their distribution coefficients (Kd) and Koc derived from suspended particles and sediment, revealing that biofilms are a competitive environmental compartment for capturing EDCs, particularly during the mature period. A positive logKboc-logKow relationship suggests hydrophobic partitioning as a primary interaction mechanism between the biofilm and EEs. Moreover, high risks from biofilm-associated ECs and EEs might have posed to the fluvial ecosystem. This study provides original insights into the occurrence, fate, and risk of ECs in natural biofilms for the first time and demonstrates that biofilms may not only serve as reservoirs but also serve as sentinels for fluvial EDC contamination. These results contribute to the further understanding of the behavior and fate of EDCs in aquatic environments.

Propofol exerts anti-anhedonia effects via inhibiting the dopamine transporter.

Lasker's award-winning drug propofol is widely used in general anesthesia. The recreational use of propofol is reported to produce a well-rested feeling and euphoric state; yet, the neural mechanisms underlying such pleasant effects remain unelucidated. Here, we report that propofol actively and directly binds to the dopamine transporter (DAT), but not the serotonin transporter (SERT), which contributes to the rapid relief of anhedonia. Then, we predict the binding mode of propofol by molecular docking and mutation of critical binding residues on the DAT. Fiber photometry recording on awake freely moving mice and [18F] FP-CIT-PET scanning further establishes that propofol administration evokes rapid and lasting dopamine accumulation in nucleus accumbens (NAc). The enhanced dopaminergic tone drives biased activation of dopamine-receptor-1-expressing medium spiny neurons (D1-MSNs) in NAc and reverses anhedonia in chronically stressed animals. Collectively, these findings suggest the therapeutic potential of propofol against anhedonia, which warrants future clinical investigations.

Suspended particulate matter-associated environmental corticosteroids in the Pearl River, China: Occurrence, distribution, and partitioning.

Suspended particulate matter (SPM) plays an important role in the geochemical behavior and fate of organic micropollutants in aquatic environments. However, the presence of trace emerging endocrine disruptors such as environmental corticosteroids (ECs) in SPM is less well understood. This study focused on the occurrence, distribution, and partitioning of SPM-associated ECs in the Pearl River system, China. Ubiquitous particulate ECs were found in the surface water of the rivers at average concentrations (dry weight) between 0.46 ng/g (flumethasone) and 8.83 ng/g (clobetasone butyrate). The total EC (∑ECs) concentrations of the 24 selected target compounds varied from <1.03 ng/g to 62.3 ng/g, with an average and median of 17.6 ng/g and 13.7 ng/g, respectively. Higher SPM-bound EC levels were commonly observed in winter (dry season), and spatially, their relatively high contamination in urban tributary networks decreased while flowing to mainstreams and then gradually attenuated from upstream to the estuary. Despite the approximately 90 % mass distribution of ∑ECs in the aqueous phase, approximately 50 % of their effect burden was derived from the suspended particulate fractions. For the first time, in situ SPM-water partitioning coefficients (Kp) and their organic carbon-normalized ones (Koc) of ECs were determined in surface waters, and a field-derived preliminary linear equation was proposed to estimate Koc for ECs using basic physicochemical parameters n-octanol/water partitioning coefficient (Kow), which is of importance with regard to the assessment of transport, fate, and risk of these emerging hazardous chemicals. Furthermore, the significant logKoc-logKow relationship for ECs reveals that nonspecific hydrophobic partitioning is a major association mechanism between SPM and ECs. Moreover, hydrogen bonding is suggested to be a prevailing specific binding mechanism and provides more contribution to nonhydrophobic interactions between ECs and particulate organic matter than environmental estrogens.

Characterization of a Novel Polysaccharide Derived from Rhizospheric Paecilomyces vaniformisi and Its Mechanism for Enhancing Salinity Resistance in Rice Seedlings.

Soil salinity is an important limiting factor in agricultural production. Rhizospheric fungi can potentially enhance crop salinity tolerance, but the precise role of signaling substances is still to be systematically elucidated. A rhizospheric fungus identified as Paecilomyces vaniformisi was found to enhance the salinity tolerance of rice seedlings. In this study, a novel polysaccharide (PPL2b) was isolated from P. vaniformisi and identified as consisting of Manp, Glcp, GalpA, and Galp. In a further study, PPL2b showed significant activity in alleviating salinity stress-induced growth inhibition in rice seedlings. The results indicated that under salinity stress, PPL2b enhances seed germination, plant growth (height and biomass), and biochemical parameters (soluble sugar and protein contents). Additionally, PPL2b regulates genes such as SOS1 and SKOR to decrease K+ efflux and increase Na+ efflux. PPL2b increased the expression and activity of genes related to antioxidant enzymes and nonenzyme substances in salinity-induced oxidative stress. Further study indicated that PPL2b plays a crucial role in regulating osmotic substances, such as proline and betaine, in maintaining the osmotic balance. It also modulates plant hormones to promote rice seedling growth and enhance their tolerance to soil salinity. The variables interacted and were divided into two groups (PC1 77.39% and PC2 18.77%) based on their relative values. Therefore, these findings indicate that PPL2b from P. vaniformisi can alleviate the inhibitory effects of salinity stress on root development, osmotic adjustment, ion balance, oxidative stress balance, and growth of rice seedlings. Furthermore, it suggests that polysaccharides produced by rhizospheric fungi could be utilized to enhance crop tolerance to salinity.

Enhanced Biosynthesis of Fatty Acids Contributes to Ciprofloxacin Resistance in Pseudomonas aeruginosa.

Antibiotic-resistant Pseudomonas aeruginosa is insensitive to antibiotics and difficult to deal with. An understanding of the resistance mechanisms is required for the control of the pathogen. In this study, gas chromatography-mass spectrometer (GC-MS)-based metabolomics was performed to identify differential metabolomes in ciprofloxacin (CIP)-resistant P. aeruginosa strains that originated from P. aeruginosa ATCC 27853 and had minimum inhibitory concentrations (MICs) that were 16-, 64-, and 128-fold (PA-R16CIP, PA-R64CIP, and PA-R128CIP, respectively) higher than the original value, compared to CIP-sensitive P. aeruginosa (PA-S). Upregulation of fatty acid biosynthesis forms a characteristic feature of the CIP-resistant metabolomes and fatty acid metabolome, which was supported by elevated gene expression and enzymatic activity in the metabolic pathway. The fatty acid synthase inhibitor triclosan potentiates CIP to kill PA-R128CIP and clinically multidrug-resistant P. aeruginosa strains. The potentiated killing was companied with reduced gene expression and enzymatic activity and the returned abundance of fatty acids in the metabolic pathway. Consistently, membrane permeability was reduced in the PA-R and clinically multidrug-resistant P. aeruginosa strains, which were reverted by triclosan. Triclosan also stimulated the uptake of CIP. These findings highlight the importance of the elevated biosynthesis of fatty acids in the CIP resistance of P. aeruginosa and provide a target pathway for combating CIP-resistant P. aeruginosa.

Repressed Central Carbon Metabolism and Its Effect on Related Metabolic Pathways in Cefoperazone/Sulbactam-Resistant Pseudomonas aeruginosa.

Metabolic shift and antibiotic resistance have been reported in Pseudomonas aeruginosa. However, the global metabolic characteristics remain largely unknown. The present study characterizes the central carbon metabolism and its effect on other metabolic pathways in cefoperazone-sulbactam (SCF)-resistant P. aeruginosa (PA-RSCF). GC-MS-based metabolomics shows a repressed central carbon metabolism in PA-RSCF, which is confirmed by measuring expression of genes and activity of enzymes in the metabolism. Furthermore, expression of the genes that encode the enzymes for the first step of fatty acid biosynthesis, glutamate metabolism, and electron transport chain is reduced, confirmed by their enzymatic activity assay, and the key enzyme for riboflavin metabolism is also reduced, indicating the decreased metabolic flux to the four related metabolic pathways. Moreover, the role of the reduced riboflavin metabolism, being related to ROS generation, in SCF resistance is explored. Exogenous H2O2 potentiates SCF-mediated killing in a dose-dependent manner, suggesting that the decreased ROS resulted from the reduced riboflavin metabolism that contributed to the resistance. These results indicate that the repressed central carbon metabolism and related riboflavin metabolism contribute to SCF resistance, but increasing ROS can restore SCF sensitivity. These findings characterize the repressed central carbon metabolism and its effect on other metabolic pathways as the global metabolic features in PA-RSCF.

[Clinical observation of chiropractic manipulation in the treatment of degenerative scoliosis].

OBJECTIVE: To observe clinical efficacy of chiropractic manipulation in the treatment of degenerative scoliosis (DS). METHODS: From June 2017 to September 2019, 120 patients with degenerative scoliosis were randomly divided into treatment group (60 cases) and control group(60 cases). The patients in treatment group were treated with chiropractic manipulation once every other day for 4 weeks. The patients in control group were treated with eperisone hydrochloride tablets combined with thoracolumbar orthopedic(TSLO)brace, oral eperisone hydrochloride tablets 50 mg three times a day, wearing TSLO brace for not less than 8 hours a day. The course of treatment was 4 weeks. After the patients were selected into the group, visual analogue scale (VAS) and Oswestry Disability Index (ODI) were recorded before treatment, 1, 2, 3, 4 weeks after treatment and 1 month after treatment. The full length X-ray of the spine was taken before and 4 weeks after treatment, and the scoliosis Cobb angle, sagittal vertical axis (SVA) and lumbar lordosis (LL) were measured and compared. The adverse reactions during the treatment were recorded. RESULTS: There were significant differences in VAS and ODI between two groups at each time point after treatment (P<0.001), VAS and ODI at 2 weeks after treatment (PVAS=0.025, PODI=0.032) and 3 weeks after treatment(PVAS=0.040, PODI=0.044) in treatment group were significantly different from those in control group, but there was no significant difference in VAS and ODI at other time points between treatment group and control group (P>0.05). There was significant difference in Cobb angle between treatment group(P=0.010) and control group(P=0.017) after treatment, but there was no significant difference in LL and SVA between treatment group and control group. There was no significant difference in Cobb angle, LL and SVA between two groups before and after treatment. During the treatment, there were 4 mild adverse reactions in the control group and no adverse reactions in the treatment group. CONCLUSION: Chiropractic manipulation can effectively relieve pain and improve lumbar function in patients with degenerative scoliosis. The onset of action is faster than that oral eperisone hydrochloride tablets combined with TSLO brace, and it has better safety and can improve Cobb angle of patients with degenerative scoliosis.

[Influence of degenerative scoliosis on the treatment of lumbar spinal stenosis by MIS-TLIF].

OBJECTIVE: To evaluate the effect of degenerative scoliosis on the difficulty and efficacy of minimally invasive transforaminal lumbar interbody fusion(MIS-TLIF) in the treatment of lumbar spinal stenosis. METHODS: From September 2016 to September 2019, 52 patients with lumbar spinal stenosis treated by MIS-TLIF were retrospectively analyzed, including 16 males and 36 females, aged from 42 to 71(63.44±5.96) years old, the course of disease from 1.5 to 6.5 years, with an average of (3.69±1.10) years. All patients had lower extremity root pain or numbness, 41 patients had intermittent claudication. There were 31 cases of L4, 5 and 21 cases of L5S1. There were 18 cases in scoliosis group, lumbar spinal stenosis combined withdegenerative scoliosis, and 34 cases in stenosis group, lumbar spinal stenosis alone. The perioperative data and postoperative complications were recorded, the postoperative interbody fusion was evaluated by CT, and the clinical outcomes were evaluated by VAS score, Oswestry Disability Index (ODI). RESULTS: All patients were followed up for 12 to 36 months, with an average of (19.58±5.33) months. The operation time and intraoperative bleeding in stenosis group were better than those in scoliosis group (P<0.05). There were no significant differences in postoperative drainage volume, postoperative Hb, CRP, postoperative landing time, discharge time, VAS score at discharge and follow-up, ODI score at 3 months and follow up, postoperative complications and interbody fusion rate between two groups (P>0.05). CONCLUSION: For patients with lumbar spinal stenosis undergoing MIS-TLIF, degenerative scoliosis can lead to prolonged operation time and increased bleeding. However, it has no significant effect on therelief of postoperative symptoms, postoperative complications and the recovery of lumbar function.

Astrocyte-Derived Lactate Modulates the Passive Coping Response to Behavioral Challenge in Male Mice.

Every organism inevitably experiences stress. In the face of acute, intense stress, for example, periods of passivity occur when an organism's actions fail to overcome the challenge. The occurrence of inactive behavior may indicate that struggling would most likely be fruitless. Repeated serious stress has been associated with mood disorders such as depression. The modulation of passive coping response patterns has been explored with a focus on the circuit level. However, the cellular and molecular mechanisms are largely uncharacterized. Here, we report that lactate is a key factor in the astrocytic modulation of the passive coping response to behavioral challenge in adult mice. We found increased extracellular lactate in the medial prefrontal cortex (mPFC) when mice experienced the forced swimming test (FST). Furthermore, we discovered that disturbing astrocytic glycogenolysis, which is a key step for lactate production in the mPFC, decreased the duration of immobility in the FST. Knocking down monocarboxylate transporter 4 (MCT4), which is expressed exclusively in astrocytes and transports lactate from astrocytes to the extracellular space, caused similar results in the FST. The behavioral effect of both the pharmacological disturbance of astrocytic glycogenolysis and viral disruption of MCT4 expression was rescued via the administration of L-lactate. Moreover, we found that both pharmacological and viral modulation of astrocyte-derived lactate in mPFC slices increased the excitability of layer V pyramidal neurons, and this enhancement was reversed by exogenous L-lactate administration. These results highlight astrocyte-derived lactate as a biological mechanism underlying the passive coping response to behavioral challenge and may provide new strategies to prevent mood disorders.

Glucose-Potentiated Amikacin Killing of Cefoperazone/Sulbactam Resistant Pseudomonas aeruginosa.

Multidrug-resistant Pseudomonas aeruginosa has become one of global threat pathogens for human health due to insensitivity to antibiotics. Recently developed reprogramming metabolomics can identify biomarkers, and then, the biomarkers were used to revert the insensitivity and elevate antibiotic-mediated killing. Here, the methodology was used to study cefoperazone/sulbactam (SCF)-resistant P. aeruginosa (PA-RSCF) and identified reduced glycolysis and pyruvate cycle, a recent clarified cycle providing respiratory energy in bacteria, as the most key enriched pathways and the depressed glucose as one of the most crucial biomarkers. Further experiments showed that the depression of glucose was attributed to reduction of glucose transport. However, exogenous glucose reverted the reduction to elevate intracellular glucose via activating glucose transport. The elevated glucose fluxed to the glycolysis, pyruvate cycle, and electron transport chain to promote downstream proton motive force (PMF). Consistently, exogenous glucose did not promote SCF-mediated elimination but potentiated aminoglycosides-mediated killing since aminoglycosides uptake is PMF-dependent, where amikacin was the best one. The glucose-potentiated amikacin-mediated killing was effective to both lab-evolved PA-RSCF and clinical multidrug-resistant P. aeruginosa. These results reveal the depressed glucose uptake causes the reduced intracellular glucose and expand the application of metabolome-reprogramming on selecting conventional antibiotics to achieve the best killing efficacy.

Potential Role of Cellular Senescence in Asthma.

Cellular senescence is a complicated process featured by irreversible cell cycle arrest and senescence-associated secreted phenotype (SASP), resulting in accumulation of senescent cells, and low-grade inflammation. Cellular senescence not only occurs during the natural aging of normal cells, but also can be accelerated by various pathological factors. Cumulative studies have shown the role of cellular senescence in the pathogenesis of chronic lung diseases including chronic obstructive pulmonary diseases (COPD) and idiopathic pulmonary fibrosis (IPF) by promoting airway inflammation and airway remodeling. Recently, great interest has been raised in the involvement of cellular senescence in asthma. Limited but valuable data has indicated accelerating cellular senescence in asthma. This review will compile current findings regarding the underlying relationship between cellular senescence and asthma, mainly through discussing the potential mechanisms of cellular senescence in asthma, the impact of senescent cells on the pathobiology of asthma, and the efficiency and feasibility of using anti-aging therapies in asthmatic patients.

Further insights into the composition, source, and toxicity of PAHs in size-resolved particulate matter in a megacity in China.

Concentrations of particulate matter with an aerodynamic diameter less than 10 µm (PM10 ) and PM with an aerodynamic diameter less than 2.5 µm (PM2.5 ), and 16 polycyclic aromatic hydrocarbons (PAHs) were measured. The average concentrations of PM10 and PM2.5 reached 209.75 µg/m(3) and 141.87 µg/m(3) , respectively, and those of ΣPAHs were 41.46 ng/m(3) for PM10 and 36.77 ng/m(3) for PM2.5 . The mass ratio concentrations were 219.23 µg/g and 311.01 µg/g in PM10 and PM2.5 , respectively. Three sources and their contributions for PAHs were obtained. For individual input mode, diesel exhaust contributed 46.77% (PM10 ) and 41.12% (PM2.5 ) for mass concentration and 48.69% (PM10 ) and 39.47% (PM2.5 ) for mass ratio concentration; gasoline exhaust contributed 31.02% (PM10 ) and 39.47% (PM2.5 ) for mass concentration and 28.95% (PM10 ) and 36.46% (PM2.5 ) for mass ratio concentration; and coal combustion contributed 22.22% (PM10 ) and 19.41% (PM2.5 ) for mass concentration and 22.36% (PM10 ) and 15.89% (PM2.5 ) for mass ratio concentration. For combined input mode, the same source categories were obtained. Source contributions to PM10 and PM2.5 were diesel exhaust (40.70% and 36.64%, respectively, for mass concentration; 49.19% and 38.47%, respectively, for mass ratio concentration), gasoline exhaust (35.09% and 38.47%, respectively, for mass concentration; 32.50% and 33.43%, respectively, for mass ratio concentration), and coal combustion (24.21% and 24.89%, respectively, for mass concentration; 18.31% and18.17%, respectively, for mass ratio concentration). Source risk assessment showed that vehicle emission was a significant contributor. The findings can help elucidate sources of PAHs and provide evidence supporting further applications of the Unmix model and additional studies about PAHs. Environ Toxicol Chem 2015;34:480-487. © 2014 SETAC.